Document 6428420

Transcription

Document 6428420

Poster Session I
www. AJOG.org
Thursday, February 14, 2013 • 10:00 am – 12:00 pm • Grand Ballroom
CLINICAL OBSTETRICS, EPIDEMIOLOGY, FETUS, MEDICAL-SURGICAL
COMPLICATIONS, NEONATALOGY, PHYSIOLOGY/ENDOCRINOLOGY,
PREMATURITY
Abstracts 87 – 236
87 Does change in BMI between pregnancies increase
the risk for adverse pregnancy outcomes?
Adi Hirshberg1, Lisa Levine1, Sindhu Srinivas1
1
University of Pennsylvania Perelman School of Medicine, Maternal and
Child Health Research Program, Department of Obstetrics and Gynecology,
Phildelphia, PA
OBJECTIVE: Obesity is a risk factor for adverse pregnancy outcomes
(APO). Data are limited on interval weight change between pregnancies and subsequent pregnancy outcomes. Our objective is to evaluate
distribution of change in BMI categories between two pregnancies
and its effect on APOs in a subsequent pregnancy (Preg2).
STUDY DESIGN: We performed a retrospective cohort study of women
with 2 consecutive deliveries from 2005-2010. Term spontaneous labor
and inductions in the index pregnancy (Preg1) were included. Analysis
was limited to women with 1st prenatal BMI ⬍20 wks for both pregnancies. BMI was defined as normal (NW):18.5-24.9, overweight (OW):
25.0-29.9, obese (OB): ⱖ30, and morbidly obese (MOB): ⬎40kg/m2.
Maternal information was obtained through chart abstraction. The composite APO includes preterm birth ⬍37 wks, preeclampsia, and IUGR.
Women who changed BMI categories between pregnancies were compared to those who remained in same category, regardless of Preg1 BMI.
Strata specific analyses within each BMI category were performed. ␹2
analyses were used to compare categorical variables.
RESULTS: 480 women were analyzed (43% NW, 28% OW, and 25% OB
in index). Of these, 24% increased BMI category between pregnancies.
205 women started Preg1 NW. 83% stayed NW at the start of Preg2; 16%
progressed to OW or OB. 134 women started Preg1 OW. 60% remained
OW or went to NW; 40% went to OB. 121 women started Preg1 OB. 95%
remained OB and of those, 16% progressed to MOB. There was no association between increase in BMI category and APO (p⫽0.6) or mode of
delivery (p⫽0.8) in Preg2. When restricting to NW and OW in Preg1,
there was no association between increase vs. unchanged BMI category
and APO (NW; p⫽0.1, OW; p⫽ 0.5).
CONCLUSION: A significant number of women increased BMI category
between pregnancies. There are public health implications associated
with obesity. Future research should assess implications of interval
BMI change and whether current weight gain guidelines can prevent
an increase in BMI category between pregnancies.
losses and 5 women with previous normal pregnancy, matched for
age, menstrual period and body mass index. Exclusion criteria were
chronic diseases, autoimmune and connective tissue disorders, or
cancer. A RT2 Profiler PCR Array System - Human Cytokines &
Chemokines (PAHS - 150D) was used to profile the expression of 96
genes in RPL samples and controls. Data were confirmed by quantitative real-time PCR and western blot. Significance was set at p⬍0.05.
RESULTS: In women with RPL, 4 genes were significantly up-regulated
(PPBP, BMP2 and 7, CCL21), and 28 significantly down-regulated.
The proinflammatory chemokines BMP2 and CCL21 were found upregulated. Significant downregulation was detected for several genes
involved in angiogenesis (IL22,IL23), interleukines implicated in
Th1/Th2 balance (IL4, IL5) and CSF1, which is involved in the development of placenta.
CONCLUSION: The gene expression profile of the endometrium of
women with RPL, obtained through PCR array technology, is consistent with a proinflammation state, a shift fromTh1/Th2, a decreased
angiogenesis and an improper placental development.
88 Deregulated cytokine and chemokind expression in
endometrium from women with recurrent pregnancy loss
Alessandra Corardetti1, Monia Cecati1, Davide Sartini1,
Irene Lucibello1, Alessandra Tozzi1, Franca Saccucci1,
Monica Emanuelli1, Andrea Tranquilli1
1
Università Politecnica Marche, Department of Clinical Sciences, Ancona,
Italy
OBJECTIVE: Implantation in humans is a complex process that is temporally and spatially restricted. Using a one-by-one approach, several
gene products that may participate in this process have been identified. Our objective was to explore if those genes are differentially expressed in endometrium from women with recurrent pregnancy loss
(RPL).
STUDY DESIGN: Endometrial samples were obtained through hysteroscopic biopsy from 5 patients with 2 or more consecutive pregnancy
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Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity
89 Neonatal respiratory morbidity and mode of delivery
between 34ⴙ0 and 36ⴙ6 weeks of gestation
Giuliana Simonazzi1, Alessandra Curti1, Elisa Moro1, Andrea
Pedrazzi1, Tiziana Martina1, Antonio Farina1, Nicola Rizzo1
1
St. Orsola Malpighi Hospital, University of Bologna, Department of
Obstetrics & Gynecology, Bologna, Italy
OBJECTIVE: To assess the impact of mode of delivery on respiratory
morbidity among late-preterm neonates.
STUDY DESIGN: Singleton pregnancies complicated by premature rupture of membranes (PROM) between 34⫹0 and 36⫹6 weeks were
studied retrospectively. Pregnancies with corticosteroid administration after 34⫹6 weeks were excluded. Patients were divided into cesarean section (CS) and vaginal delivery groups, matched 1:3 for gestational age. The primary outcome was the rate of respiratory distress
syndrome (RDS). Logistic regression was performed to assess the risk
of RDS within groups.
RESULTS: Between 2005 and 2012, 360 patients delivered between 34
and 36 weeks after premature rupture of membranes at St. OrsolaMalpighi Hospital, Bologna (Italy). In 90 cases elective caesarean section was performed for previous CS (n⫽50), breech presentation
(n⫽31) or maternal medical indications (n⫽9). No difference was
found for antenatal betamethasone within groups. The overall RDS
rate was 15%, while it was 30% and 10% in case of CS and vaginal
delivery, respectively (p-value 0.0001). CS seems to be a risk factor for
RDS (OR 4.2, p-value 0,0001), as does earlier gestational age at delivery (OR 0.9, p-value 0,0001). Table 1 shows the median risks of RDS in
the study population according to the logistic regression model.
CONCLUSION: After preterm PROM, CS is associated with a higher risk
of neonatal RDS. This is more evident with increasing gestational age,
when respiratory morbidity is thought to be less frequent.
Median estimated risk of RDS
90 Oral misoprostol vs vaginal dinoprostone for
labor induction in nulliparous women at term
Allison Faucett1, Kay Daniels1, Yasser El-Sayed2,
Henry Lee3, Yair Blumenfeld2
1
Stanford University School of Medicine, Obstetrics & Gynecology, Palo Alto,
CA, 2Stanford University School of Medicine, Obstetrics & Gynecology,
Division of Maternal-Fetal Medicine, Palo Alto, CA, 3University of
California, San Francisco, Pediatrics, Division of Neonatology,
San Francisco, CA
OBJECTIVE: To compare the effectiveness and safety of oral misoprostol to the vaginal dinoprostone insert for the induction of labor of
nulliparous women at term.
STUDY DESIGN: Records of women admitted to Lucile Packard Children’s Hospital from January 2008 to December 2010 for labor induction with an unfavorable cervix were reviewed. Patients receiving oral
misoprostol as the primary induction agent were compared with
those receiving vaginal dinoprostone. Multiparous patients and those
with multiple or preterm gestations, membrane rupture, or use of
other primary induction agents were excluded. The primary outcome
was defined as time interval from administration of the primary induction agent to vaginal delivery. Secondary outcomes included vaginal delivery in less than 24 hours, use of secondary ripening or augmentation agents, and maternal and fetal outcomes.
RESULTS: 1016 patient records were reviewed. 680 met inclusion criteria: 483 (71%) received vaginal dinoprostone and 197 (29%) received oral misoprostol. Patients receiving oral misoprostol were
more likely to be Hispanic (40% vs. 35%, p⫽0.04), and to have greater
cervical dilation on admission (mean ⫽ 0.63 cm vs. 0.98 cm,
Poster Session I
p⬍0.001). Time interval from induction to vaginal delivery was
shorter with oral misoprostol (27.2 vs. 21.9 hours, p⬍ 0.001). This
difference remained significant when controlling for cervical dilation,
regional anesthesia, and birthweight. After risk adjustment, the odds
of vaginal delivery in less than 24 hours was two times greater with oral
misoprostol (OR 2.26, CI⫽1.42-3.58). Patients receiving oral misoprostol were more likely to deliver vaginally (71% vs. 63%, p⫽0.04);
however no difference was seen after adjusting for possible confounders. There were no differences in any of the secondary maternal or fetal
outcomes.
CONCLUSION: In nulliparous women, oral misoprostol as the primary cervical ripening agent resulted in a shorter interval to vaginal delivery.
91 Second trimester cervical length and persistence
of placenta previa in the third trimester
Amanda Trudell1, Molly Stout1, Alison Cahill1, Anthony Odibo1,
George Macones1, Methodius Tuuli1
1
Washington University in St. Louis, Obstetrics and Gynecology, St. Louis,
MO
OBJECTIVE: Transvaginal ultrasound prior to 20 weeks identifies placenta previa in 1/20 pregnancies, but only about 10% persist in the
third trimester. Prior studies have associated decreased cervical length
(CL) in the setting of placenta previa with adverse obstetric outcomes
including maternal hemorrhage, preterm birth, emergency cesarean
and abnormally adherent placenta. However, the association between
CL and persistence of placenta previa has not been evaluated. We
sought to test the hypothesis that cervical shortening with associated
development of the lower uterine segment in the setting of placenta
previa is associated with impaired placental migration away from the
internal cervical os, and persistent placenta previa.
STUDY DESIGN: A retrospective cohort study of singleton pregnancies
presenting for routine fetal anatomic survey (17w0d- 23w6d).
Women with multiple gestations, major uterine anomalies and those
without third trimester follow up ultrasound were excluded. The primary outcome was persistence of placenta previa on ultrasound in the
third trimester (28w0d-36w6d). CL at the time of the anatomic survey
in women with persistence and resolution of placenta previa in the
third trimester were compared. The predictive value of second trimester CL for persistent placenta previa in the third trimester was assessed
using the receiver-operating characteristics (ROC) curve.
RESULTS: 294 women diagnosed with placenta previa at anatomic survey in the second trimester met inclusion criteria. Of these, 16 (5.4%)
had placenta previa on follow-up ultrasound in the third trimester. CL
was not significantly different in women with persistent placenta previa compared to those with resolution (45.1⫾8.8mm versus 43.4⫾
8.2mm, p⫽0.42). The area under the ROC was 0.58, and no CL cutoff
was significantly associated with persistence of placenta previa (Table).
CONCLUSION: These data suggest that second trimester CL is not predictive of persistence of placenta previa in the third trimester.
92 Placental pathology, first-trimester biomarkers,
and adverse pregnancy outcomes (APO)
Amanda Spitalnik1, Kalyani Patel2, Linda Odibo1,
Phyllis Huettner2, Anthony Odibo1
1
MO, 2Washington University in St. Louis, Pathology, St. Louis, MO
OBJECTIVE: To investigate the association of placental pathology
(Path) findings in pregnancies with APO and first-trimester
biomarkers.
STUDY DESIGN: This is a prospective study of first-trimester screening
for APO. Path were reviewed by two perinatal pathologists blinded to
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
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clinical outcomes. First, we determine the association between Path
lesions and APO including: preterm birth [PTB (delivery ⬍ 37
weeks)], preeclampsia (PE), gestational hypertension (GH) and small
for gestational age (SGA) infants (birthweight ⬍10th percentile). We
then compare the mean levels of serum analytes (PAPP-A, PP13,
ADAM12s, PLGF), and uterine artery Doppler PI (UADPI) obtained
at 11-14 weeks gestation in cases with APO and abnormal placental
histology (PlacHist) to a control group without APO or abnormal
Path. Path were classified as: lesions of maternal under perfusion
(LMUP) including a composite of: infarct, decidual vasculopathy, distal villous hypoplasia); lesions of reduced placental reserve (LRPR)including: avascular villi, perivillous fibrin/intervillous thrombo-hematoma, villitis); and Infectious/inflammatory (INFL) lesions
(chorioamnionitis, funisitis/chorionic vasculitis). Statistical analysis
was performed using chi-squared, paired t-test and ANOVA.
RESULTS: Among 193 Path reviewed, LMUP were seen in 59 (30.7%);
LRPR in 63 (32.85),and INFL in 65 (34.2%). PE was significantly
associated with LMUP (p⫽0.005) and INFL (p⫽0.003). PTB ⬍ 28
weeks was the only sub-group of PTB with a significant association
with INFL: 75% versus 31% (p⬍⫽0.002). SGA and GH were not
significantly associated with any PlacHist abnormality. Significant
differences were seen in mean levels of PAPPA, ADAM12s and PLGF
in cases of PE and PTB with specific Path lesions compared with controls (Table).UADPI was not significantly different between the cases
with APO and abnormal Path.
CONCLUSION: Our findings provide evidence linking placental pathology with mal-secretion of analytes in first-trimester in pregnancies
with APO, especially PE.
Placental lesions seen in cases with
preeclampsia and preterm birth
*Significant at P ⬍ .05.
93 The impact of gestational weight gain on
perinatal outcomes in obese women
Amelia Sutton1, Jennifer Durst1, Suzanne Cliver1,
Alan Tita1, Joseph Biggio1
1
University of Alabama at Birmingham, Obstetrics and Gynecology,
Birmingham, AL
OBJECTIVE: To evaluate the relationship between gestational weight
gain and maternal and neonatal outcomes in obese women.
STUDY DESIGN: Retrospective cohort study of obese women, defined as
having a body mass index (BMI) of ⬎30, delivering singletons ⬎20
weeks between 2000-2009. All included women had a weight documented in the first trimester and within 3 weeks prior to delivery.
Women were stratified into quartiles according to the average gestational weight gain in kg/week. Maternal and neonatal outcomes were
compared using the chi-squared test and the Mantel-Haenszel test for
trend.
RESULTS: 6251 obese women were eligible for the study. As shown in
the Table, increased gestational weight gain (⬎0.53 kg/week; highest
quartile of gestational weight gain) was associated with a multitude of
adverse maternal and neonatal outcomes, including cesarean delivery,
infections, shoulder dystocia, hypertensive disorders, and macrosomia. Minimal weight gain (⬍0.16 kg/week; lowest quartile of gestational weight gain) was associated with lower birthweights. Several
outcomes, such as spontaneous preterm delivery, 5-minute Apgar
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⬍5, and fetal demise, displayed a bimodal distribution, with increased
rates associated with minimal and increased gestational weight gain.
CONCLUSION: Both minimal and excessive gestational weight gain in
obese gravidas is associated with adverse maternal and neonatal outcomes. Obese women with moderate weight gain have the most favorable perinatal outcomes.
Perinatal outcomes (%) in obese women according
to gestational weight gain
BWT, birthweight; DM, diabetes mellitus; HTN, hypertension; LGA, large for gestational age; PTB,
preterm birth; SGA, small for gestational age.
94 What is the optimal time to deliver dichorionic
diamniotic twins when one twin has
intrauterine growth restriction?
Amy Doss1, Allison Allen1, Rachel Pilliod2, Sarah Little2,
Anjali Kaimal3, Teresa Sparks2, Aaron Caughey1
1
Oregon Health & Science University, Obstetrics & Gynecology, Portland,
OR, 2Brigham & Women’s/Mass General Hospital, Obstetrics & Gynecology,
Boston, MA, 3Massachusetts General Hospital, Obstetrics & Gynecology,
Boston, MA
OBJECTIVE: Determining the optimal timing of delivery of a twin gestation involves balancing the risk of complications against the potential morbidity of late preterm/early term birth. Timing of delivery
becomes more challenging if one twin has intrauterine growth restriction (IUGR), as this increases the risk of IUFD. We used decision
analysis to estimate the optimal gestational age (GA) for delivery of
dichorionic diamniotic (DCDA) twin gestations when one has IUGR.
STUDY DESIGN: A decision-analytic model was created using TreeAge
to compare the outcomes of delivery at 34, 35, 36, 37 and 38 weeks in
a theoretical cohort of DCDA twin pregnancies when one twin has
IUGR. Our baseline assumption was that a twin with IUGR was at
7.06-fold increased risk of IUFD. Strategies involving expectant management (EM) until a later GA accounted for the probabilities of
spontaneous delivery, indicated delivery, and IUFD during each successive week. GA associated risks of neonatal complications including
major neurodevelopmental disability, perinatal and neonatal mortality. Baseline assumptions were derived from the literature. Total quality-adjusted life years (QALYs) were calculated, accounting for both
neonatal and maternal utilities. Sensitivity analyses were conducted to
evaluate the impact of baseline assumptions on model outcomes.
RESULTS: Our model showed that earlier GAs were associated with
increased neonatal morbidity, but lower overall IUFD rates (Table).
Balancing these outcomes, the optimal delivery strategy was EM until
35 weeks, which maximized the total QALYs. Sensitivity analysis
showed that optimal GA at delivery was sensitive to the increased risk
of IUFD associated with IUGR. EM until 35 weeks was the optimal
strategy until the increased risk of IUFD in an IUGR twin fell below
5.82-fold, when delivery strategies at later GAs became preferred.
CONCLUSION: Weighing the risks of IUFD against the outcomes of iatrogenic prematurity, the ideal GA to deliver DCDA twins when one
has IUGR is 35 weeks.
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Poster Session I
of IUFD associated with major cardiac anomalies. EM until 38 weeks
was the optimal strategy until the increased risk of IUFD in an cardiac
anomaly twin increased beyond a relative risk of 21.6, when delivery
strategies at earlier GAs became preferred.
CONCLUSION: Weighing the risks of IUFD against the outcomes of iatrogenic prematurity, the ideal GA to deliver DCDA twins in one with
a major cardiac anomaly is 38 weeks.
Dichorionic diamniotic twins in the setting of IUGR
96 The effect of CenteringPregnancy Group prenatal
care on enrollment in the post-partum family
planning Medicaid waiver program
Optimal delivery strategy with varying risk of IUFD
Nathan Hale1, Amy Picklesimer2, Deborah Billings3,
Sarah Covington-Kolb2
As shown above, if the relative risk of IUFD in an IUGR twin is less than
4.54-fold greater than a non-IUGR twin, the optimal time of delivery increases to 37 weeks.
95 What is the optimal GA to deliver dichorionic diamniotic
twins when one twin has a major cardiac anomaly?
Amy Doss1, Keenan Yanit1, Allison Allen1, Brian Shaffer1,
Yvonne Cheng2, Aaron Caughey1
1
OR, 2University of California San Francisco, Obstetrics, Gynecology, &
Reproductive Sciences, San Francisco, CA
OBJECTIVE: Optimal timing of twin delivery involves balancing the
risk of IUFD against the potential morbidity of late preterm/early
term birth, which becomes more challenging if one twin has a major
cardiac anomaly, as this increases the IUFD risk and neonatal morbidity/mortality. We used decision analysis to estimate the optimal
GA for delivery of dichorionic diamniotic (DCDA) twins when one
has a cardiac anomaly.
STUDY DESIGN: A decision-analytic model was created using TreeAge
to compare the outcomes of delivery at 34 through 38 weeks in a
theoretical cohort of DCDA twin pregnancies when one twin has a
major cardiac anomaly. Our baseline assumption was that a twin with
a cardiac anomaly was at 10-fold increased risk of IUFD. Strategies
involving expectant management (EM) until a later GA accounted for
the probabilities of spontaneous delivery, indicated delivery, and
IUFD during each successive week. GA associated risks of neonatal
complications including major neurodevelopmental disability, perinatal and neonatal mortality. Baseline assumptions were derived from
the literature. Total quality-adjusted life years (QALYs) were calculated, accounting for both neonatal and maternal utilities. Sensitivity
analyses were conducted.
RESULTS: Our model showed that earlier GAs were associated with
increased neonatal morbidity, but lower overall IUFD rates (Table).
Balancing these outcomes, the optimal delivery strategy was EM until
38 weeks, which maximized the total QALYs. Sensitivity analysis
showed that optimal GA at delivery was sensitive to the increased risk
1
University of South Carolina Arnold School of Public Health, Health
Services Policy and Management, Columbia, SC, 2Greenville Hospital System
University Medical Center, Obstetrics and Gynecology, Greenville, SC,
3
University of South Carolina Arnold School of Public Health, Health
Promotion, Education and Behavior, Columbia, SC
OBJECTIVE: To evaluate the effect of participation in group prenatal
care (GPNC) compared with participation in traditional prenatal care
(TPNC) on enrollment in the post-partum family planning waiver
program among South Carolina women enrolled in Medicaid during
pregnancy.
STUDY DESIGN: South Carolina Medicaid billing data was linked to
birth certificate records to create a retrospective cohort of women
delivering at a single hospital between May 2009 and May 2010.
Women who chose to participate in GPNC were matched with
women in TPNC using propensity scores. Multivariate logistic regression was used to examine differences in rates of participation in the
Medicaid family planning waiver program by 3 months post-partum.
RESULTS: 339 women participating in GPNC were compared with 602
in TPNC. With the exception of tobacco use during pregnancy, the
propensity matched cohort was balanced across all descriptive covariates. The rate of enrollment in the family planning waiver was 57.8%
(n⫽196) for GPNC, as compared with 43.7% (n⫽263) in TPNC
(p⬍0.05). Multivariate analysis confirmed women in GPNC were
more likely to enroll in family planning by 3 months post-partum
(AOR 2.02, 95% CI 1.48-2.75).
CONCLUSION: This study found GPNC to be associated with improved
enrollment in the family planning Medicaid waiver program. It expands the evidence base supporting GPNC by documenting improved
transitioning into other important health service programs during the
post-partum period compared to a rigorously matched cohort of
women receiving TPNC. Previous studies have found participation in
GPNC to be associated with improved birth outcomes. The current
project evaluates ways GPNC participation could have a more lasting
impact on women’s health.
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97 Magnesium sulfate exposure and neonatal
intensive care unit admission
Anna Girsen1, Mara Greenberg2, Yasser El-Sayed2,
Brendan Carvalho2, Deirdre Lyell2
1
Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland,
Stanford University/Lucile Packard Children’s Hospital, Obstetrics and
Gynecology, Stanford, CA
2
OBJECTIVE: To examine the effect of antenatal magnesium sulfate
(MS) treatment on neonatal intensive care unit (NICU) admission
among term newborns of mothers with preeclampsia.
STUDY DESIGN: Secondary analysis of the Maternal-Fetal Medicine
Unit Network Cesarean Registry including primary and repeat cesareans, and failed and successful vaginal births after cesarean delivery.
Singleton pregnancies among women with preeclampsia and ⬎37
weeks of gestation were included. Pregnancies with chorioamnionitis
were excluded. Logistic regression analysis was used to determine associations between MS exposure and important outcomes. P⬍0.05
was considered statistically significant.
RESULTS: 2224 pregnancies of women with preeclampsia were included, of whom 1,795 (81%) received MS for eclampsia prophylaxis
and 429 (19%) did not. MS exposure was associated with increased
NICU admission (23% vs. 14% unexposed, p⬍0.0001) whereas no
significant difference was found in the length of newborn stay in
NICU (median 5 days (range 2-91) vs. 6 days (range 3-37) in unexposed, p⫽0.45). MS-exposed women were more likely to receive public insurance (51% vs. 40% unexposed, p⫽0.0008) and have a labor
induction (43% vs. 9% unexposed, p⫽0.02), and less likely to be Caucasian (23% vs. 31% unexposed, p⬍0.0001), be diagnosed with
chronic hypertension (7% vs. 9% unexposed, p⫽0.04), or undergo
cesarean delivery (90% vs. 94% unexposed, p⫽0. 03). MS-exposed
newborns had significantly lower birthweights (3288 vs. 3442 grams
unexposed, p⬍0.0001) and similar gestational ages at delivery (39.2
vs. 39.1 unexposed, p⫽0.11). Logistic regression analysis adjusting for
receipt of public insurance, race, chronic hypertension, labor induction, cesarean delivery, birthweight and gestational age found that
NICU admission was significantly associated with MS exposure [OR
2.60, 95% CI 1.68-4.20, p⬍0.0001].
CONCLUSION: Antenatal magnesium sulfate treatment is associated
with an increase in NICU admission among exposed term newborns
of mothers with preeclampsia.
98 Maternal obesity and the risk
of postpartum hemorrhage
Annelee Boyle1, Julia Timofeev1, Maisa Feghali1, Sameer Desale2,
Menachem Miodovnik1, Rita Driggers1
1
MedStar Washington Hospital Center, Obstetrics and Gynecology,
Washington, DC, 2MedStar Health Research Institute, Biostatistics and
Epidemiology, Hyattsville, MD
OBJECTIVE: To determine if overweight and obese women are at increased risk of postpartum hemorrhage (PPH) and, if so, if the risk of
PPH correlates with the degree of obesity.
STUDY DESIGN: A retrospective cohort analysis of data in the MedStar
PeriBirth labor database from 2009 to 2012. Overweight women
[body mass index (BMI) 25.0-29.9 kg/m2], obese women (BMI 30.039.9 kg/m2), and extremely obese women (BMI ⱖ 40.0 kg/m2) were
compared to women of normal weight (BMI 18.5-24.9 kg/m2) who
delivered a singleton pregnancy at term (37.0-41.9 weeks’ gestation).
Women were classified by pre-pregnancy BMI. Postpartum hemorrhage was defined as an estimated blood loss of ⬎500 ml following
vaginal delivery or ⬎1,000 ml following Cesarean delivery. Multivariate analysis was performed controlling for maternal age, race, parity,
mode of delivery, fetal macrosomia (⬎4,000 grams), polyhydramnios, magnesium sulfate administration, clinical chorioamnionitis,
mode of delivery, and episiotomy. ␹2 and Fisher’s exact tests were used
for categorical variables. Statistical significance was set at a p-value
of ⬍0.05.
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RESULTS: A total of 6,865 women were included in the analysis: 788
(11.5%) had normal BMI, 2,161 (31.5%) were overweight, 2,965
(43.2%) were obese, and 951 (13.8%) were extremely obese. Extremely obese women were significantly more likely to experience
PPH than women of normal weight [OR 1.8, 95% confidence interval
(CI) 1.05-3.12, p ⫽ 0.0328]. There was no significant difference
among overweight (OR 1.2, 95% CI 0.73-2.01, p ⫽ 0.4620) or obese
women (OR ⫽ 1.2, 95% CI 0.74-1.99, p ⫽ 0.4392) compared to
women of normal weight.
CONCLUSION: Extremely obese women are at a higher risk of postpartum hemorrhage compared to women with normal BMI. Even a modest decrease in pre-pregnancy BMI can reduce this risk.
99 Obstetrical outcomes in women with epilepsy enrolled
in the North American Antiepileptic Drug Registry (NAAPR)
Autumn Klein1, Hillary Keenan2, Robert Mittendorf3,
Sonia Hernandez-Diaz4, Page Pennell5, Nichelle Llewellyn5,
Caitlin Smith6, Lewis Holmes6, Thomas McElrath7
1
University of Pittsburgh Medical School, Neurology and Obstetrics and
Gynecology, Pittsburgh, PA, 2Joslin Diabetes Center, Genetics and
Epidemiology, Boston, MA, 3Loyola University, Obstetrics and Gynecology,
Chicago, IL, 4Harvard School of Public Health, Epidemiology, Boston, MA,
5
Harvard Medical School, Neurology, Boston, MA, 6Harvard Medical School,
Pediatrics, Boston, MA, 7Harvard Medical School, Obstetrics and
Gynecology, Boston, MA
OBJECTIVE: Little is known about obstetrical and neonatal outcomes
in women with epilepsy (WWE) taking antiepileptic drugs (AEDs).
This study aims to determine the rate of C-section (CS) in WWE on
AEDs compared to women without epilepsy not taking an AED
(WWoE) and to determine if there is an indication for CS, including
seizure.
STUDY DESIGN: The NAAPR, which began in 1997, is a voluntary
call-in registry of pregnant women taking AEDs. Participants are
asked a series of questions twice during pregnancy and once postpartum. We determined how many WWE and WWoE reported having a
CS and classified their responses into different indications. WWE
were compared to WWoE.
RESULTS: There were 6,253 WWE reporting AED use at the time of last
menstrual period and 469 WWoE. WWE were slightly younger
(29.5 ⫾ 5.4 v. 31.5 ⫾ 4.1 years) (p⬍0.001) and were less likely to have
had a previous delivery (parity 0.8 ⫾ 0.9 v. 1.0 ⫾ 0.9, p⬍0.001), but
were likely to have had an equal number of pregnancies (gravidas
2.2 ⫾ 1.3 v. 2.3 ⫾ 1.3, p⫽0.1). WWE were more likely to report
smoking during the first trimester (14.1% v. 6.8%, p⬍0.05). There
was a higher proportion of whites among WWoE (p⬍0.001), and the
most common AEDs were lamotrigine (26.1%) followed by carbamazepine (22.9%). A total of 34.5% of WWE had a CS as compared to
29.8% of WWoE (p⫽0.05), but when adjusted for age, parity and
pre-existing hypertension, these findings are no longer significant
(OR: 1.03 95% CI: 0.54, 2.0, p⫽0.9). Of WWE, 10.5% reported seizure
as a reason for their CS.
CONCLUSION: There is borderline difference in the rate of CS between
WWE and WWoE when adjusted for the confounders of age, parity,
and pre-existing hypertension. Seizure was reported as an indication
for CS in a significant number of WWE and suggests that WWE may
benefit from specialized multi-disciplinary care at larger hospitals.
Future studies will examine other obstetrical and neonatal outcomes
including CS and SGA by AED.
100 Comparing estimated fetal weight by ultrasound
and clinical assessment with actual birthweight
Benjamin Solomon1, Geralyn O’Reilly1, Pedro Arrabal1,
David Schwartz1, Stephen Contag1
1
Sinai Hospital of Baltimore, Obstetrics and Gynecology, Baltimore, MD
OBJECTIVE: To evaluate if there is a significant difference between two
antepartum methods of estimating fetal weight immediately before
birth and the actual birthweight.
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STUDY DESIGN: Fetal ultrasound was performed within 48 hours of
delivery on term fetuses in women admitted to Sinai Hospital of Baltimore. Clinical estimates of fetal weight were obtained by attending
and resident physicians. These estimates were then compared to the
actual birthweight after delivery.
RESULTS: We analyzed 47 of 51 recruited women. The median age was
28 years, median gestational age was 40 weeks, median BMI was 29.7
with 50% of patients between 26 and 32.8 kg/m2 and the mean birthweight was 3,451 ⫾ 343 grams. There were 47% African American and
51% Caucasian women. The majority of patients were nuliparous
(53%). The clinical fetal weight estimates by the attendings correlated
better with the birthweight than did the resident’s ((Pearson correlation 0.49 vs. 0.20). When attendings and residents estimated fetal
weight on the same patient, only attendings’ estimates were significant, r⫽ 0.46 (p ⫽0.01). Clinical estimates consistently overestimated
birthweight at lower values and underestimated it at higher values
(Figure). Multiple regression adjusting for maternal parity, age and
BMI demonstrated that ultrasound correlated better with birthweight
than clinical estimates (0.73). Attending but not resident estimates
were significantly associated with birthweight in the model. Experience with ultrasound increased the correlation with birthweight
(Pearson correlation 0.68 first half vs 0.79 second half). Various published equations for calculating fetal weight using different biometric
parameters found that Hadlock ‘85 formula with BPD, HC, AC and FL
was the best predictor (Table).
CONCLUSION: Ultrasound was the best method to predict birthweight.
Physician experience improves clinical prediction. No formula to predict fetal weight was better than the Hadlock ‘85 formula that includes
cephalic, abdominal and femoral measurements.
Multivariate models for predicting birthweight
Poster Session I
previa was compared to women with a posterior previa. Stratified
analysis was performed based on primary versus repeat cesarean. Logistic regression was performed to control for potential confounders.
RESULTS: 48,229 women delivered during the study timeframe. 285
women (0.6%) underwent cesarean delivery for placenta previa. 42
(14.5%) women received a hysterectomy or blood transfusion.
The anterior and posterior previa groups were similar with respect to
age, tobacco use and BMI. Women with an anterior previa were more
likely to have a prior cesarean delivery, be multiparous and have a
singleton gestation compared to women with a posterior previa. The
mean blood loss during cesarean was higher for women with an anterior previa (p⫽0.0005) compared to those with a posterior previa.
Women with an anterior previa were more likely to require a blood
transfusion (p⫽0.014) and to undergo hysterectomy (p⫽0.0001).
Consistent with prior studies, women undergoing repeat cesarean had
higher likelihoods of hysterectomy (OR 9.8, 95% CI 3.1-31.5), blood
transfusion (OR 2.1, 95% CI 1.0-4.2) and accreta (OR 5.3, 95% CI
2.1-13.4). In stratified analysis, primary cesareans with anterior previa
had higher rates of blood transfusion (aOR 3.09; 95% CI: 1.16-8.17)
and hysterectomy (p⫽0.001) than posterior previas. Women undergoing repeat cesarean with anterior previa had higher rates of hysterectomy (aOR 4.72; 95% CI 1.12-19.78) compared to those with posterior previa.
CONCLUSION: Compared to a posterior placenta previa, an anterior
previa increases the risk of hysterectomy for both primary and repeat
cesareans and increases the likelihood of blood transfusion at primary
cesareans. This information may be useful for pre-operative planning.
Subgroup analysis of operative morbidity based
on cesarean order and placental location
Data presented as: N (%) or odds ratios (95% confidence interval). Regression covariates: BMI, age, multiple gestation.
AC, abdominal circumference; BPD, biparietal diameter; FL, femur length; HC, head circumference.
102 Postpartum elevation of Toll-like receptor 1:
innate immune system activation persists
beyond the prototypical postpartum period
Brett Young1, Aleksandar Stanic1, Britta Panda2,
Alexander Panda3, Bo Rueda1
1
Massachusetts General Hospital, Vincent Obstetrics and Gynecology,
Boston, MA, 2Tufts Medical Center, Obstetrics and Gynecology, Boston, MA,
3
Yale University, Internal Medicine, New Haven, CT
101 Does placenta previa location matter? Surgical
morbidity associated with previa location
Brett Young1, Allan Nadel1, Britta Panda1, Anjali Kaimal1
1
Massachusetts General Hospital, Obstetrics-Gynecology, Boston, MA
OBJECTIVE: To evaluate the effect of placenta previa location (anterior
versus posterior) on surgical morbidity in primary and repeat cesarean deliveries.
STUDY DESIGN: Retrospective cohort undergoing cesarean for placenta
previa. The rate of operative morbidity for women with an anterior
OBJECTIVE: Toll-like receptors are important mediators of the innate
immune system that recognize structurally conserved protein sequences that are expressed by specific microorganisms. TLR 1 recognizes triacyl lipoproteins which are specifically expressed by bacteria.
Immune system dysfunction may be causal or serve as a stimuli to
preterm labor. There is limited information regarding basal expression of TLR 1 during pregnancies not affected by preterm labor. In this
study, our objective was to investigate whether TLR 1 expression in
healthy pregnant women changes longitudinally during a pregnancy
and postpartum.
STUDY DESIGN: We prospectively evaluated TLR expression in dendritic cells (DCs) of 20 healthy women during the 1st trimester (Collection 1), 2nd trimester (Collection 2), the day of delivery (Collection
3) and 6 weeks postpartum (Collection 4). TLR1/2 expression on DCs
was measured by multicolor flow cytometry. TLR levels from each
collections were compared to non-pregnant controls and to the postpartum collection. ANOVA and T-tests were used to assess statistical
significance.
RESULTS: Basal expression of TLR 1 was elevated throughout pregnancy in all trimesters and the postpartum collection relative to a
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Poster Session I
non-pregnant cohort (p⬍0.001). TLR 1 expression was highest postpartum compared to the non-pregnant controls with mean TLR 1
expression being 78% (p⬍ 0.001) above the non-pregnant control
level.
CONCLUSION: TLR 1 is elevated during pregnancy and postpartum in
uncomplicated pregnancies. Since TLR 1 ligands are specifically associated with bacteria, we hypothesize that basal expression of TLR 1
increases following transient exposure to bacteria at delivery and remains elevated into the postpartum period. Postpartum TLR 1 levels
have not yet returned to non-pregnant control levels suggesting that
immune system adaptations persist beyond the prototypical puerperal stage. This information may be useful for future studies evaluating TLR 1 and preterm labor.
Percentage increase in TLR 1 positive cells
when compared to non-pregnant controls
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Higher MWT and GA were associated with higher
CSR by logistic regression analysis
a: significant difference between FL vs. NL, and FL vs. CL; b: significant difference between FL and NL;
c: NS between FL and CL; d: NS between FL and NL; e: significant difference between FL and CL.
104 Optimization of competences in obstetrical
emergencies: a place for simulation training?
Cécile Monod1, Cora Voekt1, Martina Gisin1,
Stefan Gisin2, Irene Hoesli1
1
University Hospital Basel, Department of Obstetrics, Basel, Switzerland,
University Hospital Basel, Swiss Center for Medical Simulation “SimBa”,
Department of Anesthesia, Basel, Switzerland
2
* Significant P ⬍ .05 compared to non-pregnant controls.
103 Implementation of a full-time laborist
program is associated with a substantial
reduction in cesarean section rate
Brian Iriye1, Wilson Huang1, Jennifer Condon2,
Lyle Hancock1, Judy Hancock1, Thomas Garite3
1
High Risk Pregnancy Center, Las Vegas, NV, 2Sunrise Hospital and Medical
Center, Department of Women’s Services, Las Vegas, NV, 3Pediatrix Medical
Group, Sunrise, FL
OBJECTIVE: Laborist programs have grown as a means to improve patient safety and lower physician work hours. While laborist programs
have expanded, there has been limited research examining their effect
on patient outcomes. Within many community hospitals, physicians
are often located off site dividing time between office and hospital
settings. This traditional model results in reduced physician oversight,
inefficiency, and incentive to move towards earlier cesarean delivery.
Our hypothesis is that the initiation of a full-time dedicated laborist
staff decreases cesarean section rate (CSR) in term primiparous
patients.
STUDY DESIGN: A hospital database was examined to look at delivery
data from 2006-2011 for 3 historical groups based upon laborist status: no laborist, 24 hour in hospital laborist coverage by community
staff, or 24 hour in hospital coverage by a full-time laborist team. Data
was examined for primiparous patients who delivered at ⭌ 37 weeks.
RESULTS: Data was available on 6396 term primiparous patients. A
significant reduction in CSR was seen with the full-time laborist team
as compared to the no laborist and community laborist groups. No
significant difference was found between the no laborist and community laborist group in CSR. Logistic regression analysis was utilized to
examine the effects of birthweight, gestational age, diabetes, maternal
weight, and physician group upon CSR. An adjusted odds ratio revealed a 27.5% reduction in risk of cesarean section with provision of
care by the full time laborist group when compared either the no
laborist or community laborist groups.
CONCLUSION: A large reduction in CSR was seen with term primiparous delivery when a full-time laborist staff was utilized. In contrast,
in-hospital coverage with community physicians who are not committed full-time as laborists resulted in no significant change in CSR.
This study supports the formation of dedicated full-time laborist staff
models at community hospitals to lower the CSR.
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OBJECTIVE: In emergency situations inducing intense stress, optimal
management requires an immediate coordinated action of the multidisciplinary and multi-professional team. This study investigates the
influence of simulation training on 3 specifics skills: control of the
emergency situation, knowledge of algorithms, team communication.
STUDY DESIGN: Clinical algorithms are first presented to the participants including obstetricians and midwives. Six emergency situations
(shoulder dystocia, postpartum hemorrhage, eclampsia, maternal basic life support, neonatal resuscitation, operative vaginal birth) are
trained on high fidelity simulation mannequins, with subsequent debriefing. The 3 above-mentioned skills are evaluated anonymously
through a self-assessment questionnaire with a five points Likert scala
immediately after the training and 3 months later.
RESULTS: Since 2010, 168 participants took part in the training. The
return rate of questionnaires after 3 months was 36.3%. The proportion of junior doctors, specialist doctors and midwives was 31.1%,
34.7% and 34.2%. 40.2 % of the participants had less than 5 years
professional experience, 23.6 % between 5 and 10 years and 36.2%
more than 10 years. In comparison to the self-assessment collected
directly after the course, 3 months later, the participants had emergency situations completely or rather better under control (61.5% vs.
22.8%) and the algorithms completely or rather better present (69.2%
vs. 46.5%). 3 months after the training 89.7% of the participants had
improved their team communication. The participants who most
benefited of the training for the control of emergency situation and
presence of algorithms had a professional experience between 0-5
years. The participants with a professional experience between 5-10
years improved most their team communication.
CONCLUSION: The implementation of simulation training strengthens
the professional competence sustainably and contributes to optimize
the peripartum care of mother and child in emergency situations.
105 Decreased expression of endostatin (ES) and
hypoxia-inducible factor 1␣ (HIF-1␣) is associated
with excessive trophoblast invasion and aberrant
angiogenesis in placenta accreta
Christina Duzyj1, Irina Buhimschi1, John Hardy1, Megan
McCarthy1, Guomao Zhao1, Sarah Cross1,
Thomas Rutherford1, Mert Bahtiyar1, Catalin Buhimschi1
1
Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT
OBJECTIVE: ES, a bioactive C-terminus proteolytic cleavage fragment
of extracellular matrix collagen XVIII, inhibits migration/proliferation of cancer epithelial cells. ES has powerful anti-angiogenic activities via down-regulation of vascular endothelial growth factor
(VEGF), which is modulated by HIF-1␣ signaling. We hypothesized
that in focal areas of excessive trophoblast invasion, ES interferes with
angiogenesis and HIF-1␣ induction of VEGF.
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STUDY DESIGN: We explored serum levels of ES and HIF-1␣ in 22
patients with histological-confirmed invasive placentation (GA:
29⫾5w, accreta: n⫽5; increta: n⫽11; percreta: n⫽6) by ELISA and
Western blot. Samples (total n⫽30) were retrieved prospectively and
in a serial fashion prior to blood transfusion or steroids. We controlled for pregnancy and possible GA variation using blood samples
(n⫽43) of 10 healthy nonpregnant and 10 healthy pregnant (GA:
26⫾9w) subjects. Full-thickness myometrial-villous hysterectomy
sections were immunostained and scored for ES, HIF-1␣, VEGF, and
cytokeratin-7 (CK7, epithelial cell marker). Myometrium opposite
from the accreta insertion site and normal placental bed biopsies
(n⫽4) served as tissue controls (CRL).
