Placentitis in Horses

Placentitis in Horses
— A Major Cause of Late Term Foetal Loss —
RIRDC Publication No. 10/156
RIRDC
Innovation for rural Australia
Placentitis in Horses
A Major Cause of Late Term Foetal Loss
by Joan Barbara Carrick
October 2010
RIRDC Publication No. 10/156
RIRDC Project No. PRJ-000744
© 2010 Rural Industries Research and Development Corporation.
All rights reserved.
ISBN 978-1-74254-075-7
ISSN 1440-6845
Placentitis in Horses: A Major Cause of Late-term Foetal Loss
Publication No. 10/156
Project No. PRJ-000744
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Researcher Contact Details
Joan Barbara Carrick
Scone Veterinary Hospital
106 Liverpool Street
Scone NSW 2337
Phone: 02 6454 1333
Fax:
02 6545 2903
Email: joan.carrick@sconevet.com.au
In submitting this report, the researcher has agreed to RIRDC publishing this material in its edited form.
RIRDC Contact Details
Rural Industries Research and Development Corporation
Level 2, 15 National Circuit
BARTON ACT 2600
PO Box 4776
KINGSTON ACT 2604
Phone:
Fax:
Email:
Web:
02 6271 4100
02 6271 4199
rirdc@rirdc.gov.au.
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Electronically published by RIRDC in October 2010
Print-on-demand by Union Offset Printing, Canberra at www.rirdc.gov.au
or phone 1300 634 313
ii
Foreword
Foetal losses and intensive care of critically ill neonates cost the horse industry an estimated $10
million to $20 million each year. Placentitis or inflammation of the placenta is most often caused by
infection.
A major problem for horse breeders is that in many cases, placental pathology presents no clinical
signs until the condition is so far advanced that effective treatment is difficult and frequently
inadequate. Hence, placentitis is an extremely difficult condition to prevent and treat, primarily due to
lack of knowledge about the development and progression of the condition. Improved understanding
of the incidence and development of placentitis is critical, so that appropriate monitoring and
prevention programs can be initiated in order to reduce the significant economic losses to the industry.
This study clearly demonstrates that detailed placental and foetal ultrasound examinations of
broodmares in the field can be readily accomplished. Utilisation of the information collected to direct
treatment of the mares resulted in an increase in the number of healthy foals produced by mares with a
previous history of abortion or premature labor. This technology allows the early identification of
brood mares that are at risk of pregnancy loss or delivery of a compromised foal so that early
treatment can be initiated. In addition, the early initiation of treatment in this study dramatically
improved neonatal foal health and survival. During the past three breeding seasons, many progressive
thoroughbred breeders who participated in this research or were aware of the program have initiated
proactive ultrasound monitoring of mares with a poor breeding history or of extremely high value.
Widespread adoption of the program by horse breeders will significantly reduce reproductive wastage
in the equine breeding industry.
This project was funded by industry contributions which were matched by funds from the Australian
government through RIRDC.
This report is an addition to RIRDC’s diverse range of over 2000 research publications and it forms
part of our Horse R&D program, which aims to assist in developing the Australian horse industry and
enhancing its export potential.
Most of RIRDC’s publications are available for viewing, free downloading or purchasing online at
www.rirdc.gov.au. Purchases can also be made by phoning 1300 634 313.
Craig Burns
Managing Director
Rural Industries Research and Development Corporation
iii
Acknowledgments
The assistance and support from owners, managers and staff at the thoroughbred brood mare farms
involved in the project is gratefully acknowledged. In addition, I would like to acknowledge the
invaluable assistance from the staff at Scone Veterinary Hospital, particularly, Dr Cameron Collins
who convinced his clients to participate in the study, and Drs David O’Meara and Chris Quinn who
examined numerous placentas. The assistance of Dr Angela Begg who assessed the histopathology of
the placental samples is greatly appreciated. I would also like to acknowledge the assistance of Dr
Arron Hodder and Dr Catherine Chicken who reviewed this report.