RESULTS: In CRL subjects, systemic ES levels were unaffected by pregnancy status or GA (P⫽.752), while serum HIF-1␣ was undetectable.
Women with advanced trophoblast invasion (increta & percreta) had
lower serum levels of ES compared with less invasion (accreta)
(P⫽.009). The site of excessive trophoblast invasion (⫹CK7) lacked
immunostaining for ES and HIF-1␣ relative to the deeper myometrium and the opposite myometrial site (P⬍.001). In an opposing
pattern, VEGF was highly expressed at the site of excessive myometrial
invasion and aberrant vascularization (P⬍.001).
CONCLUSION: The local imbalance among expression of ES and VEGF
likely contributes to the invasive phenotype of the accreta trophoblasts. This effect seems to occur independent of HIF-1␣.
106 The impact of the Bakri Balloon on the rate of cesarean
hysterectomy at a single university hospital
Christopher Houlihan1, Karanvir Virk1, William Lowe1,
Pushpinder Dhillon1, Edwin Guzman1
Poster Session I
late-onset preeclampsia has been associated with excessive placentation manifest as hyperplasia. Our purpose was to evaluate the placental pathology in women with preeclampsia occurring at varying gestational ages.
STUDY DESIGN: This was a secondary analysis of a prospective observational study of placentas from pre-specified complicated pregnancies routinely submitted for standardized examination. For this study,
a database of placental diagnoses of liveborn singleton gestations
without major malformations was linked to a computerized obstetric
database. The rates of standardized placental findings including vascular (atherosis; infarction) and non-vascular (hyperplasia) changes
were evaluated according to gestational age and diagnosis of severe
preeclampsia.
RESULTS: A total of 7,122 women with pregnancies complicated by
preeclampsia were delivered at our institution between January 1,
2001 and September 30, 2007. Of these, 1,210 had placental examinations. Within this cohort, 209, 355, and 646 were diagnosed with preeclampsia at ⬍ 34, 34 - 36 6/7, and ⱖ 37 weeks gestation, respectively.
Selected placental findings in women with preeclampsia are shown in
the Table.
CONCLUSION: The placentas of women with preeclampsia developing
before 34 weeks gestation were significantly different from those with
preeclampsia at term. The former group demonstrated placental findings predominantly consistent with insufficiency due to vascular abnormalities whereas placental hyperplasia was significantly associated
with preeclampsia at term. Such differing placental findings support
the hypothesis that preeclamsia is a different disease depending on the
gestational age at diagnosis.
1
Saint Peter’s University Hospital, Department of OB/GYN,
New Brunswick, NJ
OBJECTIVE: To evaluate the impact on the rate of Cesarean Hysterectomy when a Bakri Balloon was added as part of the management of a
postpartum hemorrhage.
STUDY DESIGN: We reviewed all cases of postpartum hemorrhage at
our hospital from January, 2004- December, 2010. We compared the
incidence of Cesarean Hysterectomy between January, 2004 -September, 2007, prior to the availability of the Bakri Balloon at our hospital,
and a similar period of time after the device was available, from October, 2007-December, 2010. The primary outcome was the rate of
cesarean hysterectomy for postpartum hemorrhage in these two time
periods. Cases of placenta accreta, increta, and percreta were
excluded.
RESULTS: Between January, 2004 - September, 2007 there were 35
cases of Postpartum hemorrhage, of which 10 had a Cesarean Hysterectomy (28.5%). After the Bakri balloon was introduced (October,
2007-December, 2010), there were 45 cases of postpartum hemorrhage, of which 1 had a C-Hysterectomy (2.2%). The Bakri balloon
was used in 23 of the 45 cases. The p-value by Chi Square analysis was
0.00068.
CONCLUSION: Since the introduction in our hospital of the Bakri balloon as an option in the treatment of postpartum hemorrhage, there
has been a 92.3% reduction in the rate of Cesarean Hysterectomies
performed.
107 Placental findings suggesting preeclampsia
is at least two different diseases
David Nelson1, Mandolin Ziadie2, Donald McIntire1,
Kenneth Leveno1
1
University of Texas Southwestern Medical Center, Obstetrics and
Gynecology, Dallas, TX, 2University of Texas Southwestern Medical Center,
Pathology, Dallas, TX
OBJECTIVE: It has long been suspected that hypertension specific to
pregnancy represents at least two different diseases depending on the
timing during gestation when preeclampsia is first diagnosed. Earlyonset preeclampsia has often been observed to be associated with placental insufficiency attributable to vascular abnormalities; in contrast,
108 Maternal and perinatal consequences
of a primary elective cesarean delivery
Emily Miller1, William Grobman1
1
Northwestern University, Obstetrics and Gynecology, Chicago, IL
OBJECTIVE: To estimate cumulative risks of maternal and perinatal
morbidity associated with the choice of elective cesarean for a first
delivery.
STUDY DESIGN: A decision analytic model was designed to compare
major adverse outcomes across a woman’s reproductive life associated
with the choice of primary elective cesarean versus a trial of labor at a
first delivery. Maternal outcomes assessed included maternal transfusion, hysterectomy, thromboembolism, operative injury, and death.
Perinatal outcomes assessed included cerebral palsy (CP) and permanent brachial plexus (BP) palsy in the offspring.
RESULTS: Choosing an initial cesarean resulted in a 0.3% increased
risk of a major adverse maternal outcome in the first pregnancy. In
each subsequent pregnancy, the difference in maternal morbidity increased between strategies, such that by the fourth pregnancy, the
cumulative risk of a major adverse maternal outcome was nearly 10%
in the elective primary cesarean group, three times higher than among
women who initially underwent a trial of labor. Although the choice of
an initial cesarean resulted in 2.4 and 0.41 fewer cases of CP and BP
palsy, respectively, per 10,000 women in the first pregnancy, by a
fourth pregnancy, the risk of either adverse neonatal outcome was
higher among offspring of women who had chosen the initial elective
cesarean (0.368% vs. 0.363%).
CONCLUSION: Maternal morbidity associated with the choice of a primary elective cesarean increases in each subsequent pregnancy and is
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Poster Session I
greater in magnitude than that associated with the choice of trial of
labor. These increased risks are not offset by a substantive reduction in
the risk of neonatal morbidity.
Composite adverse outcomes per pregnancy
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110 Evidence to support the safety and efficacy of vaginal
delivery of twins gestation complicated by very low
birthweight of second twin
Eran Barzilay1, Hila de Castro1, Jigal Haas1, Eyal Sivan1,
Eyal Schiff1, Shali Mazaki-Tovi1, Yoav Yinon1
1
Sheba Medical Center, Tel-Aviv University, Obstetrics and Gynecology, TelHashomer, Israel
109 The association between mid-trimester cervical
length and cesarean delivery at term
Emily Miller1, William Grobman1
1
Northwestern University, Obstetrics and Gynecology, Chicago, IL
OBJECTIVE: An ultrasonographically diagnosed short cervix has been
associated with an increased risk of preterm birth, but the obstetric
consequences of longer cervical lengths have been less well defined.
The objective of this study was to determine the association between
cervical length and cesarean delivery among women at term.
STUDY DESIGN: This is a cohort study of women with a singleton gestation who underwent routine mid-pregnancy transvaginal cervical
length assessment and delivered at term. Women who underwent
planned cesarean delivery without intent to labor were excluded from
analysis. Women were grouped into quartiles based on cervical length,
and the association of their cervical length quartile with cesarean delivery was determined in both univariable and multivariable analysis.
RESULTS: 5806 subjects were included in this analysis, of whom 58.1%
were nulliparous. There were multiple differences among women in
the different cervical length quartiles (Table). The frequency of cesarean delivery among the cohort was 18.9%. As cervical length increased, the chance of cesarean delivery increased as well (14.7%,
19.5%, 19.1%, and 22.4% from the 1st through 4th quartiles, respectively). After controlling for potential confounding factors, cervical
length quartile remained significantly associated with an increased
odds of cesarean for the second (aOR 1.49, 95% CI 1.18-1.88), third
(aOR 1.47, 95% CI 1.16-1.85) and fourth (aOR 1.89, 95% CI 1.502.38) quartiles, compared to the first quartile. This relationship held
true for nulliparous as well as multiparous women.
CONCLUSION: Increasing mid-trimester cervical length is associated
with increasing frequency of cesarean delivery in both nulliparas and
multiparas. Preparatory uterine changes that enable successful labor
may be initiated as early as the mid-trimester.
Population characteristics and
cervical length per quartile
Median (IQR), mean ⫾ SD, or n (%).
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OBJECTIVE: To determine whether neonatal outcome is associated
with the mode of delivery in very low birthweight twins.
STUDY DESIGN: This was a retrospective cohort study. Inclusion criteria included: 1) twin gestation; 2) second twin birthweight of ⱕ1500
grams. Exclusion criteria included: 1) gestational age at delivery of less
than 24 gestational weeks 2) fetal demise of one or both twins. A total
of 206 twin gestations met the criteria and patients were classified into
2 groups according to the planned mode of delivery: 1. Cesarean delivery (n⫽152) and 2. Vaginal delivery (n⫽54). In the vaginal delivery
group 24 pairs were cephalic-cephalic, 28 pairs were cephalic-non
cephalic, and 2 pairs were non cephalicnon cephalic. The rates of
Apgar score ⬍7 at 5 minutes and cord blood PH⬍7.1 in either twin A
or B were determined in the two groups.
RESULTS: The mean gestational age at delivery was 31 weeks in the
cesarean delivery group compared to 30 weeks of gestation in the
vaginal delivery group (p⫽0.01). However, the mean birthweight of
both twins was similar among the two groups (Twin A: 1452 grams vs.
1358 grams, p⫽0.18 and Twin B: 1186 grams vs. 1182 grams, p⫽0.9
respectively). There were no significant differences between the cesarean and vaginal delivery groups in the rates of low Apgar score (Twin
A: 4.0% vs. 1.9%, p⫽0.5 and Twin B: 9.7% vs. 3.7%, p⫽0.2) and cord
PH ⬍ 7.1 (Twin A: 2.4% vs. 0%, p⫽0.3 and Twin B: 1.7% vs. 0%,
p⫽0.4). A sub-group analysis of the vaginal delivery group revealed
comparable rates of cesarean section (8.3% Vs 3.3%, p⫽0.4) as well as
neonatal Apgar score ⬍ 7 among the cephalic-cephalic and cephalicnon cephalic groups (Twin A: 4.2% vs. 0%, p⫽0.3 and Twin B: 0 vs.
6.7%, p⫽0.2).
CONCLUSION: Vaginal delivery of very low birthweight twins is a safe
regardless of second twin presentation. This information should provide reassurance for pregnant women and clinicians alike.
111 Decreased sleep duration in the third-trimester is
not associated with excessive gestational weight gain
Kristin Knight1, Eva Pressman1, Loralei Thornburg1
1
University of Rochester, OB/GYN, Division of Maternal-Fetal Medicine,
Rochester, NY
OBJECTIVE: Obesity and excessive gestational weight gain (GWG) are
significant public health problems that lead to an increased incidence
of adverse perinatal outcomes. Decreased sleep duration is associated
with increased rates of obesity in non-pregnant populations as well as
with prolonged weight retention in postpartum women. We sought to
determine if there is an association between decreased sleep duration
and excessive GWG.
STUDY DESIGN: We conducted a prospective cohort study of non-diabetic women with singleton gestations from Feb 2011–Mar 2012. Maternal weight gain, 3rd-trimester sleep habits (collected over 7 days),
and fetal/neonatal biometry were collected. Cohorts were defined as
sleeping ⬍7 and ⱖ7 hours/night on average. Student’s T-test, MannWhitney U, and Chi-square analysis were used to compare groups.
RESULTS: 35 women sleeping ⬍7 hours/night were compared with
124 women sleeping ⱖ7 hours/night in the 3rd trimester. The average
nightly sleep duration was 6.2 hours and 8.7 hours, respectively
(p⬍0.001). Demographic characteristics were similar in both groups.
There were no significant differences in overall weight change (38 vs.
32 lbs, p⫽0.15) or incidence of weight gain exceeding that recommended by the IOM (65.7% vs. 61.3%, p⫽0.63). Those sleeping ⬍7
hours/night had a higher percentage of total weight gain in the 1st
trimester (23.6% vs. 14.2%, p⫽0.03), however the percentages of total
weight gained in the 2nd and 3rd trimesters were similar. There were
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no differences in estimated fetal weight, birthweight, or gestational
age at delivery.
CONCLUSION: Unlike non-pregnant populations, sleep duration during pregnancy, when measured in the 3rd trimester, is not associated
with excessive GWG. This is likely due to altered physiology in pregnancy and additional factors contributing to sleep disruption. Additional data, especially sleep characteristics in the 1st and 2nd trimesters, is needed to further evaluate a possible association between sleep
duration and weight gain in pregnancy.
112 Is there a difference in the risk profile of women
who develop thrombo-embolic events in the
puerperium or later in life?
Maor Waldman1, Eyal Sheiner1, Ilana Shoham Vardi2
1
Soroka University Medical Center, Department of Obstetrics and
Gynecology, Beer-Sheva, Israel, 2Ben Gurion University of the Negev,
Department of Epidemiology and Health Services Evaluation, Beer-Sheva,
Israel
OBJECTIVE: Venous thrombo-embolic events (VTE) (mainly pulmonary embolism [PE] and deep vein thrombosis [DVT]) are currently
the primary cause for maternal death in the developed world. The
study objective was to identify whether risk factors for VTE during the
puerperium are different from these of thrombo-embolic events developed later in life during more than 10 years of follow-up.
STUDY DESIGN: A nested case-case study was designed, comparing
women who experienced VTE in the puerperium period to women
who experienced such an event over a period of a more than a decade.
The study included women (n⫽316) with VTE from a cohort of
48,319 women that gave birth between the years 1987-1998 and had a
follow up period until 2011. Multiple logistic regression model was
constructed in order to define independent risk factors associated
with early (6 weeks) vs. late thrombo-embolic events.
RESULTS: VTE during puerperium occurred in 81 women, and in 235
within at least 10 years after the puerperium. Patients encountered
VTE during the puerperium had more PE events (n⫽16, 19.8%) and
less DVT events (n⫽42, 51.9%), compared with the late VTE group
(PE n⫽15, 6.4%; DVT n⫽159, 67.7%; p⬍ 0.001).
While baseline characteristics of the two VTE groups were similar
(table), women undergoing cesarean section (CS) in the delivery preceding the VTE were more likely to develop early VTE (OR⫽1.8, 95%
Cl⫽1.05-3.2, P⫽0.032). Using a multivariate analysis, controlling for
confounders such as maternal age, CS was noted as an independent
risk factor for early vs. late VTE (adjusted OR⫽1.9; 95% CI 1.1-3.5;
p⫽0.023).
CONCLUSION: The risk profile of both earlier and late VTE are similar,
except for cesarean section which is an independent risk factor for
early (vs. late) VTE. Women encountered venous thrombo-embolic
event during the puerperium are more likely to suffer from pulmonary emboli than women encountering VTE after the puerperium.
Index pregnancy characteristics by
time of VTE occurrence
Poster Session I
113 Placenta accreta in a previous pregnancy
and its significance on subsequent births
Tamar Eshkoli1, Eyal Sheiner1, Adi Y Weintraub1,
Gershon Holcberg1, Fernanda Press1
1
Soroka University Medical Center, Ben-Gurion University of the Negev,
Obstetrics and Gynecology, Faculty of Health Sciences, Beer-Sheva, Israel
OBJECTIVE: To investigate the perinatal outcomes of women that had
a placenta accreta in a previous pregnancy.
STUDY DESIGN: We retrospectively compared all subsequent singleton
cesarean deliveries (CD) of women with a previous placenta accreta,
with CD of women with no such history, during the years 1988-2011.
RESULTS: Out of 34,567 singleton CD that occurred during the study
period, 0.1% (n⫽30) were of women with a previous placenta accreta.
Recurrent placenta accreta occurred in 23.3% (7/30) of patients with
placenta accreta in their previous pregnancy. Previous placenta accreta was significantly associated with uterine rupture, peripartum
hysterectomy and the need for blood transfusions. Nevertheless, increased risk for adverse perinatal outcomes such as low Apgar scores at
5 minutes and perinatal mortality was not found in these patients
(table).
CONCLUSION: A pregnancy following a previous placenta accreta is at
increased risk for adverse maternal outcomes such as recurrent accreta, uterine rupture and peripartum hysterectomy. However, adverse perinatal outcomes are not demonstrated.
Selected pregnancy and perinatal outcomes
of patients with and without a
previous placenta accrete
Data are presented as percentages.
114 A proportion score of pelvic and neonatal head
circumference is highly predictive of instrumental delivery
and cesarean section due to cephalo-pelvic disproportion
Gadi Liberty1, Lina Linov2, Irena Sionov1, Alona Koval2, Bord
Ilia1, Eyal Anteby1
1
Barzilai Medical Center, Obstetrics and Gynecology, Ashkelon, Israel,
Barzilai Medical Center, Radiology, Ashkelon, Israel
2
OBJECTIVE: To evaluate the risk for instrumental delivery (ID) and
cesarean section due to cephalo-pelvic disproportion (CS-CPD), according to maternal pelvic CT parameters, and neonate weight and
head circumference.
STUDY DESIGN: We studied patients who delivered at term a singleton
fetus in vertex presentation, and had underwent an abdominal CT in
our institution. Pelvimetry was performed retrospectively. We analyzed the relation between maternal pelvic parameters, neonatal
weight and head circumference (HC), and the mode of delivery.
RESULTS: We enrolled 111 cases: 84 patients had NVD, 7 had ID and
20 had CS-CPD. The neonatal HC was significantly larger in ID and
CS-CPD in comparison to NVD (34.9⫾1.1, 34.9⫾2.5 and 33.8⫾1.7
cm, respectively, p⫽0.03). The transverse diameter of the mid pelvis
was significantly smaller in ID and CS-CPD in comparison to NVD
(9.5⫾1.1, 9.8⫾0.9 and 10.4⫾0.8 cm respectively, p⫽0.002). We expressed the composed A-P and lateral parameters of the pelvic inlet,
mid and outlet, with a “naive formula” of estimated ellipse circumference (EEC). The mid pelvic EEC was significantly smaller in ID and
CS-CPD in comparison to NVD (32⫾2.6, 33.5⫾3.5 and 34.8⫾2.3 cm
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respectively, p⫽0.034). We used the ratio between the pelvic EEC and
HC to express a proportion score (PS) for CPD. The PS was significantly smaller in ID and CS-CPD, in comparison to NVD, in all pelvic
levels: inlet (1.08⫾0.1 and 1.09⫾0.1 VS 1.15⫾0.08, p⫽0.006); mid
(0.92⫾0.09 and 0.97⫾0.1 VS 1.03⫾0.08, p⫽0.0003); and outlet
(0.77⫾0.04 and 0.81⫾0.07 VS 0.84⫾0.08 p⫽0.011). ROC analysis
showed that a mid pelvis PS of 1 had a 68% sensitivity, 58% specificity
and a positive predictive value of 89% for CS-CPD.
CONCLUSION: Low proportion score of maternal pelvic parameters and
neonate head circumference, is highly correlated with ID and CSCPD.
115 Placental abruption as a marker for long
term cardiovascular mortality: a follow up period
of more than a decade
Gali Pariente1, Ilana Shoham-Vardi2, Roy Kessous1, Eyal Sheiner1
1
Soroka University Medical Center, Department of Obstetrics and
Gynecology, Beer sheva, Israel, 2Soroka University Medical Center, Faculty of
Health Sciences, Beer sheva, Israel
OBJECTIVE: To investigate the risk for subsequent cardiovascular
events in women having placental abruption, during a follow-up period of more than 10 years.
STUDY DESIGN: A population-based study comparing consecutive
pregnancies of women with and without placental abruption was conducted. Deliveries occurred during the years 1988-1999 and had a
follow up until the year 2010. Associations between placental abruption and maternal long-term cardiovascular hospitalizations, morbidity and mortality were investigated. Multivariable analysis was
used to control for confounders.
RESULTS: During the study period, there were 47,909 deliveries who
met the inclusion criteria, of these 1.4% (n⫽653) occurred in patients
with placental abruption. No significant differences were noted regarding subsequent long term hospitalizations due to cardiovascular
causes during at least a decade of follow-up (OR⫽ 1.2, 95% CI 0.8-1.8,
P⫽0.314), as well as regarding invasive procedures (OR⫽1.5 95% CI
0.7-3.3, P⫽0.312; table). However, placental abruption was noted as a
risk factor for long term cardiovascular mortality (OR⫽ 6.6, 95% CI
2.3-18.4, P⫽0.004). The case fatality rate for placental abruption was
13.0% vs. 2.5% in the comparison group. ( P⬍0.001). In a multivariate logistic regression model, after controlling for confounders such
as ethnicity and maternal age, placental abruption was noted as an
independent risk factor for maternal long-term cardiovascular mortality (adjusted OR⫽ 4.5; 95% CI-1.1-19.1, P ⫽ 0.041).
CONCLUSION: Placental abruption is a significant risk factor for longterm cardiovascular mortality in a follow-up period of more than a
decade.
Subsequent cardiovascular events in
women having placental abruption
116 Giving birth to a small for gestational age infant is a
risk factor for long-term maternal cardiovascular morbidity
Gali Pariente1, Roy Kessous1, Ilana Shoham-Vardi2, Eyal Sheiner1
1
Soroka University Medical Center, Ben-Gurion University of the Negev,
Department of Obstetrics and Gynecology, Beer-Sheva, Israel, 2Soroka
University Medical Center, Ben-Gurion University of the Negev, Faculty of
Health Sciences, Beer-Sheva, Israel
OBJECTIVE: To investigate whether women with a prior occurrence of
small-for-gestational-age (SGA) are at an increased risk for subsequent long term maternal cardiovascular morbidity.
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STUDY DESIGN: A population-based study comparing consecutive
pregnancies of women with and without a previous delivery of a SGA
neonate was conducted. Deliveries occurred during the years 19881999, with a follow-up period until 2010. Incidence of long-term cardiovascular morbidity was compared between women with SGA neonate and women who gave birth at the same period to an appropriate
for gestational age neonate. Logistic regression was conducted to obtain adjusted odds ratios (AOR) and 95 % confidence intervals (CI)
for the association between SGA and subsequent cardiovascular
morbidity.
RESULTS: During the study period 47612 deliveries met the inclusion
criteria; 9.3% (n⫽4411) occurred in patients with a prior occurrence
of SGA. Women with a prior occurrence of SGA had higher rates of
long term complex cardiovascular events such as congestive heart failure, cardiac arrest etc. (OR⫽2.3; 95% CI 1.3-4.4, P⫽0.006) and long
term cardiovascular mortality (OR⫽ 3.4; 95% CI 1.5-7.6, P⫽0.006;
table). Using a multivariable logistic regression model, controlling for
confounders such as maternal age and ethnicity, having delivered a
SGA neonate was noted as an independent risk factor for long-term
maternal cardiovascular hospitalizations (AOR⫽ 1.4; 95% CI-1.11.6, P ⬍ 0.001).
CONCLUSION: Delivery of a previous SGA infant is an important predictor of long-term maternal cardiovascular morbidity during a follow-up period of more than a decade.
Long term cardiovascular morbidity and
mortality in patients with and without a
prior occurrence of SGA
117 Misoprostol for treatment of intrauterine
fetal death at 14-28 weeks of pregnancy
Hillary Bracken1, Nguyen thi Nhu Ngoc2, Erika Banks3,
Paul Blumenthal4, Richard Derman5, Ashlesha Patel6,
Marji Gold7, Beverly Winikoff8
1
Gynuity Health Projects, New York, NY, 2Center for Research and
Consultancy in Reproductive Health (CRCRH), Ho Chi Minh City, Viet
Nam, 3Albert Einstein College of Medicine, Department of Obstetrics and
Gynecology, New York, NY, 4Stanford University, Family Planning Services
and Research, Palo Alto, CA, 5Christiana Care Hospital, Department of
Obstetrics and Gynecology, Newark, DE, 6JH Stroger Jr. Hospital of Cook
County, Department of Obstetrics and Gynecology, Chicago, IL, 7Albert
Einstein College of Medicine, Department of Family Medicine, New York,
NY, 8Gynuity Health Projects, New York, NY
OBJECTIVE: To systematically assess whether misoprostol has high
safety and effectiveness for the treatment of intrauterine fetal death at
14-28 weeks of pregnancy and to help establish the best dose of misoprostol for this purpose.
STUDY DESIGN: This double-blind trial randomized 153 women, 14-28
weeks gestation, into two groups. Women received either 100mcg
buccal misoprostol (Group 1) or 200 mcg buccal misoprostol (Group
2) every 6h for a maximum of 8 doses. The primary outcome was
successful evacuation within 48h.
RESULTS: The 200mcg dose was significantly more effective than the
100 mcg dose at evacuating the uterus within 48h (Group 1: 66.7%;
Group 2: 84.2% (RR 0.79 (95%CI: 0.65-0.95). The mean time to evacuation was significantly shorter in Group 2 (18.9h ⫹11.9h) than
Group 1 (24.0 ⫹12.4h) (p⫽0.03). The side effect profile was similar in
the two groups. Few women reported nausea (Group 1: 19%; Group 2:
24%), vomiting (Group 1: 10%; Group 2: 16%), chills (Group 1: 24%;
Group 2:21%) or headache (Group 1: 16%; Group 2: 21%). However,
significantly more women in the 200mcg group reported diarrhea
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(Group 1: 10%; Group 2: 33%; p-value: 0.05). Most women in both
groups found the side effects either acceptable or highly acceptable
(Group 1: 74.8%; Group 2: 89.5%). Most women in both groups
found the procedure satisfactory or very satisfactory (Group 1: 74.3%;
Group 2: 88.1%). However, significantly more women in Group 1
cited that the length of hospitalization was the worst aspect of the
procedure (Group 1: 18.9%; Group 2: 7.9%; p-value⫽0.05).
CONCLUSION: Misoprostol is a safe and effective method for medical
induction of labor after intrauterine fetal demise. A 200mcg dose is
significantly more effective than 100mcg for evacuating the uterus
within 48h. The side effects and treatment are highly acceptable to
women.
118 An evaluation of the role of investigations
for women with second trimester miscarriage
James Castleman1, Victoria Hodgetts1, Julie Moore1,
Mary Molloy1, Ramesh Ganapathy1
1
Sandwell and West Birmingham Hospitals NHS Trust, Department of
Maternity and Perinatal Medicine, Birmingham, United Kingdom
OBJECTIVE: Our data looked at the value of offering the Royal College
of Obstetricians and Gynaecologists (RCOG) recommended tests to
women with second trimester miscarriages. We present our experience from the Pregnancy Loss Clinic at City Hospital, Birmingham,
which serves a diverse urban population in the UK. We currently
follow RCOG guidance for managing women with second trimester
miscarriage. The routine tests offered (haematological and biochemical, histology/pathology and radiological) are varied with limited evidence for their role in improving future pregnancy outcomes. These
tests are also expensive and time consuming.
STUDY DESIGN: Retrospective review of results of investigations performed for women with second trimester miscarriage. 82 women with
second trimester miscarriages were seen over a 20 month period.
Blood tests (for autoimmune disease and coagulopathy) were performed 6 to 8 weeks following the pregnancy loss. Genetics tests, placental histology and post mortem examination were offered to all
women and were performed where informed consent was given.
RESULTS: In this cohort post mortem offered no additional insight
provided the woman had had an anomaly scan. Results of biochemical
tests correlated with clinical findings and on no occasion was previously undiagnosed pathology (autoimmune disorders) found that
would have an impact on future pregnancy outcome.
CONCLUSION: Despite the devastating impact of fetal loss, part of our
duty of care as clinicians is to adopt an evidence-based approach and
offer only those investigations which are of proven value. In a woman
with known fetal anomalies, immunological/haematological and histological investigations may not be of added value. In women with no
obvious abnormality on antenatal fetal scans, the investigations do
not seem to add value to the management of future pregnancies. Cervical length assessment only has value during ongoing care of subsequent pregnancies. We suggest a more targeted approach to managing
these women.
119 Maternal body mass index (BMI) and stillbirth: analysis
for potential causal pathophysiological mechanisms
Janna Nijkamp1, Fleurisca Korteweg1, Henk Groen2, Joke Ravisé1,
Jozien Holm1, Albertus Timmer3, Jan Jaap Erwich1
1
University Medical Center Groningen, Department of Obstetrics and
Gynecology, Groningen, Netherlands, 2University Medical Center
Groningen, Epidemiology, Groningen, Netherlands, 3University Medical
Center Groningen, Pathology and Medical Biology, Groningen, Netherlands
OBJECTIVE: To determine in a cohort of women with fetal death the
association between maternal BMI and cause of fetal death; a search
for potential underlying pathophysiological mechanism.
STUDY DESIGN: In a multicenter prospective cohort study from 2002 to
2008, 1025 women with a intra-uterine fetal death (IUFD) ⬎20 weeks
of gestation were studied. An extensive diagnostic workup was performed including maternal blood tests, coagulation tests (antithrom-
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bin, protein C activity, total protein S antigen, von Willebrand factor
and the trombophilias factor V Leiden, prothrombin G20210A and
lupus anticoagulant), autopsy and placental examination. Cause of
death was classified according the Tulip classification. Odds ratios for
each outcome were estimated for BMI classes (underweight BMI ⬍
18.5; overweight BMI 25.0-29.9; obesity BMI ⬎30.0) compared with
normal weight women (BMI 18.5-24.9) by using logistic regression.
RESULTS: We analyzed 1025 women and their IUFD. For 233 women
(22.7%) BMI was missing. These cases were excluded. Obese women
smoke more (OR 1.84, 95% CI 1.19 - 2.85) and have a higher prevalence of hypertension (OR 3.57, 95% CI 1.76 –7.24), gestational diabetes (OR 6.60, 95% CI 2.28 –19.08), pregnancy induced hypertension (OR 2.87, 95% CI 1.59 –5.19) and preeclampsia/HELLP
syndrome (OR 1.79, 95% CI 0.92–3.49). Obese women have more
placental causes of fetal death (OR 1.55, 95% CI 1.02–2.36). Smoking
is a confounding factor (adjusted OR 1.37, 95% CI 0.89 –2.11), other
risk factors have no influence. Percentage of abnormal testing for
C-reactive protein was higher in obese women (OR 2.42, 95% CI
1.57–3.74). We did not find any differences in trombophillic defects
between normal weight and obese women.
CONCLUSION: Potential pathophysiological mechanism contributing
to IUFD in obese women are placental dysfunction and possible a
systemic inflammatory response. Trombophillic defects have no influence. Further research for the underlying mechanism of IUFD in
obese women is necessarily.
Cause of fetal death in relation to
maternal body mass index
Results are given in N (%).
NA, P value was not applicable.
*P value ⬍ .05 for comparison with reference group BMI 18.5–24.9.
120 Recurrence risk of stillbirth in a subsequent
pregnancy: a population-based cohort study
Janna Nijkamp1, Anita Ravelli2, Jelle Schaaf2,
Henk Groen3, Jan Jaap Erwich1, Ben Mol4
1
University Medical Center Groningen, Obstetrics and Gynecology,
Groningen, Netherlands, 2Academic Medical Center Amsterdam, Medical
Informatics, Amsterdam, Netherlands, 3University Medical Center
Groningen, Epidemiology, Groningen, Netherlands, 4Academic Medical
Center Amsterdam, Obstetrics and Gynecology, Amsterdam, Netherlands
OBJECTIVE: To estimate the risk of recurrence of stillbirth in a subsequent pregnancy.
STUDY DESIGN: We studied in retrospect a nationwide birth cohort in
the Netherlands from 1999 to 2007. In total, records of 252.827
women with a singleton birth in a first pregnancy could be linked to
records of their second pregnancy using data obtained from the national Perinatal Registry. Stillbirth was defined as antepartum or intrapartum fetal death from 22 weeks of gestation. Fetal deaths associated with a major congenital anomaly were excluded. Small for
gestational age (SGA) was defined as birthweight ⬍10th percentile.
RESULTS: Of 252.827 first pregnancies, 2058 pregnancies ended in a stillbirth (8.1 per 1000). At the subsequent pregnancy there were 815 stillbirths. For women whose first pregnancy resulted in a stillbirth, the rate of
stillbirth in their subsequent pregnancy was 5.8 per 1000, versus 3.2 per
1000 for women without a stillbirth in their first pregnancy (OR 1.8 [95%
CI 1.02-3.60]. After adjustment for maternal age, ethnicity, social-economic status and SGA in the first pregnancy the risk was 2.4 [95% CI
1.32-4.21]). Highest risk of recurrence of stillbirth occurred in women
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with a history of a stillbirth between 22 and 28 weeks of gestation during
the first pregnancy (15.0 per 1000, OR 2.54 [95% CI 0.72-8.98]). Women
with a history of a stillbirth ⱖ 37 weeks of gestation appeared to have no
risk of recurrence (1.1 per 1000, OR 0.37 [95% CI 0.05-2.64]). This might
be related to the 68% induction of labor rate for women with a history of
stillbirth ⱖ 37 weeks of gestation was, versus 22% for women without a
history of stillbirth.
CONCLUSION: Women with a prior stillbirth have a higher risk of recurrence
in their next pregnancy. This risk was mainly observed when stillbirth had
occurred in early gestation (22-28 weeks). The absence of this association in
late pregnancy might be due to more inductions of labour.
Recurrence risk of stillbirth in a second
pregnancy by gestational age
#
Risk of stillbirth in a second pregnancy with a history of stillbirth in the first pregnancy (per 1000
births); *Odds ratio adjusted for maternal age, ethnicity, low-social economic status and small for
gestational age.
121 A silk-based gel for cervical injection:
controlled gelation with sonication
Jeannie Kelly1, Simona Socrate3, Errol Norwitz1,
David Kaplan2, Michael House1
1
Tufts Medical Center, Maternal-Fetal Medicine, Boston, MA, 2Tufts
University, Biomedical Engineering, Medford, MA, 3Massachusetts Institute
of Technology, Health Sciences Technology, Cambridge, MA
OBJECTIVE: To develop an injectable, silk-based biomaterial as an alternative
to cervical cerclage for the management of cervical insufficiency. Here, we
studied sonication to achieve controlled gelation of a silk-based biomaterial
and determined feasibility of cervical injection in a rat model.
STUDY DESIGN: A purified silk solution (6% w/w) was prepared as
previously reported. The solution was concentrated to 10% or 15% by
dialysis against a polytheylene glycol solution. Solutions were autoclaved for sterilization. Using a 3mL syringe, a 1.5mL silk solution was
sonicated with Branson 450 Sonifier and a 1/8⬙ diameter tapered microtip. Solutions were sonicated for 10-25 sec at 15% amplitude and
20kHz frequency. To determine the effect of temperature on gelation,
solutions were sonicated at room temperature and in an ice bath.
Time to gelation was measured. Gelation was determined by an
opaque appearance on visual inspection and a positive vial inversion
test. Sprague Dawley rats (n⫽5) were used to test the feasibility of
cervical injections. A nasal speculum and arthroscope (5mm, 30 degree) were used to visualize the cervix. Cervical injections (200 uL)
were performed with a 23 gauge needle using direct visualization. The
cervices were dissected for histological examination to determine anatomical localization.
RESULTS: No gelation was observed in the absence of sonication. At
20-25 sec of sonication, immediate gelation occurred and the gel
could not be pushed through a 23 gauge needle. Variables associated
with more rapid time to gelation included sonication at room temperature, increased silk concentration, and longer sonication times
(p⬍.01 for each). Rat cervical injections were technically feasible with
the aid of the arthroscope. The gel was visualized in the cervical stroma
on H&E histology.
CONCLUSION: Sonication results in controlled gelation of a silk-based
biomaterial. Injection of this biomaterial into the cervical stroma of a
rat is feasible. Further studies are needed to assess this biomaterial in
vivo.
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122 The Institute of Medicine guidelines for gestational
weight gain: effect on perinatal outcomes in obese,
morbidly obese, and super obese women
Jennifer Durst1, Amelia Sutton1, Suzanne Cliver1,
Alan Tita1, Joseph Biggio1
1
University of Alabama at Birmingham, Obstetrics and Gynecology,
Birmingham, AL
OBJECTIVE: To evaluate the impact of the updated Institute of Medicine (IOM) guidelines for gestational weight gain in obese, morbidly
obese, and super obese women on maternal and neonatal outcomes.
STUDY DESIGN: Retrospective cohort of obese women, defined as body
mass index (BMI) ⬎ 30, delivering singletons ⬎ 36 weeks between 20002009. Women were included if they had a weight documented in the first
trimester and one within 10 days prior to delivery. Women were stratified
by obesity category: obese (BMI 30-39), morbidly obese (BMI 40-49),
and super obese (BMI ⬎ 50). Gestational weight gain was categorized
according to IOM guidelines, which recommend a gain of 5-9.1 kg for
obese women. Selected perinatal outcomes were analyzed, and logistic
regression was used to adjust for potential confounders.
RESULTS: Of the 5364 women eligible for the study, 74% were obese,
21% were morbidly obese, and 5% were super obese. Compared to
obese women who gained within the IOM guidelines, women with a
BMI ⬎ 30 and gestational weight gain exceeding the IOM guidelines
had a 38% increased risk of cesarean delivery and hypertensive disorders and a 60% increased risk of macrosomia. Weight gain less than
the IOM guidelines was associated with a 30% decreased risk of amnionitis and a 39% decreased risk of macrosomia. When compared to
obese women, morbidly obese and super obese women had increased
risks of a multitude of perinatal morbidities (Table). Morbidly obese
women exceeding the guidelines had an increased risk of hypertensive
disorders. Super obese women with weight gain less than recommended had a decreased risk of hypertensive disorders.
CONCLUSION: Gestational weight gain exceeding 2009 IOM guidelines
is associated with increased risks of adverse outcomes in obese
women. Weight gain less than recommended appears to be protective
against some morbidities. Strategies to promote limited gestational
weight gain may improve perinatal outcomes in this population.
Perinatal outcomes in obese, morbidly obese, and
super obese women according to gestational
weight gain per IOM guidelines
BWT, birthweight; HTN, hypertension; LGA, large for gestational age.
*Referent group is women with gestational weight gain within IOM guidelines (5-9.1kg).
123 Optimal timing of delivery in women with
prior stillbirth: a decision analysis
Jessica Fowler1, Allison Allen1, Jenna Emerson1, Jessica Page1,
Brian Shaffer1, Yvonne Cheng2, Aaron Caughey1
1
Oregon Health & Science University, Department of Obstetrics &
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Gynecology, Portland, OR, 2University of California San Francisco,
Department of Obstetrics & Gynecology, San Francisco, CA
OBJECTIVE: The purpose of this study was to determine the optimal gestational age of delivery of a patient with a prior stillbirth by accounting for
common neonatal morbidities associated with early term delivery.
STUDY DESIGN: A decision-analytic model was designed using TreeAge software to determine the optimal gestational age for delivery of a theoretical
cohortof10,000womenwithahistoryofapriorstillbirth.Themodeloptions
ranged from delivery at 37 weeks up to 41 weeks’ gestation. At each week the
model accounts for expectant management with four possible outcomes: (1)
spontaneous delivery; (2) medically-indicated delivery; (3) recurrent stillbirth; or (4) expectant management with scheduled induction. Probability
andcostestimateswerederivedfrompublishedliterature.Primaryoutcomes
included recurrent antepartum stillbirth, neonatal death, respiratory complications, and cerebral palsy. Utility values were assigned to various outcomes
andappliedtolifeexpectancytogeneratequality-adjustedlifeyears(QALYs).
RESULTS: Planned delivery at 38 weeks gestation leads to the best outcomes when considering risk of recurrent stillbirth, neonatal morbidities, and maximizing total QALYs (Table). In the cohort of 10,000
women, delivery at 38 weeks gestation leads to 6 fewer recurrent stillbirths than 39 weeks gestation, but 2 additional cases of neurodevelopmental morbidity. Sensitivity analyses confirm that delivery at 38
weeks was optimal assuming a women has a 1.03 to 5.97-fold greater
risk for recurrent still birth in comparison to the general population.
Above a 5.97-fold increase, delivery at 37 weeks gestation was shown
to be optimal up to an 8.5-fold increased risk (Figure).
CONCLUSION: Scheduled delivery at 38 weeks gestation is consistent
with optimal outcomes in women with prior stillbirth as it decreases
the risk of recurrence, while acceptably balancing the risk of early term
neonatal morbidities.
Neonatal outcomes by gestational age of delivery
for women with prior stillbirth (in theoretical
cohort of 10,000 women)
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124 Buprenorphine vs methadone for maintenance of opioid
addiction during pregnancy: a cost-effectiveness analysis
Jessica Fowler1, Jenna Emerson1, Allison Allen1, Sarah Dilley1,
Nicholas Gideonse2, Traci Rieckmann2, Amanda Risser2,
Aaron Caughey1
1
Oregon Health & Science University, Department of Obstetrics &
Gynecology, Portland, OR, 2Oregon Health & Science University,
Department of Family Medicine, Portland, OR
OBJECTIVE: Recent estimates of opiate use in pregnancy have been reported as high as 7.4% in certain age groups. Methadone is currently the
standard of care for opioid-dependency in pregnancy. Emerging evidence suggests that Buprenorphine should be considered a first-line
treatment option. Studies have shown improved neonatal outcomes with
Buprenorphine, yet low maternal retention rates in treatment. This
model investigates maternal and neonatal outcomes and cost-effectiveness of Buprenorphine vs. Methadone for opioid-maintenance during
pregnancy.
STUDY DESIGN: A decision-analytic and cost-effectiveness model was constructed using TreeAge software for opioid-dependent pregnant women
started on either Buprenorphine or Methadone for replacement therapy. A
comparison of each strategy in a theoretical cohort of 1,000 mother-baby
dyads was performed. Primary outcomes included maternal retention in
maintenance treatment, neonatal abstinence syndrome (NAS) and preterm
birth. Probability and cost estimates were derived from published literature.
Utility values were assigned to various outcomes and applied to life expectancy to generate quality-adjusted life years (QALYs).