Abbreviations
CUPT
Combined Utero-Placental Thickness
cm
Centimetres
mm
Millimetres
ml
Millilitres
ng
Nanograms
mmol
Milimoles
TMPS
Potentiated Sulphonamide Antibiotic
iv
Contents
Foreword ............................................................................................................................................... iii
Acknowledgments................................................................................................................................. iv
Abbreviations ........................................................................................................................................ iv
Executive Summary ............................................................................................................................ vii
Introduction ........................................................................................................................................... 1
Assessment and Treatment of the High Risk Pregnant Mare. .......................................................... 2
Treatment .......................................................................................................................................... 3
Prevention Monitoring Program ....................................................................................................... 4
Objectives ............................................................................................................................................... 6
Specific Objectives ........................................................................................................................... 6
Methodology .......................................................................................................................................... 7
Mare Selection .................................................................................................................................. 7
Ultrasound Examination ................................................................................................................... 7
Foal Health and Placental Assessment ............................................................................................. 9
Mare Treatment................................................................................................................................. 9
Statistical Analysis............................................................................................................................ 9
Results .................................................................................................................................................. 11
Mare Treatment............................................................................................................................... 11
Foal Health Outcomes from High Risk and Normal Mares ........................................................... 11
Placental Pathology of High Risk and Normal Mares .................................................................... 13
Placental Pathology and Neonatal Foal Health .............................................................................. 14
Ultrasound Parameters of High Risk and Normal Mares ............................................................... 17
Ultrasound Parameters Associated with Gestational Age and Treatment ...................................... 19
Ultrasound Parameters Associated with Foal Health and Placental Pathology.............................. 21
Incidence of Abnormal Scans and Placental Pathology ................................................................. 23
Discussion ............................................................................................................................................. 26
Overall Objectives .......................................................................................................................... 26
Specific Objectives ......................................................................................................................... 26
Implications.......................................................................................................................................... 28
Recommendations ............................................................................................................................... 29
References ............................................................................................................................................ 30
v
Tables
Table 1
Foal health parameters in foals from high risk and normal mares. ................................... 13
Table 2
The number of placentas with pathology present in the different regions of the
placenta in normal and high risk mares. ............................................................................ 14
Table 3
Health parameters in foals from placentas with and without pathology. .......................... 15
Table 4
Foal Health or Placental Pathology Variables that were correlated with ultrasound
parameters have highlighted boxes with p values in the box ............................................ 22
Table 5
The percentage of ultrasound parameters that were abnormal in the entire study
population of mares. .......................................................................................................... 24
Table 6
The percentage of ultrasound parameters that were abnormal in untreated mares
that produced healthy foals. .............................................................................................. 24
Table 7
Mean rectal and abdominal CUPT and median ultrasound score in normal mares
that were not treated and produced a healthy foal............................................................. 25
Figures
Figure 1
Mares were examined in the facilities used for normal reproductive examinations ........... 8
Figure 2
The foaling percentages for mares included in the study in the three years before the
study during which they received no treatment, the two years during the study when
they received treatment based on ultrasound parameters and the two years after the
study, when only mares that received no ultrasound directed treatment were included ... 12
Figure 3
The white blood cell count in foals from mare that had pathology at the cervical pole of
the placenta was lower than in foals from mare with no pathology at the cervical pole .. 16
Figure 4
Pathology present in the body of the placenta reduced the size of the foal and
increased the time taken for the foal to stand.................................................................... 17
Figure 5
The rectal CUPT increased with gestational age similarly in both normal and high
risk mares........................................................................................................................... 18
Figure 6
The abdominal CUPT increased with gestational age similarly in both normal and
high risk mares. ................................................................................................................. 18
Figure 7
The rectal and abdominal CUPT were very well correlated. Dotted lines represent
95% confidence interval. ................................................................................................... 19
Figure 8
The foetal heart rate decreased with gestational age. Dotted lines indicate 95%
confidence interval. ........................................................................................................... 20
Figure 9
The aortic diameter increased with gestational age. Dotted lines indicate 95%
confidence interval. ........................................................................................................... 20
Figure 10
Mosaic plot of amniotic and allantoic fluid turbidity in treated compared with
untreated mares.................................................................................................................. 21
Figure 11
The derived model ultrasound index was correlated with the time taken for the foal
to stand. ............................................................................................................................ .23
vi
Executive Summary
What the report is about
This report describes a project that investigated the use of regular ultrasound examination of two
groups of pregnant mares; one group had a normal foaling rate (normal) and the other group had
repeatedly aborted or delivered premature foals (high risk). The mares were treated based on
abnormalities identified during the ultrasound examinations. The regime of intensive examination
and treatment resulted in a foaling rate of 90% for the high risk group. This was similar to the foaling
rate for the normal mares. The project identified the ultrasound parameters that are important in the
development of a high-risk pregnancy. Treatment of mares limited the validity of this aspect of the
project, however an ultrasound index was developed. This index needs to be validated by use in a
further prospective study.