RESULTS: Buprenorphine for maintenance therapy in an opioid-dependent mother led to better outcomes when considering NAS and preterm
birth and maximizing total QALYs (Table). In a cohort of 1,000 women,
treating with Buprenorphine resulted in 145 fewer cases of NAS, 44 fewer
preterm births resulting in cost savings of over $12.4 million healthcare
dollars. Sensitivity analysis confirms that Buprenorphine is dominant
(costs less, better outcomes) up to a drop out rate of 56.4%, yet continues
to be cheaper when compared to Methadone (Figure).
CONCLUSION: Buprenorphine should be considered a first-line treatment
option for opioid-dependency in pregnancy in select individuals, as it
leads to decreased incidence of NAS, preterm birth, decreased hospitalization and better utilization of healthcare dollars than Methadone.
Buprenorphine vs methadone for management of
opioid dependence in pregnancy (theoretical
cohort of 1000 women)
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Outcomes of teenage pregnancies: all deliveries
Adjusted for nulliparity, African American race, gestational hypertension,
prior cesarean, birthweight ⬎4000 grams.
126 The impact of cervical length on the cost-effectiveness
of vaginal progesterone as a preterm birth intervention
Jessica Page1, Jenna Emerson1, Alison Cahill2, Allison Allen1,
Jessica Fowler1, Leonardo Pereira1, Aaron Caughey1
125 Adverse outcomes of teenage pregnancies
Jessica McPherson1, Methodius Tuuli1, Kimberly Roehl1,
Qiuhong Zhao1, Anthony Odibo1, Alison Cahill1
1
Washington University in St. Louis, Obstetrics and Gynecology,
St. Louis, MO
OBJECTIVE: Data on pregnancy outcomes of teenage women who deliver are limited. Given pelvic immaturity, there is concern for adverse
events. The objective of this study was to compare pregnancy outcomes of women ⬍18 years of age to those ⱖ18 years of age.
STUDY DESIGN: This was a retrospective cohort study of all consecutive
women who underwent labor between 2004 and 2008. Pregnancy outcomes
including vaginal laceration, postpartum hemorrhage (PPH), shoulder
dystocia, umbilical cord gas pH ⬍7.2 or ⬍7.05, and neonatal intensive care
unit (NICU) admission in women ⬍18 years of age were compared to
women ⱖ18. A second analysis comparing only term deliveries was performed. Exclusion criteria included multiple gestations and congenital
anomalies. Univariable and multivariable analyses were performed; logistic
regression analyses were used to adjust for confounders.
RESULTS: Of 8,390 women, 663 were ⬍18 years of age. After adjusting
for nulliparity, African American race, gestational hypertension, prior
cesarean, and birthweight ⬎4000 grams teen women were at an increased risk of vaginal laceration (aOR 1.59, CI 1.33-1.89), but there
was no difference in postpartum hemorrhage, shoulder dystocia, umbilical cord gas pH ⬍7.2 or pH ⬍7.05, or NICU admission. There
were 5,386 women who delivered at term, 500 were teenage women.
After adjusting for nulliparity, African American race, gestational hypertension, gestational diabetes, prior cesarean, or birthweight ⬎4000
grams there was no difference in laceration, postpartum hemorrhage,
shoulder dystocia, umbilical cord gas pH ⬍7.20 or pH ⬍7.05.
CONCLUSION: Our results suggest, while the teenage pelvis may not be
mature, risks of postpartum hemorrhage, shoulder dystocia, abnormal umbilical cord gases, or NICU admission are similar when comparing women ⬍18 years of age and those ⱖ18 years of age. There is,
however, an increased risk of vaginal laceration in teenage women.
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OR, 2Washington University in St. Louis, Obstetrics & Gynecology,
St. Louis, MO
OBJECTIVE: To determine the cost-effectiveness of vaginal progesterone treatment for the prevention of preterm birth (PTB) over a wide
range of short cervical length (CL) measurements.
STUDY DESIGN: Decision-analytic models were built using TreeAge
software comparing vaginal progesterone to no intervention at four
different CL ranges (10-14mm, 15-19mm, 20-24mm, 25-29mm)
measured once at 20-24 wks. Baseline preterm birth probabilities were
adjusted to reflect the relative risk associated with each CL range as
well as the relative risk reduction with vaginal progesterone treatment
as estimated from the literature. The primary outcome was preterm
birth at ⬍37wks, with secondary outcomes of preterm birth ⬍28wks
and ⬍35wks as well as neonatal death and cerebral palsy. The costeffectiveness threshold was set at $100,000/QALY (quality-adjusted
life years).
RESULTS: Vaginal progesterone was found to be an effective and inexpensive intervention for preterm birth. The greatest reduction in PTB
was observed in the 10-14mm CL group with a cost difference of
$9,136 ($17,136 vs. $26,272). Vaginal progesterone remained dominant in all cervical length ranges with lower costs and fewer PTBs
(15-19mm $13,846 vs. $20,660, 20-24mm $10,063 vs. $14,209, 2529mm $7,702 vs. $10,183). Correspondingly, with the reduction in
PTB, rates of cerebral palsy and neonatal death were decreased in the
treatment arm.
CONCLUSION: Vaginal progesterone is an effective and relatively noninvasive treatment strategy for women with CL measurements of
10-30mm.
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Poster Session I
127 Advanced maternal age: what is the risk of
stillbirth & infant death by each additional week of
expectant management?
Jessica Page1, Jonathan Snowden1, Emily Griffin1, Yvonne Cheng2,
Amy Doss1, Melissa Rosenstein2, Aaron Caughey1
1
Oregon Health and Science University, Obstetrics and Gynecology, Portland,
OR, 2University of California, San Francisco, Obstetrics and Gynecology, San
Francisco, CA
OBJECTIVE: To determine the composite risk of stillbirth and infant
death by week of gestation at term in advanced maternal age (AMA)
pregnancies compared to pregnancies not complicated by AMA.
STUDY DESIGN: A retrospective cohort study was conducted using
2005 National birth certificate data including AMA pregnancies.
Term stillbirth by gestational age (GA) was calculated using a denominator of 10,000 ongoing pregnancies. Infant death was defined as
mortality within the first year of life and was calculated per 10,000
deliveries at each GA. Advanced maternal age was defined as age 35 or
greater. A composite mortality rate was used to estimate the risk of
stillbirth by remaining pregnant for an additional week and infant
death risk at the next week of gestation. Exclusion criteria included
fetal anomalies and multiple gestations.
RESULTS: The risk of stillbirth was higher in the AMA population by
GA at term and interestingly, infant death rates were lower in AMA
pregnancies throughout all term GAs. Composite risk of expectant
management, defined as the ongoing risk of stillbirth during the additional week plus the risk of infant death at the following week, was
higher at GAs ⬎38wks in the AMA population, indicating that the risk
of stillbirth exceeds that of infant death at these GAs. The point at
which risk of expectant management surpassed that of infant death in
the non-AMA population occurred at 39 wks GA, reflecting the increased risk of stillbirth in AMA pregnancies.
CONCLUSION: The composite risk of expectant management of AMA
pregnancies at term exceeds the infant mortality risk at 38 weeks due
to the continuing increases in risk of stillbirth at later GAs. These risks
should be taken into account when determining the optimal time of
delivery for AMA pregnancies.
Risk of stillbirth, infant death & expectant
management by week of gestational age
at Term in AMA pregnancies
128 Opiate abuse/usage in pregnancy and
newborn head circumference
Kevin Visconti1, Kerry Hennessy1, Craig Towers1,
Mark Hennessy1, Bobby Howard1
1
University of Tennessee Medical Center, Obstetrics & Gynecology,
Maternal-Fetal Medicine, Knoxville, TN
OBJECTIVE: To evaluate whether opiate abuse/usage in pregnancy affects newborn head circumference. Opiate abuse in pregnancy has
significantly increased in our location and large dosages of strong oral
agents (oxycodone, oxymorphone, and buprenorphine) are the primary drugs ingested. Most of the literature to date in pregnancy has
evaluated heroin and methadone.
STUDY DESIGN: All newborns admitted to the neonatal intensive care
unit for treatment of neonatal abstinence syndrome were prospectively collected. The birth and perinatal ultrasound information were
retrospectively obtained and analyzed. Data collected included the
gestational age (GA) at delivery, gender, birthweight, head circumference (HC) at birth, the opiate type, and the perinatal ultrasound assessment of growth parameters prior to delivery.
RESULTS: From January 1, 2010 to June 30, 2012, 323 neonates were admitted for the treatment of NAS. A total of 93 (28.8%) had a HC ⬍10th percentile for GA (p ⬍ 0.01) compared to controls. Of these 93, 25 (7.7%) were
⬍3rd percentile and 68 (21.1%) were ⬎3rd ⬍10th percentile; however,
62.4% were AGA in birthweight at delivery. Of the 323 total cases, 196 (61%)
had at least one ultrasound evaluation in the perinatal unit prior to delivery
and of these, 141 were within 10 days of birth. Based on the ultrasound parameters, a HC ⬍ 5th percentile was found in 38.4% of cases of which 73%
were consistent with the post-delivery findings. Of interest, the femur length
measurements were ⬍ 5th percentile in 36.3% of fetuses in these 141 ultrasound evaluations; however, 69.4% were AGA for birthweight at delivery.
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Poster Session I
CONCLUSION: Opiate abuse/usage in pregnancy in the form of oxy-
codone, oxymorphone, and buprenorphine appears to increase the risk
for a head circumference ⬍ 10th percentile and ⬍ 3rd percentile when
compared to controls. Further research is needed to determine whether
this effect involves bone growth (because femur lengths were also small in
many cases) or if brain growth is hampered. Long term infant follow-up
is also needed.
129 Neonatal outcomes following in utero exposure
to buprenorphine/naloxone or methadone
Kristen Gawronski1, Katherine Lehman1, Debra Gardner1,
Peter Giannone2, Mona Prasad3
1
Wexner Medical Center at The Ohio State University, Pharmacy, Columbus,
OH, 2Wexner Medical Center at The Ohio State University, Neonatology,
Columbus, OH, 3Wexner Medical Center at The Ohio State University,
Obstetrics and Gynecology, Columbus, OH
OBJECTIVE: As there is little known about the use of combination buprenorphine/naloxone (B/N) in pregnant women, we compared B/N
with standard methadone maintenance (MM) for treatment of opioid
during pregnancy.
STUDY DESIGN: Retrospective analysis of 132 pregnant, opioid-addicted women who received B/N or MM and their neonates. The
primary outcome was total amount of oral morphine equivalents required to treat neonatal abstinence syndrome (NAS). Secondary outcomes included number of neonates requiring treatment, duration of
treatment (DOT), and medication-associated cost (MC). The primary treatment outcome was analyzed using a multivariable logistic
regression model. In the subset of infants who received NAS treatment, a linear model was used to compare the total dose. In the secondary analyses, DOT and MC outcomes were log-transformed.
RESULTS: Maternal baseline characteristics were not significantly different among groups except for maximum dose of stabilized medication, benzodiazepine use, and smoking history. 49 neonates were exposed to B/N in utero, and 83 neonates were exposed to MM. Mean
gestational age was 38.4 ⫾ 2 weeks in B/N group vs 38.1 ⫾ 2 wks in
MM group (p⫽0.11). Mean birthweight was 2954 ⫾ 553 grams in B/N
group vs 2903 ⫾ 535 grams in MM group (p⫽0.29). Approximately
25% of infants in each group were admitted to the NICU (p⫽0.42).
The proportion of babies receiving methadone treatment for NAS did
not differ significantly between groups (63% vs 71%, respectively,
p⫽0.35). Among infants receiving NAS treatment, neonates exposed
to B/N required significantly less morphine (7.6 mg vs 10.7 mg,
p⫽0.04) and had a significantly shorter DOT (5.7 days vs 7.8 days,
p⫽0.03) compared to MM. MC were significantly lower in those exposed to B/N vs MM ($43 vs $68, p⫽0.01).
CONCLUSION: B/N treatment for opioid addiction during pregnancy
confers favorable outcomes with respect to neonatal abstinence when
compared to standard of care MM. It should be considered a suitable
first-line treatment option.
Neonatal outcomes, frequency (%)
or mean (SD)
*Corresponds to analysis of log-transformed data.
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130 Disparity in post-treatment maternal circulating
magnesium sulfate levels between twin and
singleton gestation: Is this the missing link
between plurality and adverse outcome?
Lilach Marom-Haham1, Shali Mazaki-Tovi1, Itamar Zilberman1,
Anat Kalter1, Mordechai Dulitzky1, Eyal Sivan1, Eyal Schiff1, Yoav
Yinon1
1
OBJECTIVE: Magnesium sulfate (MgSO4) administered to women at
risk for preterm delivery decrease the risk of cerebral palsy. However,
the beneficiary effect of MgSo4 in twin gestation has been shown to be
reduced. Thus, the aim of this study was to determine maternal serum
levels of magnesium in twins versus singleton pregnancies following
intravenous treatment of MgSO4.
STUDY DESIGN: Case control study including two groups of pregnant
women who received intravenous MgSO4: 1) twin gestations (n⫽65)
and 2) singleton pregnancies (n⫽65). The groups were matched for
maternal BMI and gestational age at treatment. The indications for
treatment included severe preeclampsia, fetal neuroprotection and
preterm labor. Maternal serum magnesium levels 6 and 24 hours after
initiation of treatment were determined in both groups.
RESULTS: Maternal age, BMI, serum creatinine and gestational age at
treatment were similar among both groups. Maternal serum levels of
magnesium were significantly lower among patients with twin gestations compared to singletons both 6 and 24 hours after initiation of
treatment (4.4 mg/dl vs 4.7 mg/dl, p⫽0.006; 4.8 mg/dl vs 5.9 mg/dl,
p⫽0.014, respectively). Moreover, the rate of pregnant women who
did not obtain therapeutic level was significantly higher in twins compared with singleton gestations (34% vs 12%, p⫽007). Multiple regression analysis revealed that twin gestations as well as hematocrit
level were independently and significantly associated with low maternal serum magnesium levels at 6 hours after adjustment for BMI,
gestational age at treatment and creatinine.
CONCLUSION: Maternal serum levels of magnesium are decreased in
twin pregnancies compared to singletons following MgSO4 treatment. This observation might explain the decreased neuroprotective
effect of MgSO4 treatment in twins. Therefore, further studies are
urgently needed to determine the optimal dosage of MgSO4 treatment
in twin gestations.
131 Moderate-intensity exercise in pregnancy:
in search of a simple prescription
Linda Szymanski1, Andrew Satin1
1
Johns Hopkins University School of Medicine, Gynecology and Obstetrics,
Baltimore, MD
OBJECTIVE: Guidelines for exercise in pregnancy are unclear. ACOG
encourages healthy pregnant women to perform regular, moderate
exercise without defining what constitutes ‘moderate’ exercise. In
non-pregnant populations, Health & Human Services defines ‘moderate’ exercise as: 1) activity requiring 3-5.9 metabolic equivalents
(METs); 2) 40-59% of aerobic capacity or heart rate reserve (ie, target
heart rate,THR); or 3) rating of perceived exertion (RPE) of 5-6 on
10-point scale. Exercise physiologists suggest that individualized
THRs derived from exercise tests, as opposed to age-predicted THRs,
are more accurate for prescribing exercise. This study evaluates the use
of METs, age-predicted THRs, and RPE compared to individualized
THRs derived from an exercise test for prescribing moderate exercise.
STUDY DESIGN: 45 women in the 3rd trimester performed a peak exercise test. THRs for moderate intensity (40-59%) were individually
calculated using resting and peak maternal heart rates. Women then
exercised 30 minutes on the treadmill, adjusting speed/grade to maintain their THR. METs were determined using standard equations.
RPE was recorded. Age-predicted THRs were calculated and compared to individualized THRs using t-tests.
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RESULTS: Data for the moderate exercise session are in the table, stratified by baseline physical activity level. Age-predicted THRs were
higher than individually prescribed THRs in all women. Exercisers
achieved higher METs.
CONCLUSION: Although exercise testing provides an accurate THR, it
may not be practical for prescribing moderate exercise. However, providing a THR using readily available age-predicted ranges (eg, health
club charts) may be inappropriate, as it might cause women to work
harder than necessary. RPE was not accurate. When exercising in individualized THRs, average MET level was in the moderate range for
all women. Thus, the simple recommendation to perform activities
requiring 3-5.9 METs (readily available information) may be a practical method of conveying ‘moderate’ exercise to pregnant women.
Poster Session I
SDS height and SDS weight
from birth till 2 years of age
Data from the moderate exercise session
Data are expressed as mean ⫾ standard deviation.
* Age-predicted different from Individualized target heart rate (P ⬍ .05); † Non-exerciser different from
Exerciser (P ⬍ .05.
132 Post-natal catch-up growth after
suspected IUGR at term
Linda van Wyk1
1
Leiden University Medical Centre, Obstetrics & Gynecology, Leiden,
Netherlands
133 Labor progression in elderly parturients
OBJECTIVE: To study neonatal growth patterns of children born after
suspected intra-uterine growth restriction at term.
STUDY DESIGN: We performed a long-term follow-up of the DIGITAT-RCT (n⫽650). This nationwide trial compared in women with a
pregnancy with suspected IUGR at term induction of labor (IoL) with
expectant management (EM). We collected growth data of these children until the age of 2 years using a postal enquiry. Standard deviation
scores (SDS) for height and weight were calculated at different ages.
Subsequently we assessed the effects of IoL compared with EM and the
effects of a birthweight below or above the 10th centile on catch-up
growth. Target height SDS were calculated using the height of both
parents.
RESULTS: We approached 582 of the 650 randomized patients, of
whom 267 (46 %) responded. At birth the average SDS was ⫺1.8 for
height and ⫺2.0 for weight. At 2 years of age the SDS for height was
⫺0.9 and ⫺1.1 for weight, significantly lower than in a normal population and significantly lower than expected based on the parents’
target height SDS (⫺0.3). We found a significant increase in SDS in
the first 2 years of life, suggesting neonatal catch-up growth. When
comparing IoL to a policy of EM we found that at birth, the weight
SDS in the EM group was significantly lower (⫺2.1 vs ⫺1.9,
p⫽0.004), but children in the EM group showed significantly more
catch-up growth in the first month after birth and the SDS were comparable thereafter. The increase in SDS for weight from birth till 2
years was 1.3 for children ⬍p10 and for children ⬎p10 it was 0.6
(p⫽0.045).
CONCLUSION: Children born after IUGR at term show catch-up growth
in the first 2 years after birth. After an expectant management, children show more catch-up growth during the first month. Children
born with a birthweight ⬍p10 show significantly more catch-up
growth in weight than children born with a birthweight ⬎p10. Based
on the fact that these children have not yet reached their target height
SDS, we can conclude that catch-up growth is incomplete at two years
of age.
Liron Kogan1, Uri Dior1, Yossef Ezra1, Neta Eisenberg3, Ronit
Calderon-Margalit2
1
Hebrew University, Department of Obstetrics and Gynecology, Hadassah
Medical Center, Jerusalem, Israel, 2Hebrew University, Epidemiology unit,
School of Public Health, Jerusalem, Israel, 3Tel aviv university, The Helen
Schneider Hospital for Women, Tel Aviv, Israel
OBJECTIVE: A major demographic trend of the last thirty years is increased mean age at first birth. Advanced maternal age has been
shown to be associated with obstetric complications. Yet, there is limited data regarding labor progression of elderly parturients. Hence, we
investigated the influence of maternal age on the labor curve.
STUDY DESIGN: A retrospective cohort study of all singleton, term,
cephalic, ⬎1500 gram, spontaneous live vaginal deliveries between
2003 and 2010 in a tertiary medical center. Detailed information was
collected on maternal demographics, cervical exams (enabling reconstruction of labor curves) and maternal and neonatal outcomes. A
mixed models analysis of repeated measures were used to construct
adjusted labor curves stratified by maternal age (⬍40, ⫽⬎40 years)
and parity (1, 2-5, ⬎6). General linear models were used to compare
durations of the first and second stages of labor by maternal age, controlling for potential confounders (e.g. birthweight, oxytocin augmentation) and producing adjusted means.
RESULTS: Of 44,121 births, maternal age was ⬍40 years in 42,544, and
⫽⬎40 years in 1,577. Labor curves, stratified by age and parity, were
similar (Figure). Duration of labor did not show a statistically significant difference between the age groups. Mean durations from hospital admissions to 10cm dilation for nulliparous parturients were 7.7
and 7.5 hours for maternal age ⬍40 and ⫽⬎40 years, respectively
(p⫽0.77); and for multiparous parturients, 4.5 and 4.7 hours for maternal age ⬍40 and ⫽⬎40 years, respectively (p⫽0.27) [Table]. Mean
durations of the second stage of labor for nulliparous parturients were
81.9 and 94.2 minutes for maternal age ⬍40 and ⫽⬎40 years, respectively (P⫽0.08); and for multiparous parturients, 20.0 and 22.6 min-
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Poster Session I
utes for maternal age ⬍40 and ⫽⬎40 years of age, respectively
(p⫽0.04).
CONCLUSION: Progression of labor in the first and second stages is not
significantly influenced by maternal age. This supports implementation of similar clinical standards in the first and second stages of labor
regardless of age.
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CONCLUSION: The use of the classification of the SD severity is not
predictive of the risk for recurrent SD, thus even mild SD with no
neonatal injury should be taken into account as a major risk factor for
recurrence in future vaginal birth, possibly with worse neonatal outcome. Furthermore, if vaginal birth is attempted, induction of labor
should be considered cautiously.
Duration of first stage of laborⴤ stratified by
age and parity groupsⴥ
⬀Admission to 10 cm; ⬁Adjusted for birthweight, oxytocin augmentation.
134 WITHDRAWN
135 Is repeated shoulder dystocia a predictable event?
M. Bas-Lando1, D. Goldberg1, V. Sery1, R. Farkash1,
S. Grisaru-Granovsky1, A. Samueloff1
1
Shaare Zedek Medical Center, Hadassah Hebrew University Hospital,
Hebrew University Medical School, Deptartment of Obstetrics and
Gynecology, Jerusalem, Israel
OBJECTIVE: Shoulder dystocia (SD) is an event often followed by a
recommendation for “preventive” CS in future births. We aimed to
evaluate the risk factors for repeated SD and to set criteria for allowing
safe subsequent vaginal deliveries.
STUDY DESIGN: Retrospective cohort review at a single center, between
2005-2012, based on computerized database. All women with SD and
subsequent births were included. The primary event of SD was reviewed for each case according to medical records and categorized
into 2 groups: mild SD- less than a minute and no neonatal injury and
severe SD- more than a minute with neonatal injury. The subsequent
vaginal deliveries were divided into 2 groups: Group A - repeat SD and
Group B- no recurrence. Group A & B were further compared for
demographic and risk factors (Table). Statistics: Descriptive,
means⫾SDs , medians⫹IQR. Comparisons: chi-square, Fisher’s exact test, Mann-Whitney Test.
RESULTS: Between 2005-2012 89,282 births were registered. SD was
recorded for 235 women (0.26%) and 110 (46%) experienced deliveries following the event of SD: 84(76%) women were vaginal and 26
(24%) were planned CS births. Ten (11.9%) women that delivered by
vaginal route experienced repeat SD (Figure). Analysis showed that
the main risk factors for repeated SD were macrosomia
(p⫽0.02.OR⫽5 [1.3-19.3]), larger fetal weight at repeat birth
(p⫽0.001), induction of labor (p⫽0.051) and longer interval between
births (mean 5.1 ⫾1.4 years vs 3.1⫾1.0 years, p⬍0.0001). However,
all cases of repeated SD occurred in group of mild SD according to the
first event description (0.068), 7 of them had mild SD and 3 severe SD.
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136 Duration of expulsive efforts and postpartum
hemorrhage risk in nulliparous women
Marie-Danielle Dionne1, Catherine Deneux-Tharaux2, Corinne
Dupont3, Olga Basso1, René-Charles Rudigoz3, Marie-Hélène
Bouvier-Colle2, Camille Le Ray2
1
McGill University, Obstetrics and Gynecology, Montréal, QC, Canada,
INSERM, u953, Paris, France, 3Réseau périnatal Aurore, Obstetrics and
Gynecology, Lyon, France
2
OBJECTIVE: Several studies found an association between duration of
the second stage of labor and postpartum hemorrhage (PPH). Most of
these studies do not differentiate the passive and active (i.e. expulsive
efforts (EE)) phases of second stage. However, the intra uterine pressure is higher during the EE, thus the risk of PPH caused by atony
might be higher. Our study investigates the relationship between the
duration of expulsive efforts (DEE) and risk of PPH.
STUDY DESIGN: A case-control study was performed from the data of
PITHAGORE6 cluster randomized trial carried out in 106 French
maternities (146 781 deliveries). All nulliparous women with a cephalic vaginal delivery were included. Exclusion criteria were: high
risk of PPH and contraindications to EE. Cases of PPH (n⫽3852) were
defined by a blood loss ⱖ500 ml and/or peripartum Hb decrease ⱖ2g/
dl. Cases of severe PPH (n⫽1048) were defined by a peripartum Hb
decrease ⱖ4g/dl and/or the transfusion of ⱖ2 RBC units. The control
group (n⫽762) came from a representative sample of non-hemorrhagic deliveries from the same population. The relationship between
DEE and PPH was analyzed using multilevel logistic regression models with adjustment on individual and organizational factors.
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RESULTS: We found a significant positive linear association between
DEE and PPH and severe PPH. After adjustment, risks for PPH and
severe PPH remained increased for each supplementary 10 minutes of
EE (see Table). Forceps delivery and episiotomy were also significantly
associated with risk of PPH and severe PPH (aOR⫽1.79[1.34-2.38]
and 2.12[1.52-2.97] for forceps, compared with spontaneous delivery
and aOR⫽1.74[1.35-2.33] and 2.46[1.75-3.48] for episiotomy).
CONCLUSION: Duration of expulsive efforts is associated with an increased risk of PPH and severe PPH. However, options to reduce this
phase, i.e. performs forceps or episiotomy, are also associated with a
higher risk of PPH and severe PPH. Physicians should take these results into consideration for management of the active second stage of
labor.
Association between duration of expulsive efforts
and risk of postpartum hemorrhage
*Adjustment for maternal age, gestational age, induction of labor, total dose of oxytocin, analgesia,
duration of labor, mode of delivery, episiotomy, perineal tears, birthweight, maternity size and
PITHAGORE6 randomization group.
137 Incidence, risk factors and outcomes associated with
cesarean delivery of a 2nd twin following vaginal
delivery of the first infant
Mark Hehir1, Stephen Carroll1, Rhona Mahony1
1
National Maternity Hospital, Holles St., Dept of Obstetrics and Gynaecology,
Dublin 2, Ireland
OBJECTIVE: We sought to examine all cases of Cesarean delivery of a
2nd twin following vaginal delivery of the 1st infant in a large tertiary
referral center over an 11-year period.
STUDY DESIGN: This was a prospective observational study of all twin
deliveries, from 2001-2011. Maternal demographics, intrapartum
characteristics and neonatal outcomes were examined in cases where
the 2nd twin required Cesarean delivery following vaginal delivery of
twin 1, and compared with details of cases where successful vaginal
delivery of both twins took place.
RESULTS: During the study there were 1,457 twin deliveries ⬎24 weeks
gestation. The vaginal delivery rate of the first twin was 47.5% (693/
1457). 3.9% (27/693) of 2nd twins required Cesarean delivery following vaginal delivery of their sibling. The incidence of Cesarean delivery
following vaginal delivery of twin 1 was 5.7% (15/262) in nulliparas
and 2.8% (12/431) in multiparas. There was no difference in maternal
age (p⫽0.37), gestational age (p⫽0.13), use of epidural anesthesia
(p⫽0.15), or induction of labor rates (p⫽0.32) between groups where
the 2nd twin was delivered by Cesarean and the group where a vaginal
delivery took place. There was a trend towards labors being longer in
women who required Cesarean delivery of a 2nd twin (309⫾341min
vs. 238⫾190min; p⫽0.06). Blood loss was found to be greater in
women who underwent Cesarean delivery (527⫾211ml vs.
407⫾106ml; p⬍0.0001). A 2nd twin delivered by Cesarean section
was more likely to have an Apgar of ⬍7 at 5 mins (18.5% vs. 2.2%;
p⫽0.007), they were also more likely to have a cord pH⬍7.1(18.5%
vs. 3.3%; p⫽0.003), and to require admission to the neonatal
unit(66% vs. 38.6%; p⫽0.004).
CONCLUSION: This large cohort has clearly indicated the incidence of
emergency Cesarean delivery of a 2nd twin after the vaginal delivery of
twin 1. No risk factors, apart from nulliparity were identified. Maternal and neonatal morbidity are significantly increased when Cesarean
delivery of a 2nd twin is necessary.
Poster Session I
138 Contemporary management and outcomes of twin
pregnancies in multiparous patients at a large tertiary
referral center
Mark Hehir1, Stephen Carroll1, Rhona Mahony1
1
National Maternity Hospital, Holles St., Dept of Obstetrics and Gynaecology,
Dublin 2, Ireland
OBJECTIVE: We sought to investigate contemporary management and
outcomes of all twin pregnancies in multiparous patients over an 11year study period.
STUDY DESIGN: This was a prospective observational study carried out
at a large tertiary referral centre serving a single urban population over
an 11-year period from 2001-2011. Details of maternal demographics,
intrapartum characteristics and neonatal outcomes were recorded on
a computerized database for analysis.
RESULTS: During the study period there were 50523 multiparous deliveries and 721 twin pregnancies ⬎24 weeks gestation, giving an incidence of 1.4/100 multiparous pregnancies. The mean maternal age
was 33.5 ⫾ 4.8 years, the median parity was 1 and 161 mothers
(22.3%) had at least 1 previous Cesarean delivery. A total of 41.8% of
women (302/721) required Cesarean delivery. Approximately 25%
(184/721) of twins underwent elective Cesarean delivery and a further
106 (14.7%) sets of twins required emergency Cesarean delivery, finally 1.6% (12/721) required Cesarean delivery of the 2nd twin after
vaginal delivery of the first baby. The rate of induction of labor was
32.1% (232/721). Approximately 9.8% (142/1442) of babies had a
vaginal breech delivery and 3.6% (52/1442) required instrumental
delivery. Of the liveborn babies 26 (1.8%) had an Apgar of ⬍7 at 5
minutes, and 20 (1.4%) infants had a cord pH of ⬍7.1. Approximately
33% (488/1442) of babies required admission to the neonatal unit.
The perinatal mortality rate was 1.2% (18/1442). A total of
140(19.4%) women had a blood loss of ⬎500ml. An episiotomy was
performed in 16% (67/419) women who delivered vaginally and anal
sphincter injury occurred in just 0.7% (3/419).
CONCLUSION: We consider this robust and significant data relating to
contemporary practice and outcomes relating to twin pregnancies in
multiparous patients. It provides valuable data for the counseling of
patients and may allow further audit of management of multiparous
twin pregnancy.
139 Perinatal outcomes in singleton and twin
pregnancies following first-trimester bleeding
Miha Lucovnik1, Natasa Tul1, Ivan Verdenik1,
Ziva Novak Antolic1, Isaac Blickstein2
1
University Medical Center Ljubljana, Ob/Gyn, Division of Perinatology,
Ljubljana, Slovenia, 2Kaplan Medical Center, Ob/Gyn, Rehovot, Israel
OBJECTIVE: To investigate the relation between first-trimester bleeding and adverse perinatal outcomes in singleton and twin pregnancies.
STUDY DESIGN: A registry-based survey of all singleton and twin pregnancies delivered at ⬎24 weeks’ between 2002 and 2010 was performed. Study cohorts were singleton and twin pregnancies complicated by first-trimester bleeding. Controls were singleton and twin
pregnancies without first-trimester bleeding. Student’s t test and Chisquare test were used to compare cases and controls. Multivariable
logistic regression was used to examine the associations between firsttrimester bleeding and perinatal outcomes, controlling for potential
confounders.
RESULTS: 9,924 singleton and 275 twin pregnancies complicated by
first-trimester bleeding as well as 160,099 singleton and 2,710 twin
controls were included. Bleeding increased the risk of preterm birth
(odds ratio (OR) 1.50, 95% confidence interval (CI) 1.40-1.62), preterm-premature-rupture-of-membranes (OR 1.71, 95% CI 1.531.91), abruption (OR 1.52, 95% CI 1.23-1.87), previa (OR 1.70, 95%
CI 1.24-2.34), stillbirth (OR 1.37,95% CI 1.06-1.75), and congenital
anomalies (OR 1.27, 95% CI 1.10-1.45), with a reduced risk of preeclampsia (OR 0.82, 95% CI 0.70-0.96) in singleton gestations. The
differences remained significant after adjustment for potential con-
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Poster Session I
founders. In twin pregnancies, bleeding was not significantly associated with any of the perinatal outcomes analyzed.
CONCLUSION: In twins there is no significant association between firsttrimester bleeding and adverse perinatal outcomes. In singletons the
risk of pregnancy complications is increased.
140 Effects of low pre-pregnancy body mass index and
gestational weight gain on neonatal outcomes
Milana Berguig1, Julia Timofeev2, Helain Landy1
1
MedStar Georgetown University Hospital, Obstetrics and Gynecology,
Washington, DC, 2MedStar Washington Hospital Center, Obstetrics and
Gynecology, Washington, DC
OBJECTIVE: To evaluate the effect of low pre-pregnancy body mass
index (BMI) and low gestational weight gain on neonatal outcomes as
compared to parturients with normal BMI and normal or excessive
weight gain.
STUDY DESIGN: A retrospective review of a multicenter cohort of deidentified data in the Consortium on Safe Labor (NICHD). This database includes information on 233,844 births from 228,668 deliveries
from 2002-2008. Maternal factors and neonatal outcomes were analyzed by BMI (low BMI ⬍18.5 kg/m2, normal 18.5-24.9 kg/m2) and
weight gain during gestation as recommended by the Institute of
Medicine 2009 guidelines (normal weight gain of 28-40lbs for women
with low BMI, and 25-35lbs for women with normal BMI). Chi square
and Fisher’s exact tests were used for statistical analysis, with significance determined at two-tailed ␣⫽0.05.
RESULTS: Low pre-pregnancy BMI showed statistically significant increases in the risk of small for gestational age (SGA) infants (OR ⫽
1.96, CI ⫽ 1.93 - 2.00), NICU admission (OR ⫽ 1.24, CI ⫽ 1.21 1.26), and neonatal death (OR ⫽ 1.62, CI ⫽ 1.47 - 1.79). No statistically significant differences were seen in gestational age at delivery or
need for newborn resuscitation. When considering recommended
weight gain, women who gained less weight (⬍28 lbs for low BMI, and
⬍25 lbs for normal BMI) had higher risks of poor pregnancy outcomes (SGA, 5-minute Apgar score ⬍ 7, NICU admission, antepartum and intrapartum stillbirth (Table).
CONCLUSION: Pregnancy outcomes are influenced by both pre-pregnancy BMI and weight gain during pregnancy. These findings suggest
that women can minimize their risk of neonatal morbidity and mortality by optimizing their weight prior to conception and gaining the
recommended weight amount throughout the pregnancy.
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typing studies and was the population for this study. Buccal swabs
were used for SNP genotyping. SNPs for VEGF and FLT were identified from dbSNP, Bio-Carta, and KEGG. Smoking status was defined
as current smoking during the pregnancy. Due to SNP variation by
race only Black women were included in this analysis. Univariable
analysis was performed to assess the association between vascular
SNPs and PTB, and smoking and PTB. Multivariable regression was
used to test for interactions between vascular SNPs and smoking for
the risk of PTB.
RESULTS: Of 932 Black women with smoking and SNP data, 15% delivered ⬍37 weeks, 6% delivered ⬍34 weeks and 13% were current
smokers. Twenty-two VEGF and 128 FLT SNPs were investigated for
association with smoking and PTB. Two VEGF variants rs833060 and
rs3025035 demonstrated a statistically significant interaction with
smoking and PTB, with an increased risk for PTB in smokers and no
increased risk in nonsmokers. Five FLT SNPs demonstrated a similar
interaction for increased PTB in smokers, whereas one variant
rs1324058 demonstrated a protective effect (Table).
CONCLUSION: In a population of Black women, the risk for PTB in
patients who smoke is likely mediated by the genotypes of SNPs in
important vascular genes. These data provide evidence for genetically
susceptible or protective genotypes mediating the effects environmental exposures on the risk for PTB.
Neonatal outcomes by weight gain
141 Protective and high risk genotypes mediate the
risk for preterm birth in smokers
Molly Stout1, Heather Frey1, Methodius Tuuli1, Alison Cahill1,
Anthony Odibo1, Jenifer Allsworth1, George Macones1
1
MO
OBJECTIVE: Smoking during pregnancy is associated with adverse obstetric outcomes, in part via vasculo-toxic effects of cigarette exposure. We investigated whether single nucleotide polymorphisms
(SNPs) in vascular regulatory genes (vascular endothelial growth factor VEGF and a VEGF receptor fms-like tyrosine kinase FLT) affect
the risk for preterm birth (PTB) in smokers.
STUDY DESIGN: A secondary analysis of singleton pregnancies enrolled
in a multicenter randomized control trial investigating the association
between periodontal disease and PTB. One group of women without
periodontal disease was enrolled as an observational group for geno-
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142 Human leukocyte antigen-g tissue expression at the
maternal fetal interface is increased in preterm birth
Molly Stout1, D. Michael Nelson1, George Macones1,
Indira Mysorekar1
1
Washington University in St. Louis, Obstetrics and Gynecology, Saint Louis,
MO
OBJECTIVE: Human leukocyte antigen-G (HLAG) is a major histocompatibility complex protein expressed on extravillous trophoblast
cells. HLAG functions to down-regulate maternal immune response
as non-self fetal cells invade maternal uterine tissue. We tested the
hypothesis that HLAG tissue expression at the maternal-fetal interface
(basal plate) of human placentas is altered in preterm birth (PTB).
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STUDY DESIGN: A nested case control study within a prospective cohort
investigating infection related pathways for PTB. Demographics,
medical history and pregnancy outcomes were collected prospectively. Women with PTB were compared to those who delivered at
term. Basal plate tissue was paraffin embedded. Immunohistochemical expression of HLAG positive cells was quantified using digital
brightfield microscopy. Basal plate tissue % surface area positive for
HLAG was considered both as a continuous and dichotomous (high
HLAG defined as ⱖ75th percentile) variable. Univariable, bivariable,
and multivariable regression were used to test the association between
HLAG expression and PTB.
RESULTS: Of 135 pregnancies, 32.6% delivered ⬍37 weeks. Of these,
79.6% were spontaneous. Basal plate HLAG positivity was significantly increased in PTB compared to term birth (36.6% vs. 32.6%,
p⬍0.01). HLAG tissue positivity remained higher when the analysis
was restricted to spontaneous labor (Table). When comparing patients with and without labor there was no difference in HLAG positivity (33.8% vs. 33.9%, p⫽0.9) suggesting that the differences noted
are not due to the labor process alone. High HLAG (defined as ⱖ75th
percentile) was associated with an 8-fold increased risk for PTB (aOR
8.9, 95%CI 2.0-38.5, p⬍0.01) after controlling for steroid administration and prior PTB.
CONCLUSION: Increased HLAG tissue expression at the maternal fetal
interface of human placentas is associated with spontaneous PTB. We
speculate that HLAG may alter immunotolerance and mediate the
role of infection and inflammation in the pathogenesis of PTB.
Poster Session I
ondary outcomes were maternal demographics, obstetric outcome as
rate of premature rupture of membranes (PROM), GA at delivery,
pregnancy loss at ⬍24 wks and neonatal outcome.
RESULTS: As compared to control, cases had no significant difference
in baseline characteristics (table). Mean GA at cerclage placement was
20.4 ⫾2.3 wks. In those receiving cerclage,there was significant increase in CL as compared pre to post cerlcage (13.73⫾ 6.9 vs. 27.0⫾
8.3 mm, p⬍0.05). As compared to controls, cases had a significantly
lower rate of preterm labor admissions and acute tocolysis but significantly higher rate of PPROM (39% vs. 20%,p⫽0.038). There were no
significant difference among groups in regard to primary outcome
and neonatal outcome. When data were analyzed according to CL ⱕ
15mm vs. ⬎15mm there was no significant difference in outcome
data.
CONCLUSION: We found that performance of cerclage in twin pregnancies with short CL does not reduce rate of PTD. In addition, contrary
to results of metaanlaysis it did not increase composite neonatal morbidity. Thus, there is a need for a multicenter randomized trial to
answer the potential benefits/risks of cerclage in twins with short CL.
144 Understanding the decision to breastfeed:
a survey of postpartum mothers
Nicole Rankins1, Lucy Rice1, Gretchen Brayman1,
Suneet Chauhan1
Left, IHC of preterm placenta; Right, Digital microscopy of same image.
1
Eastern Virginia Medical School, Obstetrics and Gynecology, Norfolk, VA
OBJECTIVE: To assess breastfeeding intentions, beliefs, and knowledge
*After adjusting for corticosteroid administration and bacterial vaginosis.
143 Is there a role for cerclage in twin gestation with short
cervical length (CL)? Single center experience
Natallie Stoval1, Baha Sibai2, Mounira Habli1
1
Good Samritan Hospital, Obstterics, Cincinnati, OH, 2University of Texas
Houstonl, Obstetrics, Houston, TX
OBJECTIVE: A recent meta-analysis of 49 twins with short cervix and
cerclage showed a significant doubling in incidence of preterm delivery(PTD) as compared to no cerclage, but statistically similar perinatal mortality among groups .Our aim in this large, single center case
control study is to compare pregnancy outcome between women receiving cerclage vs. no cerclage in twin pregnancies with ultrasound
evidence of short CLⱕ 25 mm.
STUDY DESIGN: A retrospective study of 105 diamniotic twin pregnancies with CLⱕ 25mm between 16-24 weeks(wks) of gestation(GA): 54
received cerclage and 61 served as control. Exclusion criteria included
chromosomal or congenital malformations and twin to twin transfusion syndrome. Primary outcome was rate of PTD at ⱕ 34 wks. Sec-
through survey of mothers postpartum.
STUDY DESIGN: A 24 question anonymous survey was administered to
eligible mothers from June to August 2011 during their postpartum
hospitalization at an urban medical school. Univariate analysis included frequencies with percentages or mean (central tendency) with
standard deviation (variation) as appropriate. Bivariate comparisons
of continuous variables with breastfeeding plans were completed using t-test. Bivariate comparisons of categorical variables with breastfeeding plans were done utilizing Chi-square test. P ⬍ 0.05 was considered statistically significant.
RESULTS: There were 344 eligible participants. The response rate was
59% (N⫽202). Overall, 69% (N⫽135) planned to breastfeed before
coming to the hospital and among them 94% (N⫽127) planned to
breastfeed at discharge. Only 6% (N⫽8) who did not plan to breastfeed prior to coming to the hospital planned to breastfeed at discharge. Almost half planned to breastfeed for ⬎ 6 months (48%).
Those with a family member who breastfed were more likely to breastfeed than those without (63% vs. 48%, p⫽0.001). If the partner supported breastfeeding (N⫽114), 94% of those mothers planned to
breastfeed, whereas if the partner did not support breastfeeding
(N⫽30), 97% of those mothers did not plan to breastfeed (p⬍0.001).
Gravidity, hours worked/week, attending a breastfeeding class, or receiving information prenatally from a healthcare provider did not
differ between those who planned to breastfeed and those who did
not. The most common reason (65%) for not breastfeeding was “I did
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Poster Session I
not like it”. Less than 10% knew how many US women begin breastfeeding at birth or how many continue to breastfeed at 6 months.
CONCLUSION: In this population most women made the decision to
breastfeed prior to coming to the hospital. Having a family member
who breastfed and partner support for breastfeeding significantly impacted this decision and suggest expanding target populations for
breastfeeding education.
145 Maternal and neonatal complications in subsequent
pregnancy after first birth cesarean section or vaginal
delivery; a nationwide comparative cohort study
Nienke Kok1, Brenda Kazemier1, Ben Willem Mol1, Eva Pajkrt1
1
Academic Medical Center, Obstetrics and Gynaecology, Amsterdam,
Netherlands
OBJECTIVE: To compare the risks of maternal and neonatal complications in a pregnancy after a first birth Cesarean Section (CS) for non
progressive labour and a first vaginal delivery (VD).
STUDY DESIGN: Prospective national cohort study using the Netherlands Perinatal Registry. Women with a first and second delivery between 1 January 2000 and 31 December 2007 were included. Exclusion criteria were preterm delivery (⬍37 weeks), hypertensive
disorders, diabetes, growth restriction (⬍p5), elective CS and CS due
to fetal distress in the first pregnancy. Two groups were distinguished:
women with an initial emergency CS due to non progressive labour
(previous CS cohort) and women who had vaginally delivered at first
attempt (previous VD cohort). We compared complications in the
second pregnancy between the two groups and calculated odds ratios
(OR) for maternal and neonatal adverse events.
RESULTS: We analyzed data of 169.792 women, 15.045 women in the
previous CS cohort, and 154.747 women in the VD cohort. In the
previous CS cohort, 31% of the women had an elective CS, 45% had a
vaginal birth and 24% had an emergency CS at second delivery. In the
previous VD cohort, 95% delivered vaginally again, 3% had an elective CS and 2% had an emergency CS. We found significantly more
uterine rupture, instrumental delivery, hemorrhagia postpartum and
bloodtransfusion in the previous CS cohort. However, antenatal and
neonatal death rates were lower after initial CS than after initial VD.
CONCLUSION: Women with an emergency CS for non progressive labour in the first pregnancy have, as compared to women who delivered vaginally more often repeat CS and maternal complications.
However, antenatal and neonatal death rates are low after a first CS.
Risk of complications in second pregnancy:
previous CS vs previous VD
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146 Induction of labor in twin gestation:
lesson from a population based study
Batel Hamou1, Offer Erez1, Moshe Mazor1, Tamar Wainstock2,
Ruthy Beer Weisel1, Orna Staretz-Chacham3, Doron Dukler1,
Tal Rafaeli1
1
Soroka University Medical Center, School of Medicine, Faculty of Health
Sciences, Ben Gurion University of the Negev, Department of Obstetrics and
Gynecology, Beer Sheva, Israel, 2Faculty of Health Sciences, Ben Gurion
University of the Negev, Department of Epidemiology, Beer Sheva, Israel,
3
Soroka University Medical Center, School of Medicine, Faculty of Health
Sciences, Ben Gurion University of the Negev, Department of Neonatology,
Beer Sheva, Israel
OBJECTIVE: The constantly increasing rate of twin gestations has contributed to the sharp increase in cesarean sections (CS). Induction of
labor can serve as an alternative mode of obstetric intervention in
these patients. The aims of this study were to determine the safety and
efficacy of induction of labor in twin gestations and its association
with adverse maternal and neonatal outcome.
STUDY DESIGN: We conducted a retrospective population based cohort study of twin gestation (n⫽4605 deliveries) including the following groups: 1) Elective CS (n⫽1171); 2) spontaneous delivery
(n⫽2762); and 3) Induction of labor (n⫽672). Since some of the
patients were included in more than one pregnancy generalized estimating equation (GEE) regression models were used to adjust for
confounding factors.
RESULTS: The rate of labor induction in twin gestations was 14.6%
(672/4605). In comparison to the other study groups, the rate of nuliparity was higher in the induction groups (p⬍0.001), these patients
were also more likely to conceive spontaneously, to deliver at term,
and to have a lower rate of previous CS (p⬍0.001 for all comparisons).
Induction of labor was successful in 81.1% of the patients (545/672).
The rate of labor dystocia was higher in women who had induction
than in those with spontaneous labor (p⬍0.001). The CS rate on both
twins was lower in the induction than in the spontaneous labor group
(p⬍0.0001), however, this difference was not significant when CS was
performed only on the second twin. In a GEE model, after adjustment
for confounding factors, induction of labor in twins was independently associated with a lower risk for CS (OR 0.42; CI 0.31-0.57),
while conceiving by assisted reproduction and mal presentation of the
first twin independently increased this risk.
CONCLUSION: In a selected population, Induction of Labor in twin
gestations is safe and can contribute to the reduction of cesarean
deliveries.
147 Preterm premature rupture of the membranes
(PPROM) in twin pregnancy: comparison between
PPROM in twin-A and twin-B
Susan Pakenham1, Ori Nevo1, Eugene Ng2, Jessica Green1,
Sarah Scattolon1, Jon Barrett1
1
Sunnybrook HSC, University of Toronto, Obstetrics and Gynecology,
Toronto, ON, Canada, 2Sunnybrook Health Sciences Centre, University of
Toronto, Neonatology, Toronto, ON, Canada
*Adjusted for malpresentation, induction of labour, macrosomia (ⱖ4500 gr), social economic status
and gestational age; **Not possible due to small number of events in previous VD cohort.
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OBJECTIVE: To examine the clinical course and perinatal outcome of
twin gestation complicated by PPROM of Twin-A versus Twin-B.
STUDY DESIGN: Data was extracted from the charts of all twin gestations admitted to Sunnybrook Health Sciences Centre between January 2004 to December 2010 with ⬎24 hours latency period between
PPROM and delivery. Patients characteristics, risk factors for PPROM
, latency period, delivery details, postpartum complications and neonatal outcome were determined. Pregnancies with TTTS were
excluded.
RESULTS: 76 patients were identified. The average maternal age was
32.3 years; 46 nulliparas and 30 multiparas. 58 were dichorionic and
18 were monochorionic; 10 were Twin-B PPROM and 66 were
Twin-A. The average gestational age at twin-A PPROM was 28.1
weeks and twin-B 21.8 weeks (p⬍0.05). All twin-B PPROM occurred
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at ⬍30 weeks while 40% of PPROM in A occurred beyond 30 weeks.
The average latency from PPROM to delivery was higher in Twin-B
group relative to the Twin-A group (41.3 days vs 10.7 days, p⬍0.05).
In a subset analysis, Twin-B pregnancies were matched and compared
to Twin-A by chorionicity and gestational age. A longer latency (35.8
vs 18.2 days) in Twin-B PPROM was still identified (p⬍0.05). Placental abnormalities were identified in 22.2% of Twin-B PPROM. However, 66.7% vs 44.4% of Twin-A pregnancies were complicated by
threatened preterm labour and cerclage.The rate of retinopathy of
prematurity and neonatal death were significantly higher in twin-A
PPROM compared to B.
CONCLUSION: The earlier presentation, increased latency, and later
gestational age at delivery in Twin-B PPROM is a clinically important
finding which may be linked to a different mechanism and pathophysiology compared to PPROM in twin-A. This is likely the cause for the
better neonatal outcomes of pregnancies complicated by PPROM in
Twin-B compared to A.
148 Association between obesity during pregnancy and the
adequacy of prenatal care
Paula Zozzaro-Smith1, Ciara Conway2, Divyah Nagendra2,
J. Christopher Glantz1, Loralei Thornburg1
1
University of Rochester, Obstetrics and Gynecology, Rochester, NY,
University of Rochester School of Medicine and Dentistry, Obstetrics and
Gynecology, Rochester, NY
2
OBJECTIVE: In the United States, 1-in-4 women are obese (body mass
index (BMI) ⬎30). Although obese populations utilize health care at
increased rates and have higher health care costs than non-obese patients, the adequacy of prenatal care in this population is not well
established and assumed to be suboptimal. We therefore evaluated
adequacy of prenatal care among obese women.
STUDY DESIGN: We utilized Strong Memorial Hospital database including 7091 deliveries with pre-pregnancy BMIⱖ18.5 from 1/09
through 12/11. Subjects were categorized as normal weight 18.5-24.9
kg/m2, overweight 25-29.9 kg/m2, and obese ⬎30 kg/m2 (class I-IIIII). Adequacy of prenatal care (PNC) was evaluated using the Kotelchuck Index (KI), corrected for gestational age at delivery. Adequate care was defined as KI “adequate” or “adequate plus,” and nonadequate as “intermediate” or “inadequate.” Chi-square and logistic
regression were used for comparisons.
RESULTS: KI categorization was similar for normal and overweight
women, and between classes of obesity, thus groups were combined
into non-obese and obese. When compared to non-obese women,
obese women were more likely to have adequate PNC (68.7% vs
74.1%; OR 1.30, 95%CI 1.15-1.47). After adjusting for age, race, education, diabetes, hypertension, and practice type, obesity remained a
significant predictor of adequate prenatal care (OR 1.29, 95%CI 1.141.46). While age and hypertension were not significant independent
predictors of adequate PNC, college education, Caucasian, diabetes,
and resident or MFM care had positive associations.
CONCLUSION: Maternal obesity is associated with increased adequacy
of prenatal care. Although some comorbidities associated with obesity
increase utilization of prenatal services, this did not explain the improvement in PNC adequacy associated with obesity.
149 Incremental increases in prepregnancy BMI, not only
BMI category, increase the risk of cesarean delivery
Poster Session I
and determine the risk of primary cesarean delivery by prepregnancy
BMI.
STUDY DESIGN: IRB approval was obtained for a retrospective review
of the electronic delivery database at the University of Vermont between 2003 and February 2012. Prepregnancy body mass index
(BMI), gestational age at delivery, mode of delivery and indication for
CD were collected. Complete data was available for 12,986 singleton
pregnancies. CD rates were determined by individual BMI and BMI
categories and were limited to primary CD at term. Statistical significance was determined by chi-square test with p ⬍ 0.05. Simple linear
regression was used to estimate change in CD rate by BMI.
RESULTS: In our population, 3.6% are underweight, 54.4% healthy
weight, 22.4% overweight, and 19.5% obese. Among the obese group,
53.7% are obese class I, 27.3% are obese class II, and 19.0% are obese
class III. The primary CD rate increases linearly with increasing BMI
with CD rates of 16.0%, 21.0%, 24.1%, 29.9%, and 34.0% for normal
weight, overweight, obese class I, II, and III, respectively. Overall,
when adjusted for diabetes, hypertension, and prior CD, for each unit
(mg/kg) increase in prepregnancy BMI, the risk of CD increases by
4%.
CONCLUSION: With increasing rates of obesity, particularly morbid
obesity, CD rates will continue to escalate. Obese women, in particular, are at high risk of complications associated with anesthesia and
with surgery, extending their hospital stay and raising healthcare
costs. Prepregnancy weight loss should be encouraged to minimize
pregnancy related complications of obesity. Even a modest decrease in
prepregnancy BMI can have a significant impact on the CD rate.
150 Abnormal placental cord insertion (aPCI) increases risk
of umbilical artery (UA) Doppler abnormalities associated
with iatrogenic preterm delivery in twins
Richelle Olsen1, Dolores Pretorius2, Yvette LaCoursiere1,
David Schrimmer1, Neha Trivedi3, Andrew Hull1
1
University of California, San Diego, Reproductive Medicine, San Diego, CA,
University of California, San Diego, Radiology, San Diego, CA, 3Sharp Mary
Birch, Maternal Fetal Medicine, San Diego, CA
2
OBJECTIVE: To determine the effect of aPCI on UA Doppler indices in
twins.
STUDY DESIGN: Retrospective comparison of twin pregnancies with
pathology confirmed aPCI (marginal or velamentous PCI) in at least
one twin and matched controls with central PCI. We defined abnormal UA Doppler as absent or reversed end diastolic flow (aEDF,
rEDF) within 24 hours of delivery. We determined the odds ratio
(OR) for abnormal UA Doppler in each instance. The impact of aPCI
was compared using logistic regression.
RESULTS: aPCI is associated with a significantly increased risk of abnormal UA Doppler within 24 hours of delivery in twins regardless of
chorionicity. Velamentous PCI is more likely to be associated with
abnormal UA Doppler than marginal PCI, OR 5.1 [2.2–11.6] vs 3.2
[1.4 –7.5] (Table).
CONCLUSION: aPCI is strongly associated with an increased risk of
aEDF or rEDF within 24 hours of indicated delivery in twins. Velamentous PCI has a greater impact than marginal PCI. Assessment of
PCI should be part of routine imaging in all twins.
Julie Phillips1, Richard Adams1, Alison Howe2
1
University of Vermont College of Medicine, Obstetrics, Gynecology, and
Reproductive Sciences, Burlington, VT, 2University of Vermont College of
Medicine, Pediatrics, Burlington, VT
OBJECTIVE: Obese women are at an increased risk of adverse pregnancy outcomes, including an increased likelihood of cesarean delivery (CD). CD is associated with maternal morbidity, longer hospital
stays, and increased healthcare expenditures. The objective of this
study is to review delivery data from a single academic medical center
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151 Celiac disease serum markers and
recurrent pregnancy loss
Rita Sharshiner1, Stephanie Romero1,
Robert Silver1, D. Ware Branch2
1
University of Utah, Department of Obstetrics and Gynecology, Salt Lake
City, UT, 2Intermountain Healthcare, Department of Maternal Fetal
Medicine, Murray, UT
OBJECTIVE: Celiac disease has been associated with numerous unfavorable health outcomes including adverse reproductive and pregnancy outcomes such as infertility, preterm birth, and preeclampsia.
However, the association between celiac disease and recurrent pregnancy loss (RPL) remains uncertain. Our purpose was to compare
celiac disease serum markers in women with and without RPL.
STUDY DESIGN: Case-control study design with 134 women with unexplained RPL, defined as two or more pregnancy losses with no more
than one live birth and 134 age-matched controls with at least one full
term uncomplicated pregnancy and no more than one pregnancy loss.
Maternal serum was analyzed for IgA and IgG tissue transglutaminase
and endomysial antibodies using immunofluorescence assays. Results
were compared between groups using Student’s T test and Chi square
analysis.
RESULTS: Groups were similar with regard to age, race/ethnicity, and
BMI. Cases had higher levels of IgG tissue transglutaminase compared
to controls (3.97 ⫾ 0.19 versus 3.28 ⫾ 0.11; p ⫽ 0.0015). However,
IgA tissue transglutaminase antibodies were similar in cases and controls (5.31 ⫾ 0.24 versus 6.19 ⫾ 1.08; p ⫽ 0.21). Also, cases (N ⫽ 1)
and controls (N ⫽ 2) had a similar proportion of women with positive
tests (ⱖ 20 Units) for IgA tissue transglutaminase antibodies. None were
positive for IgG antibodies. Only one patient in either group (a control)
had a positive test for either IgA or IgG endomysial antibodies.
CONCLUSION: Serum levels of tissue transglutaminase IgG antibodies
were increased in women with RPL compared to controls. This observation deserves further investigation into mechanisms of RPL.
However, elevated levels of tissue transglutaminase and endomysial
antibodies consistent with celiac disease were rare in women with RPL
and similar to women without pregnancy loss. Thus, testing for celiac
disease is not advised in women with RPL.
152 Physical exam indicated cerclage versus expectant
management: a systematic review and metaanalysis
Robert Ehsanipoor1, Neil Selligman2, LInda Szymanski1,
Christina Wissinger3, Erika Werner1, Vincenzo Berghella4
1
The Johns Hopkins University School of Medicine, Gynecology and
Obstetrics, Baltimore, MD, 2University of Rochester Medical Center,
Obstetrics and Gynecology, Baltimore, MD, 3The Johns Hopkins University
School of Medicine, Welch Medical Library, Baltimore, MD, 4Thomas
Jefferson University, Obstetrics and Gynecology, Baltimore, MD
OBJECTIVE: To compare cerclage versus expectant management for
mid-trimester cervical dilation by systematic review and meta-analysis of published studies.
STUDY DESIGN: Medline, EMBASE, Scopus, Web of Science, and the
Cochrane Library (1966-2010) were systematically searched for articles comparing physical exam indicated cerclage to expectant man-
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agement. Studies were included if they compared cerclage to no cerclage in women with a physical exam that revealed a cervical dilation
of ⬎ or ⫽ 1 cm between 14 and 27 weeks. Two authors independently
determined eligibility and abstracted data. The primary outcome was
perinatal death. Odds ratios (OR) with 95% confidence intervals or
weighted mean difference (WMD) were calculated using random effect or fixed effects models for outcomes with and without significant
heterogeneity respectively using Review Manager v5.1.
RESULTS: A total of 11 studies, which included 772 women, met inclusion criteria. A total 496 received a cerclage and the remaining 276
were expectantly managed. One study was a randomized controlled
trial, two were prospective cohort studies, and eight were retrospective cohort studies. Perinatal survival was higher in the cerclage group
(70.9%) compared to the expectantly managed group (41.5%) (OR
4.0, 95% CI 2.0-7.7; figure). Likewise, physical exam-indicated cerclage resulted in significantly longer time from diagnosis to delivery
(WMD 39.5 days, 95% CI 35.3,43.6) later gestational age at delivery
(WMD 5.4 weeks, 95% CI 4.2,6.5), and birthweight (WMD 830.0
grams, 95% CI 308.3, 1351.8).
CONCLUSION: The available evidence suggests that, in women with cervical dilation ⬎ or ⫽ 1 cm between 14 and 27 weeks, physical exam
indicated cerclage significantly decreases perinatal mortality, and prolongs pregnancy.
Perinatal survival: physical exam indicated
cerclage compared to expectant management
153 The obstetric impact of opioid use
and detoxification during pregnancy
Robert Stewart1, David Nelson1, Emily Adhikari1,
Donald McIntire1, Jodi Dashe1, Jeanne Sheffield1
1
University of Texas Southwestern Medical Center, Obstetrics and
Gynecology, Dallas, TX
OBJECTIVE: Opioid use in pregnancy can have devastating consequences to the neonate and mother. We have previously demonstrated that methadone detoxification is safe and effective during
pregnancy, with lower methadone doses at delivery associated with
decreased neonatal withdrawal. Our aim was to analyze the obstetric
impact of opioid use and a detoxification program during pregnancy
in the setting of contemporary opioid usage.
STUDY DESIGN: This is a retrospective cohort study of women electing
inpatient detoxification and subsequently delivering at our hospital
from January 1, 2006 to December 31, 2011. Successful detoxification
was defined as women without illicit drug supplementation at the
time of delivery. Women undergoing methadone detoxification or
maintenance at the time of delivery without illicit supplementation
were not a failure. Clinical and laboratory findings of the obstetric and
neonatal outcomes were ascertained and analyzed based on maternal
success at delivery.
RESULTS: A total of 97 women entered our inpatient methadone detoxification program, and 55 (57%) were considered successful at delivery.
Obstetrical outcomes were available in 92 liveborn, singleton infants
without malformations. Maximum neonatal abstinence syndrome
scores (NAS), infant duration of hospitalization, and infant treatment for
opioid withdrawal were all decreased in those women who successfully
entered and completed detoxification, as shown in the table. Obstetrical
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outcomes showed a clinically relevant, although not statistically significant, improvement in birthweight ⬍2500 grams and preterm delivery in
those women who successfully completed detoxification.
CONCLUSION: Maternal opioid detoxification during pregnancy results in
improved neonatal outcomes and decreased neonatal duration of hospitalization. The stability of our success rate and improvement in neonatal
outcomes justifies continued maternal opioid detoxification in select patients.
154 Risk of intrauterine death in monochorionicdiamniotic (MCMD) twins
Robin Kalish1, Gloria Felix1, Shane Wasden1
1
Weill Cornell Medical College, Obstetrics and Gynecology, New York, NY
OBJECTIVE: As MCMD pregnancies are at higher risk of perinatal mor-
bidity and death compared to singletons and dichorionic twins, the
optimal gestational age of planned delivery is controversial. This study
calculates the prospective gestational age specific risk of fetal death in
MCDA twins.
STUDY DESIGN: We performed a review of all MCDA twins who where
followed antenatally and delivered ⱖ24 weeks gestation from 20002012 at our institution. Study subjects were identified from our ultrasound database. Maternal and neonatal charts were reviewed. The
prospective risk of fetal demise was calculated for 2 week blocks starting at 24 weeks. Fisher’s exact and Mann-Whitney U tests were used
for analysis of categorical and continuous variables. Binomial distribution 95% confidence intervals were calculated using standard statistical formulas.
RESULTS: 147 pregnancies were included. Ten intrauterine deaths occurred in 147 pregnancies, giving a 3.4% fetal mortality rate. Twintwin transfusion syndrome (TTTS) was diagnosed in 13/147 pregnancies (8.8%).The risk of fetal death was higher in pregnancies
complicated by TTTS (15.4% vs 3.0%, p⫽ .03).The prospective risk of
fetal death was 4.1% at 24-25wks, 3.5% at 26-27wks, 2.2% at 2829wks, 2.2% at 30-31wks, 2.3% at 32-33wks, 1.8% at 34-35wks, and
1.4% at ⱖ36wks (see Table).Of 284 live newborns in our study there
were 4 neonatal deaths from 3 pregnancies (1.4%).All 3 pregnancies
were delivered severely prematurely at 24-25 weeks and 2 pregnancies
were complicated by TTTS. The overall risk of perinatal death was 14
per 294 fetuses (4.8%).
CONCLUSION: There is a high risk of intrauterine death in MCDA pregnancies. Elective pre-term delivery may reduce the perinatal mortality
rate. However, planned delivery at ⬍36 weeks would likely increase
the rate of neonatal complications associated with prematurity. The
optimal age for delivery in MCDA pregnancies not complicated by
TTTS remains controversial and warrants further investigation in
prospective trials.
Prospective gestational age
specific risk of fetal death
*95% CI is given in parenthesis.
Poster Session I
155 Outcomes of pregnancies with incidentally
detected unicornuate uterus
Sarah Anderson1, Stephen Chasen1
1
Weill Medical College of Cornell University, Obstetrics and Gynecology,
New York, NY
OBJECTIVE: Unicornuate uterus is associated with high rates of cervical
insufficiency and spontaneous preterm birth. A limitation of existing
data is that imaging often is done for a history of poor OB outcomes,
and those diagnosed with unicornuate uterus are at high risk based on
history. Our objective was to evaluate OB outcomes in those with
unicornuate uterus ascertained for reasons unrelated to poor OB
history.
STUDY DESIGN: Retrospective review of OB database from 2005-2012
identified women with unicornuate uterus at ⬎12 weeks. Diagnoses
were confirmed by HSG and/or MRI. Cases in which imaging was
performed due to history of midtrimester loss or preterm birth were
excluded. Records were reviewed to identify outcomes. SGA was defined as birthweight ⬍10th%ile based on a US growth curve. MannWhitney U was used for statistical comparison.
RESULTS: 27 patients with 37 pregnancies were included. Most diagnoses (85%) were made during infertility workup, with remaining
cases diagnosed following findings at the time of OB ultrasound, cesarean delivery, or surgery for ectopic pregnancy. Prophylactic cerclage was placed in only 6 pregnancies (16%). Outcomes are listed in
the Table. The midtrimester loss at 16 weeks was associated with vaginal bleeding, but not painless dilation. All spontaneous preterm
births occurred at ⬎34 weeks. Indicated preterm births were for fetal
indications (2), placenta previa (2), and vasa previa (1), and were at
earlier gestational ages compared to spontaneous preterm births (median 34 vs. 36 weeks; p⫽.03). Cesarean delivery was performed in 27
cases (75%), with malpresentation the most common indication.
CONCLUSION: In those with unicornuate uterus but no history of adverse OB outcome, rates of midtrimseter loss and spontaneous preterm birth were lower than described in published studies. Half the
preterm births, including all at ⱕ34 weeks, were indicated. The relatively high rate of SGA newborns and placental abnormalities suggests
that abnormal placentation may be a greater concern than spontaneous preterm birth.
Obstetric outcomes in women with incidentally
detected unicornuate uterus
156 Time from LEEP to pregnancy: impact on
adverse pregnancy outcomes
Shayna Norman1, Alison Cahill1, Methodius Tuuli1, David
Stamilio1, Anthony Odibo1, Kimberly Roehl1, George Macones1
1
St. Louis, MO
OBJECTIVE: Prior studies have shown conflicting results for pregnancy
outcomes after loop electrode excision procedure (LEEP), however no
study has evaluated pregnancy outcome with respect to time elapsed
from LEEP to pregnancy. We investigated risk of spontaneous abortion (SAB) and preterm birth associated with time elapsed from a
LEEP to pregnancy.
STUDY DESIGN: A 7-year, multicenter cohort study of reproductiveaged women who underwent LEEP was performed between 2000 and
2006. Subjects were identified by review of pathology records at 9
tertiary and community hospitals. Trained research nurses conducted
closed-ended phone interviews with all subjects to complete historical
and medical data extraction unavailable in charts. Median time interSupplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
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Poster Session I
vals from LEEP to pregnancy were evaluated for SAB ⬍ 12 weeks and
preterm birth ⬍34 and ⬍37 weeks for women with a history of LEEP.
Patients with time intervals of ⬍12 months vs. ⱖ 12 months from
LEEP to pregnancy were compared to identify crude odds ratios (OR)
and adjusted OR for SAB and preterm birth.
RESULTS: For 596 women with history of a LEEP, the median time to
pregnancy was 30.8 (2.0-147.1) months. For women whose pregnancy
ended in SAB, their time from LEEP to pregnancy was significantly
shorter than those who did not have an SAB (20.3 months, range
3.4-89 vs. 31.2 months, range 2-147.1, p-value 0.01). However, there
was no difference in time interval for women with a term birth compared to women with a preterm birth. In women with a time interval
of ⬍ 12 months compared to ⱖ 12 months from LEEP to pregnancy,
there was a significantly increased risk for SAB (17.9% vs. 4.6%, aOR
5.6, 95%CI 2.5-12.7). No increased risk was identified between the
two groups for preterm birth ⬍ 34 or ⬍37 weeks (Table).
CONCLUSION: Women with a shorter time interval from LEEP to pregnancy have an increased risk for SAB, but not preterm birth. When
pregnancy occurs within 12 months of LEEP, there is greater than a
5-fold increased risk of pregnancy loss prior to 12 weeks.
*Adjusted for age. Race, smoking, prior preterm birth, and BMI dropped out of model.
157 The effects of degree of obesity on risk for
post-cesarean wound complication
Shayna Norman1, Juliana Verticchio1, Anthony Odibo1,
Methodius Tuuli1, George Macones1, Alison Cahill1
1
Washington Unversity in St. Louis, Obstetrics and Gynecology, St. Louis,
MO
OBJECTIVE: To estimate the effect of increasing severity of obesity on
post-cesarean wound complications.
STUDY DESIGN: We performed a retrospective cohort study of wound
complications among 2543 consecutive cesarean deliveries performed
at a tertiary care facility from 2004-2008. Four comparison groups
were defined by body mass index (BMI) ⬍30 (n⫽768), 30-39.9
(n⫽1134), 40-49.9 (n⫽436), or ⱖ50 (n⫽205). The primary outcome
was wound complication, defined as the occurrence of a wound seroma, hematoma, separation, dehiscence or infection from time of
delivery to 6 weeks post-operative. Multivariable logistic regression
was used to estimate risk while adjusting for diabetes and prior
cesarean.
RESULTS: Of the 2543 women who underwent a cesarean, 95 (3.7%)
developed a wound complication. Increasing BMI was significantly
associated with an increased risk of wound complications even after
adjusting for confounders (1.6% vs. 2.7%, aOR 1.5 [95% CI 0.7-2.9]
vs. 7.0%, aOR 4.0 [95% CI 2.0-8.1] vs. 12.1%, aOR 7.1 [95% CI 3.414.8] for BMI ⬍30, 30-39.9, 40-49.9, and ⬎50 respectively) (Table).
CONCLUSION: Obese women have a significantly increased risk for
post operative wound complications after cesarean; a dose-response relationship exists between increasing BMI and risk of
wound complications.
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158 Symptomatic placenta praevia: short cervix at
admission is a predictive factor for delivery within 7 days
Stephanie Friszer1, Camille Le Ray1, Julie Tort1,
Francois Goffinet1, Vassilis Tsatsaris1
1
Cochin-Broca-Hotel Dieu Hospital, Assistance Publique des Hôpitaux de
Paris, Port Royal Maternity, Department of Obstetrics and Gynaecology,
Paris, France
OBJECTIVE: Symptomatic placenta praevia (PP) is a situation at high
risk for adverse issues. Our objective was to investigate risk factors for
adverse obstetrical outcomes among patients admitted for symptomatic PP. We specifically assessed the ultrasonographic cervical length
most predictive of a delivery within 7 days.
STUDY DESIGN: A retrospective cohort of all symptomatic (i.e. haemorrhagic) PP hospitalised before 37 weeks, between June 2007 and
December 2010, in a tertiary centre. Delivery within 7 days was studied as primary outcome. Secondary outcomes were recurrent bleeding
and preterm premature of membranes (PPROM). Clinical, biological
and ultrasonographic predictive factors were studied using univariate
and multivariate analysis to determine risk factors for adverse obstetrical issues. ROC curve analysis was used to assess the cervical length
threshold most predictive of a delivery ⱕ7 days.
RESULTS: 105 patients were included. In univariate analysis, the risk
for delivery within 7 days was significantly associated with uterine
contractions at admission (p⫽0.02), cervical length ⱕ25mm at admission (p⬍0.01), haemoglobin decrease during the first hospitalisation ⱖ2g/dL (p⬍0.01) and the need for prenatal transfusion (p⫽0.1).
No factor was significantly associated with recurrent bleeding or
PPROM. After multivariate analysis, only short cervix ⱕ25mm
(OR⫽8.8 95%CI [1.8-42.5]) and haemoglobin decrease ⱖ2g/dL
(OR⫽14.1 95%CI [2.1-92.6]) were associated with a delivery within 7
days. ROC curve analysis found that a cervical length of 30mm was the
most predictive cut-off of a delivery within a week (AUC⫽0.86) with
a sensitivity of 100% and negative predictive value of 100%.
CONCLUSION: In symptomatic PP before 37 weeks, only a short cervix
and a haemoglobin decrease ⱖ2g/dL are associated with delivery
within 7 days. We found no predictive factor for bleeding recurrence
and PPROM. Physicians could use these results to inform patients
admitted for symptomatic placenta praevia.
159 Intravaginal prostaglandin E2 versus double balloon
catheter for labor induction in term isolated oligohydramnios
Gil Shechter-Maor1, Tal Biron-Shental1, Gabi Haran1,
Yael Ganor-Paz1, Moshe Fejgin1
1
Meir Medical Center, Sackler School of Medicine, Tel Aviv University,
Obstetrics and Gynecology, MFM unit, Kfar Saba, Israel
OBJECTIVE: Induction of labor for term patients with oligohydramnios is advocated by experts to reduce perinatal morbidity and mortality. The better mode of cervical ripening for those patients has not
been determined. The aim of this study was to compare mechanical
and pharmacological ripening methods for term patients with oligohydramnios.
STUDY DESIGN: 50 patients with a singleton term pregnancy who were
diagnosed with amniotic fluid index (AFI ) below 5 cm and an unripe
cervix were randomized for induction of labor with double balloon
catheter or with slow release vaginal prostaglandin E2 (PGE2; Cervidil®). The primary outcome measure was a 10-hour difference in time
from induction to active labor. Labor and delivery course, maternal
satisfaction, and early neonatal outcomes were evaluated.
RESULTS: There were no demographic differences between groups.
Time from induction to delivery was 19.1 hours in the PGE2 group vs.
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23.4 hours in the catheter group. The differences in were not statistically significant, although more mothers in the catheter group received oxytocin after ripening (84.6% vs. 54.2%; P⫽.019), respectively. More fetuses had insignificant fetal heart rate decelerations
during ripening while using PGE2 (33.3%) compared to the catheter
(0%; P⫽0.002). Induction was stopped earlier than planned in 75% of
the PGE2 group compared to 27% of the catheter group (P⫽0.001),
mostly due to progression to active labor. No differences in delivery
methods or early neonatal outcomes were found. Higher maternal
satisfaction rates were reported with PGE2.
CONCLUSION: Intravaginal dinoprostone and double balloon catheter
are comparable for cervical ripening in oligohydramnios at term
pregnancies.
Poster Session I
studies, as well as an evaluation of the accuracy of prenatal sonographic diagnosis of abnormal cord insertion.
All models adjusted for placental abruption/
chorioamnionitis, maternal diabetes
and maternal hypertension
Main results
161 Is velamentous/marginal cord insertion associated with
adverse outcomes in singletons?
Tharwat Stewart Boulis1, Burton Rochelson1, Natalie Meirowitz1,
Adiel Fleischer1, Michelle Smith-Levitin1, Morris Edelman2, Lisa
Rosen3, Alex Williamson2, Nidhi Vohra1
160 Are there adverse pregnancy outcomes associated with
concordant or discordant velamentous/marginal
cord insertion in twins?
Tharwat Stewart Boulis1, Burton Rochelson1, Natalie Meirowitz1,
Adiel Fleischer1, Michelle Smith-Levitin1, Morris Edelman2, Lisa
Rosen3, Alex Williamson2, Nidhi Vohra1
1
Hofstra North Shore-LIJ School Of Medicine, Division of Maternal-Fetal
Medicine, Manhasset, NY, 2Hofstra North Shore-LIJ School Of Medicine,
Pathology Department, New Hyde Park, NY, 3Hofstra North ShoreLIJ Health System, Biostatistics, Long Island, NY
OBJECTIVE: To evaluate adverse pregnancy outcomes in twins with
concordant or discordant velamentous (VCI)/ marginal cord insertion (MCI).
STUDY DESIGN: Retrospective chart review 2002 - 2012 was performed
to evaluate adverse outcomes in pathology confirmed cases of abnormal cord insertions. Group A: Both fetuses in a twin set had normal
cord insertion (NCI). Group B: Both fetuses in a twin set had either
VCI or MCI, MCI was defined as cord insertion at the placental edge.
Group C: One fetus in a twin set had NCI and the other had VCI or
MCI. Exclusion criteria: ⬍ 20 weeks of gestation; iatrogenic terminations. Outcomes were delivery ⬍ 37 weeks, cesarean section (C/S),
small for gestational age (SGA) defined as ⬍ 10 % tile for at least one
fetus of the twin set, intrauterine fetal demise (IUFD), neonatal Apgar
scores ⬍7 at 1 minute and 5 minutes, arterial and venous cord PH.
Analysis of variance (ANOVA) and the chi-square test were used to
compare maternal characteristics between the three groups. Multivariate logistic regression was used to model each outcome as a function
of group.
RESULTS: The study included 1420 sets of twins; 1340 in Group A, 19
in Group B and 61 in Group C. There were no significant associations
between cord group and delivery less than 37 weeks or C/S. There was
a significant association between cord group and IUFD (P ⬍ 0.04).
Group B was at higher risk of IUFD than Group A (P ⬍ 0.01). Group
C was at higher risk for SGA as compared to Group A (P ⬍ 0.04).
Neither Apgar scores at 1 minute or 5 minutes nor arterial or venous
cord PH had a significant association with cord group.
CONCLUSION: There is a higher risk of SGA in twins discordant for cord
insertion and an over fivefold increased risk of IUFD in twins both of
whom have abnormal cord insertion. This increase in adverse fetal
outcomes in such pregnancies needs to be confirmed by additional
1
Hofstra North Shore-LIJ School Of Medicine, Maternal-Fetal Medicine,
Manhasset, NY, 2Hofstra North Shore-LIJ School Of Medicine, Pathology
Department, Manhasset, NY, 3Hofstra North Shore-LIJ Health System,
Biostatistics, Long Island, NY
OBJECTIVE: To evaluate the association of velamentous (VCI) and
marginal cord insertion (MCI) with adverse outcomes in singleton
pregnancies.
STUDY DESIGN: Retrospective chart review 2002 - 2012 to evaluate adverse outcomes in singletons with pathology confirmed VCI or MCI.
Exclusion criteria: ⬍ 20 weeks of gestation; iatrogenic terminations.
MCI was defined as cord insertion at the placental edge. Primary outcomes were delivery ⬍37 weeks, cesarean section (C/S), small for
gestational age (SGA), low birthweight (LBW) (less than 2500 grams),
intrauterine fetal demise (IUFD), neonatal Apgar scores, arterial and
venous cord PH.
RESULTS: The study included 122 singletons; 50 MCI and 72 VCI. The
average maternal age was 33 years ⫾ 5.82, and 38.26% were multiparous. The frequency of placental abruption/ chorioamnionitis was
14.8%, maternal diabetes was 9 % and maternal hypertension was
11.5%. Overall, 29.51% of all abnormal cord insertions had delivery ⬍
37 weeks (MCI: 28.00%, VCI: 30.56%). 82 (69.49%) were born by C/S
(MCI: 80.00%, VCI: 61.76%). IUFD rate was 4.1% (MCI: 4.00%, VCI:
4.17%). 31% were SGA (MCI: 30.61%, VCI: 31.25%). One third of
babies with an abnormal cord insertion had LBW (MCI: 40.82%, VCI:
27.69%). 9.7 % had Apgar scores ⬍ 7 at 1 minute. 5.3 % had Apgar
scores ⬍7 at 5 minutes (Figure 1). Of 64% of singletons with cord
blood gas measurements,16.67% had an arterial cord pH ⬍ 7.2 .
CONCLUSION: Singletons with abnormal cord insertion had a high incidence of SGA, LBW, preterm delivery and C/S. The incidence of an
arterial cord pH ⬍7.2 and a low 5 minute Apgar score were also high.
Close observation of pregnancies complicated by VCI and MCI for
adverse outcomes should be considered. Prospective studies are
needed to establish a management protocol for VCI and MCI pregnancies as well as an evaluation of the accuracy of prenatal sonographic diagnosis of abnormal cord insertion.
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Poster Session I
162 Evaluation of the efficacy of the intrauterine balloon
tamponade as a second-line procedure in the management
of severe postpartum hemorrhage within a perinatal network
order multiples, delivery ⬍ 24 weeks, incomplete records and indicated preterm delivery. Demographic and obstetrical factors were
compared between women with an AS to delivery latency of ⬍7d and
those with a ⬎7d latency. Appropriate parametric and non parametric
tests were used. P ⬍0.05 denotes statistical significance, and relative
risks with 95% confidence intervals were calculated.
RESULTS: 345 patients were included for review. Median latency from
AS to delivery was 41d (range 0-119). Only 68 patients (20%) received
AS within 7d of delivery while 277(80%) received AS ⬎7d before
delivery. 92% of patients who delivered preterm between 2009 and
2010 received AS. See table 1. Of the patients with PPROM none had
a cervical length ⬍2cm or were ⬎2cm dilated.
CONCLUSION: 80% of patients receive suboptimal timing of AS administration (⬎7d from delivery). Factors associated with suboptimal
timing of AS administration are: cervical length ⬎2cm, cervical dilation ⬍2cm and intact membranes, but not fFN results. Since maximal
neonatal benefit is achieved when AS are given within 7d of delivery,
assessment of the cervix should be a key factor in the decision for their
administration.
Thomas Popowski1, Pierre Raynal2, Patrick Rozenberg1
Table
1
Poissy Saint-Germain Hospital, Versailles Saint-Quentin-en-Yvelines
University, research unit EA 7285, Department of Obstetrics and Gynecology,
Poissy, France, 2Mignot Hospital, Department of Obstetrics and Gynecology,
Le Chesnay, France
OBJECTIVE: To evaluate the efficacy of the intrauterine balloon tamponade (IUBT) as the initial second-line procedure when medical
management fails in the management of severe postpartum hemorrhage (PPH).
STUDY DESIGN: We carried out a prospective cohort study within a
perinatal network comprising 10 perinatal units managing around
20,000 deliveries per annum. The protocol for management of PPH
followed the French national guidelines. In April 2008, the IUBT using Bakri balloon was introduce in the tertiary referral university hospital and the protocol was modified to require that an IUBT test be
used before any invasive procedure in PPH unresponsive to prostaglandin. The modified protocol was progressively extended to the 9
other maternities. The tamponade test was considered successful if
control was achieved following inflation of the balloon.
RESULTS: Between April 2008 and June 2012, 166 IUBT tests were
performed. The mean maternal age was 30.4 (SD 5.2) years, the mean
gestational age 39.1 (SD 2.5) WG, and the mean parity 1.1 (SD 1.2).
Nineteen (11.5%) patients had a previous history of cesarean section
(CS), 25 (15.1%) a previous history of PPH, 14 (8.4%) were multiple
pregnancies, and 8 (4.8%) presented a placenta previa. Among the 166
patients, the mean blood loss was 1484 (SD 602) mL, 105 (63.3%)
patients had blood transfusion with a mean of 3.9 (SD 2.8) units of
packed red blood cells. Among the 122 patients delivered vaginally,
the IUBT failed in 17 (13.9%) patients leading to 11 embolizations, 2
conservative surgical procedures, and 4 hysterectomies. Among the 44
patients delivered by CS, the IUBT failed in 10 (22.7%) patients leading to 5 embolizations, 3 conservative surgical procedures, and 2 hysterectomies. The global success rate of the IUBT was 83.7%.
CONCLUSION: In the setting of PPH unresponsive to medical management, IUBT should be used as the initial second-line procedure.
163 Timing of antenatal corticosteroid administration:
are we giving it too early?