Who is the report targeted at?
This report is aimed primarily at stud managers and veterinarians in the equine breeding industry.
Application of the technology is expensive; however the successful delivery of healthy, valuable foals
and reduced need for neonatal intensive care justifies the cost.
Background
Placentitis and placental abnormalities are a major cause of reproductive loss, which costs the equine
industry a large amount of money each year due to lost foals and the treatment of critically ill foals.
Because clinical signs of placental pathology are variable, typically the first indication of a problem is
abortion or still birth. Due to undetected cases, the true incidence of placental pathology may be
higher than current estimates. In addition, placental pathology contributes to development of critical
illness in the equine neonate by predisposing to conditions such as prematurity, sepsis and perinatal
asphyxia syndrome. Ultrasound examination of the foeto-placental unit can identify placental
pathology before abortion or premature delivery occurs and is used to monitor clinical cases of mares
with a systemic disease or precocious signs of imminent parturition to determine foetal health and
development.
Aims/objectives
The primary objective of this study is to document the development and consequences of placental
abnormalities occurring during the second half of gestation in thoroughbred broodmares and to
determine whether treatment based on these findings improves foetal and neonatal foal health.
Methods used
During 2005 and 2006, ultrasound examinations were conducted every four weeks on 106 pregnant
mares on three thoroughbred breeding farms in the Hunter Valley, NSW. The mares were treated with
antibiotics and various combinations of anti-inflammatory drugs and altrenogest, a progesterone
analogue. There were two groups of mares; a group with a normal breeding record and a group that
had repeated abortions or delivery of a critically ill foal. Foaling of each mare was observed, the foal’s
health recorded, a blood sample obtained and the placenta examined for abnormalities. All the
ultrasound parameters were examined and found to have interaction with the gestational age at the
time of data collection and with treatment of the mares; hence these two variables were included in all
analysis. The ultrasound variables were used in a multivariable analysis of variance or logistic
regression to determine association with foal health parameters and placental pathology. An
ultrasound index was determined based on the parameters that had significant correlations.
vii
Results/key findings
Repeated ultrasound examinations and treatment of pregnant mares resulted in a foaling rate of 90%
in the mares with a previous history of pregnancy loss which was the same as the foaling rate of the
normal mares (91%). Foal health and placental pathology was correlated with placental width detected
during both the trans-abdominal and trans-rectal examination, placental separation and folding
detected during the trans-abdominal examination, foetal heart rate and foetal aortic diameter. An
ultrasound index was derived using these parameters and found to be correlated with the time taken
for the foal to stand.
Although there was correlation between foal health and placental pathology, the incidence of
placental pathology (53%) was much higher than the incidence of critical illness in neonatal foals
(9%). Intensive treatment of the mares during pregnancy may account for the observed improvement
in neonatal foal health.
Implications for relevant stakeholders
Ultrasound examination and treatment of mares with a poor breeding history significantly improves
the probability of delivery of a live, healthy foal. Adoption of this technology by the horse breeding
industry and their veterinarians has the potential to reduce the losses in the breeding industry due to
placental pathology.
Recommendations
Mares with a history of repeated abortion or delivery of a critically ill foal should, from midpregnancy through to delivery, have regular ultrasound examinations and treatment regimes should be
based on these examinations.