Tracy Adams1, Wendy Kinzler2, Elyana Matayeva2,
Martin Chavez2, Anthony Vintzileos2
1
Winthrop University Hospital- Stony Brook University Hospital, Obstetrics
and Gynecology, Mineola, NY, 2Winthrop University Hospital, Obstetrics
and Gynecology, Mineola, NY
OBJECTIVE: To determine the factors associated with antenatal corticosteroid (AS) administration more than 7days before delivery.
STUDY DESIGN: This was a retrospective chart review of patients at our
institution who received betamethasone between 2009 and 2010,
identified through our pharmacy database. Exclusion criteria: high
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*P ⬍ .01.
164 Use of Sengstaken tube for management
of severe postpartum hemorrhage
Tsz Kin Lo1, Wai Lam Lau1, Wing Cheong Leung1
1
Kwong Wah Hospital, Obstetrics & Gynecology, Hong Kong, China
OBJECTIVE: Like Bakri balloon, Sengstaken tube has a built-in drain-
age channel for monitoring of bleeding. Unlike Bakri, it’s a lot
cheaper. In this largest series reported so far, we reviewed our experience in management of severe postpartum hemorrhage (PPH) with
Sengstaken tube.
STUDY DESIGN: Cases delivered in our department from July 2008 to
July 2012 complicated by severe PPH managed with Sengstaken tube
were reviewed. Clinical details were obtained by reviewing the case
notes of individual woman. Sengstaken tube was inserted using aseptic technique under antibiotic cover into uterine cavity guided by
ultrasound, or into vagina depending on site of bleeding. The Esophageal balloon was inflated by normal saline until no more bleeding
clinically. It was left in-situ for at least 6 hours and no longer than 24
hours before removal.
RESULTS: In the review period, Sengstaken tube was considered in 20
cases of severe PPH. (Table 1) Insertion failed in 1 case (5%) due to
tight cervical os. She delivered abdominally. Among 19 cases of successful insertion, the amount of normal saline infused into the esophageal balloon before achieving hemostasis varied between 150-500ml
(median 350ml). In one case, two sengstaken tubes were used, for
tamponade inside uterine cavity and vagina respectively. All cases received optimal uterotonics, including oxytocin, misoprostol and
hemabate. Two cases (10%) required uterine artery embolization
(UAE) in addition, after temporizing control of acute torrential bleeding by Sengstaken made transfer to Radiology Department feasible.
Blood loss had been ⬎3000ml and PPH ⬎3hrs before Sengstaken
insertion in 3 cases; two required hysterectomy (p⫽0.016). Uterus
was preserved in 18 cases (90%): one died of eclampsia postpartum
and normal menstruation returned in 17.
CONCLUSION: Sengstaken tube is useful in management of severe PPH
in a wide variety of settings. To save the uterus, consideration for
insertion should not be delayed.
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Characteristics of 20 cases of PPH
Poster Session I
Summary of 12 cases of accreta
Figures in median [range] or number (%).
*2 cases had submucosal fibroids of 8 & 10cm respectively.
165 Conservative management of placenta accreta
Tsz Kin Lo1, Wai Lam Lau1, Wing Cheong Leung1
1
Kwong Wah Hospital, Obstetrics & Gynecology, Hong Kong, China
OBJECTIVE: To review and share our experience in conservative man-
agement of placenta accreta during cesarean delivery.
STUDY DESIGN: From 2006, cesarean delivery in our unit for cases high
risk for accreta (placenta previa with either uterine scar, sonographic
evidence of accreta, or both) followed a proforma, which included
insertion of femoral sheaths by radiologist before operation, classical
cesarean section if necessary to avoid placental incision, leaving behind adherent part of placenta should it fail to separate, followed by
uterine artery embolization (UAE) and/or other appropriate hemostatic measures. Postpartum, 2-week antibiotics was given. Cases
managed this way with accreta confirmed intra-operatively were included in this review. The clinical details were retrieved from the case
notes for individual cases.
RESULTS: A total of 12 cases of accreta had the adherent part of their
placenta left behind during caesarean section. (Table) Absence of
sonographic features of accreta was not associated with smaller extent
of placental retention or less intra-operative blood loss. Those with
⬎50% of placenta left behind due to lack of separation from placental
bed had lower risk of heavy bleeding intra-operatively compared to
those with ⱕ50% of placenta retained (bleeding ⱖ3000ml: 14% vs
60%, significant clinically although statistically p⫽0.222) but higher
chance of passing placental tissue postpartum (passage rate 71% vs
0%, p⫽0.028) The extent of placenta left behind, while not affecting
the timing of menstrual return, correlated positively with the time
taken for sonographic resolution of retained placenta (p⫽0.012).
CONCLUSION: It’s our experience that in high risk cases (major placenta
previa with uterine scar), sonographic features have relatively low
sensitivity for accreta. A dedicated proforma to leave accreta untouched intra-operatively allows high risk cases to be delivered safely.
The postpartum course is favorable.
Figures in median [range] or number (%).
*Histology confirmed accrete; **Case of hysterectomy excluded; ***Normal secretary endometrium on
endometrial aspirate.
166 The peri-partum period is characterized by a major
alteration in brain neurotransmitters levels–a possible
connection to postpartum depression
Yael Hants1, Yosefa Avraham3, David Mankuta1, Lia Vorobeiv3,
Shira Merchavia3, Eithan Galun2, Elliot Berry3, Sagit Arbel-Alon1
1
Hadassah Hebrew University Medical Center, Obstetrics & Gynecology,
Jerusalem, Israel, 2Hadassah Hebrew University Medical Center, Goldyne
Savad Institute of Gene Therapy, Jerusalem, Israel, 3Hadassah Hebrew
University Medical Center, Clinical Nutrition, Jerusalem, Israel
OBJECTIVE: Postpartum depression (PPD) which affects 10% to 15%
of pregnant women is detrimental to both mother and child. The
mechanisms of PPD development are poorly understood. It was recently shown that the placenta is the source of fetal brain serotonin
levels and essential for normal fetal brain development. This observation raised a thought that the placenta could also affect maternal serotonin levels, and that upon delivery, major abrupt serotonin level
changes take place that may lead to PPD. In this study we investigated
the levels of brain serotonin and catecholamines at different stages of
pregnancy including midpregnancy, prepartum and postpartum
periods.
STUDY DESIGN: We monitored the levels of brain catecholamines, serotonin and their metabolites of 48 BALB/C mice, 12 weeks old which
were divided into five experimental groups: control (10 mice, not
pregnant), on days 11, 16 and 19 of pregnancy (11 mice each group)
and one week postpartum (5 mice). The levels of serotonin, tryptophan, norepinephrine and dopamine were assessed in the hypothalamus, hippocampus, and striatum performed by HPLC-ECD and
GC-MS while the assessment of 5HT1A message levels were performed by Real Time PCR.
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Poster Session I
RESULTS: We found a significant decrease of brain norepinephrine in
the hippocampus of postpartum mice (Fig 1). In the hypothalamus,
the levels of serotonin, dopamine and norepinephrine decreased significantly during pregnancy and postpartum (Table).
CONCLUSION: These findings indicate that during pregnancy and the
postpartum period there are major changes in mother’s brain of catecholamines levels at sites known to be connected to behavioral
changes. The depletion of catecholamines and serotonin during pregnancy and postpartum may be a result of the ageing process of the
placenta during pregnancy or the removal of the placenta during labor. Additional data, including that from other mouse strains and
behavioral investigations which are on-going will be presented.
Hippocampus norepinephrine level measured in
non-pregnant BALB/C mice
(controls) at 11th, 16th, and 19th day of
pregnancy and one week post delivery
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to estimate the independent relation of exposures with BMI z-score,
adjusting for maternal height, medical and demographic factors. Data
were analyzed using STATA IC10.1.
RESULTS: Of 3305 dyads, 46% of mothers were African American,
44% privately insured, and 25.8% were obese prior to pregnancy. 453
(9.8%) of the children were LBW, 51 (1.5%) VLBW; 584 (12.4%) were
SGA. At 4 years of age, 23.9% of children born LBW and 22.0% born
SGA were overweight or obese, compared to 29.0% for the remaining
sample. Bivariate LR showed a decreased odds of overweight or obesity for those born LBW (OR⫽0.72, 95% CI⫽0.55-0.95) or SGA
(OR⫽0.66, 95%CI⫽0.51-0.84), but no significant association with
VLBW. Multivariable LR showed LBW (aOR⫽0.68, 95% CI⫽0.451.02) and SGA (aOR⫽0.73, 95% CI⫽0.56-0.96) had a smaller odds of
overweight or obesity, adjusting for other factors, but only the latter
was statistically significant.
CONCLUSION: There was no evidence that healthy 4 year olds born
LBW or SGA had greater odds of overweight or obesity than other
children in their community. Instead, children in this group appeared
to be relatively protected.
168 No additional value of first trimester maternal
vitamin D over risk factor screening for predicting
adverse pregnancy outcomes
Francisco Schneuer1, Natasha Nassar1, Vitomir Tasevski2,
Anthony Ashton1, Christine Roberts1, Jonathan Morris1
1
Kolling Institute of Medical Research, University of Sydney, Clinical and
Population Perinatal Health Research, Sydney, NSW, Australia, 2Royal North
Shore Hospital, Fetal Maternal Medicine (Pacific Laboratory Medicine
Services), Sydney, NSW, Australia
Hypothalamic neurotransmitters and tryptophan
measured in BALB/C mice at
11th, 16th and 19th day of pregnancy and
one week post delivery
*P value ⬍ .05; **P value ⬍ .01 vs control group.
167 Early childhood overweight and obesity among children
born low birthweight or small for gestational age
Deborah Ehrenthal1, Kristin Maiden1,
Louis Bartoshesky2, Samuel Gidding3
1
Christiana Care Health System, Obstetrics and Gynecology, Newark, DE,
Christiana Care Health System, Pediatrics, Newark, DE, 3AI Dupont
Hospital for Children, Pediatric Cardiology, Wilmington, DE
2
OBJECTIVE: To determine whether children born low birthweight or
small for gestational age had greater odds of early childhood obesity
than other children in their community.
STUDY DESIGN: We used linked data from electronic obstetrical and
medical records for a sample of 4852 singletons born 2004-2007 at a
regional obstetrical hospital and who received well child care from a
large pediatric practice network. Children with a major birth defect or
chronic disease (n⫽171) and those without a 4 year well-child visit
(n⫽1336) were excluded. Exposures were low birthweight (LBW,
⬍2500 g) and very low birthweight (VLBW, ⬍1500 g); or small for
gestational age (SGA) defined as BW ⬍10th percentile for sex. Outcome was BMI z-score ⬎85th percentile at 4 years of age using 2000
CDC growth curves. Multivariable logistic regression (LR) was used
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OBJECTIVE: To assess whether serum vitamin D in early pregnancy
adds any value to risk factor information for predicting adverse pregnancy outcomes.
STUDY DESIGN: We measured maternal 25-hydroxyvitamin D
[25(OH)D] in first trimester (10-14 weeks) serum samples from 5,172
women with singleton pregnancies. Information on maternal and infant outcomes was obtained through record linkage to birth and hospital data. Pregnancy outcomes included small for gestational age
(SGA) ⬍10th and ⬍3rd percentile, preeclampsia, early-onset preeclampsia (ⱕ34 weeks), miscarriage and stillbirth. Multivariate logistic regression was conducted to assess the association between
25(OH)D with each pregnancy outcome and a composite of any severe adverse pregnancy outcome (SGA⬍3rd centile, preterm
birth⬍34 weeks or early-onset preeclampsia). Predictive accuracy was
assessed by determining area under the receiver operator characteristic curve (AUC ) using a 25(OH)D cut-point of ⬍37.5 nmol/L. Models were adjusted for seasonality, maternal age, parity, weight, smoking, country of birth and socio-economic disadvantage and previous
diagnosis of hypertension.
RESULTS: The median (IQR) 25(OH)D for the total population was
56.5 nmol/L (43.4-70.2). 25(OH)D ⬍37.5nmol/L was not associated
with any of the adverse pregnancy outcomes. The crude relative risk
(99% CI) of a severe pregnancy outcome for 25(OH)D ⬍37.5 nmol/L
was 1.38 (0.97-1.98). However, adding 25(OH)D information to prior
risk factors did not improve the ability to predict adverse pregnancy
outcomes (X2⫽1.15, P⫽0.28). Predictive accuracy results for a composite of severe adverse pregnancy outcome (SGA⬍3rd centile, preterm birth⬍34 weeks or early-onset preeclampsia) are included in
table 1:
CONCLUSION: Low Vitamin D levels in first trimester do not predict
adverse pregnancy outcomes any better than routinely collected risk
factor information.
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Table
169 Are twin to twin transfusion syndrome and selective
intra-uterine growth restriction a continuum? Evidence from
a longitudinal study of circulating angiogenic factors
Yoav Yinon1, Elad Ben Meir1, Boaz Weisz1, Eyal Schiff1,
Shali Mazaki-Tovi1, Shlomo Lipitz1
1
OBJECTIVE: To determine maternal plasma levels of soluble fms-like
tyrosine kinase-1(sFlt-1), placental growth factor (PLGF) and soluble
endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin to twin transfusion syndrome (TTTS) or
selective intra-uterine growth restriction (sIUGR).
STUDY DESIGN: A longitudinal cohort study of pregnant women with
MC/DA twins who were classified into 3 groups: 1. Uncomplicated
MC/DA twins (n⫽22) 2. TTTS (n⫽23) and 3. sIUGR (n⫽15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks
of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sFlt-1, PLGF and sEng were measured
by ELISA.
RESULTS: sFlt-1 and sEng levels were significantly higher in TTTS at
the early (13-20 weeks) and late (21-28 weeks) second trimester compared to normal monochorionic pregnancies (p⬍0.01). In contrast,
sFlt-1 and sEng levels were significantly higher in the sIUGR group
only at the late second trimester (p⬍0.05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and
sIUGR compared to controls (p⬍0.01). Plasma concentrations of
sFlt-1 were significantly higher among TTTS pregnancies compared
to sIUGR at the late second trimester (p⫽0.027). Within TTTS pregnancies who underwent fetoscopic laser ablation, the procedure resulted in elevation of PLGF levels and reduction of sFlt-1 levels. Cord
blood analysis revealed significantly higher levels of sFlt-1 in the
smaller IUGR twin compared to the normal co-twin.
CONCLUSION: Monochorionic pregnancies complicated by TTTS and
sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the anti-angiogenic state between TTTS and sIUGR
suggests that these two conditions may represent a continuum. Collectively, the findings reported herein shed new light on the pathophysiologic mechanisms of these severe complications of pregnancy.
170 Predictive modeling of anti-Xa activity
with enoxaparin use in pregnancy
Avinash Patil1, Chad Grotegut1, Sarah Dotters-Katz1,
Geeta Swamy1, Amy Murtha1, Andra James2
1
Duke University, Obstetrics & Gynecology, Durham, NC, 2University of
Virginia, Obstetrics & Gynecology, Charlottesville, VA
OBJECTIVE: To determine anti-Xa activity due to the use of enoxaparin
in pregnancy and the postpartum period.
STUDY DESIGN: A secondary analysis was performed on data from a
prospective Hemostasis and Thrombosis Center (HTC) patient registry at Duke University Medical Center. Subjects ⱖ18 years of age
receiving full-dose anticoagulation with enoxaparin during pregnancy or the postpartum period were analyzed. Therapeutic monitoring of anti-Xa activity was performed monthly to capture the peak
activity of enoxaparin (4 hours post-dose). Anti-Xa activity was characterized as a function of time post-dose by modeling of the elimination phase of enoxaparin using linear regression.
Poster Session I
RESULTS: Of 153 subjects enrolled in the HTC registry, 39 had therapeutic monitoring of full-dose anticoagulation with enoxaparin during pregnancy and/or postpartum. The pregnant subgroup included
110 observations from 24 subjects from onset of pregnancy to 37
weeks gestation. The postpartum subgroup included 29 observations
from 17 subjects up to 4 months postpartum. Anti-Xa measurements
occurred 2-15 hours post-dose. Enoxaparin achieved therapeutic anti-Xa levels at doses ranging from 1.1 to 3.6 mg/kg/day. Linear regression revealed that the rate of decline of anti-Xa levels was not significantly different between the pregnant (⫺0.032 IU/mL/hr) and
postpartum (⫺0.031 IU/mL/hr) subgroups (p⫽0.90). Peak anti-Xa
activity (4 hours post-dose) was estimated to be 0.1 IU/ml higher
postpartum than during pregnancy (p⫽0.009).
CONCLUSION: Though peak activity is higher in the postpartum subgroup, the rate of decline of anti-Xa activity is similar between pregnancy and the postpartum period. Lower peak anti-Xa activity in the
pregnant subgroup may relate to decreased bioavailability or increased volume of distribution of enoxaparin. Knowledge of the rate
of decline of anti-Xa activity during the elimination phase of enoxaparin can allow monitoring of anti-Xa levels to be performed at random intervals with extrapolation of values to either the peak or trough
periods.
171 Ulcerative colitis in pregnancy
Jenna Emerson1, Allison Allen1, Jessica Page1, Jessica Fowler1,
Aaron Caughey1
1
Oregon Health & Sciences University, Obstetrics and Gynecology, Portland,
OR
OBJECTIVE: This study aims to estimate the risk of various pregnancy
outcomes in women with ulcerative colitis (UC).
STUDY DESIGN: This is a retrospective cohort study including 502,186
singleton, nonanomalous pregnancies recorded in the 2006 California
Birth Registry, of which 129 were complicated by UC. Outcomes recorded include preeclampsia, preterm delivery, low birthweight, macrosomia and mode of delivery stratified by nulliparous and multiparous patients. Chi squared tests and multivariable logistic regression
analyses were used for statistical analysis.
RESULTS: Women with UC delivered premature (⬍37 weeks) and
very premature (⬍32 weeks) neonates with greater frequency than
controls. They also delivered low birthweight babies more frequently
(10.9% v. 4.9%, p⫽.002). Interestingly, women with UC also delivered children weighing ⱖ 4,000 g. at higher rates than controls (15.8%
v. 9.1%, p⫽.02). Among nulliparas, women with UC had increased
rates of primary cesarean, although the result was not statistically significant (39.4% vs 29.7%, p ⫽.085).
CONCLUSION: Ulcerative colitis is associated with increased rates of
preterm birth, low birthweight and macrosomia. The finding that
women with UC deliver macrosomic infants with greater frequency
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Poster Session I
than controls has not been previously reported, and warrants further
investigation.
Pregnancy outcomes in ulcerative colitis
172 Induction of labor at less than 38 weeks in
cholestasis of pregnancy: a six-year cohort
Jonathan Mays1, Gladys Lee-Hwang1, Aleksandr Fuks1,
Emad Ghaly2, Kavitha Ram1, Sari Kaminsky1
1
Metropolitan Hospital Center/New York Medical College, Obstetrics and
Gynecology, New York, NY, 2Metropolitan Hospital Center New York
Medical College, Neonatology, New York, NY
OBJECTIVE: The purpose of this study is to evaluate the effectiveness of
our institutional protocol for the active management of cholestasis of
pregnancy.
STUDY DESIGN: From Jan. 1, 2006 to Dec. 31, 2011, 332 patients were
diagnosed with cholestasis of pregnancy (pruritus associated with Total Bile Acids ⬎14mg/dl) and managed using a single institutional
protocol. The protocol recommended the induction of labor for
women diagnosed with mild (TBA ⬍40) and severe cholestasis (TBA
ⱖ 40) between 36 and 38 weeks gestation after verifying lung maturity
via amniocentesis. Patients diagnosed with severe disease between
34-36 weeks were also offered amniocentesis to verify lung maturity
and to rule out the presence of meconium. The average TBA level, the
average gestational age at delivery, birthweight, primary cesarean delivery rate, stillbirths, and the incidence of respiratory distress syndrome were reviewed.
RESULTS: Out of the 332 women diagnosed, 195 underwent induction
of labor at less than 38 weeks. The average TBA level for the cohort was
54.45 ⫹/⫺ 33.0mg/dl. The average gestational age at time of delivery
was 36.52 ⫹/⫺ 0.95 weeks. The average birthweight was 2902 ⫹/⫺
320gm. The primary cesarean was 12.8% (16/125) for those induced
⬍38 weeks and 12.8% (25/195) for all patients induced. This compares favorably with our institutions’ primary cesarean rate over this
time period of 14.5%. The incidence of respiratory distress was also
not increased versus our general obstetric population. There were 3
stillbirths recorded with an adjusted stillbirth incidence of 1 out of 332
pregnancies.
CONCLUSION: This study is the largest prospective U.S. cohort to date.
Our institutional protocol for the management of cholestasis reduces
perinatal morbidity and mortality without increasing the primary cesarean rate or the incidence of respiratory distress syndrome. Induction of labor between 36-38 weeks is a viable clinical option for patients diagnosed with cholestasis of pregnancy.
173 The relationship between gestational
diabetes and postpartum depression
Kristen Lady1, Corrine Williams1, Wendy Hansen1,
Rebecca Epstein1
1
University of Kentucky, Obstetrics and Gynecology, Lexington, KY
OBJECTIVE: Patients with gestational diabetes mellitus (GDM) are at
increased risk of obstetrical and perinatal complications. In studies of
non-pregnant women and men, rates of any depression are significantly higher in patients with diabetes relative to the general population. There are several proposed mechanisms of how depression and
diabetes are interrelated: hypothalamic-pituitary-adrenal axis dysregulation, pro-inflammatory state, serotonin system dysregulation,
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and behavioral issues. We sought to identify if this association held
true in pregnant women. Does a diagnosis of GDM convey an increased risk of postpartum depression (PPD)?
STUDY DESIGN: The Pregnancy Risk Assessment Monitoring System
(PRAMS) data, a survey of new mothers identified by the birth certificate files of 37 participating states for deliveries between 2004-2008,
was used for this analysis (n⫽102,540). Logistic regression analyses
were used to estimate the association between GDM and PPD, adjusting for maternal demographics, low birthweight, birth defects, number of prenatal visits, gestational age at delivery, NICU admission, and
co-morbid medical conditions. We also evaluated the relationship
between pre-existing diabetes and PPD.
RESULTS: PPD was noted in 16.9% of women with GDM vs. 13.7%
without GDM. Adjusting for covariates, women with GDM are more
likely to have PPD (aOR: 1.14, 95% CI: 1.02-1.27). When we added
preexisting diabetes to the model, there was no association between
preexisting diabetes and postpartum depression (aOR: 1.08, 95% CI:
0.85-1.36), while the association of GDM and PPD remained statistically significant (aOR: 1.13, 95% CI: 1.01-1.27).
CONCLUSION: This data suggests an association between GDM and
PPD. Physicians should consider increased depression screenings for
women with GDM and education regarding the signs of depression
and the risk of developing PPD.
174 Postpartum weight retention: risk factors and
relationship to obesity at one year
Loraine Endres1, Heather Straub1, Beth Plunkett1, Elizabeth
Clark-Kauffman2, Kim Wagenaar3, Ying Zhou2, Sharon Ramey4,
Madeleine Shalowitz for the Community Child Health Network2
1
Northshore University HealthSystem, Obstetrics and Gynecology, Evanston,
IL, 2Northshore University HealthSystem, Research Institute, Evanston, IL,
3
Lake County Health Department, Primary Care Services, Waukegan, IL,
4
Virginia Tech Carilion School of Medicine, Research Institute, Roanoke, VA
OBJECTIVE: Postpartum (PP) weight retention has been proposed as a
contributor to lifetime obesity. This abstract explores risk factors for
weight retention and BMI status at one year PP.
STUDY DESIGN: The sample of 822 women with data on prepregnancy
and 1 yr PP BMI was drawn from 2510 participants in the NIH Community Child Health Network (CCHN), a national five-site, mixed
urban, suburban and rural study of women 18-40 years of diverse
backgrounds. CCHN was conducted according to principles of community-based participatory research to better understand multi-level
sources of parental stress and resiliency on pregnancy outcomes. Participants were enrolled primarily in-hospital immediately following
delivery. They were interviewed at 1, 6, and 12 mo PP. Weights were
obtained at 6 mo and 1 year PP up to 350 lbs. Medical records provided prepregnancy weight and delivery information.
RESULTS: Typically, women were 26 yr, primiparous, with a prepregnancy weight of 162 lbs (BMI 35.4). Women gained 30 lbs while pregnant, with a weight at 1 yr PP of 173 lbs (BMI 38.4) for 11 lbs of weight
retention. 70% were heavier at 1 yr PP than prepregnancy, including
44% retaining over 10 lbs and 23% over 20 lbs. Women retaining at
least 20 lbs were younger (p⬍.0001), smokers (p⬍.05), working at 1
yr (p⬍.05), African American (p⬍.0001), and low SES (p⬍.0001).
They were less likely to have planned the pregnancy (p⬍.0001) and to
use birth control at 1 yr (p⬍.05). They breastfed less frequently
(p⬍.05), and if they did so, fewer still nursed at 1 mo (p⬍.01) and at
6 mo (p⬍.0001). PP weight retention was not related to parity, maternal education, or exercise. Strikingly, of 38% with normal prepregnancy BMI, one third became overweight or obese at 1 yr PP.
CONCLUSION: Postpartum weight retention is a significant contributor
to overweight and obesity 1 year PP even for those with a healthy
prepregnancy BMI. Findings confirm the need for additional focus on
healthy lifestyles during pregnancy and PP to alleviate the lifetime
burden of obesity.
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175 The effect of subclinical hypothyroidism on
IQ in seven to eight year old children
176 Perinatal risk factors for severe hypoxic-ischemic
encephalopathy in neonates treated with whole
body hypothermia
Niamh Murphy1, Mairead Diviney4, Jennifer Donnelly1, Sharon
Cooley1, Colin Kirkham3, Adrienne Foran2, Fionnuala
Breathnach1, Fergal Malone1, Michael Geary1
Christopher Wayock1, Benjamin Greenberg2, Jacky Jennings3,
Frances Northington2, Ernest Graham1
1
Rotunda Hospital, Department of Obstetrics and Gynaecology, Dublin,
Ireland, 2Rotunda Hospital, Department of Neonatology and Paediatrics,
Dublin, Ireland, 3Rotunda Hospital, Department of Statistics, Dublin,
Ireland, 4National University of Ireland, Maynooth, Department of
Psychology, Co. Kildare, Ireland
OBJECTIVE: In our practice, pregnant women are not routinely
screened or treated for subclinical hypothyroidism (SCH), although
overt hypothyroidism is treated. Our objective was to compare the IQ
of children whose mothers had been diagnosed with SCH antenatally
(in a prior observational trial) with closely matched controls.
STUDY DESIGN: In a previous study from our group, 1000 healthy nulliparous patients were screened anonymously for SCH. Those with
overt hypothyroidism were informed and treated, whereas those with
SCH were contacted postnatally for paediatric follow-up. SCH (defined as reduced free T4 with normal TSH, or normal free T4 with
raised TSH) was found in 4.6% (n⫽46) of the study population. These
cases were matched for gestational age, gender and mode of delivery
with 47 controls. All children underwent a formal neurodevelopmental assessment at age 7 to 8 years by a single psychologist blinded to the
original maternal thyroid status. WISC-IV assessment scores were
used to compare the groups.
RESULTS: From the cohort of cases, 23 mothers agreed to assessment
of their children as well as 47 controls. The children in the control
group had higher mean scores than those in the case group across the
categories of Verbal Comprehension Intelligence, Perceptual Reasoning Intelligence, Working Memory Intelligence, Processing Speed Intelligence and Full Scale IQ. Mann Whitney U testing confirmed a
statistically significant difference in IQ between the cases (composite
score 103.87) and the controls (composite score 109.11) This had a
95% confidence interval (.144, 10.330).
CONCLUSION: Our results highlight significant differences in IQ of children of mothers who had unrecognised SCH during pregnancy. While
our study size and design prevents us from making statements on
causation, our data suggests significant potential public health implications in terms of routine thyroid function screening in pregnancy.
The results of prospective intervention trials to address a causative
association will be vital to address this issue.
Summary of WISC-IV assessment
scores for cases and controls
Poster Session I
1
Johns Hopkins University School of Medicine, Division of Maternal-Fetal
Medicine, Department of Gynecology and Obstetrics, Baltimore, MD, 2Johns
Hopkins University School of Medicine, Division of Neonatology,
Department of Pediatrics, Baltimore, MD, 3Johns Hopkins University School
of Medicine, Department of Pediatrics, Baltimore, MD
OBJECTIVE: Whole body hypothermia has been shown to reduce the
risk of death or neurologic injury in neonates with hypoxic-ischemic
encephalopathy (HIE). However, newer regimens and other therapies
may also benefit the most severely injured neonates. Our objective is
to identify perinatal risk factors that identify the most severely injured
neonates.
STUDY DESIGN: A case-control study was conducted from 1/2007 to
5/2012 among 104 neonates ⬎35 weeks with suspected HIE treated
with whole body hypothermia of which 99 underwent an MRI at 7-10
days of life. Of the 5 neonates that did not have an MRI 3 died. 39%
were born within our system, and 61% were transferred. Cases were
defined as those neonates who died or had an abnormal brain MRI at
7-10 days. Controls were surviving neonates with a normal MRI. Logistic regression models were used to determine the predictive value of
factors hypothesized to impact neurologic injury.
RESULTS: Cases and controls did not differ on gestational age, birthweight, mode of delivery, sentinel events, initial neonatal blood gas,
positive neonatal blood cultures, histologic chorioamnionitis, funisitis or diagnosis of nonreassuring fetal heart rate prior to delivery.
Cases were significantly more likely to have an abruption, a cord blood
gas showing metabolic acidosis, elevated initial neonatal WBC count
and seizures. In multivariable logistic regression, decreased cord pH
(p⫽0.001) and increased initial neonatal WBC count (p⫽0.026) predicted an increased risk of neurologic injury. Cord pH and initial
neonatal WBC count can predict an abnormal brain MRI with a sensitivity of 59.4%, specificity of 77.6%, positive predictive value of
66.7% and negative predictive value of 71.7%.
CONCLUSION: Worsening metabolic acidosis in cord blood at birth and
elevated initial neonatal WBC correlate with neurologic injury among
neonates with HIE treated with whole body hypothermia. These cases
may be candidates for new hypothermia regimens as well as other
therapies.
Perinatal risk factors for severe HIE among all
neonates treated with
whole body hypothermia
NS, nonsignificant; CI, confidence interval.
Data are n (%) where applicable.
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Poster Session I
177 Two-year neurodevelopmental outcomes in
children treated with laser surgery for twin-twin
transfusion syndrome (TTTS)
Douglas Vanderbilt1, Sheree Schrager2, Arlyn Llanes3,
Anita Hamilton4, Istvan Seri5, Ramen Chmait3
1
Childrens Hospital Los Angeles, USC Center for Excellence in
Developmental Disabilities, Los Angeles, CA, 2Childrens Hospital Los
Angeles, Division of Adolescent Medicine, Los Angeles, CA, 3Keck School of
Medicine, University of Southern California, Department of Obstetrics and
Gynecology, Division of Maternal-Fetal Medicine, Los Angeles, CA,
4
Childrens Hospital Los Angeles, Clinical Research, Los Angeles, CA,
5
Childrens Hospital Los Angeles, Division of Neonatal Medicine,
Los Angeles, CA
OBJECTIVE: To determine risk factors for neurodevelopmental function among children treated with laser for TTTS.
STUDY DESIGN: Data were prospectively collected from surviving children treated between 2008-2010. Neurodevelopment at age 24
months (⫾6 weeks) was assessed via the Battelle Developmental Inventory (BDI) total standardized score. Vital statistics and socio-demographic covariates were obtained. Clinical metrics were collected
from a TTTS database. Power analysis determined that the a priori
sample size required 100 children for adequate power (0.80). Multilevel linear regression models were used to evaluate risk factors for
BDI at both child- and pregnancy/family-levels. Non-significant predictors with pⱖ0.10 were removed sequentially to arrive at the final
model.
RESULTS: 100 of 206 children (57 of 122 families) were evaluated.
There were no differences between evaluated and non-evaluated enrollees in donor/recipient status and survival rates, fetal demise
(IUFD), growth restriction (IUGR), Quintero stage, and gestational
age (GA) of surgery or delivery. Total BDI score was within normal
range (mean⫽101.3, SD⫽12.2), with only one child having a BDI of
ⱕ70. Child risk factors for lower BDI included male sex (␤⫽⫺0.37,
p⬍0.01), lower head circumference (␤⫽0.28, p⬍0.01), and higher
diastolic blood pressure (␤⫽⫺0.29, p⬍0.01). At the pregnancy/family level, lower maternal education (␤⫽0.60, p⬍0.001), higher Quintero stage (␤⫽⫺0.36, p⬍0.01), lower GA at birth (␤⫽30, p⬍0.01),
married parents (␤⫽⫺0.25, p⬍0.05), and older corrected age
(␤⫽⫺0.20, p⬍0.05) were associated with worse outcome. Donor/
recipient status, GA at surgery, IUGR, and IUFD were not risk factors
for neurodevelopmental outcomes.
CONCLUSION: This cohort of TTTS children showed developmental
quotients in the normal range. The above-identified clinical and socio-economic characteristics may be useful to identify at-risk children
that may benefit from early clinical and psychosocial interventions.
178 Higher neonatal serum magnesium levels
correlate with improved neurodevelopmental
outcomes in early preterm infants
Joshua Bonkowski2, Erin A. S. Clark1, Elizabeth Doll2, Jacob
Wilkes2, Roger Faix2
1
University of Utah School of Medicine, Department of Obstetrics and
Gynecology, Salt Lake City, UT, 2University of Utah School of Medicine,
Department of Pediatrics, Salt Lake City, UT
OBJECTIVE: Preterm birth is associated with significant risk for chronic
neurodevelopmental deficits. Magnesium sulfate administration
prior to preterm birth has been shown to reduce the rate of cerebral
palsy. Our work in an animal model demonstrated that magnesium
protects against disruptions in axonal connectivity in the developing
brain. We aimed to determine whether neonatal serum magnesium
levels are associated with neurodevelopmental outcomes in a cohort
of very low birthweight preterm infants.
STUDY DESIGN: We examined a well-defined cohort of 80 surviving
very low birthweight preterm infants (⬍1200 grams, gestational age
⬍27 weeks) with neurodevelopmental follow-up between 20 and 36
months of age. Our outcomes for neurodevelopment included Bayley
III scores (composite communication and cognition), a diagnosis of
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epilepsy, or abnormal neurological motor exam (defined by the presence of spasticity, hypotonia, or cerebral palsy). Multivariate linear
and logistic regression analyses evaluated the association between
mean serum magnesium level in the neonate during newborn intensive care unit stay, and the neurodevelopmental outcomes of interest,
adjusted for birthweight, gender, length of mechanical ventilation,
multiple gestation, and exposure to antenatal corticosteroid and antenatal magnesium sulfate.
RESULTS: Higher neonatal mean serum magnesium levels during hospitalization were correlated with a decreased risk for abnormal motor
exam (OR 0.245; 95% CI 0.067-0.898; p 0.034), and a lower risk for
epilepsy (OR 0.056; 95% CI 0.004-0.755; p 0.023), at 20 to 36 months
of age. There was a trend between serum magnesium level and composite Bayley III scores, but this did not reach statistical significance
(p⫽0.77).
CONCLUSION: Postnatal magnesium could play a neuroprotective role
in preterm infants. Higher serum magnesium levels may be associated
with decreased long-term risks for epilepsy and for abnormal motor
exam.
179 Head sparing and neonatal outcome in
small for gestational age neonates
Gayle Olson1
1
National Institute of Child Health and Human Development Maternal-Fetal
Medicine Units Network, for the Eunice Kennedy Shriver, Bethesda, MD
OBJECTIVE: To compare the outcome of small for gestational age
(SGA) infants identified using birthweight (BW) %ile versus Ponderal
index (PI), and determine if there is an association between head
sparing (HS) and outcome among infants with SGA.
STUDY DESIGN: This is a secondary analysis of a randomized multicenter trial for prevention of pregnancy associated hypertension. Low
risk nulliparous women with singleton pregnancies were enrolled between 9-16 weeks and were randomized to antioxidants versus placebo. BW ⬍ 10th %ile (Alexander et al.), PI ⬍ 10th %ile and HS
defined as a head circumference/length ⱖ 25th %ile were identified.
Neonatal outcomes evaluated were a respiratory composite and an
overall composite outcome. BW %ile and PI were compared using
McNemar’s Test.
RESULTS: After exclusions for missing data, congenital malformations, and stillbirth, 9,228 subjects were available for the analysis. SGA
was identified in 11.1% of neonates by BW%ile and 10.0% by PI. SGA
identified by PI had worse outcomes than those identified by BW%ile
(p⬍0.0001). Adverse respiratory and overall composite outcomes
were significantly more frequent in the SGA neonates with HS compared with those without HS, when identified by PI, but not when
identified by BW%ile (Table 1).
CONCLUSION: Compared with BW%ile, Ponderal index is a better indicator of adverse neonatal outcomes in SGA. Head sparing in a neonate who is SGA by Ponderal index confers an even higher risk of
adverse outcomes.
Head sparing and composite outcomes among
neonates with SGA
*Includes RDS, early ventilation, O2, CLD, BPD; **Includes respiratory composite, seizure, sepsis,
NEC, IVH3/4, ROP.
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180 Can contraction patterns predict
adverse neonatal outcomes?
Heather Frey1, Methodius Tuuli1, Kimberly Roehl1,
Anthony Odibo1, George Macones1, Alison Cahill1
1
St. Louis, MO
OBJECTIVE: Uterine contractions influence placental perfusion and
maternal-fetal gas exchange. Therefore, uterine activity during labor
may impact fetal and consequently, neonatal wellbeing. We sought to
estimate the association between contraction patterns in labor and
neonatal outcomes.
STUDY DESIGN: We conducted a nested case-control study within a
consecutive term birth cohort of all women admitted in labor with
intrauterine pressure catheters (IUPCs) who reached the second stage
over a five year period. Cases were defined as women delivering neonates with composite morbidity, defined as: intensive care unit
(NICU) admission, umbilical artery pH ⱕ7.1, or 5-minute Apgar
score ⬍7. Women in the control group delivered without any elements of the neonatal composite morbidity. Exclusion criteria included multiple gestations, intrauterine fetal demise, and major fetal
anomalies. Uterine contraction patterns measured by intrauterine
pressure catheters (IUPCs) in the last 30 minutes prior to delivery
were abstracted by formally trained obstetric research nurses. Contraction frequency, duration, Montevideo units (MVUs), and baseline tone were compared. Multivariable logistic regression was used to
adjust for potential confounders. The ability of contraction parameters to predict adverse neonatal outcomes was evaluated using receiver
operating characteristic curves.
RESULTS: Sixty-three cases of adverse neonatal outcomes and 2,294
controls without the composite outcome were compared. Contraction duration, MVUs, and baseline uterine tone did not significantly
differ between cases and controls. Contraction frequency also was not
significantly different in the two groups after controlling for oxytocin
use. Neither individual parameters nor models including multiple
parameters predicted the composite adverse outcome (AUC⫽0.59).
CONCLUSION: Using standard measures of uterine activity, contraction
patterns 30 minutes prior to delivery do not differ among women with
and without adverse neonatal outcomes, and cannot be used to predict neonatal outcome.
*Adjusted for oxytocin use.
181 Symptoms of sleep disturbance are associated
with elevated umbilical cord C-reactive peptide
Judette Louis1, Shannon Ho2, John Tsibris1,
Anna Shaw3, Angel Luciano4
1
Morsani College of Medicine, University of South Florida, Division of
Maternal Fetal Medicine, Department of Obstetrics & Gynecology, Tampa,
FL, 2Boonshoft School of Medicine, Wright State University, Division of
Maternal Fetal Medicine, Department of Obstetrics & Gynecology, Dayton,
OH, 3MetroHealth- Case Western Reserve University, Division of Maternal
Fetal Medicine, Department of Obstetrics & Gynecology, Cleveland, OH,
4
Morsani College of Medicine, University of South Florida, Division of
Neonatology, Department of Pediatrics, Tampa, FL
OBJECTIVE: We previously reported an increased risk of neonatal respiratory morbidity associated with maternal sleep disorders but the
mechanism of the finding is unknown. We sought to evaluate the
Poster Session I
effect of severe sleep disturbance on umbilical cord plasma biomarkers of hypoxia and inflammation.
STUDY DESIGN: A nested prospective cohort study was performed of
term pregnancies enrolled in a sleep disorders protocol. Subjects completed validated sleep questionnaires to assess for sleep duration; hypersomnolence and symptoms of sleep disordered breathing (Epworth Sleepiness Scale and Berlin Sleep Questionnaire). Severe sleep
disturbance (SSD) was defined as ⱕ5 hours per night of sleep along
with an abnormal sleep survey. Neonatal respiratory morbidity was
defined as respiratory distress syndrome (RDS) or transient tachypnea of the newborn (TTN). Umbilical cord blood at delivery was
collected and erythropoietin (Epo), highly sensitive C-reactive peptide (hs-CRP) and Soluble vascular cell adhesion molecule 1 (sVCAM-1) levels were measured. Statistical analysis was performed using chi square and Wilcoxon test; P⬍0.05 was considered significant.
RESULTS: The cohort included 57 women. Comorbid conditions included obesity (30%), gestational diabetes (6%) and chronic hypertension (8%). Among the cohort, 12% had SSD. Women with SSD
compared to those without had a similar delivery gestational age
(38⫾1.2 weeks vs. 39⫾1, p⫽0.21) and birthweight (3141⫾491 vs.
3330⫾429gm p⫽0.36) but had more neonatal respiratory morbidity
(50 vs. 7.6%, p⫽0.003). They also had similar levels of umbilical cord
s-VCAM-1 (2783⫾685 vs. 2892⫾330ng/ml, p⫽0.82) and Epo (45⫾7
vs. 31⫾14, p⫽0.94 mIU) but had a higher level of hs-CRP (177⫾75 vs.
61⫾50 ng/ml, p⫽0.02) compared to women without SSD.
CONCLUSION: Severe sleep disturbance was associated with more neonatal respiratory morbidity and higher umbilical cord hs- CRP levels.
Further investigations are needed to identify the mechanisms linking
neonatal respiratory morbidity and maternal sleep disturbance.
182 Follow up on infants at the corrected age of
24 months after their mothers participated in a
maintenance nifedipine trial
Laura Seinen1
1
Dutch consortium for Studies in Women’s Health and Reproductivity,
Obstetrics & Gynecology, Amsterdam, Netherlands
OBJECTIVE: We previously reported in the APOSTEL II trial, that in
women with threatened preterm labor, who had initial rescue tocolysis with nifedipine or atosiban, subsequent maintenance tocolysis
with nifedipine for 12 days was not effective over placebo in prolongation of pregnancy. The objective of the present two-year follow up
study was to test whether maintenance treatment with nifedipine was
neuroprotective.