Further research should be conducted using the ultrasound index derived in this project in a
prospective study of normal brood mares that receive no treatment.
viii
Introduction
Each year approximately 20-30% of all mares bred in Australia fail to produce a live foal. Almost half
of this failure is due to losses in the second half of gestation. Causes of pregnancy loss later in
gestation may be due to foetal or placental anomalies, conception of twins, infection (viral, bacterial
or fungal), hydrops amnion or allantois, loss of the structural integrity of the mare’s body wall or
systemic illness in the mare.1, 2 Placental pathology is the primary contributing factor in the majority
of cases of equine foetal loss.3, 4, 5, 6 In addition, placental pathology is a significant contributor to the
delivery of premature, septic or dysmature foals that require expensive intensive care. The relative
contribution of different placental pathologies to equine foetal and neonatal death varies with the
definitions used by each investigator and by geographical location. However, placentitis is the single
most common cause of placental pathology. Conception of twins has significantly reduced as a cause
of abortion during the past 20 years 5, 6. This is most likely due to the increased use of ultrasound
examination allowing early diagnosis. Umbilical elongation and torsion has become a more important
cause of foetal and neonatal losses 5, 6. Placental pathology is frequently associated with umbilical
cords longer than 85 cm and results in a reduction of the nutrient supply to the developing foetus.
Limitation of nutrients reduces intrauterine growth rate of foals and frequently results in the
presentation of a small for gestational age foal or in severe cases, abortion or stillbirth. In addition,
regions of the placenta with reduced perfusion associated with an excessively long umbilical cord are
more prone to infection and subsequent development of bacterial placentitis.
Typically placentitis is associated with bacterial or fungal infection which induces an acute or chronic
response. The most common bacteria isolated from infected placentas are Streptococcus equi
subspecies zooepidemicus, Escherichia coli, Klebsiella pneumonae and Pseudomonas sp.3, 5. Recently
a model of ascending bacterial placentitis has been developed by a group of investigators at the
University of Florida. This model is quite severe with the loss of approximately 90% of the foals. Not
all mares exhibited clinical signs of infection nor gave indication of impending parturition, which is
consistent with field cases of the condition7. The model has also provided valuable information about
the pathophysiology of ascending placentitis and allowed investigation of some different treatment
regimes8-12. The development of the ascending placentitis in this model was monitored using transrectal ultrasonography to measure the thickness of the combined utero-placental unit and a significant
increase in thickness and separation of the utero-placental unit was detected by ultrasound
examination 8.
The most common clinical presentation of placentitis is an ascending infection through the cervix1.
The causes of a compromised cervical seal are varied. Stress to the foetus or mare can induce
alteration of progesterone synthesis and metabolism which may result in abnormal relaxation of the
cervix. It is apparently common for normal mares to have intermittent relaxation of the cervix and the
specific factors that determine an individual mare’s risk of developing placentitis as a result of this
relaxation are unknown. However the frequency and duration of relaxation of the cervix and the
anterior vaginal micro flora may be significant factors. Bacterial vaginosis is an important risk factor
in women at high risk for premature labour. Monitoring vaginal bacterial flora with early antibiotic
treatment significantly improves the likelihood of a successful pregnancy in these women13. Once
infection has been established in the placenta, the severity of the inflammatory response is critical.
There is activation of the placental inflammatory cascade, primarily through resident macrophages,
with synthesis of a range of cytokines and prostaglandins 14-16. These inflammatory mediators
adversely affect the foetal metabolism resulting in significant foetal stress, induction of a foetal
inflammatory response syndrome and enhanced myometrial contractility. Infection may be controlled
by the use of antibiotics; however the foetus frequently remains severely compromised due to the
inflammatory response. Improved identification and monitoring to allow early intervention is essential
to improve outcomes for mares carrying a high risk pregnancy.
1
Assessment and Treatment of the High Risk Pregnant Mare.
History and Physical Examination
A detailed history of the mare’s previous pregnancies, previous parturitions, last date of service, the
type of insemination, the number of services or inseminations required and the incidence of early
embryonic loss is essential. A complete physical examination should be conducted on all mares
carrying a high risk pregnancy. Any vaginal discharge, premature perineal relaxation or precocious
mammary development is significant. If there is a vaginal discharge, some of the purulent material
may be aseptically collected from the caudal vaginal without significantly disrupting the vestibular
sphincter seal.
Examination of the udder and mammary secretions can provide useful information about the readiness
of the foetus for extra uterine life. A sudden rise in milk calcium concentration greater than12 mmol/L
indicates that the foetus is sufficiently mature for extra uterine life and that parturition is likely within
48 hours. Unfortunately the clinical signs of a high risk pregnancy can be very subtle and the first
indication of a significant problem is acute abortion or impending premature labour. To significantly
reduce foetal and neonatal losses it is essential to improve the clinical procedures used to assess high
risk pregnant mares.
Hormonal Evaluation
Progesterone
The foeto-placental unit is the sole source of pregnanes and progestagens to maintain pregnancy from
approximately 120 days through to parturition. The concentration of progesterone in the maternal
circulation from mid-gestation to approximately 300 days of gestation is normally low. Commercial
assays for progesterone measure variable amounts of the pregnanes and progestagens due to cross
reactivity of the assay components which varies between different commercial assays. Placentitis
induces a precocious rise in plasma progesterone levels but there is no clear link between plasma
progesterone levels and placental pathology or foetal survival8, 17-19. The rise in maternal plasma
progestagens may be due to dysregulation of progesterone synthesis in the abnormal placenta,
excessive precursor secretion by the stressed foetal adrenal gland or a combination of both aetiologies.
However, clinical signs of placentitis associated with low maternal progesterone levels, indicates a
very poor prognosis for foetal survival and even with intensive monitoring and treatment of these
cases the outcome is invariably disappointing.
Oestrogen
Between days 150 to 280 maternal concentration of oestrogen is highest and levels less than 500
ng/ml indicate severe foetal compromise and imminent abortion. After 280 days of gestation,
interpretation of maternal oestrogen concentrations is limited and not well correlated with foetal
survival. 19
Relaxin
From 70 days of gestation, relaxin is produced by the placenta and is detectable in the maternal
circulation. There is an excellent correlation between low relaxin concentration and foetal-placental
compromise, and maternal relaxin concentration could be used to monitor high risk pregnancies.
Unfortunately validated assays of equine relaxin are not available commercially in Australia.
2
Ultrasound Examination of the Foetal-placental Unit
Ultrasound examination has been used to monitor late gestation pregnant mares with precocious signs
of imminent parturition and the development of experimentally induced placentitis8, 20, 21, 22-25. Transrectal ultrasound examination allows investigation of the caudal section of the placenta, including the
cervical pole region. This is the region through which most bacterial infections of the placenta occurs,
hence is an excellent section of the placenta to monitor for ascending infections. After mid-gestation,
trans-rectal ultrasound examination provides limited information about foetal development and health.
Trans-abdominal ultrasound examination significantly increases the amount of the placenta that can
be evaluated and allows monitoring of foetal activity, heart rate and growth rate. A biophysical score
has been developed to assist in the prediction of foetal viability; however, the predictive accuracy of
the published normal ultrasound parameters for foal survival has not been tested in a prospective
clinical trial.
Repeated ultrasound assessment is also very useful for monitoring the response to treatment.
Thickening of the combined utero-placental thickness (CUPT), degree of folding of the placenta and
turbidity of the fluid all improve with successful treatment. Mares showing precocious signs of
imminent parturition, that have no improvement in the ultrasonographic parameters after treatment,
have a worse outcome than mares where improvement is recorded. (Carrick J., clinical experience)
Women with signs of preterm labour frequently undergo ultrasound assessment of the pregnancy.
Several ultrasound parameters are associated with the risk of premature delivery and can be used to
select women for referral to hospitals with tertiary level neonatal intensive care units prior to
delivery26-29. There are numerous ongoing investigations into the use of ultrasound examination to
evaluate women at risk for preterm labour so that treatment can be appropriately directed and
preparations for the delivery of a compromised neonate can be initiated as required27.