STUDY DESIGN: In the APOSTEL II trial, 406 women were randomized
to either nifedipine (201/406) or placebo (205/406). At the corrected
age of 24 months parents were asked to fill out the Ages and Stages
Questionnaire (ASQ). We compared the score on the ASQ in both
groups with the Mann Whitney U and Student T test. All separate ASQ
domains were also analyzed. Children born below 30 weeks gestation
were also separately analyzed.
RESULTS: Because of delay in start of follow up, 311 out of 406 women
were eligible for follow up with the ASQ. We were able to approach
276 out of 311 women (89%), of whom 146 (53%) returned the ASQ.
For this abstract, questionnaires from 122 respondents could be analyzed, of whom 62/122 (51%) had received nifedipine and 60/122
(49%) placebo. Mean gestational age at delivery was 34 weeks and
22/122 (18%) women delivered before 30 weeks. Mean overall ASQ
score was 236.5 (range 5-300).There was no significant difference in
overall ASQ score between the two groups (Mann Whitney U test;
p⫽0.297, Student’s T test; p⫽0.539 [95% CI ⫺11.5 to 21.9]). All
separate domains did not show significant differences (Table 1). The
number of children with a score below 2 SD was 3/59 (5%) in the
nifedipine group and 2/58 (3%) in the placebo group (RR 1.5 [95% CI
0.25 to 8.4]). The number of children born below 30 weeks with a
score below 2 SD was 0/12 in the nifedipine group and 1/10 (10%) in
the placebo group (RR 0.31 [CI 0.014 to 6.9]).
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Poster Session I
CONCLUSION: Our analysis does not support neuroprotective effects of
prolonged nifedipine in women with threatened preterm birth.
Table
183 Human Wharton’s jelly-derived mesenchymal
stem cells express neurotrophic factors in vitro
Marianne Messerli1, Martin Müller2, Andreina Schoeberlein1,
Ruth Sager1, Daniel Surbek2
1
University of Bern, Department of Clinical Research, Bern, Switzerland,
University Women’s Hospital Bern, Obstetrics & Feto-Maternal Medicine,
Bern, Switzerland
2
OBJECTIVE: Perinatal brain damage is a major neurological problem in
surviving premature infants. Transplantation experiments in various
animal models suggest a neuro-regenerative potential of multipotent
mesenchymal stem cells (MSC). The curative effect of MSC might be
due to their production of neurotrophic factors. The Wharton’s jelly
represents a promising source of MSC. Thus, the aim of the study is to
assess the expression and release of neurotrophic factors by human
Wharton’s jelly-derived MSC and induced neural progenitor cells in
vitro.
STUDY DESIGN: MSC from Wharton’s jelly of term and pre-term (gestational age ⬍ 37 weeks) pregnancies were evaluated. Adaptations of previously published multistep protocols (Portmann-Lanz et al, AJOG 2010;
Fu et al, Acta Neurobiol Exp 2007; Zhang et al, Differentiation 2010) were
used to produce neural progenitors (neurospheres). The transcription of
neurotrophic factors was assessed by real-time PCR. The release of neural
growth factors into the cell culture medium was measured by a membrane-based cytokine antibody array.
RESULTS: At passage five MSC from term and preterm pregnancies
were expressing key neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NTF3) and glial cell-derived neurotrophic factor (GDNF), and the cytokine interleukin
(IL)-6, at the mRNA level. BDNF and IL-6 were detected in the cell
culture supernatant after 48h of cultivation. The transcription of
BDNF and NTF3 were significantly reduced in neurospheres relative
to MSC, independent of gestational age. However, the gene expression
of GDNF was up-regulated in neurospheres compared to the noninduced MSC derived from term pregnancies.
CONCLUSION: MSC derived from Wharton’s jelly of term and preterm
pregnancies, and the induced neural progenitor cells produce neurotrophic factors in vitro. The role of the released factors in neurogenesis
and neuro-regeneration is currently analyzed in co-culture experiments
with neural stem cells. Financial support by Cryosave Switzerland.
www.AJOG.org
survivors of TTTS who had undergone FLS (n⫽14), (B) MCDA twins
without TTTS (n⫽12) and (C) dichorionic twins (n⫽8). Each scan
was graded blindly as either normal, minor abnormality or an abnormality likely to be of clinical significance. The primary study outcome
was abnormal findings on MRI brain or fetal demise.
RESULTS: The primary outcome occurred in 9/14 (64.3%) within the
TTTS group, versus 4/12 (33.3%) in the MCDA group. No primary
outcome occurred in the DC group.There was a significant difference
across all study groups for the primary outcome [p(1,2) ⫽ 0.01; ␹2 ⫽
9.1]. 2/7 (28.6%) of the abnormal MRI’s in the TTTS group were
deemed to be of immediate clinical significance (Figure) and in both
cases CUS were normal. Cranial ultrasound as the sole imaging modality yielded an abnormality in 1/12(8.3%) in TTTS group versus
2/12(16.7%) in the MCDA group. The primary outcome was present
in 5/26 (19.2%) of study participants when CUS was analysed as the
sole imaging modality. With MRI the primary outcome was present in
13/26 (50%) of the study participants; P ⫽ 0.041; ␹2 ⫽5.44. Sensitivity
analysis was performed comparing the two imaging modalities and
referencing MRI with a sensitivity of 100%. Against this MRI benchmark CUS had a significantly poorer sensitivity of 37.9% (22.6, 56.0).
CONCLUSION: CUS as the sole imaging modality in TTTS survivors can
miss significant abnormalities and under-states the true rate of abnormality as shown using MRI. This has implications for how patients are
counseled prior to FLS and methods of neonatal surveillance following
delivery.
Figure
184 Neonatal MRI brain following fetoscopic laser
surgery for twin-twin transfusion syndrome: implications
for clinical practice
Michael Boyle1, Aisling Lyons1, Stephanie Ryan2, Fergal Malone3,
Adrienne Foran1
1
Rotunda Hospital, Neonatology, Dublin, Ireland, 2The Children’s
University Hospital, Radiology, Dublin, Ireland, 3Rotunda Hospital, Fetal
Medicine, Dublin, Ireland
Top row; T1 (right) and T2 (left) images of Twin A (1) focal cortical migration abnormality (arrow).
Bottom row; Twin G (2) Periventicular leukomalacia (arrow).
OBJECTIVE: To date, neonatal outcome studies of TTTS survivors following fetoscopic laser surgery (FLS) have relied upon cranial ultrasound (CUS) to confirm normality. Our objective was to evaluate
intracranial abnormalities in surviving twins following FLS using
term-corrected MRI.
STUDY DESIGN: For this prospective, blinded, case-control study,
term-corrected MRI brain scans were performed on 3 groups; (A)
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185 Transcriptions factors which regulate surfactant protein
B (SPB) expression during neonatal development are
dysregulated in an Erk3ⴚ/ⴚ knockout model of RDS
Milenka Cuevas Guaman2, Lori Showalter1, Cynthia Shope1,
Min Hu1, Kjersti Aagaard1
1
Baylor College of Medicine, Division of Maternal-Fetal Medicine and
Departmetns of Obstetrics&Gyencology and Molecular&Cell Biology,
Houston, TX, 2Baylor College of Medicine, Pediatrics, Division of
Neonatology, Houston, TX
OBJECTIVE: Surfactant B is regulated via promoter targeting motifs for
mulitple transcription factors (CCAAT/Enhancer-Binding Proteins
(C/EBPs), thyroid transcription factor-1/NK2 homeobox 1 (Ttf1)
and, hepatocyte nuclear factor 3/forkhead box A1 (Foxa1)). Our objective was to extend our prior findings in a murine model of RDS
demonstrating Erk3-dependent expression of SPB. Specifically, we
aimed to evaluate expression of Cebp␣, Cebp␤, Cebp␦, Ttf1 and
Foxa1 in lung tissue from neonatal pups, including response to antenatal dexamethasone (dex) and postnatal surfactant therapy.
STUDY DESIGN: We compared mRNA gene expression (qRT-PCR,
n⫽9) and translated protein (Western Blot, n⫽6) from three treatment groups (saline/saline, dex/saline and dex/surfactant) in both
Erk3⫹/⫹ (WT) and Erk3⫺/⫺ (KO). Data were analyzed by ANOVA
or independent samples t-test as appropriate.
RESULTS: In the absence of antenatal glucocorticoids and postnatal
surfactant, deletion of Erk3 is neonatal lethal. We observed no significant difference in mRNA or protein expression of Ttf1 by virtue of
either genotype or treatment group. However, Foxa1 expression varied with both deletion of Erk3 (p⫽0.03), as well as antenatal glucocorticoid treatment (dex/saline, p⬍0.01; dex/surfactant, p⫽0.002,
Fig. A). Similarly, Cebp␣ and Cebp␤ mRNA is significantly increasedfollowing antenatal dex in both WT (p⫽0.02) and KO (p⫽0.006 and
p⫽0.02, respectively), as well as with dex/surfactant in WT
(p⫽0.0005, p⫽0.009). Cebp␦ mRNA and protein expression is significantly increased with antenatal glucocorticoids (p⬍0.05) in both
genotypes, with significant (15 fold increase, p⫽0.05; Fig.B) following
dex/surfactant therapy.
CONCLUSION: The transcription factors Cebp␣, Cebp␤, Cebp␦, and
Foxa1 are dysregulated in Erk3 null mice which demise from RDS if
left untreated. Taken together, these data reinforce the notion that
Erk3 regulation is integral to SFTPB production and fetal pulmonary
maturity.
Poster Session I
membrane. The apical chamber was seeded with human umbilical
vein endothelial cells (HUVEC) and incubated with conditioned media from astroglial cells to increase tight junctions. Membrane integrity was assessed by voltohmmeter measurement of transendothelial
electrical resistance (TEER) across the apical (“blood”) and basal
(“brain”) compartments. Membrane permeability was assessed by the
diffusion rate of fluorescently-conjugated dextran. Tumor necrosis
factor-␣ (TNF-␣) and matrix metalloproteinase 9 (MMP-9) treatments simulated inflammation. Tight junctions were assessed with
immunocytochemstry and epifluorescence microscopy with antibodies to the zona occludens-1 (ZO-1).
RESULTS: Overnight incubation with astroglial conditioned media decreased dextran transit across the HUVEC monolayer (from permeability scores of 2.9⫾2.1 to 1.88⫾0.4; n⫽4 replicates). TNF-␣ and
MMP-9 treatment increased dextran transit (permeability scores
2.9⫾0.5 in vehicle, 13.3⫾2.5 in TNF-␣ (n⫽13; p⬍0.05); 6.0⫾1.4 in
0.25␮g/ml MMP-9 (n⫽4); 9.7⫾ 2.0 in 1.0␮g/ml MMP-9 (n⫽4;
p⬍0.05). TNF-␣ decreased TEER across the monolayer, from
276.7⫾4.4⍀-cm2 in vehicle to 262.1⫾4.1⍀-cm2 in TNF- ␣ (n⫽5-8
replicates; p⬍0.05). ZO-1 immunostaining was evident at the
HUVEC junctional interfaces.
CONCLUSION: HUVEC-astroglial co-cultures in a transwell apparatus
recapitulate features of the blood brain barrier, including increased
permeability with decreased TEER after TNF-␣ and MMP-9 exposure, and ZO-1 junctional protein expression at cellular interfaces.
This model can be used to study mechanisms of magnesium sulfate
neuroprotection.
Membrane permeability to flourescently-conjugated
dextran after exposure to tumor necrosis factor
alpha and matrix metalloproteinase 9
*P ⬍ .05.
187 Cord blood glucose and MRI findings in
encephalopathic neonates treated with whole body cooling
Sarahn Wheeler1, Elisabeth Nigrini1, Andrew Satin1,
Michael Johnston2, Ernest Graham1, Irina Burd3
186 Development of an in vitro blood brain barrier
model to investigate cellular mechanisms of
neuroprotection in preterm infants
1
Johns Hopkins University School of Medicine, GYN/OB, Baltimore, MD,
Kennedy Krieger Institute, Department of Neurosciences, Baltimore, MD,
3
Johns Hopkins University School of Medicine, GYN/OB & Neurology,
Baltimore, MD
2
Monica Lutgendorf1, Danielle Ippolito1, Deborah Tinnemore2,
Brad Dolinsky2, Peter Napolitano1
1
Madigan Army Medical Center, Maternal Fetal Medicine, Tacoma, WA,
2
Madigan Army Medical Center, Clinical Investigation, Tacoma, WA
OBJECTIVE: Magnesium sulfate decreases the risk of cerebral palsy in
preterm infants, possibly by preventing inflammation from degrading
the blood brain barrier. We developed an in vitro blood-brain-barrier
model to study effects of inflammation on cellular permeability.
STUDY DESIGN: An in vitro blood-brain-barrier model was constructed with a two-chamber transwell separated by a permeable
OBJECTIVE: Glycemic derangements are associated with adverse neonatal outcomes; however, cord blood glucose levels have never been
investigated as a predictor of neurological outcomes in encephalopathic neonates. We hypothesized that suboptimal glucose levels in
cord blood samples would be associated with adverse MRI findings in
term neonates who qualified for whole body cooling due to a diagnosis
of hypoxic-ischemic encephalopathy.
STUDY DESIGN: Case control study was conducted. Term neonates
with a diagnosis of encephalopathy underwent whole body cooling as
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Poster Session I
per institutional protocol. Encephalopathic infants with abnormal
MRI findings at 6 weeks of life (cases) were compared to those with
normal MRI findings following whole body cooling (controls). Glucose levels were obtained from their cord blood. ELISA-like colorimetric tests were performed at standard conditions. Maternal demographics, antepartum and intrapartum complications were
compared. Standard statistics including T- tests, chi-square and logistic regression were performed using STATA version 11. Power calculations were performed. Sensitivity and specificity were calculated.
RESULTS: Thirty one infants were identified; 19 with normal MRI and
12 with abnormal MRI findings. The neonates with abnormal MRIs
had a median gestational age (GA) of 39.0 wks (SD 1.40), mean birthweight 3325g (SD 683.6) and mean cord pH of 6.92 (SD 0.05). The
neonates with normal MRIs had a median GA of 39.26 wks (SD 1.73),
mean birthweight of 3403g (SD 133.6) and mean cord pH of 6.96 (SD
0.03). Logistic regression modeling revealed an odds ratio 0.64 (95%
CI 0.0006-0.625) for abnormal MRI findings associated with glucose
above 85 mg/dL (even after controlling for confounders) with a sensitivity of 92% and specificity of 63%.
CONCLUSION: Cord glucose above 85 mg/dL in term encephalopathic
neonates who qualified for whole body cooling is associated with improved MRI findings. Cord blood glucose may prove to be an additional risk stratification tool for encephalopathic neonates.
188 Association of cord blood digitalis-like factor and
necrotizing enterocolitis in the neonate
1
Steven Graves , Sean Esplin
1
1
For the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, Maternal-Fetal Medicine Units Network,
Bethesda, MD
OBJECTIVE: Endogenous digoxin-like factor (EDLF) has been linked
to vasoconstriction and altered membrane transport. Our objective
was to determine if increased EDLF in the cord sera of preterm infants
was associated with an increased incidence of intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC).
STUDY DESIGN: Cord sera from pregnant women enrolled in a randomized trial of MgSO4 for fetal neuroprotection were analyzed for
EDLF using a red cell Rb⫹ uptake assay and inhibition of sodium
pump mediated Rb⫹ transport used as a functional assay of EDLF.
Specimens were assayed blinded to neonatal outcome. Cases (neonates with stage 3⫹ or 4⫹ IVH (n⫽9) or NEC (n⫽25)) and controls
(neonates not developing these complications, n⫽35) were matched
for maternal characteristics. No woman had preeclampsia. Comparisons of cases versus controls were made by 2-tailed Kruskall-Wallis
test for continuous and by Fisher’s exact test for categorical variables.
Logistic regression analysis was used to assess odds ratio (OR) of case/
control status by EDLF level, adjusting for gestational age (GA), treatment group, race, and PPROM.
RESULTS: Cases and controls were not significantly different for GA,
race, maternal steroid use, PPROM or MgSO4 treatment. Median
EDLF level was not significantly different between cases and controls
(p⫽0.10), however it differed between NEC cases and controls
(p⫽0.04). In logistic models adjusted for treatment group, race,
PPROM and GA, cord sera EDLF was not significantly predictive of
cases (combined IVH and NEC) versus controls (p⫽0.063), however,
it was significantly predictive of infants with NEC (p⫽0.025). So for
example, for a 20-unit increase in EDLF, the OR is increased to 1.80
(1.08, 3.02).
CONCLUSION: These preliminary data raise the possibility of an interaction between cord sera EDLF and the later development of
NEC. Studies specifically designed to test this possibility should be
considered.
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Box plot of EDLF by disease status, with “ⴙ”
symbolizing the mean
189 Neonatal end organ damage with elective repeat
cesarean delivery versus trial of labor with cesarean:
analysis based on propensity scores
Suneet Chauhan1, Hind Beydoun2,
Ibrahim Hammad3, Cande Ananth4
1
Eastern Virginia Medical School, Department of Obstetrics and Gynecology,
Norfolk, VA, 2Eastern Virginia Medical School, Department of Public
Health, Norfolk, VA, 3Eastern Virginia Medical School, Department of
Obstetrics and Gynecology, Norfolk, VA, 4Columbia University Medical
Center, Department of Obstetrics and Gynecology, New York, NY
OBJECTIVE: To compare the risk of neonatal end organ damage (EOD)
among women who had an elective repeat cesarean delivery (ERCD)
versus a trial of labor with cesarean (TOLAC).
STUDY DESIGN: This is a secondary analysis of the Maternal-Fetal Medicine Units (MFMU) network’s prospective cohort registry of cesarean deliveries. This study was restricted to women with ⱖ1 prior cesarean delivery who delivered non-anomalous singletons at ⱖ34
weeks with vertex presentation, and had either ERCD or TOLAC.
EOD was defined as newborns with any of the following diagnosis:
neonatal seizure, cardiac, renal, hepatic dysfunction, or neonatal intubation in the first 24 hours. To address issues of selection bias and
unobserved confounding, a propensity score analysis was performed.
Propensity scores for ERCD (versus TOLAC) were calculated using a
logistic regression model based on baseline characteristics including
maternal age, parity, ethnicity, education, marital status, smoking,
alcohol and drug use, body-mass index, hypertension, diabetes, and
general anesthesia, as well as significant two-way interactions. The
propensity scores were then used to predict the risk of neonatal EOD.
RESULTS: The composite risks of neonatal EOD were 15.5 and 16.0 per
1,000 in the ERCD and TOLAC groups, respectively (Table). In comparison to the ERCD group, the risk ratios for seizures and cardiac
dysfunction were over two-fold higher, and the risk ratios of renal and
hepatic dysfunction over six-fold higher in the TOLAC group.
CONCLUSION: This prospective cohort study underscores substantially
increased risks of neonatal EOD to infants delivered of pregnancies
that undergo TOLAC. Despite the small absolute risks of neonatal
EOD, these observations are robust and safeguard against biases due
to patient selection and unobserved confounding through the application of propensity score methods.
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Poster Session I
Cellular origin and tissue factor expression of
circulating microparticlesa
a
Values expressed as median (interquartile range) percentage; bReflects percentage of MPs out of
MPs of any cellular origin; cReflects percentage of MPs out of MPs of indicated cellular origin.
191 Punicalagin attenuates hypoxia-induced
apoptosis by down regulating p53 activity in cultured
human placental syncytiotrophoblasts
Baosheng Chen1, Mark S Longtine1, D Michael Nelson1
190 Microparticle source and tissue
factor expression in pregnancy
1
2
1
Washington University School of Medicine, Department of Obstetrics and
Gynecology, St. Louis, MO
1
Amy Wong , Hau Kwaan , William Grobman ,
Ivy Weiss2, Cynthia Wong3
1
Northwestern University, Feinberg School of Medicine, Department of
Obstetrics and Gynecology, Chicago, IL, 2Northwestern University, Feinberg
School of Medicine, Department of Medicine, Chicago, IL, 3Northwestern
University, Feinberg School of Medicine, Department of Anesthesiology,
Chicago, IL
OBJECTIVE: Microparticles (MPs) are potent activators of the coagulation system. To investigate whether MPs originating from platelets
or trophoblast cells that express tissue factor (TF) contribute to coagulation changes in pregnancy, we aimed to characterize whether pregnancy, labor, and delivery are associated with changes in the source
and composition of MPs.
STUDY DESIGN: Blood samples were collected in 20 non-pregnant
women, 20 term pregnant women not in labor (presenting for induction or scheduled cesarean delivery), and 20 term pregnant women in
labor. Two samples were collected in the pregnant groups, one prior
to delivery and the second one hour after delivery. Using flow cytometry, we used CD41a and NDOG2 antibodies to identify MPs from
platelets and trophoblasts, respectively, and TF antigen to identify
MPs expressing tissue factor. Comparisons were made between the
non-pregnant and pregnant groups, non-laboring and laboring
groups, and pre-delivery and post-delivery groups within the pregnant groups.
RESULTS: There was no difference among the non-pregnant, pregnant
pre-delivery non-laboring, and pregnant pre-delivery laboring
groups with regard to the proportion of MPs originating from platelets or expressing TF. Also, the presence of labor did not affect the
proportion of MPs originating from trophoblasts. Conversely, the
proportion of platelet-derived MPs present among women in labor
increased after delivery (8.5 vs. 20.5%, p⫽0.02).
CONCLUSION: In the current study, pregnancy was not associated with
changes in cell origin of MPs or in the number of TF-expressing MPs.
However, delivery appears to be associated with an increase in the number of platelet-derived MPs. Further investigation may determine
whether this increase contributes to the clinically meaningful coagulation
changes in pregnancy and the puerperium, as well as to identify other
possible MP sources or antigens that may affect coagulation.
OBJECTIVE: Punicalagin is a promiment polyphenol in pomegranate
juice (PJ), and both punicalagin and PJ reduce oxidative stress and
apoptosis in human placental trophoblasts (Chen et al. Am J Physiol
302:E1142, 2012). The mechanism for this effect is unknown. We
tested the hypothesis that punicalagin attenuates apoptosis in cultures
of syncytiotrophoblasts exposed to hypoxia by regulating the expression of p53, MDM2, Hif-1␣, and Bcl-2 family member proteins.
STUDY DESIGN: Primary human trophoblasts were cultured in 5%
CO2/air for 28 h in DMEM with 10% FBS and then for 24 h in phenolred free DMEM with 10% charcoal-stripped FBS. Syncytiotrophoblasts formed during this time, and at 52 h the cultures were exposed
to 24 h of ⬍1% oxygen with 5% CO2, 10% H2, and 84% N2, in
medium containing 33.8 mM punicalagin or 7.5 mM glucose as control. Protein extracts of cultures were harvested at 76 h and western
blotting quantified expression levels of p53, MDM2, Hif-1␣, Bcl-2,
Bcl-XL, Bak and Bax.
RESULTS: Levels of p53 were significantly decreased after exposure to
punicalagin compared to control in the syncytiotrophoblasts under
hypoxia (p⬍0.05). Moreover, in hypoxic syncytiotrophoblast punicalagin exposure increased expression (p⬍0.05) of MDM2, the major
negative regulator of p53 levels, and reduced expression of Hif-1␣,
which interacts with p53. There were no differences in expression
between punicalagin-exposed and control exposed syncytiotrophoblasts for any of the four proteins of the Bcl-2 family examined.
CONCLUSION: Punicalagin, a prominent polyphenol in pomegranate
juice, reduces p53 activity and modulates the p53 pathway to limit, in
part, hypoxia-induced apoptosis in syncytiotrophoblasts. NIH RO1
HD 29190.
192 Pomegranate juice decreases hypoxia-induced
apoptosis and oxidative stress in mouse placenta
Baosheng Chen1, Mark S Longtine1, D Michael Nelson1,
Joan Riley1
1
Washington University School of Medicine, Department of Obstetrics and
Gynecology, St. Louis, MO
OBJECTIVE: Oxidative stress associates with sub-optimal outcomes in
human pregnancy. Pomegranate juice (PJ) is a potent source for antioxidants, and we showed that PJ reduces oxidative stress in human
trophoblasts in vitro and in vivo (Chen et al. Am J Physiol 302:E1142,
2012). We test the hypothesis that PJ decreases hypoxia-induced placental oxidative stress and apoptosis in hypoxic mice.
STUDY DESIGN: Embryonic day 0.5 (E 0.5) was defined as the morning
of vaginal plug detection. Pregnant C57BL6 mice were gestated in four
conditions: 1) Hypoxia: FiO2 ⫽ 12%, E15.5 -18.5, ad lib food 2) Normoxia-FR: FiO2 ⫽ 20%, E15.5 -18.5, food restricted to that of
hypoxia, 3) Hypoxia-PJ: FiO2 ⫽ 12%, E15.5-18.5, gavaged daily with
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250␮l PJ E12.5-E18.5 4) Hypoxia-PJ control: FiO2 ⫽ 12%, E15.518.5, gavaged daily with 250 ␮l glucose (13.5% w/v ⫽ glucose concentration in PJ) Food intake and body weight of pregnant mice were
recorded daily, and placentas and fetuses were weighed at E18.5.
Western blots of placental extracts were quantified for the oxidative
stress marker, Hsp90, and apoptosis markers, cleaved caspase 3 and
cleaved PARP.
RESULTS: Compared to normoxia-FR, hypoxia significantly increased
placental expression of Hsp90, cleaved caspase 3, and cleaved PARP.
Importantly, hypoxia-PJ, compared to hypoxia-PJ control, showed
significantly (p⬍0.05) reduced expression of all three markers of placental injury. Although placentas from hypoxia-PJ weighed less than
hypoxia-PJ control, there were no differences in the number of nidations per pregnancy, fetal weights, or the placenta:fetal weight ratios
between these two groups.
CONCLUSION: PJ limits hypoxia induced oxidative stress and apoptosis
in placentas of pregnant mice. We speculate that PJ is a potential
therapeutic agent to limit exogenous injury to human placentas. NIH
RO1 HD 29190.
www.AJOG.org
Skin autofluorescence during and after
normal pregnancy
193 Skin autofluorescence, a marker of advanced
glycation endproducts accumulation, increases
during normal pregnancy
Bart Groen1, Pieter-Dirk Boekel2, Paul van den Berg1, Helen
Lutgers3, Douwe Mulder2, Marijke Faas4, Petronella GeelhoedDuijvestijn5, Thera Links3, Joop Lefrandt2
1
University of Groningen, University Medical Center Groningen, Obstetrics
and Gynecology, Groningen, Netherlands, 2University of Groningen,
University Medical Center Groningen, Internal Medicine, Groningen,
Netherlands, 3University of Groningen, University Medical Center
Groningen, Endocrinology, Groningen, Netherlands, 4University of
Groningen, University Medical Center Groningen, Medical Biology,
Groningen, Netherlands, 5Medical Center Haaglanden, Internal Medicine,
the Hague, Netherlands
OBJECTIVE: Parity is an independent risk factor for cardiovascular
(CV) disease, resulting in an increased risk for CV events in women
with ⱖ4 children. Since pregnancy is associated with relative insulin
resistance and increased glycemic and oxidative stress, the cumulative
metabolic burden of pregnancy may contribute to this increased risk.
Advanced glycation endproducts (AGEs) are sugar-modified proteins
that accumulate during normal ageing, driven by glycemic and oxidative stress. This process is accelerated in diabetes mellitus (DM),
contributing to vascular disease. Skin autofluoresence (SAF), a validated non-invasive measure of AGEs accumulation, has a strong predictive value for mortality in type 2 DM. Earlier, we showed that SAF
is increased in recently pre-eclamptic women but it is unclear if SAF
increases during normal pregnancy. The aim of the present study is to
investigate SAF during normal pregnancy.
STUDY DESIGN: 54 consecutive healthy pregnant women from the
UMCG midwifery clinic were included. 13 women dropped out: 4
moved to another clinic, 3 were unable to attend all measurements
and 6 had a complicated pregnancy. SAF was measured with the AGEreader (DiagnOptics, Netherlands) in the 1st (T1), 2nd (T2) and 3rd
(T3) trimester of gestation; in 20 women also 12-16 weeks after delivery (PP). ANOVA and paired sample t-tests were used. A p-value
of ⬍0.05 was considered as significant. Data as mean⫾SEM.
RESULTS: 41 women (age 32⫾1 yrs) completed the study at term after
an uncomplicated pregnancy. SAF increased from 1.48⫾0.03 (T1) to
1.60⫾0.03 AU (T3), p⫽0.014; SAF did not change thereafter in 20
women: 1.57⫾0.05 (T3) to 1.57⫾0.05 AU (PP), p⫽0.938 (Figure).
CONCLUSION: SAF, a marker of AGEs accumulation, increases during
normal pregnancy. This may reflect the cumulative metabolic burden
of pregnancy and contribute to the increased CV risk associated with
ⱖ4 pregnancies. Further studies should address if increase in SAF is
exaggerated during pregnancies complicated by pre-eclampsia
or DM.
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194 Omentin, a novel adipokine with insulin-sensitizing
properties is associated with insulin resistance
indices in normal gestation
Benny Brandt1, Shali Mazaki-Tovi1, Yoav Yinon1, Eyal Schiff1,
Rina Hemi1, Hannah Kanety1, Eyal Sivan1
1
Sheba Medical Center, Department of Obstetrics and Gynecology,
Tel-Hashomer, Israel
OBJECTIVE: Omentin, a newly identified adipokine, enhances insulin
mediated glucose uptake in human adipocytes, thus inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with
insulin resistance indices and to assess which compartment, maternal,
fetal or placental, is the source of omentin in maternal circulation.
STUDY DESIGN: Fasting serum glucose, insulin and omentin were determined in 25 healthy pregnant women at the third trimester, before
and 3 days after elective cesarean section. Cord blood omentin was
measured in their 25 neonates. The Homeostasis Model Assessment
(HOMA) was used to evaluate insulin sensitivity before and after delivery. Non-parametric statistical methods were employed.
RESULTS: Antepartum maternal omentin levels were negatively correlated with insulin levels (r⫽⫺0.41, p⫽0.04) and insulin resistance
(HOMA-IR; r⫽ ⫺0.41, p⫽0.03) and positively correlated with insulin sensitivity (HOMA-%S; r⫽0.4, p⫽0.04). Postpartum omentin
levels were negatively correlated with maternal BMI (r⫽⫺0.44,
p⫽0.02), antepartum HOMA-IR (r⫽⫺0.49, p⫽0.01), and beta cell
function (HOMA-%B; r⫽⫺0.47, p⫽0.01). Median maternal omentin levels was comparable before and after delivery (57.2, IQR: 38.276.2 ng/ml vs. 53.4, 39.8-69.4 ng/ml, respectively, p⫽0.25) and highly
correlated (r⫽0.83, p⬍0.001). Antepartum maternal and neonatal
omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/ml,
p⫽0.77) and did not correlate (p⫽0.6).
CONCLUSION: Circulating maternal omentin levels are correlated with
insulin resistance indices, implying that this adipokine may play a role
in metabolic adaptations of normal gestation. The strong correlation
between anteparum and postpartum maternal omentin levels, as well
as the lack of association between maternal and neonatal omentin
levels, suggest that the placental or fetal compartments are unlikely the
source of circulating maternal omentin.
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195 Critical enzymes for endocannabinoid metabolism in a
baboon model of maternal obesity
Brian Brocato1, Zorica Janjetovich2, Andrzej Slominski2,
Mari Giancarlo1, Gene Hubbard3, Edward Dick4
1
University of TN Health Science Center, Obstetrics and Gynecology,
Division of Maternal Fetal Medicine, Memphis, TN, 2University of TN
Health Science Center, Pathology, Memphis, TN, 3University of Texas Health
Science Center at San Antonio, Pathology, San Antonio, TX, 4Texas
Biomedical Research Institute, Pathology, San Antonio, TX
OBJECTIVE: Maternal obesity is a risk factor for adverse fetal outcomes
including fetal loss and abnormal growth. It has been suggested that
the increase in endocannabinoid (ECB) system tone found in obesity
may cause early fetal loss. We hypothesized that expression of ECB
degrading enzymes (FAAH, MAGL and DAGL) will be altered in placentas of obese baboons.
STUDY DESIGN: Four obese and four non-obese baboons (Papio spp)
were studied as previously described. Placenta was retrieved during
C-section and was flash- frozen and stored at ⫺80°. RNA was isolated
using Trizol. 5 ␮g RNA was used for cDNA synthesis (Roche, Basel
Switzerland). Primate specific primers and TagMan probes (Roche
Universal probes library) were used for Real-time PCR performed on
a Roche Light Cycler 480. The amounts were compared to a reference
gene (␤- actin) using a comparative CT method. All reactions were
performed in triplicate with the appropriate controls. Relative gene
expression data were calculated using ⌬Ct method. Data are expressed
as mean ⫾ SEM. Two-tailed t-Student test was used to compare the
variables; p⬍0.05 was considered significant.
RESULTS: There were no differences in the relative expression of gene
transcripts between obese and non-obese animals. The expression of
FAAH was 0.55 ⫾0.1 in obese (Ob) vs. 0.76 ⫾0.2 in non-obese (nOb)
animals, DAGL 0.69 ⫾0.2 (Ob) vs. 0.75⫾0.04 (nOb) and MAGL 5.9
⫾0.9 (Ob) vs. 5.62⫾0.4 (nOb).
CONCLUSION: This is the first report regarding the expression of ECB
enzyme gene transcripts in term non-human primate placentas. The
detected 38% decrease in FAAH expression seen in the placenta of
obese baboons was not statistically significant. Further studies are
necessary to determine whether placental ECB metabolizing enzymes
might serve as a potential target for intervention to possibly improve
poor fetal outcomes associated with maternal obesity.
Poster Session I
to lean women (Figure). There was no significant difference in serum
free IGF-II median levels between obese (25.3 [17.9-41.1] ng/mL) and
lean (34.4 [26.6-62.0] ng/mL) women. There was no significant up- or
down-regulation of placental Igf1r (FC 1.21, p ⫽ .15) or Igf2r (FC
1.04, p ⫽ .58) expression among obese women.
CONCLUSION: Serum free IGF-I levels are decreased in obese women
during the first trimester. This may be a result of an obesity-induced
insulin resistance blunting effect on IGF-binding protein levels. Further analysis of the IGF-axis is required to clarify this finding, which
includes determination of serum levels of total IGF, IGF-binding proteins, and PAPP-A.
197 Maternal race and gestational age dependent
changes in maternal serum lipids
Christina Scifres1, Janet Catov1, Hygriv Simhan1
1
University of Pittsburgh, Department of Obstetrics, Gynecology, and
Reproductive Sciences, Pittsburgh, PA
196 The insulin-like growth factor axis in healthy
obese and lean women in the first trimester
Carlton Schwab1, Mark Alanis2
1
Medical University of South Carolina, Obstetrics and Gynecology,
Charleston, SC, 2Colorado Springs Memorial Hospital, Maternal-Fetal
Medicine, Colorado Springs, CO
OBJECTIVE: To examine serum free IGF-I and IGF-II levels and transcript levels for placental IGF receptors (Igf1r and Igf2r transcripts) in
obese and lean women in the first trimester.
STUDY DESIGN: Serum and placental specimens were collected at the
time of voluntary termination of pregnancy in obese (BMI ⱖ 30) and
lean (BMI 18.5-24.9) subjects between 8 0/7 and 13 6/7 weeks of gestation. Subjects were matched 1:1 by race/ethnicity, smoking status,
and gestational age. Serum was analyzed by ELISA for free IGF-I and
IGF-II, and RNA was extracted from placental samples to measure
Igf1r and Igf2r transcript levels by RT-qPCR. Serum IGF levels were
log transformed to induce normality. Student’s t-tests were performed on normally distributed data to compare differences in
means. Skewed data were analyzed by the Wilcoxon rank sum test.
Fold-changes in Igf1r and Igf2r were calculated by the delta-delta Cq
calculation. Two-tailed p values ⬍ 0.05 were considered statistically
significant. A sample size calculation (n ⫽ 25 matched pairs) was
performed to provide ⬎ 80% power to detect a relative 25% difference
in serum IGF-I levels between groups.
RESULTS: Fifty-four women (27 matched pairs) were enrolled consecutively. There were no differences in age, parity, or other demographic
variables. Serum free IGF-I was significantly lower in obese compared
OBJECTIVE: Maternal adaptation to pregnancy involves alterations in
serum lipids, and aberrations have been linked to adverse pregnancy
outcomes with significant race disparities. We considered that maternal serum lipids in the 1st and 2nd trimesters would vary by maternal
race.
STUDY DESIGN: 185 women who had maternal serum cholesterol,
HDL, LDL, and triglycerides measured at less than 13 weeks and between 24-28 weeks’ gestation were included in this analysis. Individual
species of fatty acids were also measured at both time points in a subset
of 127 women. We analyzed differences in maternal serum lipids between black and white women using univariable and multivariable
methods.
RESULTS: Maternal serum lipids were measured in 76 (41%) white
women and 109 (59%) black women. After adjustment, maternal serum triglycerides were lower in black women at less than 13 weeks
(⫺13.1 mg/dL, 95% CI ⫺25.7,⫺0.45, p⫽0.04) and between 24-28
weeks’ gestation (⫺41.6 mg/dL, 95% CI ⫺57.6, ⫺25.6, p⬍0.01) compared to white women. Total fatty acids were also lower in black
women at less than 13 weeks (⫺28.9 mg/dL, 95% CI ⫺48.6, ⫺9.1,
p⬍0.01) and at 24-28 weeks (⫺54.9 mg/dL, 95% CI ⫺82.4,27.2,
p⬍0.01). In addition, black women had lower levels of saturated,
monounsaturated, and polyunsaturated fatty acid levels at both time
points and higher levels of omega 6 fatty acids at 24-28 weeks’ compared to white women. HDL levels were higher in black women at less
than 13 weeks (3.8 mg/dL, 95% CI 0.5-7.1, p⬍0.03) and at 24-28
weeks’ gestation (7.7 mg/dL, 95% CI 2.7-12.8, p⬍0.01).
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Poster Session I
CONCLUSION: Black women had lower levels of triglycerides and fatty
acids in the 1st and 2nd trimesters compared to white women, and
black women had higher levels of omega-6 fatty acids at 24-28 weeks.
Triglycerides and fatty acids are essential for fetal growth and development, and higher levels of omega-6 fatty acids have been linked to
preterm birth. Further investigation is necessary to determine
whether these lipid differences contribute to race disparities in pregnancy outcomes.
198 Prolactin derived vasoinhibins are associated with
inflammation in mid-gestation
Christy Pearce1, Linah Al-Alem2, John O’Brien2, Kristine Lain3,
Wendy Hansen2, Thomas Curry2
1
Vanderbilt University, OB/GYN, Nashville, TN, 2University of Kentucky,
OB/GYN, Lexington, KY, 3Norton Healthcare, Maternal Fetal Medicine,
Louisville, KY
OBJECTIVE: Prolactin derived vasoinhibins have been implicated in
the pathophysiology of preeclampsia and peripartum cardiomyopathy via a pro-inflammatory mechanism. We sought to determine the
presence and examine the relationship of these prolactin derived vasoinhibins and inflammation in mid-gestation.
STUDY DESIGN: Women with a singleton gestation between 16-23
weeks without exclusion for preexisting medical conditions were recruited as the study cohort. Women with preeclampsia at 24-42 weeks
were recruited as physiologic standards. Serum was tested for C-reactive protein with a turbidimetric assay, prolactin with an immunoassay, and prolactin derived vasoinhibins via immunoprecipitation and
Western blot. A sample by which to normalize vasoinhibin expression
across different Western blots was selected from one of the recruited
preeclamptic standards. Statistical analysis included t-test and correlation coefficients.
RESULTS: Sixty subjects were recruited at an average of 19.9 ⫾ 1.5
weeks gestation for the study cohort. The mean age was 22.4 ⫾ 3.6
years and mean body mass index (BMI) was 27.9 ⫾ 7.1 kg/m2. Most
women were primigravidas (n⫽47, 78.3%) and Caucasian (n⫽43,
71.7%). Forty-nine (81.7%) of samples expressed a significant measurable optical density of PRL fragment on Western blot. Increasing
prolactin derived vasoinhibins and the ratio of vasoinhibins to prolactin was associated with increasing C-reactive protein (rho⫽0.3,
p⫽0.04 and rho⫽0.3, p⫽0.04). See figure 1. Significant differences in
mean C-reactive protein were noted between samples above and below the median prolactin derived vasoinhibin optical density
(9.7⫾8.1 vs. 6.3⫾6.1, p⫽0.03) and the median ratio of vasoinhibins
to prolactin (9.9⫾8.1 vs. 6.2⫾6.1, p⫽0.02).
CONCLUSION: Prolactin derived vasoinhibins are associated with inflammation in mid-gestation. Further examination of these prolactin
fragments in larger, high risk cohorts may be instructive in the pathophysiology of obstetrical conditions.
Correlation of CRP with prolactin derived
vasoinhibin and ratio of prolactin derived
vasoinhibin to prolactin
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199 Maternal obesity suppresses placental
fatty acid uptake in male offspring
Elizabeth Brass1, Kent Thornburg2, Perrie O’Tierney2
1
OR, 2Oregon Health & Science University, Heart Research Center, Dept
Cardiovascular Medicine, Portland, OR
OBJECTIVE: The fetus is dependent on the placenta for its supply of
long chain polyunsaturated fatty acids (LCPUFA), which are essential
in fetal growth and development. Previous work suggests that maternal body mass index is associated with fetal LCPUFA delivery and that
males have greater fatty acid requirements than females during development. We hypothesized that male placental fatty acid uptake would
be more sensitive to maternal BMI compared to females.
STUDY DESIGN: Women were recruited upon admission to Labor &
Delivery for cesarean section (n⫽25). At delivery, placental samples
were collected for fatty acid uptake studies using 14C-labeled oleic
acid (OA), arachidonic acid, (AA) and docosahexanoic acid (DHA) in
placental explants. Uptake was calculated as nmol fatty acid/mg protein at 15 minutes. Results were stratified by fetal sex and maternal
first trimester BMI (normal BMI⬍25, obese BMI⬎26). Women with
significant co-morbidities were excluded. Dichotomous outcomes
were analyzed using 1 way ANOVA followed by Tukey post-hoc testing; p⬍0.05 was used to indicate statistical significance.
RESULTS: Placental fatty acid uptake of OA and AA in males of obese
women was decreased 62% and 60% respectively compared to normal
BMI women (p⬍0.001). In females, placental fatty acid uptake was
not suppressed in the setting of obesity; OA and AA uptake in normal
BMI women was reduced 49% and 48% respectively compared to its
male cohort (p⬍0.01). There was no difference in DHA uptake between sex or BMI groups. Fatty acid transporter CD36 and binding
protein FABP5 gene expression levels in males mirrored the fatty acid
uptake suppression seen in obesity.
CONCLUSION: Placentas from males with obese mothers had suppressed uptake of unsaturated fatty acids and expression of their
transporters, while uptake in females was unaffected by maternal
BMI. This data suggest that males born to high BMI mothers may have
inadequate LCPUFA acquisition. Males may pay a higher developmental price in the setting of maternal obesity.
200 Fetoplacental endothelium demonstrate unique
responses to physiologic hypoxemia
Emily Su1, Hong Xin1, Chunfa Jie2, Nadareh Jafari3,
Matthew Dyson1, Serdar Bulun1
1
Northwestern University Feinberg School of Medicine, Obstetrics and
Gynecology, Chicago, IL, 2Northwestern University Feinberg School of
Medicine, Surgery/Organ Transplantation, Chicago, IL, 3Northwestern
University Feinberg School of Medicine, Center for Genetic Medicine,
Chicago, IL
OBJECTIVE: Although physiologic, fetoplacental pO2 is relatively hypoxemic in comparison to postnatal life, ranging from 12-50 mm Hg
(1.5 - 8% O2). In adults, hypoxic conditions have profound effects on
endothelial cell function that are often deleterious. We sought to de-
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termine the effects of physiologic hypoxia on fetoplacental endothelial
cell gene expression in contrast with ambient oxygen tension, which is
the setting in which most endothelial cells are cultured. We hypothesize that normal fetoplacental endothelial response to physiologic hypoxemia results in a unique gene regulation that optimizes fetoplacental vascular function.
STUDY DESIGN: Villous endothelial cells from uncomplicated deliveries were isolated and cultured immediately after unlabored C-sections. Cells were subjected to either ambient oxygen tension (21% O2;
N⫽6) or to physiologic hypoxia (1.5% O2; N⫽6) in a hypoxia incubator chamber for 24 hours. Total RNA with high RNA Integrity
Number (RIN) were analyzed using the Illumina Human HT-12 v4
Expression Beadchip. Differentially expressed genes (DEGs) were
identified by the criteria of adjusted p⬍0.01 and expression foldchange ⬎ 1.5. Gene Ontology and pathway analyses were performed
on the DEGs. Real-time PCR and western blot analyses confirmed
microarray results of interest.
RESULTS: Vascular endothelial growth factor A (VEGFA) mRNA expression (p⬍0.05) and hypoxia inducible factor 1-alpha (HIF1A)
protein expression (p⬍0.01) were up-regulated after exposure to hypoxia. Microarray demonstrated 86 genes with differential expression,
including those regulating angiogenesis, glucose homoestasis, and
surprisingly, steroid hormone metabolism. In contrast to published
literature on adult endothelium and hypoxia, fetoplacental endothelium did not demonstrate induction of cellular adhesion molecules,
heat shock proteins, or pro-apoptotic genes.
CONCLUSION: Fetoplacental endothelium demonstrate unique responses to their physiologic hypoxemic environment that contribute
to optimal fetoplacental vascular function.
201 The role of candidate oxidative stress genes in the
developmental programming of adult disease
Giuseppe Chiossi2, Maged Costantine1, Huaizhi Yin1, Tamayo
Esther1, Gary Hankins1, George Saade1, Monica Longo1
1
The University of Texas Medical Branch, Dept. Obstetrics and Gynecology,
Galveston, TX, 2Arcispedale Santa Maria Nuova, Dept. Obstetrics and
Gynecology, Reggio Emilia, Italy
OBJECTIVE: Mice developing in an adverse uterine environment lacking endothelial nitric oxide synthase (NOS3) have altered vascular
phenotype and are hypertensive later in life. This was reversed by
prenatal supplementation with methyl-donor rich diet. Antioxidant
enzymes, like superoxide dismutase (SOD), glutathione peroxidase
(GPx) and catalase (CAT), were also upregulated in the kidneys of
these offspring. Our aim was to determine whether the altered gene
expression of these enzymes might play a role in the altered vascular
programming, and whether these changes can be reversed by methyldonor enriched diet, using a model of vascular programming.
STUDY DESIGN: Homozygous NOS3 knockout and wild type mice were
cross-bred to produce heterozygous offspring developing in a WT
mother with a normal uterine environment (KOP) versus offspring
from a KO mother lacking a functional NOS3 (KOM). Mothers were
placed on a methyl-donor enriched (MD) or control diet (CD) during
pregnancy and pups weaning. Offspring were then kept on CD until
sacrifice (14 weeks). Offspring kidneys were isolated and RNA extracted for SOD, GPx and CAT gene expression. One-way-ANOVA
and Student t-test were used as appropriate for statistical analysis
(significance: p⬍0.05).
RESULTS: In male offspring, CAT, GPx and SOD gene expression was
significantly lower in the KOM compared with KOP, whether from
the CD or MD groups. CAT, GPx expression was lower in female
KOM compared with KOP on CD. Female KOM offspring on MD
show a significant increased in CAT, GPx and SOD expression
compared with KOM on CD to a level similar to KOP on CD
(Figure 1A, 1B).
CONCLUSION: An adverse uterine environment lead to altered gene expression of antioxidant genes in the offspring kidney in a gender specific manner, and this effect can be reversed by maternal methyl-do-
Poster Session I
nor supplementation. Epigenetic regulation of oxidative stress genes
may be responsible for the fetal origin of adult hypertension, opening a window to a new therapeutic approach using folate supplementation.
202 The role of oxidative stress in developmental
programming of the adult vascular phenotype
Giuseppe Chiossi2, Maged Costantine1, Talar Kechichian1,
Phillis Orise1, Gary Hankins1, George Saade1, Monica Longo1
1
The University of Texas Medical Branch, Dept. Obstetrics and Gynecology,
Galveston, TX, 2Arcispedale Santa Maria Nuova, Dept. Obstetrics and
Gynecology, Reggio Emilia, Italy
OBJECTIVE: Mice developing in an adverse uterine environment lacking endothelial nitric oxide synthase (NOS3) are hypertensive and
have altered vascular phenotype later in life. By using an established
murine model of fetal programming, our aim was to determine the
role of oxidative stress in this process by evaluating specific antioxidant enzyme like superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in their kidneys, and whether prenatal
methyl-donor enriched diet could modulate it.
STUDY DESIGN: Homozygous NOS3 knockout and wild type mice were
cross-bred to produce heterozygous offspring: KOP born to a WT
mother with normal uterine environment and KOM born to KO
mothers lacking NOS3. Mothers were placed on a methyl-donor enriched (MD) or control (CD) diet during pregnancy and pup weaning. Offspring were then placed on CD until sacrifice (14 weeks). Female kidneys were isolated, SOD, CAT, and GPx protein expression
quantified by Western blot. Hydrogen peroxide (H2O2), an indicator
of oxidative stress, measured in serum. One-way-ANOVA and Student t-test used for statistical analysis.
RESULTS: KOM offspring had significantly lower CAT and GPx protein levels compared with KOP, both on CD. Prenatal MD supplementation significantly increased GPx level in KOM to a value similar
to KOP on CD. Indeed CAT level was decreased in KOM and KOP on
MD compared with KOM and KOP on CD. SOD levels were similar
between groups. Serum H2O2 was higher in KOM versus KOP on CD
and was decreased by prenatal MD supplementation in KOM offspring to levels similar to KOP on CD (Figure).
CONCLUSION: An adverse uterine environment results in altered antioxidant enzymes level in the kidney of female offspring later in life.
Maternal methyl-donor supplementation reverses these changes, decreasing the oxidative stress load. Epigenetic regulation of oxidative
stress in the kidney appears to play a role in the fetal origin of adult
hypertension, opening the way for sensible preventive strategies, like
folate supplementation.
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204 Maternal microchimerism in cord blood
203 Placenta growth factor in pregnancies conceived by
assisted reproductive technology
Hayley Quant1, Samuel Parry1, Rita Leite1, Nadav Schwartz1
1
University of Pennsylvania Perelman School of Medicine, Maternal and
Child Health Research Program, Department of Obstetrics and Gynecology,
Philadelphia, PA
OBJECTIVE: Assisted reproductive technology (ART) is associated with
an increased risk of placenta-mediated adverse pregnancy outcomes.
We sought to compare first trimester serum levels of Placental Protein
13 (PP13) and Placenta Growth Factor (PlGF) as well as uterine artery
Doppler pulsatility index (UPI) in ART-conceived and spontaneous
pregnancies.
STUDY DESIGN: This cohort was part of a larger prospective study investigating early predictors of adverse pregnancy outcomes. Unselected patients with singleton gestations were enrolled between 11 and
14 weeks. Dopplers were performed and serum assayed for PlGF and
PP13. Medical records were reviewed to identify ART patients. Patients who conceived via in vitro fertilization (IVF), controlled ovarian
hyperstimulation (COH) and intrauterine insemination (IUI), or ovulation induction (OI) were compared with spontaneous conceptions. Logistic regression was used to control for potential confounders.
RESULTS: ART was used in 42 (9.3%) of 534 pregnancies: 16 IVF, 5
COH, 28 OI, 1 natural cycle IUI. Significant differences in mean maternal age (35.6 vs 30.2, p⬍0.0005), black race (9.5% vs 44.3%,
p⬍0.0005) and nulliparity (78.6% vs 52.2%, p⫽0.001) were found
between ART and spontaneous groups. PlGF was significantly lower
in the ART group compared to the spontaneous group (0.92 vs 1.20
MoM; P⬍0.008) (Figure). This association remained significant after
controlling for maternal age, race, parity, BMI, screening blood pressure and chronic hypertension. There were no differences in PP13 or
in UPI between ART and spontaneous groups.
CONCLUSION: Low levels of serum PlGF, a proangiogenic protein, have
been linked to adverse pregnancy outcomes. Our study suggests that
despite normal placental perfusion as demonstrated by uterine artery
Doppler, angiogenic derangements early in gestation may contribute
to placenta-mediated adverse outcomes in ART pregnancies. These
findings may guide future research into the mechanisms by which
ART leads to an increased risk of adverse pregnancy outcomes.
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Hilary Gammill1, Christine Luu2, Rebecca Resnick2,
Suzanne Peterson3, J. Nelson4
1
University of Washington, Obstetrics and Gynecology, Seattle, WA, 2Fred
Hutchinson Cancer Research Center, Clinical Research, Seattle, WA,
3
Swedish Medical Center, Obstetrics and Gynecology, Seattle, WA,
4
University of Washington, Rheumatology, Seattle, WA
OBJECTIVE: Transplacental exchange of cells occurs bidirectionally between mother and fetus during pregnancy, establishing microchimerism
(Mc). Reports of maternal Mc (MMc) in umbilical cord blood (CB) at
delivery have varied in approach and estimates. Sensitive and accurate
assessment of MMc in CB can yield important information about the
physiology of cell exchange and is particularly relevant in the context of
increasing use of CB for hematopoietic cell transplant. We sought to
quantify cellular MMc in CB in normal term deliveries, at midgestation,
and in pregnancies complicated by preeclampsia (PE), using a well-established and sensitive quantitative PCR approach.
STUDY DESIGN: For women with uncomplicated term deliveries or PE,
maternal blood was collected prior to delivery, and CB was collected
by sterile venipuncture from a double-clamped cord segment. For
women undergoing midtrimester pregnancy termination, CB was
collected at the time of clinical cordocentesis. DNA was extracted
from Ficoll-purified blood mononuclear cells. Maternal and fetal
HLA genotyping was conducted, and MMc was quantified with QPCR assays targeting maternal-specific HLA alleles. Prevalence and
concentration of MMc was compared.
RESULTS: Overall detection of MMc was common (20/28 samples,
71%). Preliminary analysis suggested a trend toward higher detection
rates and concentrations by groups (Table), p⫽0.08.
CONCLUSION: Our data demonstrate frequent detection of MMc in CB. In
addition, we saw a trend toward increasing detection at later gestational
ages and in pregnancies complicated by PE. These findings prompt the
question whether differences in MMc according to pregnancy outcome
may contribute to fetal origins of disease. In addition, MMc in CB may
have important implications for transplantation, including effects on
graft-versus-tumor and graft-versus-host outcomes.
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205 Progesterone maintains a balance in collagen
metabolism while estrogen drives production in
cervical stromal cells
Huiling Ji1, Joshua Dahlke1, Edward Chien1
1
Warren Alpert School of Medicine of Brown University, Obstetrics and
Gynecology, Providence, RI
OBJECTIVE: Cervical remodeling is associated with extracellular matrix (ECM) remodeling. Collagen is the main ECM component in the
cervix contributing to tissue resistance. Collagen remodeling in the
cervix during gestation is thought to be hormone regulated and involves both the production of new protein as well as degradation of
existing fibers. We have previously shown that estrogen increases collagen secretion. The purpose of this study is to investigate the effects of
estradiol and progesterone on both collagen production and degradation in rat cervical stromal cells.
STUDY DESIGN: Primary rat cervical stromal cells were cultured using
an explant method approved by the IACUC. Passage 2-6 cells were
plated on six well plates in serum free media. Cells were treated for 3
days with estradiol or progesterone. Vehicle treated cells were used as
controls. Culture medium was collected for soluble collagen assay.
The ECM collagen that was adherent to the culture dish was extracted
using 0.5M acetic acid. Sircol Red Assay was used to quantify soluble
and ECM collagen. Western Blot was performed to evaluate the expression of Type I and III collagen, MMP2, MMP9 and MMP13. Zymography was used to detect MMP2 and MMP9 expression. Data was
analyzed using Sigma Stat.
RESULTS: Similar to prior studies estradiol increased soluble collagen
secretion while no change was observed with progesterone. Estradiol
and progesterone had similar effects on ECM collagen. Estradiol stimulated collagen I /III expression and decreased MMP2 expression.
Progesterone did not change Type I/III collagen expression but increased MMP13 expression. MMP9 expression did not change in either estradiol or progesterone treated rat cervical stromal cells.
CONCLUSION: Estradiol increased overall collagen production by stimulating protein secretion and polymerization while inhibiting the production of collagenases. Collagen content was maintained by progesterone by balancing production and degradation.
206 Maintenance of fetal growth and placental
cholesterol homeostasis by NDRG1
Jacob Larkin1, Xiao-Hua Shi1, Patrick Reidy1,
Huijie Sun1, Yoel Sadovsky1
1
University of Pittsburgh, Magee-Womens Research Institute, Dept of
OBGYN-RS, Pittsburgh, PA
OBJECTIVE: Cholesterol is required for placental steroid hormone synthesis and fetal development. LXR is a key transcriptional regulator of
cholesterol metabolism. We have previously shown that NDRG1 protects primary term human trophoblasts (PHTs) from hypoxic cell
death, and deletion of NDRG1 in mice causes fetal growth restriction
and hypoxia-induced intrauterine death. We tested the hypothesis
that placental cholesterol homeostasis is regulated by LXR, and that
LXR activity is influenced by NDRG1.
STUDY DESIGN: We cultured PHTs with the LXR agonist T0901317
(10␮M) or control, and quantified transcriptional changes and lipid
droplet formation by BODIPY staining. We transfected PHTs with
plasmids encoding either NDRG1 or control, and an LXR-driven luciferase reporter (N⫽3, all in vitro experiments). Finally, we crossbred
NDRG1 heterozygous mice, sacrificed at E18.5, and quantified cholesterol concentration in fetal serum.
RESULTS: LXR activation by T0901317 increased transcription of the
cholesterol efflux mediator ABCA1 (5.1-30.4 fold), as well as drivers of
fatty acid synthesis SREBP1c (10.3-28.7 fold), FAS (2.8-12.0 fold) and
ACC1 (2.9-4.9 fold), and increased lipid droplet formation. Overexpression of NDRG1 led to a 64% reduction in LXR-driven luciferase
expression. In mouse embryos, we observed a positive correlation
between serum cholesterol and weight (pairwise correlation coeffi-
Poster Session I
cient 0.2267, p⫽0.037). Using multivariable regression to control for
sex and litter size, we found that NDRG1 deletion diminished fetal
serum cholesterol concentration (p⫽0.002).
CONCLUSION: LXR promotes cholesterol efflux, fatty acid synthesis, and sequestration of intracellular lipids in human trophoblasts. NDRG1 inhibits
LXR, and is critical for sustained levels of fetal serum cholesterol and growth.
These findings suggest a mechanistic link between fetal development and
placental lipid metabolism, and that NDRG1 maintains fetal growth through
regulation of placental cholesterol homeostasis.
207 Changes in cardiovascular biomarkers throughout
pregnancy and the remote postpartum period
Janet Burlingame1, Hyeong Jun Ahn2, W. H. Wilson Tang3
1
University of Hawaii, John A. Burns School of Medicine, Obstetrics,
Gynecology and Womens Health, Honolulu, HI, 2University of Hawaii, John
A. Burns School of Medicine, Biostatistics Core, Honolulu, HI, 3Cleveland
Clinic Foundation, Cardiovascular Medicine, Cleveland, OH
OBJECTIVE: To determine normal changes in cardiovascular biomarkers
throughout pregnancy and the early and remote postpartum periods.
STUDY DESIGN: We performed a prospective observational study between November 2007 and January 2011. Pregnant women were recruited in the first or second trimesters of pregnancy and plasma samples were obtained at 6 to 7 time points until 6 to 12 months
postpartum. Immunoassays were used to obtain biomarker levels.
Women with hypertensive or cardiac disease were excluded from
analysis. Biomarker concentrations were summarized as means and
standard deviations. To account for missing data in longitudinal studies, linear mixed models were used to evaluate the changes of each
biomarker measure over time. As a post-hoc analysis, Tukey-Kramer
method was also used for multiple comparisons considering unequal
sample sizes. P values ⬍ 0.05 were regarded as statistically significant.
RESULTS: Figure 1 outlines the changes cardiovascular biomarkers
throughout pregnancy and makes comparisons to levels found in the
non-pregnant state (6 to 12 months postpartum). Significant changes
are seen in brain natiuretic protein (BNP), NT-proBNP and C-reactive protein (CRP) levels within 48 hours of delivery.
CONCLUSION: This large observational study confirms previous data and
presents new data highlighting changes in cardiovascular physiology during
pregnancy and the puerperium. sFlt peaks with labor and returns to baseline
by 6 to 12 weeks postpartum. PlGF peaks in the third trimester but has a
significant decrease with labor. CRP and NT-proBNP increases immediately
postpartum and returns to baseline by 6 to 12 weeks postpartum. This may
reflect volume status or primary increase in contractility. Vascular and cardiac biomarker levels fluctuate during pregnancy. With this data, variances
from norm may be used used to diagnose and clinically manage women with
cardiovascular disease during pregnancy. The research described was supported in part by NIH grants NCRR U54MD007584 and NIMHD
G12MD007601.
Biomarker measurements over seven
time points in pregnancy
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208 Echocardiographic changes in maternal cardiac
structure and function from the first trimester
to 6 months postpartum
1
3
Janet Burlingame , Hyeong Jun Ahn , Todd Seto
2
1
University of Hawaii, John A. Burns School of Medicine, Obstetrics,
Gynecology and Womens Health, Honolulu, HI, 2Queens Medical Center,
Center for Outcomes Research and Evaluation, Honolulu, HI, 3University of
Hawaii, John A. Burns School of Medicine, Biostatistics Core, Honolulu, HI
OBJECTIVE: To document temporal changes in diastolic function, systolic function and cardiac structure due to pregnancy.
STUDY DESIGN: We performed a prospective observational study of
pregnant women who were recruited in the first or second trimesters
of pregnancy, and echocardiograms were done at 6 to 7 time points
until 6 to 12 months postpartum. Women with hypertensive or cardiac disease were excluded from analysis. Linear mixed models were
used to evaluate the changes of ECHO measures over time accounting
for missing data. Tukey-Kramer method was also used for multiple
comparisons as a post-hoc analysis. P values ⬍ 0.05 were regarded as
statistically significant.
RESULTS: The Figure outlines the changes in diastolic function and the
changes in structure and systolic function throughout pregnancy and
the postpartum periods. Comparisons between pregnancy and nonpregnancy were also made using visit 7 (6-12 months postpartum as
the non-pregnant measurement). Diastolic function changes included significant decreases in E/A and isovolumic relaxation time
and an increase in transmitral E/peak medial velocity (E/E’) with a
return to baseline postpartum. There was a significant increase in left
atrial volume. There were trends toward increases in left ventricular
volume and mitral valve deceleration time.
CONCLUSION: As one of the largest prospective studies and one of the
few that follows participants out to 6 months postpartum, this study
confirms previous data and presents new data highlighting changes in
cardiovascular physiology during pregnancy and the puerperium. Diastolic changes reflected a general decrease in function with return to
baseline postpartum. Cardiac output peaks in the mid trimester in our
series versus third trimester as found in previous studies. These
changes are likely related to the concomitant increase in left atrial size
as reflective of preload increase. The research described was supported
in part by the NIH grants NCRR U54MD007584 and NIMHD
G12MD007601.
www.AJOG.org
209 Vitamin D deficiency: can non-pregnant
treatment norms be used in pregnancy?
Janyne Althaus1, Sarahn Wheeler1, Haitham Baghlaf1,
Harold Fox1, Irina Burd1
1
Johns Hopkins University School of Medicine, Gynecology and Obstetrics,
Baltimore, MD
OBJECTIVE: To date, no treatment guidelines exist for vitamin D deficiency in pregnancy. A common treatment for non-pregnant adults is
50,000 international units (IU) weekly, but many OBs are reluctant to
treat vitamin D deficiency for fear of toxicity. There are varied protocols among practices and still no consensus. The purpose of this study
was to determine if treatment of low vitamin D in pregnancy with
50,000 IU weekly leads to adverse perinatal outcomes.
STUDY DESIGN: This was a retrospective cohort study (2009-2011)
comparing vitamin D-deficient patients (⬍32ng/mL) treated with
50,000 IU weekly for 12 weeks (“treated”) during pregnancy with
patients given prenatal vitamins (PNV) only (“untreated”). Inclusion
criteria was D ⬍32 ng/mL at first prenatal visit. Exclusion criteria were
treatment for vitamin D deficiency within the past year or any regimens other than PNV or 50,000 IU weekly. Study data were derived
from electronic and paper charts. Outcomes examined included rates
of preterm delivery, pre-eclampsia, and cesarean section. Neonatal
outcomes studied were rates of NICU admission, Apgar ⬍7 at 5 minutes and umbilical cord pH. Power analysis was performed, and the
two groups were compared using standard statistics.
RESULTS: 231 patients met inclusion criteria: 117 in the untreated
group and 114 in the treated group. Maternal demographics did not
differ between the two groups in regards to age, parity, or diabetes
(p⬎0.05 for all). For obstetrical outcomes, cesarean section, pre-eclampsia, and preterm delivery rates did not differ between the two
groups (p⬎0.05 for all). For neonatal outcomes, there were no differences in NICU admissions, Apgar scores, or neonatal cord pHs between the two groups (p⬎0.05 for all).
CONCLUSION: This is the first study to demonstrate that treatment of
vitamin D deficiency with non-pregnancy treatment norms during
pregnancy does not lead to increased rates of adverse perinatal outcomes. Studies with a larger n are needed.
210 The association of insulin resistance and
inflammatory response in euglycemic women
Jennifer Walsh1, Fionnuala McAuliffe1
1
School of Medicine and Medical Science, University College Dublin,
National Maternity Hospital, UCD Obstetrics and Gynaecology, Dublin,
Ireland
OBJECTIVE: Chronic low levels of inflammation have linked to obesity,
diabetes and insulin resistance. We sought to assess the relationship
between cytokine tumor necrosis factor (TNF-␣) and insulin resistance in a healthy, euglycemic population.
STUDY DESIGN: This is a prospective study of 564 non-diabetic mother
and infant pairs. Maternal body mass index (BMI), TNF-␣, glucose
and insulin were measured in early pregnancy and at 28 weeks. Insulin
resistance calculated by HOMA index. At delivery birthweight was
recorded and cord blood analysed for fetal c-peptide and TNF-␣.
Bivariate correlations were assessed using Pearson’s correlation coefficient for normally distributed data and Spearman’s rho for nonparametric data.
RESULTS: Maternal BMI was positively correlated to maternal TNF-␣
at 28 weeks gestation. Early pregnancy TNF-␣ was related to insulin
resistance (HOMA) in early pregnancy (r⫽0.56,p⬍0.001) and at 28
weeks gestation (r⫽0.38, p⬍0.001). TNF-␣ at 28 weeks gestation was
positively correlated to HOMA in early pregnancy (r⫽0.44, p⬍0.001)
and at 28 weeks (r⫽0.58, p⬍0.001). Maternal early pregnancy insulin
resistance was related to fetal TNF-␣ as assessed in cord blood
(r⫽0.11, p⫽0.05). There was also a significant relationship between
maternal TNF-␣ at 28 weeks gestation and infant birthweight
(r⫽0.09, p⫽0.02).
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CONCLUSION: Our results, in a large cohort of healthy, non-diabetic
women have shown that insulin resistance, even at levels below those
diagnostic of gestational diabetes, is associated with maternal and fetal
inflammatory response. These findings have important implications
for defining the pathway for fetal programming of later metabolic
syndrome and childhood obesity.
211 Cardiotonic steroids induce an anti-angiogenic
profile in first trimester cytotrophoblast cells
Jessica Ehrig1, Kelsey Kelso1, Russell Fothergill1, Steven Allen1,
Richard Jones1, Thomas Kuehl1, Mohammad Uddin1
1
Scott & White Memorial Hospital / Texas A&M Health Science Center
College of Medicine, Department of Obstetrics & Gynecology, Temple, TX
OBJECTIVE: Preeclampsia (preE), a hypertensive disorder unique to
pregnancy, is characterized by abnormal placentation. Our investigative team has demonstrated that marinobufagenin (MBG), one of the
cardiotonic steroids (CTSs), inhibits these critical steps for normal
placental development: proliferation, migration and invasion of cytotrophoblast (CTB) cells. The aim of this study is to determine
whether CTSs induce anti-angiogenic effects in CTB cells.
STUDY DESIGN: Cells from the human extravillous CTB cell line Sw.71,
derived from first trimester chorionic villus tissue, were incubated
with 0.1, 1, 10, and 100 nM of each of three types of CTS (MBG,
Cinobufatalin and Ouabain) for 72 h. Thereafter, the levels of angiogenic factors, vascular endothelial growth factor (VEGF), placental
growth factor (PlGF) and anti-angiogenic factors, soluble fms-like
tyrosine kinase-1 (sFlt-1), soluble endoglin (sEnd) were measured in
the cell culture media by commercially available ELISA kits. Additionally, the expression of three CTB receptors, VEGF-1, angiogenic angiotensin type 1 receptor (AT1) and anti-angiogenic angiotensin type
2 receptor (AT2) were assayed using immunoblotting (western blot)
in cell lysates.
RESULTS: sFlt-1 and sEnd secretion were significantly increased while
VEGF and PIGF were decreased in the culture media of CTB cells
treated with ⭌1 nM of all three CTSs (*p⬍0.05 for each). The AT2
receptor expression was significantly up-regulated in ⭌ 1 nM CTStreated CTB cells, whereas AT2 and VEGF-1 receptor expressions were
down-regulated (*p⬍0.05 in each case).
CONCLUSION: Exposure of CTB cells to CTSs induces an anti-angiogenic profile by: (i) up-regulating AT2 receptor expression; (ii) downregulating AT1 and VEGF-1 receptor expression; (iii) increasing secretion of sFlt-1 and sEnd; and (iv) decreasing secretion of VEGF and
PlGF.
212 Circulating adipokines in twins and singletons - linking
the bridge from plurality to restricted fetal growth
Jiga Haas1, Eyal Sivan1, Eyal Schiff1, Yoav Yinon1,
Mordechai Dulitzky1, Eran Barzilay1, Rina Hemi2,
Clara Pariente2, Hannah Kanety2, Shali Mazaki-Tovi1
1
Sheba Medical Center, Tel-Hashomer, Department of Obstetrics and
Gynecology, Ramat Gan, Israel, 2Institute of Endocrinology, Sheba Medical
Center, Tel-Hashomer, Department of Obstetrics and Gynecology, Ramat
Gan, Israel
OBJECTIVE: The condensational view is that the uterine milieu is limited in its ability to nurture more than one fetus. Yet, the mechanism(s) by which attenuated twins growth is achieved has eluded elucidation. Adipokines have been implicated in fetal growth and
development. The aim of this study is to determine cord blood adiponectin and leptin in twins and singletons.
STUDY DESIGN: This is a case-control study included 2 groups of newborns, matched for gestational age and birthweight percentile: 1. singleton (n⫽60) and 2. twins (n⫽44). Adiponectin and leptin were
determined in arterial cord blood. Non-parametric and parametric
statistical methods were used.
RESULTS: Median adiponectin (31.5 vs. 63 ␮g/dL) and leptin (2.5 vs.
5.6 ng/dL) concentrations was lower in twins vs. singletons (p⬍0.001
for both comparisons). Among SGA newborns, median concentra-
Poster Session I
tion of adiponectin (p⫽0.02), but not leptin (p⫽0.1), was lower in
twins compared to singleton. Cord blood adiponectin was strongly
correlated with gestational age (p⬍0.001, r⫽0.55) and birthweight
(p⬍0.001, r⫽0.59), as was cord blood leptin (gestational age:
p⫽0.005, r⫽0.27; birthweight: p⬍0.001, r⫽0.44). Regression analysis
revealed that plurality, gestational age and birthweight were significantly and independently associated with cord blood adiponectin
concentrations after adjustment for maternal BMI, age and gender.
Similar regression model did not revealed association between plurality and cord blood leptin concentrations.
CONCLUSION: Twins pregnancies are associated with lower cord blood
concentrations of adiponectin, but not leptin, compared with singleton gestations. These findings suggest that alterations in adiponectin
concentrations may provide a molecular mechanism to account for
the growth disparity between twins and singleton. These findings support the concept that adipokines, particularly adiponectin may play a
role in the complex and intriguing process of fetal growth.
213 Acute ascending aorta occlusion leads to decreased
cerebral perfusion pressure in a fetal sheep
Heikki Huhta1, Juha Räsänen4, Juulia Junno1, Mervi Haapsamo1,
Tiina Erkinaro2, Roger Hohimer3, Lowell Davis3,
Ganesh Acharya5
1
Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland, 2Oulu
University Hospital, Anesthesiology, Oulu, Finland, 3Oregon Health and
Science University, Obstetrics and Gynecology, Portland, OR, 4Kuopio
University Hospital, Obstetrics and Gynecology, Kuopio, Finland,
5
University Hospital of Northern Norway, Obstetrics and Gynecology,
Tromso, Norway
OBJECTIVE: The fetal aortic isthmus (AoI) is the only arterial connection between the fetal right (RV) and left (LV) ventricles. In LV outflow obstruction, blood from the ductus arteriosus flows retrograde
across the AoI to supply fetal brain. We hypothesized that in acute
ascending aorta (AA) occlusion (AAO), RV cardiac output would
increase and maintain normal arterial pressure in the carotid artery.
STUDY DESIGN: Nine ewes underwent surgery at 115-135 gestational
days (term 145 days) for the placement of a vascular occluder around
fetal AA between the aortic valve and brachiocephalic artery. Fetal
carotid artery (CA) and jugular vein, and descending aorta (DAo) via
femoral artery were cannulated. After a 4-day recovery, fetal heart rate
(FHR), right (RVCO) and left (LVCO) ventricular cardiac outputs
were measured by ultrasonography. Pulmonary (Qp) volume blood
flow and systemic CO (combined cardiac output-Qp) were calculated
at baseline, 15 and 60 minutes after AAO, and 15 minutes after release
of AAO. Mean arterial blood pressures (mABP) from CA and DAo,
central venous (CVP) pressure, and CA pO2 were monitored.
RESULTS: All the data are presented as means (SD).* p⬍0.05, compared with baseline.
CONCLUSION: In fetal sheep, acute occlusion of AA leads to increased
RV cardiac output and decreased LV and systemic cardiac outputs,
and pulmonary volume blood flow. Fetal arterial blood pressure in the
descending aorta is maintained. However, carotid artery blood pressure decreases during AA occlusion. Our results suggest that, at least
in acute conditions, retrograde blood flow shunting across AoI is not
able to maintain normal cerebral perfusion pressure.
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214 Left ventricular Tachykinin 1 gene expression is
increased in chronically anemic fetal sheep
Juulia Junno4, Juha Räsänen3, Jennifer Farwell2, Roger Hohimer2,
Olli Vuolteenaho1, Lowell Davis2, Sonnet Jonker2
1
University of Oulu, Physiology, Oulu, Finland, 2Oregon Health and Science
University, Obstetrics and Gynecology, Portland, OR, 3Kuopio University
Hospital, Obstetrics and Gynecology, Kuopio, Finland, 4Oulu University
Hospital, Obstetrics and Gynecology, Oulu, Finland
OBJECTIVE: Chronically anemic fetuses increase cardiac output by
50%. Anemia-induced cardiac remodeling is associated with diminished isovolumic contraction velocity acceleration (IVCVacc) and
isovolumic relaxation velocity deceleration (IVRVdec) in the left ventricle indicating reduced ventricular contractility and relaxation. We
therefore sought to determine if there were changes in genes that affect
ventricular function in chronically anemic fetuses.
STUDY DESIGN: 7 fetal sheep with twin gestations had catheters placed
surgically and 1 randomly selected twin was made anemic by daily
isovolumic hemorrhage for 8 days. At 126 days gestation echocardiographic studies were performed under anesthesia and tissues from the
right (RV) and left (LV) ventricles were obtained. Agilent’s 8x15K
Sheep Gene Expression array with greater than 2 fold changes were
selected for qRT-PCR.
RESULTS: Hematocrit was reduced in anemic fetuses as compared to
controls 13.1 (2.5) vs 34.9 (5.2)% means (SD) as well as oxygen content 2.3 (0.4) vs 8.4 (1.7) ml/dl. LV and RV IVCVacc and IVRVdec,
and MRNA expression/18s are shown below. All the data are presented as means (SD).* p⬍0.05.
CONCLUSION: Neither changes in ␤-adrenergic receptor 1, phospholamban, nor troponin C account for the decrease in left ventricular
contractility and relaxation in anemic fetuses. Increased Tachykinin 1
gene expression through substance P and neurokinin A may be important in mediating decreased ionotropy and lusitropy in chronic
fetal anemia.
215 Maternal biomarkers of adiposity are
associated with infant birthweight
Kataneh Salari1, Anjel Vahratian2, Marjorie Treadwell1
1
University of Michigan Health System, Department of Obstetrics and
Gynecology, Ann Arbor, MI, 2University of Michigan Health System,
Department of Obstetrics and Gynecology, Ann Arbor, MI
OBJECTIVE: The purpose of this study is to evaluate the association
between maternal biomarkers of adiposity and infant birthweight.
STUDY DESIGN: Fifty patients in the first trimester of pregnancy receiving care through the University of Michigan Health System were recruited to participate into the study. Maternal morphometry (weight,
height) was obtained at the first visit. Biomarkers related to maternal
adiposity were drawn (glucose, insulin, adiponectin, leptin, LDL,
HDL, total cholesterol, triglycerides, hemoglobin A1C) in each trimester. Maternal visceral fat indices (preperitoneal and subcutaneous
fat measurements) were also measured in each trimester. Information
regarding infant birthweight was obtained by reviewing patient
records.
RESULTS: Forty-five patients completed the study after initial enrollment. The average age of subjects enrolled was 30.4 years. The mean
birthweight was 3429 g. Using linear regression analysis, positive determinants of birthweight were gestational age, maternal fasting glucose values in the third trimester, and maternal triglyceride levels in
the first trimester. For every 10 mg/dL increase in maternal fasting
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glucose level and triglyceride level, there was a 300 g (P ⫽ 0.005) and
a 69 g (P ⫽ 0.008) increase in birthweight, respectively. Maternal
adiponectin levels in the first and second trimester were negatively
associated with birthweight. For every 1 ug/mL increase in maternal
adiponectin level, there was a 33-37 g decrease in birthweight (P ⫽
0.05). There was no association between birthweight and the remainder of maternal biomarkers of adiposity, morphometric measurements, or maternal visceral fat indices.
CONCLUSION: Maternal glucose, triglycerides, and adiponectin levels
were significantly associated with infant birthweight, consistent with
results of a recently reported study of maternal biomarkers of adiposity in pregnancy. Thus, biomarkers that accurately reflect the maternal
metabolic state may help better identify pregnant women at risk for
fetal macrosomia.
216 Relationship of mean arterial pressure, uterine artery
Doppler and placental vascular indices: placental
response to abnormal maternal perfusion
Katherine Goetzinger1, Alison Cahill1, Linda Odibo1,
George Macones1, Anthony Odibo1
1
St. Louis, MO
OBJECTIVE: Maternal mean arterial pressure (MAP), uterine artery
(UA) Doppler, and placental vascular indices have been proposed as
first-trimester screening tools for pregnancies at high risk for preeclampsia (PEC); however, their relationship is unknown. We sought
1) to evaluate the relationship between first-trimester UA Doppler
and measures of placental perfusion and 2) to determine if these measures are altered by MAP.
STUDY DESIGN: This is a prospective cohort study of singleton gestations presenting at 11-14 weeks for aneuploidy screening. MAP was
calculated at the initial visit. Placental vascularization index (VI), flow
index (FI), and vascularization flow index (VFI) were obtained with
4-D power Doppler images of the placenta using the VOCAL program. Mean UA pulsatility indices (PI) were calculated. Only pregnancies with normal outcomes were analyzed in order to establish a
physiologic basis for any relationship. Placental vascular indices were
compared between women with abnormal (⬍70 mmHg or ⬎110
mmHg) and normal MAP using Mann-Whitney U statistics. Pearson
correlation coefficients were used to evaluate the association between
UA PI and placental vascular indices.
RESULTS: Of 599 patients, 36 (6.0%) had abnormal MAP. Both FI
(47.7 vs 43.8, p⫽0.04) and VFI (9.3 vs 6.1, p⫽0.03) were significantly
higher in women with low MAP compared to normal MAP; however,
there was no significant difference in any of the placental vascular
indices in women with high MAP compared to normal MAP (Table).
There was no significant correlation between UA PI and any placental
vascular index (VI: r⫽ ⫺0.05, p⫽0.22; FI: r⫽ ⫺0.07, p⫽0.07; VFI: r⫽
⫺0.05, p⫽0.21).
CONCLUSION: A compensatory increase in placental blood flow, reflected by increased vascular indices, in patients with low MAP suggests these two parameters are not independent; however, the lack of
correlation between UA Doppler and placental vascular indices support their combined use as screening tools for PEC.
www.AJOG.org
Poster Session I
219 Profiling of microRNA by next-gen deep
sequencing reveals novel and modifiable
miRNA species in human breast milk
Kjersti Aagaard1, Erika Munch1, R. Alan Harris3, Mahmoud
Mohammad2, Ashley Benham6, Sasha Pejerrey4, Preethi
Gunaratne5, Morey Haymond2
1
Baylor College of Medicine, Maternal-Fetal Medicine, Houston, TX, 2Baylor
College of Medicine, Pediatrics, Houston, TX, 3Baylor College of Medicine,
Molecular and Human Genetics, Bioinformatics Research Lab, Houston, TX,
4
Baylor College of Medicine, Molecular and Cell Biology, Houston, TX,
5
Baylor College of Medicine, Pathology, Houston, TX, 6University of
Houston, Biology and Biochemistry, Houston, TX
*Data expressed as medians and interquartile ranges.
217 WITHDRAWN
218 Does fetal gender play a role in the
detection of fetal microchimerism?
Kimberly Ma1, J. Nelson2, V. Gadi3, Hilary Gammill1
1
University of Washington, Obstetrics and Gynecology, Seattle, WA,
University of Washington, Rheumatology, Seattle, WA, 3University of
Washington, Medical Oncology, Seattle, WA
2
OBJECTIVE: The protective association between parity and breast cancer appears to be stronger in women with sons compared to daughters. The underlying mechanism is unknown and has been hypothesized to be immunologic or endocrinologic. During pregnancy,
transplacental cellular exchange results in microchimerism (Mc). Mc
can persist and is associated with protection from breast cancer. We
sought to evaluate whether fetal Mc concentration varies according to
fetal gender, thereby potentially contributing to the differential protection of parity with sons versus daughters.
STUDY DESIGN: Pregnant women and parous, nonpregnant women
were studied. Blood samples were obtained, and DNA was extracted
from Ficoll-purified peripheral blood mononuclear cells. Maternal
and fetal HLA genotyping was conducted, and fetal Mc was quantified
employing a panel of Q-PCR assays targeting fetal-specific HLA alleles. Detection of fetal Mc was compared according to fetal gender.
Among the pregnant women, current fetal gender was used to define
male versus female exposure. Prior birth of any male child was considered male exposure in nonpregnant, parous women.
RESULTS: 97 subjects were studied, 35 during pregnancy and 62 outside of pregnancy. There were no differences in the detection of fetal
Mc according to fetal gender. In pregnant women, 6.7% (1/15) of
women with a male fetus had fetal Mc detected compared to 10.0%
(2/20) with a female fetus (p⫽0.73). Outside of pregnancy, fetal Mc
was detected in 18.9% (7/37) of those with a history of a male fetus
compared to 20.0% (5/25) of those with only a female fetus (p⫽0.92).
CONCLUSION: We observed no association of fetal gender with detection rates of fetal Mc during pregnancy or in parous women. It is
possible that fetal Mc may contribute to known epidemiological findings of differential protection of parity for diseases according to offspring gender. However, our findings suggest that if this is the case,
functional, rather than quantitative differences in Mc by fetal gender
are more likely to underlie a relationship.
OBJECTIVE: While breast milk has unique health advantages for infants, the
mechanisms by which it regulates the physiology of newborns are incompletely understood. microRNAs (miRNAs), a class of noncoding RNAs, are
criticaltranscellularmediatorsofposttranscriptionalgeneregulation.Wehypothesized that breast milk in general, and milk fat globules in particular,
contain significant numbers of known and limited novel miRNA species detectable with massively parallel sequencing.
STUDY DESIGN: Extracted RNA from 3 well-characterized cohorts of lactating women (before and after rhGH, high glucose vs galactose diet
modified, or high fat vs high carbohydrate diet modified; Figure panel A)
was smRNA-enriched. smRNA was subjected to massively parallel shotgun sequencing, and robustly analyzed on customized pipelines to identify functional targets. Data were validated with qPCR.
RESULTS: smRNA-Seq was performed to generate 124,110,646 36-nt
reads, including 308 of 1018 (29%) known mature miRNAs (miRBase
16.0). We identified 21 putative novel miRNAs, of which 12 were
validated. Collectively, these miRNAs target 9074 genes; the 10 most
abundant of these predicted to target 2691 genes with enrichment for
transcriptional regulation of metabolic and immune responses (panels B&C). Moreover, expression of several novel miRNAs were significantly and specifically altered following maternal high-fat diet modifications (p⬍0.05).
CONCLUSION: We have shown for the first time that novel (and known)
miRNAs are enriched in breast milk, and expression of several novel
miRNA species is regulated by a high fat maternal diet. Based on
robust pathway mapping, our data supports the notion that these
maternally secreted miRNAs-which are stable in the milk fat globulesplay a regulatory role in the infant and account in part for the health
benefits of breast milk. We speculate that regulation of these miRNA
by a high fat maternal diet enables modulation of fetal metabolism to
accommodate significant dietary challenges.
Identification and functional analysis of
novel miRNA in human breast milk
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220 Hair cortisol is a reliable marker of maternal and
fetal hypothalamic-pituitary-adrenal (HPA) axis
activity throughout pregnancy
M Camille Hoffman1, Kimberly D’Anna-Hernandez3,
Randal Ross2, Mark Laudenslager2
1
University of Colorado, Obstetrics & Gynecology, Denver, CO, 2University
of Colorado, Psychiatry, Denver, CO, 3California State University,
Psychology, San Marcos, CA
OBJECTIVE: Studies using various HPA axis markers have been inconclusive as to critical times in gestation where stress is detrimental and
the appropriate biomarker with which to assess perinatal stress. Maternal salivary cortisol assessment appears promising, yet data collection requires that subjects comply with multiple precise time points.
Additionally, no non-invasive marker of fetal cortisol status currently
exists. The objective of this study was to determine whether maternal
and fetus cortisol levels could be assessed via human hair, a stable
means to access chronic HPA axis function.
STUDY DESIGN: Cortisol levels were determined from the hair and saliva of 30 healthy women 3 times points in pregnancy: 15-18 and 27-30
weeks, and postpartum. Saliva was assessed 4times/day for 3 consecutive days. Neonatal hair cortisol levels were assessed post-delivery,
representing cortisol deposited in utero. Maternal perception of stress
was measured at each time point.
RESULTS: Hair and salivary cortisol levels increased over the course of
gestation. Pearson’s correlations were used to examine hair cortisol
levels vs. area under the curve salivary cortisol, with significance in the
2nd and 3rd trimester (R2⫽0.47, 0.58; p⫽0.04, 0.01, respectively).
Neonatal cortisol levels were higher than maternal hair cortisol levels
postpartum (185.9⫾71.2pg/mg vs. 13.1 ⫾ 13.3pg/mg, p ⬍0.001).
Subject compliance with salivary cortisol collection was poorer than
hair collection. No significant correlations were noted between hair or
salivary cortisol and maternal perception of stress.
CONCLUSION: Hair is a valid and useful tool to measure cortisol and
long-term maternal and fetal HPA axis function during pregnancy.
Determination of neonatal hair cortisol immediately postpartum provides a non-invasive assessment of fetal cortisol status. This method of
cortisol assessment is useful in determining critical periods of stress
exposure during pregnancy for mothers and babies.
221 Platelet reactivity in recurrent miscarriage
patients during pregnancy
Mark Dempsey1, Karen Flood1, Naomi Burke1, Brian Cotter1,
Louise Fay2, Patricia Fletcher1, Aoife Murray1,
Michael Geary2, Dermot Kenny3, Fergal Malone1
1
Royal College Of Surgeons in Ireland, Obstetrics & Gynaecology, Dublin,
Ireland, 2Rotunda hospital, Obstetrics & Gynaecology, Dublin, Ireland,
3
Rotunda hospital, Molecular and Cellular Therapeutics, Dublin, Ireland
OBJECTIVE: To critically evaluate platelet function in patients with a
history of unexplained recurrent miscarriage (RM) during a subsequent successful pregnancy.
STUDY DESIGN: A prospective longitudinal study was performed to
compare 30 patients with a history of unexplained recurrent first trimester pregnancy loss and 30 healthy age-matched controls during
pregnancy. Exclusion criteria included the use of anti-platelet medications such as aspirin and medical conditions that can affect platelet
function. Platelet reactivity was determined using a modified assay of
light transmission aggregometry where multiple agonists at different
concentrations over successive time-points were used. Dose -response
curves were created and overall best curve fits were calculated and
compared using graphpad prism software.
RESULTS: As previously shown, the healthy controls demonstrated an
increase in platelet aggregation response as pregnancy progresses. In
contrast, the platelet reactivity in patients with a history of unexplained RM peaked at 12-14 weeks gestation highlighted by the increased aggregation response to epinephrine (p⫽ 0.0008) and collagen (p ⬍0.0001).This increased platelet reactivity did not increase
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further as pregnancy progressed. Indeed, when compared to the
healthy cohort in the third trimester there was significantly decreased
platelet aggregation response to arachidonic acid (p ⬍0.0001), epinephrine (p ⬍0.0001) and Thrombin Receptor Activating Peptide
(p ⬍0.0001).
CONCLUSION: Even though the majority of the RM patients recruited
had normal pregnancy outcomes we have demonstrated that their
platelet reactivity is markedly altered throughout pregnancy when
compared to healthy controls. Further investigation is warranted to
characterise this difference and to guide future interventions. We also
note that the use of empiric aspirin in RM patients beyond the first
trimester is questionable due to the demonstration of reduced platelet
reactivity as the pregnancy progresses.
222 Maternal obesity is associated with alterations in
thyroid hormone regulation in the placenta
Melissa Suter1, Elena Sbrana2, Kiara Collins1,
Adrienne Murphy1, Kjersti Aagaard1
1
Baylor College of Medicine, Division of Maternal-Fetal Medicine,
Departments of Obstetrics and Gynecology and Cell and Molecular Biology,
Houston, TX, 2University of Texas Medical Branch, Pathology, Galveston,
TX
OBJECTIVE: While obesity is associated with adverse health outcomes
for the individual, obesity during pregnancy bears unique maternal
and fetal risks. Newborns of obese and overweight women are more
likely to be large for gestational age and are at greater risk for obstetric
complications as well as later in life metabolic disease. Using our well
characterized non-human primate (NHP) model of maternal high fat
diet consumption we have identified fetal thyroid hormones (THs)
and their associated proteins as likely molecular mediators between
maternal obesity and fetal overgrowth. We have found that fetal macaques have significantly disrupted hepatic expression of TH associated genes as well as reduced free T4 when exposed to maternal high
fat diet. We aimed to extend the findings from our NHP model to
humans. We hypothesized that maternal obesity would be associated
with changes in levels of placental TH transporters, deiodinases and
receptors.
STUDY DESIGN: Placentas from 10 normal weight (pre-pregnancy
BMIⱕ25) and 10 obese (pre-pregnancy BMIⱖ30) gravidae were uniformly collected immediately at delivery. A uniform 3 cm excisional
block at a 4 cm distance from the umbilical cord was obtained and
processed for immunohistochemistry (IHC). A similar section was
obtained and snap frozen at ⫺80°C. RNA was extracted, converted to
cDNA and used for qPCR from the frozen samples.
RESULTS: The TH transporter MCT8 is upregulated in the obese placenta compared with normal weight women as observed both by
qPCR (1.5-fold, p⫽0.004) and IHC (1.9 vs. 2.5, p⬍0.001). Furthermore, we found an increase in the deiodinase which inactivates bioactive TH, DIO3 (2-fold, p⫽0.012). The TH receptor, THRA, was
similarly increased with maternal obesity (1.5-fold, p⫽0.014).
CONCLUSION: These data demonstrate that maternal obesity is associated with an increase in TH related gene expression in the placenta.
We speculate that this serves as a potential novel mechanistic link
relating maternal obesity with fetal hypothyroidism and fetal overgrowth.
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Poster Session I
224 Role of (pro)rennin and its receptor in pathogenesis of
preeclampsia: a rat model and human patients studies
Immunohistochemistry of placenta from lean and
obese gravidae (anti-MCT8 staining)
Kelsey Kelso1, Russell Fothergill1, Steven Allen1, Richard Jones1,
Thomas Kuehl1, Mohammad Uddin1
1
Scott & White Memorial Hospital / Texas A&M Health Science Center
College of Medicine, Department of Obstetrics & Gynecology, Temple, TX
223 Progesterone inhibits cervical tissue formation in a
3D culture system in a dose-dependent fashion
Michael House1, Serkalem Tadesse3, Errol Norwitz1,
David Kaplan2
1
Tufts Medical Center, Maternal Fetal Medicine, Boston, MA, 2Tufts
University, Biomedical Engineering, Medford, MA, 3Yale University,
Obstetrics and Gynecology, New Haven, CT
OBJECTIVE: Progesterone supplementation can prevent preterm birth
in some women with cervical shortening, suggesting that progesterone may directly affect remodeling of cervical tissue. A previously
described 3D culture system was used to test progesterone effects on
cervical tissue synthesis.
STUDY DESIGN: Fibroblasts were obtained from cervical biopsies of
non-pregnant premenopausal women undergoing hysterectomy for
benign disease. Fibroblasts from passage 5 were seeded on silk sponge
scaffolds and cultured in spinner flasks using previously validated
culture system (House, Tissue Eng Part A, 2012). Culture media included DMEM ⫹ 5% charcoal-stripped FBS ⫹ estradiol 10-8M. Five
progesterone conditions were used: 0 (vehicle), 10-9M, 10-8M,
10-7M and 10-7M ⫹ 10-6M mifepristone. Scaffolds were cultured for
4 weeks and assayed for collagen production (hydroxyproline), histology and immunohistochemistry (IHC). Cervical-like tissue was assayed for estrogen and progesterone receptors using IHC and western
blot. Experiments were repeated in triplicate with cells from 3 different women.
RESULTS: Cervical cells reliably synthesized cervical-like tissue in 3D.
Both progesterone and estrogen receptors were documented by IHC
and western blot. A dose-dependent inhibitory effect of progesterone
was observed. The highest progesterone concentration (10-7M) was
associated with the least amount of collagen synthesis. Collagen synthesis increased progressively as progesterone concentration decreased (p⬍.01). This effect was abrogated by mifepristone (p⬍.05).
Differences in tissue morphology on histology and IHC correlated
with collagen synthesis.
CONCLUSION: Progesterone inhibited the synthesis of cervical-like tissue in 3D culture from cervical fibroblasts in a dose-dependent manner. This effect was abrogated by mifepristone, a progesterone receptor antagonist. This hormonally-responsive in vitro culture system
could be used to study the mechanism of progesterone effects on the
cervix.
OBJECTIVE: Preeclampsia (PreE), a syndrome manifesting with hypertension, proteinuria, and edema, is a leading cause of maternal and
fetal morbidity and mortality. While preE triggers are likely many and
elusive, the renin-angiotensin system (RAS) has been implicated in
preE pathogenesis. However, there is no data showing involvement of
(pro)renin and its receptor.
STUDY DESIGN: We recruited 32 preE and 57 normal pregnant consenting patients. (Pro)renin levels were assayed in plasma samples
using an ELISA kit. A rat model of preE was used to evaluate the role
of (pro)renin and its receptor. We used normal pregnant rats (NP,
n⫽10) and pregnant rats receiving weekly injections of desoxycorticosterone acetate and drinking water as 0.9% saline (PreE, n⫽10).
The plasma and placental levels of (pro)renin were assayed by ELISA.
The placental levels of (pro)renin receptor and ERK1/2 phosphorylation were measured by immunoblotting.
RESULTS: The mean plasma (pro)renin of 0.27 ⫾ 0.04 ␮g/mL in preE
patients differ (p ⬍ 0.001 using Student’s t test) from 0.15 ⫾ 0.05
␮g/mL in those without preE. Both plasma and placental levels of
(pro)renin were higher (p ⬍ 0.001 using Kolmogorov-Smirnov test)
in PreE rats compared to NP (Plasma (pro)renin for NP:0.21 ⫾ 0.04
and PreE:0.49 ⫾ 0.09 pg/mL; placental (pro)renin for NP:152 ⫾ 79
and PreE:302 ⫾ 42 ng/g tissue). In addition to serving as a source of
(pro)renin, the placenta is also a site for signaling as ERK1/2 phosphorylation is greater (p⬍0.05) in placental tissue of preE rats.
CONCLUSION: Together with the upregulation of ERK1/2 phosphorylation in placenta of the rat model, there is now evidence of (pro)renin
and its receptor associated novel RAS activation to play a role in preE
pathogenesis through (pro)renin receptor-mediated detrimental cellular signaling at the placental boundary. This offers an opportunity
for interventional treatments with signal inhibitors.
225 Estimation of maternal cerebrovascular hemodynamics
following routine delivery related blood loss
Nicole Hall1, Sina Haeri1, Rodrigo Ruano1, Teelkien Van Veen2,
Hossein Golabbakhsh1, Qian Chen1, Yisel Morales1,
Chawla Mason3, Michael Belfort1
1
Baylor College of Medicine & Texas Children’s Hospital, Obstetrics &
Gynecology, Houston, TX, 2University Medical Center Groningen,
Obstetrics & Gynecology, Groningen, Netherlands, 3Baylor College of
Medicine, Anesthesiology, Houston, TX
OBJECTIVE: Our aim was to determine whether acute blood loss at
delivery of ⬍ 1000ml is associated with any measurable maternal cerebrovascular hemodynamic effects as measured by transcranial Doppler ultrasound (TCD) of the middle cerebral artery (MCA).
STUDY DESIGN: In this prospective cohort study of normotensive
healthy pregnant women, we performed power M-mode maternal
TCD assessment of the MCA before and 24 hours after delivery (either
vaginal or cesarean section) and correlated (Spearman correlation)
the estimated blood loss (EBL) and the change in Hg/Hct with systolic
(PSV), mean systolic (MV) and diastolic (MDV) velocities, as well as
with various hemodynamic indices: pulsatility (PI) and resistance
(RI) indices, resistance-area-product (RAP), cerebral flow index
(CFI), and the cerebral perfusion pressure (CPP).
RESULTS: A total of 20 cases (18 vaginal and 2 cesarean deliveries),
ranging in gestational age from 37 to 41 weeks (39.1 ⫹/⫺ 1.5 weeks),
were studied. EBL did not correlate with the measured or calculated
cerebral hemodynamic parameters. Mean pre and post-delivery hemoglobin (Hb)/hematocrit (Hct) values were 11.6 ⫹/⫺ 1.2/34.8 ⫹
3.2, and 10.1 ⫹/⫺ 1.5/30.5 ⫹ 4.4, respectively. Pre-delivery Hg and
Hct were negatively correlated increased MCA PSV and MDV reflect-
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ing decreased viscosity and increased flow (p⫽ 0.04 and 0.04, respectively), the PI, RI, and CPP were not correlated within the range studied. The degree of change in Hg and Hct after a routine delivery was
not significantly associated with changes in PSV, MDV, PI, RI, CPP,
RAP, or CPP.
CONCLUSION: We have established that delivery related blood loss of ⬍
1000ml is not likely to be associated with significant cerebrovascular
hemodynamic effects. This suggests that normal healthy women will
retain functional cerebral autoregulation with this degree of blood
loss. Future studies on the interplay between postpartum hemorrhage
and maternal disease states can now be performed focusing on maternal cerebrovascular hemodynamics.
226 Maternal hemodynamic changes in multiple
gestation pregnancy: a longitudinal, pilot study
Noor Niyar Ladhani1, Natasha Milligan2, Jose Carvalho3,
Prakesh Shah4, Xiang Ye5, Mary-Jean Martin2,
Anne Jordan2, Kellie Murphy6
1
University of Toronto, Sunnybrook Health Sciences Centre, Department of
Obstetrics and Gynaecology, Toronto, ON, Canada, 2Mt Sinai Hospital,
Department of Obstetrics and Gynaecology, Toronto, ON, Canada,
3
University of Toronto, Mt Sinai Hospital, Departments of Anaesthesia and of
Obstetrics and Gyanecology, Toronto, ON, Canada, 4University of Toronto,
Mt Sinai Hospital, Departments of Paediatrics and of Health Policy,
Management, and Evaluation, Toronto, ON, Canada, 5Mt Sinai Hospital,
MICare Research Centre, Toronto, ON, Canada, 6University of Toronto, Mt
Sinai Hospital, Departments of Obstetrics and Gynaecology, and of Health
Policy, Management, and Evaluation, Toronto, ON, Canada
OBJECTIVE: Maternal hemodynamic parameters change significantly
during pregnancy. These changes are exaggerated in pregnancies involving multiple gestations. Cardiac output is thought to increase
through gestation and return to baseline in the postpartum period.
The extent of this change and the timing of return to baseline are not
well characterized. We sought to longitudinally assess the changes in
maternal cardiovascular hemodynamics in women with singletons,
twins, and triplets, throughout gestation and in the postpartum
period.
STUDY DESIGN: Women were recruited in the first trimester and hemodynamic variables were measured at four points: 10-14 weeks,
24-28 weeks, 32-26 weeks, and 4-8 weeks postpartum. Measurements
were obtained in twenty women using a bioreactance-based non-invasive cardiac output monitor, the use of which has been validated in
pregnancy.
RESULTS: Cardiac output rose during pregnancy, peaking in twin
pregnancies (n⫽5) at the 24-28 week visit, and in singleton (n⫽10)
and triplet (n⫽5) pregnancies at the 32-36 week visit. The median
peak cardiac output was highest in the triplet group (8.44 L/min).
Postpartum cardiac output remained higher in the triplet group (6.08
L/min), than in the twin and singleton groups (4.53 L/min and 5.08
L/min). The percent change in cardiac output between the first trimester and the postpartum visit was highest in the triplet group
(92%), compared to the twin and singleton groups (21% and 53%).
CONCLUSION: Cardiac output increased through gestation and peaked
in the late second or third trimester. The return to baseline was slower
in the multiple gestation groups. The percent change between the first
visit and the postpartum visit was highest in the triplet group, showing
a slower recovery to maternal baseline. The results of this pilot, prospective longitudinal study display the cardiovascular stress imposed
on women into the postpartum period and gives insight into the hemodynamic changes that occur in multiple gestation pregnancies.
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227 Maternal hemodynamics by impedance cardiography
for normal pregnancy before and after vaginal or cesarean
delivery
Rachael Morris1, Laura Rush1, Pamela Blake1, Belinda Ellis1,
Imran Sunesara2, Marie Darby1, Justin Brewer1, James Martin1
1
University of Mississippi Medical Center, Obstetrics and Gynecology,
Jackson, MS, 2University of Mississippi Medical Center, Biostatistics,
Jackson, MS
OBJECTIVE: Impedance cardiography (ICG) is a non-invasive, validated method to accurately assess maternal hemodynamics. We desired to establish normative values for pregnancy during the second
and third trimester and 24 to 48 hours postpartum; these data provide
a basis to compare values obtained in hypertensive/cardiac pregnant
patients.
STUDY DESIGN: Prospective observational study of normotensive
pregnant patients (n⫽168) using Cardiodynamics/Sonosite impedance cardiography performed at specific times during gestation. Antepartum testing was done at (a) 20-27 weeks, (b) 28-33 weeks, and (c)
34-40 weeks. Postpartum testing was done in four groups of patients:
(e) 6-23 hours after vaginal delivery; (f) 24-48 hours after vaginal
delivery; (g) 6-23 hours postcesarean; and (h) 24-48 hours postcesarean; 25 patients were recruited for each of the 7 groups. Hemodynamic as well as demographic and obstetric/neonatal data were recorded for all patients. Data analysis performed using STATA
software package.
RESULTS: Maternal cardiac output (CO) and heart rate (HR) are noted
to increase with advancing gestation; both decrease during the first 48
hours postpartum (see table). Maternal mean arterial pressure (MAP)
and the systemic vascular resistance index (SVRI) both increased over
the course of gestation and were sustained for 48 hours postpartum in
these normotensive parturients. Thoracic fluid content (TFC) increased immediately postpartum in normotensive patients following
vaginal and cesarean delivery.
CONCLUSION: These ICG data from normotensive pregnant patients
before and immediately following vaginal or cesarean delivery provide normative baseline information for comparing data obtained in
hypertensive or otherwise complicated pregnant patients during the
second half of pregnancy and immediately postpartum (48 hours).
Maternal hemodynamics
228 Micro PET imaging in pregnancy: acute and
chronic maternal nutrient availability alters
in vivo fetal and tissue glucose uptake
Scarlett Karakash1, Hye Heo1, Wade Koba2, Yongmei Zhao1,
Allison Berdichevsky1, Eugene Fine2, Francine Einstein1
1
Montefiore Medical Center/Albert Einstein College of Medicine, Obstetrics
& Gynecology and Women’s Health, Bronx, NY, 2Montefiore Medical
Center/Albert Einstein College of Medicine, Nuclear Medicine, Bronx, NY
OBJECTIVE: Micro Positron Emission Tomography (mPET) is a noninvasive,functional imaging tool used to quantify in vivo tissue glucose uptake (GU). Our goal was to measure the effect of chronic maternal diets and acute lipid load on fetal-placental GU and maternal
cardiac GU in pregnant dams using mPET.
STUDY DESIGN: Four groups of age-matched, female SD rats were studied:1)CON(n⫽6)standard chow ad libitum, 2) CR(n⫽9)Calorie Restriction,pair-fed 60%CON kcal/d of standard chow from D11 of gestation, 3) WD(n⫽7)Western Diet from 3 weeks through gestation,
and 4) ALL(n⫽7) Acute Lipid Load,normal dams fed an oral lipid
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load 4 hours prior to study. On D19 of gestation, dams were given IV
radiolabeled 18F-fluorodeoxyglucose to measure tissue GU and
mPET was performed. ASIPRO (Siemens) software was used to localize regions of interest (ROI), defined as 5 image slices representing
maximum concentration of fetus/placenta. For each animal’s ROI,
the mean GU was calculated in SUVs (standard uptake value). A
3-point scale quantified maternal cardiac GU (0⫽none, 1⫽minimal,
2⫽maximal).
RESULTS: CON weighed more than CR (302⫾8g vs 268⫾14g,p⬍0.01)
and WD more than Con and ALL(384⫾9.6g vs 302⫾8g, 297⫾18g
p⬍0.01). Pup weight and litter size were similar between groups. CR
and WD dams demonstrated increased fetal-placental GU and decreased maternal cardiac GU compared to CON [Figure]. Similarly, in
response to acute lipid load, ALL dams had increased fetal-placental
GU with a decrease in maternal cardiac GU [Table].
CONCLUSION: Similar to acute lipid load, chronic maternal CR and
WD results in increased fetal-placental GU and decreased maternal
cardiac GU. These findings suggest that both calorie restriction and
chronic high fat feeding in pregnancy induces greater maternal reliance on lipid oxidation, therefore making more glucose available for
transport to the fetus. In pregnant models, mPET may be a valuable
tool not only to measure in vivo glucose transport, but also transport
of other nutrients, such as lipids.
Poster Session I
variable linear regression model was created to control for demographic and dietary variations.
RESULTS: 280 subjects were enrolled in the study. The median urinary
iodide level in this population was 130.5 mcg/L (IQR 74 mcg/L). Iodide deficiency (⬍100 mcg/L) was seen in 35 % of the pregnant patients. (98/280) Severe iodide deficiency (⬍50 mcg/L) was noted in
11.4 %. (30/280). The iodine content of prenatal vitamins was
strongly correlated with iodide level. (p⬍.001). Taking a prenatal vitamin without iodine was associated with a significantly increased risk
for iodide deficiency. (RR 2.2 95 % CI 1.3–3.3 ). After controlling for
demographics and seafood and dairy consumption, only lack of prenatal vitamin iodine content remained significantly associated with
risk of iodine deficiency.
CONCLUSION: Iodine deficiency is common among pregnant women
and is associated with lack of iodine in prenatal vitamins. Patients
should be advised to take a prenatal vitamin containing 150 mcg of
iodine from potassium iodide, or an equivalent supplement. Iodine
should be included in prenatal vitamins as a matter of public policy.
Maternal iodine insufficiency
by prenatal vitamin
Maternal cardiac glucose uptake and
traced region of interest (ROI)
*P ⬍ .05 compared to CON.
230 Effect of labor on glucose concentrations
in umbilical veins & arteries
Shelly Soni1, Allan Jacobs1, Paul Ogburn2
1
Flushing Hospital Medical Center, Obstetrics & Gynecology, Flushing, NY,
Stony Brook- Winthrop University Hospitals, Maternal- Fetal Medicine,
Stony Brook, NY
2
229 Risk factors for iodine deficiency in pregnancy
Scott Sullivan1, Edward Tarnawa2, Laura Houston1,
Roger Newman1
1
Medical University of South Carolina, Obstetrics/Gynecology, Charleston,
SC, 2University of Texas Southwestern Medical Center,
Obstetrics/Gynecology, Dallas, TX
OBJECTIVE: Iodine deficiency during pregnancy is associated with an
increased risk for complications of pregnancy and a 13.5 decrease in
IQ in exposed offspring. The recommended daily intake of iodine is
220 mcg, of which approximately 100 mcg comes from diet. Surprisingly, many prenatal vitamins sold in the US do not contain any
iodine. To assess urinary iodide levels in a population of pregnant
women and correlate these results with iodine amounts in their prenatal vitamins and dietary intake of other sources of iodine.
STUDY DESIGN: An observational prospective study was performed
from 2010-2012 at a single academic medical center. Urinary iodide
samples were collected from pregnant women between 20-28 weeks of
gestation. Subjects completed a research validated dietary survey. Prenatal vitamin type, iodine content and compliance were recorded.
Bivariable comparisons were made with Chi-square analysis. A multi-
OBJECTIVE: To assess the effects of labor on fetal circulating glucose
concentrations as measured in umbilical vein & artery.
STUDY DESIGN: The study population included two groups - those who
had vaginal delivery after undergoing labor (Group A,n⫽20) and
those that underwent elective c-section (controls - Group B,n⫽15).
Patients with medical complications (including diabetes, hypertension, systemic infections, multiple pregnancies) were excluded. Patients in both the groups received lactate ringer’s solution. Maternal
glucose was measured at the delivery of fetus in both the groups.
Umbilical cord vessel samples were collected in heparinized syringes
immediately after delivery. From that sample, glucose was analyzed
using SureStep Flexx glucometer. The remaining sample was sent for
cord gas evaluation using GEM Premier 4000 analyzer’s iQM method.
RESULTS: The two groups, A vs B, did not differ significantly in maternal age (26.4 vs 27.3 y; p⫽0.56), gestational age (39.5⫹/⫺0.5 vs
39.2⫹/⫺0.2, p⫽0.09), parity (55% vs 86% multiparous; p⫽0.07) or
birthweight (P⫽0.96). Maternal glucose was comparable in both the
groups (97.46⫹/⫺12.9 vs 91.38⫹/⫺13.7 mg/dl,p⫽0.08). Umbilical
venous glucose was significantly higher in group A (90.2⫹/⫺13.5 vs
74.3⫹/⫺12.7,p⫽0.001). Umbilical artery glucose was also elevated in
group A (77.8⫹/⫺17 vs 62.7⫹/⫺12.6, p⫽0.008). Umbilical vein and
artery pH was similar in both the groups. Also, the umbilical vein and
artery pO2 was comparable in both groups (p⫽0.84 & 0.72 respec-
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tively). Length of labor did not correlate with either umbilical vein or
artery’s glucose concentration (p⫽ 0.82 & 0.83 respectively).
CONCLUSION: Our data indicates that labor is associated with increased
umbilical vessel glucose measurements in normal pregnancies. These
differences are not related to any variation in maternal glucose levels.
While this increase in cord glucose concentration may be related to
fetal stress in labor, cord pH and oxygen content changes (indicating
significant hypoxic/acidotic stress) were not seen in the laboring patients.
231 Prenatal hypoxia programs increased hepatic
mitochondrial gene expression in guinea pig (GP) offspring
Sheveta Jain1, Yazan Al-Hasan1, Loren Thompson1
1
University of Maryland School of Medicine, Obstetrics & Gynecology,
Baltimore, MD
OBJECTIVE: Intrauterine hypoxia is a prenatal insult that contributes
to fetal organ dysfunction. Permanent changes in organ function of
the offspring may be mediated via programming mechanisms. We
previously reported that chronic fetal hypoxia increases mitochondrial enzyme activity associated with fatty acid oxidation (FAO;
MCAD, medium chain acyl dehydrogenase) and oxidative phosphorylation (OXPHOS; CCO, cytochrome c oxidase) in 90d old GP livers
compared to their normoxic controls (SGI2012 Abstract #F120). We
hypothesize that increased mitochondrial enzyme activity by intrauterine hypoxia is mediated via upregulation of target genes [Hepatic
MCAD (protein & mRNA), PPAR ␣ & ␥ (mRNA, peroxisome proliferator-activated receptors)] associated with mitochondrial protein
expression.
STUDY DESIGN: Pregnant GPs were exposed to either room air (normoxia NMX) or 10.5% O2 (hypoxia HPX) for 14d prior to term
(65d). Fetal GPs were allowed to deliver and male offspring were selected for study and housed in room air. At 90d, offspring (N⫽11-12/
grp) were anesthetized, body and liver weights measured, and right
liver lobes excised and frozen (⫺80oC). MCAD protein of isolated
mitochondrial fractions were measured by Western analysis and normalized to Porin. MCAD & PPAR␣ & ␥ mRNA levels were measured
by RTPCR using appropriate primers, normalized to 18srRNA.
RESULTS: Chronic hypoxia had no effect on body or liver weights.
Exposure to prenatal hypoxia increased (p⬍.05) both MCAD protein
(NMX vs HPX 0.35⫾0.10 vs 0.83⫾0.17) & mRNA (NMX vs HPX
0.57⫾0.05 vs 0.81⫾0.05) levels of offspring livers. PPAR␣ (NMX vs
HPX 0.14⫾0.02 vs 0.25⫾0.03) but not PPAR␥ mRNA (NMX vs HPX
0.21⫾0.04 vs 0.28⫾0.05) levels were increased (p⬍.05) by prenatal
hypoxia in offspring livers.
CONCLUSION: These results suggest that in-utero exposure to chronic
hypoxia upregulates hepatic MCAD enzymatic activity via transcription factors that regulate FAO, suggesting that prenatal hypoxia programs altered liver metabolism in the offspring (NIH HL49999).
232 Correlation of serum fructosamine and
recurrent pregnancy loss
Stephanie Romero1, Margarita Sharshiner1,
David Branch1, Robert Silver1
1
University of Utah, Maternal Fetal Medicine, Salt Lake City, UT
OBJECTIVE: Pre-gestational diabetes is associated with an elevated risk
of pregnancy loss. However, it is unclear whether subclinical levels of
glucose intolerance are associated with pregnancy loss, especially re-
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current pregnancy loss (RPL). Thus, our objective was to compare
maternal serum fructosamine (a marker of glycemic control) in patients with and without RPL.
STUDY DESIGN: Case-control study design with 134 women with unexplained RPL, defined as two or more pregnancy losses with no more
than one live birth and 134 age-matched controls with at least one full
term uncomplicated pregnancy and no more than one pregnancy loss.
No cases or controls had a clinical diagnosis of pre-gestational or
gestational diabetes. Maternal serum fructosamine was measured using quantitative spectrophotometry.
RESULTS: The groups were similar with regard to age, race and ethnicity. The mean BMI of cases was 26.4 (17.8-51.2) compared to 26.4
(17.8-44.4), p ⫽ 0.91. Fructosamine levels were higher in women with
RPL (225.3 ⫹/⫺ 38.5) compared to controls (189.3 ⫹/⫺ 19.5, p
⬍0.001). This was also seen when the cases and controls were stratified by BMI (see table). However, the proportion of women with
elevated levels of fructosamine considered diagnostic of diabetes (ⱖ
285 ␮mol/L) was similar in cases and controls (6.0 versus 12.7%; p ⫽
0.092).
CONCLUSION: Cases and controls had a similar proportion of women
with elevated levels of fructosamine considered diagnostic of clinically
relevant glucose intolerance. However, maternal serum levels of fructosamine were increased in women with RPL compared to controls.
Thus, subclinical levels of glucose intolerance may be associated with
an increased risk of RPL. Although these data support further investigation into the mechanisms of pregnancy loss associated with glucose intolerance, they do not support testing for subclinical glucose
intolerance on women with RPL.
Fructosamine levels stratified by BMI
Fructosamine measured in umol/L.
233 Transplacental transfer of pravastatin
Tatiana Nanovskaya1, Svetlana Patrikeeva1, Maged Costantine1,
Gary Hankins1, Mahmoud Ahmed1
1
University of Texas Medical Branch, OG/GYN, Galveston, TX
OBJECTIVE: Determine the bidirectional transfer of pravastatin across
the dually perfused term human placental lobule and its distribution
between the tissue, maternal and fetal circuits.
STUDY DESIGN: The technique of dual perfusion of placental lobule
(DPPL) was utilized to determine the Maternal-to-Fetal (n⫽11) and
Fetal-to-Maternal (n⫽10) transfer of pravastatin. The concentration
of pravastatin in the maternal reservoir (50 ng/mL) was equal to the
reported mean plasma concentration of the drug in patients who received a dose of 40 mg of pravastatin daily. Pravastatin was co-perfused with its [3H]-isotope and the marker compound antipyrine
(AP, 20 ug/mL) and its [14C]-isotope. The concentration of pravastatin in the perfused tissue, the maternal and fetal circuits was determined using liquid scintillation spectrometry. Inside-out vesicles
(IOV) prepared from placental brush border membranes were utilized to investigate pravastatin interactions with efflux transporters.
RESULTS: Pravastatin was transferred from the maternal to the fetal
circuit and vise versa. In the Maternal-to-Fetal direction 14 ⫾ 5% of
the drug was retained by the tissue, 68 ⫾ 5% remained in the maternal
circuit, and 18⫾4% was transferred to the fetal circuit. The normalized transfer of pravastatin (Clearance index) to AP in the Fetal-toMaternal direction (0.48 ⫾ 0.07) was higher than its transfer in the
Maternal-to-Fetal direction (0.36 ⫾ 0.07, p⬍0.05). Furthermore,
pravastatin inhibited the ATP-dependent uptake of the [3H]-paclitaxel and [3H]-estrone sulfate by IOV.
CONCLUSION: The transfer (20%) of pravastatin across the dually perfused placental lobule suggests that fetal exposure to pravastatin is
plausible. Moreover, the higher transfer of pravastatin in the Fetal-toMaternal direction than the reverse as well as inhibition of the ATP-
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dependent uptake of [3H]-paclitaxel and [3H]-estrone sulfate
strongly suggests the involvement of efflux transporters in its transfer
across the placenta. This work was supported by NICHD ObstetricPharmacology network grant U10HD047891.
234 Inhibition of autophagy by sera from pregnant women
Tomi Kanninen1, Bruna Ramos1, Shirlee Jaffe1, Ann Marie
Bongiovanni1, Iara Linhares2, Gian Carlo Di Renzo3,
Steven Witkin1
1
Weill Cornell Medical College, Obstetrics and Gynecology, New York, NY,
University of Sao Paulo, Obstetrics and Gynecology, Sao Paulo, Brazil,
3
University of Perugia, Obstetrics and Gynecolgy, Perugia, Italy
2
OBJECTIVE: Autophagy is a process that maintains homeostasis by
eliminating senescent or damaged intracellular organelles and proteins. In addition, autophagy participates in regulation of innate and
acquired immunity. A role for autophagy in pregnancy has been
scarcely studied. We compared the influence of sera from pregnant
and non-pregnant women on autophagy induction. p62 is a cytoplasmic protein essential for induction of autophagy. Its concentration in
the cytoplasm is inversely proportional to the level of autophagy induction.
STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) from
female donors were incubated with sera from 35 women in the second
trimester of pregnancy or 35 non-pregnant reproductive age women.
After 48 hours cells were collected, lysed and assayed for p62 concentrations by ELISA. PBMCs were also incubated with the autophagy
inducer, rapamycin, in the presence or absence of sera. Sera were
tested for concentrations of immune mediators by ELISA. Clinical
data and source of sera were accessed only after completion of all
experiments.
RESULTS: Median (range) p62 concentrations were 6.7 ng/ml (1.122.7) for PBMCs incubated with pregnancy sera vs. 2.5 ng/ml (0.87.7) for non-pregnant sera (p⬍0.0001). Even in the presence of rapamycin, median p62 levels were elevated in the presence of pregnancy
sera, 1.3 ng/ml (0.06-4.9), as compared to non-pregnant sera, 0.7
ng/ml (0-3.3) (p⫽0.0191). Among the pregnant subjects, the p62 level
was inversely proportional to the results of a 50 g glucose challenge test
(GCT) (r ⫽ ⫺0.5630, p⫽0.0005). Insulin-like growth factor-1 and
interleukin-13, inhibitors of autophagy, were elevated in sera from
pregnant women.
CONCLUSION: Sera from healthy pregnant women inhibit autophagy
to a greater extent than sera from non-pregnant women. Autophagy inhibition during pregnancy may function to decrease
insulin resistance.
Poster Session I
ception, maternal race (e.g., NH black), intention to get pregnant
prior to conception (i.e., did not want or wanted it sooner), and smoking prior to conception (p⬍0.05). Overall, our preconception preterm risk model correctly classified 76.1% of preterm cases with a
negative predictive value (NPV) of 76.7%. A nomogram using a 0-100
scale illustrates our final preconception model for predicting preterm
birth (Figure).
CONCLUSION: This preconception nomogram will give providers a tool
to assist in predicting a woman’s individual preterm birth risk and to
triage high-risk women to preconception care. Future studies are
needed to validate the nomogram in the clinical setting.
Summary nomogram for predicting the probability
of preterm birth according to selected
preconception risk factors using the PRAMS
surveillance 2004-2009 data
Instructions: using a pencil and ruler, draw a line vertically up to the top
‘Points’ axis to get an estimate of the points associated with each risk factor
level for a given individual woman. Sum the points across all risk factors for
that individual to create a ‘Total Points’ score. Draw a line vertically down
from the ‘Total Points’ axis through the ‘Probability of preterm birth’ axis to
obtain an approximation of the individual’s baseline risk of preterm birth
prior to conception.
235 A preconception nomogram to predict preterm birth
Shilpi Mehta-Lee1, Anton Palma2, Peter Bernstein3,
David Lounsbury2, Nicolas Schlect2
1
New York University Medical Center, Department of Obstetrics and
Gynecology, New York, NY, 2Albert Einstein College of Medicine,
Department of Epidemiology and Public Health, Bronx, NY, 3Albert Einstein
College of Medicine, Department of Obstetrics, Gynecology and Women’s
Health, Bronx, NY
OBJECTIVE: Preterm birth is a leading cause of perinatal morbidity &
mortality. Prevention strategies rarely focus on preconception care.
We sought to create a preconception nomogram identifying women
at highest risk for preterm birth using the Pregnancy Risk Assessment
Monitoring System (PRAMS) surveillance data.
STUDY DESIGN: PRAMS data from 2004-2009 was utilized. Odds ratios
(OR) of preterm birth for each preconception variable were estimated
and adjusted analyses were conducted. A validated nomogram predicting the probability of preterm birth was created using multivariate
logistic regression model coefficients.
RESULTS: 192,208 cases met inclusion criteria. Demographic/maternal health characteristics and associations with preterm birth and ORs
are reported (Table). After validation, significant predictors of preterm birth among all women, were prior history of preterm birth or
low birthweight baby, prior SAB/TAB, maternal diabetes prior to conSupplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
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Poster Session I
Sample characteristics–Estimated
preterm birth prevalences by subgroup
www.AJOG.org
236 Ectonucleotide pyrophosphatase phosphodiesterase
1 (ENPP1) expression in adipose tissue of women
with excessive versus normal gestational weight
gain during pregnancy
Aaron Poole1, Gayle Olson1, Batbayar Tumurbaatar2, Kathleen
Vincent1, Yongquan Jiang3, Massoud Motamedi3, Gracie Vargas3,
Manisha Chandalia2, Abate Nicola2
1
University of Texas Medical Branch Galveston, Obstetrics & Gynecology,
Galveston, TX, 2University of Texas Medical Branch Galveston, Internal
Medicine–Endocrinology, Galveston, TX, 3University of Texas Medical
Branch Galveston, Center for Biomedical Engineering, Galveston, TX
OBJECTIVE: ENPP1, a transmembrane glycoprotein, has been shown
to modulate adipocyte maturation and insulin receptor signaling.
These effects have been associated with systemic insulin resistance and
increased risk for type 2 diabetes. Our objective is to measure adipocyte ENPP1 expression in response to gestational weight gain
(GWG).
STUDY DESIGN: Women scheduled for elective repeat cesarean at term
and who fasted at least 6 hours were recruited. Blood was obtained
before the initiation of intravenous fluids and subcutaneous fat was
biopsied after the skin incision. Adipose cell size was analyzed using
3D multi-photon imaging. Tissue expression level of ENPP1 and
phosphorylation of Akt (pAkt) for insulin signaling were measured by
Western Blot. Using IOM guidelines, excessive vs normal GWG were
compared. Statistical Analysis Software was utilized.
RESULTS: Fifteen subjects with excessive GWG were compared to 9
with normal GWG. Maternal age, EGA at delivery and pregestational
body mass index (BMI) were not significantly different. Delivery BMI,
birthweight, tissue expression level of ENPP1, adipocyte cell size and
phosphorylated Akt were significantly different (Table).
CONCLUSION: Increased expression level of ENPP1 in women with excessive GWG is associated with decreased adipocyte cell size and phosphorylation of Akt, indicating impaired maturation of adipocytes and
insulin signaling. These findings suggest women with excessive GWG
may be at risk for future systemic insulin resistance and type 2 diabetes.
Excessive versus normal
gestational weight gain
* BMI [weight (kg)]/[height (m)]2.
1
Weighted n may not add up to 100% due to missing data; 2Individual
stressor variables only shown for “yes” responses.
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