Treatment
Mares with clinical signs of premature delivery that are not treated have a less than 30 % chance of
delivering a live, healthy foal30, 31. In an experimental model of ascending placentitis where treatment
was not provided, all the mares aborted or delivered a weak premature foal12. Treatment with
antibiotics and anti-inflammatory drugs prolonged the gestation but did not improve foal viability.
Addition of altrenogest to the treatment regime resulted in improved foetal viability and foal health1, 9,
10
.
Antibiotics
The most common antibiotic class used to treat placentitis are potentiated sulphonamides (TMPS)2, 32.
This antimicrobial group is broad spectrum, bactericidal and has excellent penetration of the placenta,
readily reaching therapeutic concentrations in amniotic fluid and the foetus. Recently, penicillin and
gentamicin have been shown to effectively penetrate the pregnant uterus and reach therapeutic levels
in the allantoic fluid. This provides an excellent alternative treatment choice if there is a failure of
response to TMPS.
Anti-inflammatory drugs
The inflammatory response to infection contributes significantly to foetal stress and predisposes the
high risk pregnancy to premature parturition. There is significant synthesis of prostaglandins in
response to infection and these substances increase myometrial contractility33, 34. It is important to
control the inflammatory response and non-steroidal anti-inflammatory drugs should be administered
to mares with a compromised pregnancy. Flunixin meglumine is very effective at inhibiting
prostaglandin synthesis in response to many different inflammatory stimuli, particularly bacterial
3
toxins. The placental response to infection also results in significant synthesis of cytokines23, 12.
Pentoxifylline (8.5mg/kg PO TID) is effective at reducing endotoxin induced cytokine synthesis by
equine inflammatory cells35-37. In addition the drug may improve oxygenation of the placental by
improving blood flow. There have been no controlled investigations into the efficacy of antiinflammatory drugs in the treatment of placentitis.
Hormonal treatment
The use of progesterone or its synthetic analogue, altrenogest, in high risk pregnancy is widespread,
however it is controversial. Administration of additional progesterone is counter-intuitive because
maternal progesterone levels are already elevated and further increasing progestagen concentration is
illogical. Progesterone and its metabolites possibly contribute to the successful treatment of a high
risk pregnancy by maintenance of myometrial quiescence and reduction of the inflammatory response
in the foetal-placental unit34, 38. The progesterone metabolite, 5 α pregnane inhibits the formation of
oxytocin receptors, thus contributing to myometrial quiescence. Administration of a progesterone
analogue, altrenogest, increased the level of 5α pregnane in the plasma of normal mares and in a
separate study, prevented abortion of mid-term pregnancy in mares that were given a prostaglandin
analogue18, 19, 39. As mentioned above, addition of altrenogest to the treatment regime of mares in an
experimental model of ascending placentitis, greatly improved the number of foals that survived
compared with a previous experiment using antibiotics and ant-inflammatory drugs alone. There is
evidence that progesterone and its metabolites have significant anti-inflammatory effects and reduce
the production of cytokine and prostaglandins by the inflamed placenta14, 33, 40, 41. In addition, metaanalysis of several prospective studies of women at high risk for preterm labour indicates that
administration of progesterone significantly improves outcomes and prevents premature delivery, and
recently the American Society of Obstetrics and Gynaecology has published the recommendation that
progesterone should be administered to women with signs of impending preterm delivery that have a
history of previous preterm labour42.
Ancillary treatment
Tocolytics – clenbuterol has been used to inhibit uterine contractility. Unfortunately, the doses
required to reduce uterine contractility result in significant adverse side effects and the drug is not
recommended2. Intranasal oxygen, to improve foetal oxygenation, Vitamin E as an antioxidant, and
low dose aspirin, to improve placental oxygenation, have all been administered to mares at risk of
premature labour. There is no data available to indicate the success of these treatments. Although
aggressive treatment of the mare at high risk of premature parturition can improve foetal viability,
frequently the foal that arrives is disappointing.
Prevention Monitoring Program
Because placentitis frequently presents no clinical signs until late in the development of the condition,
a program to monitor mares with a poor breeding history is necessary to reduce foetal and neonatal
losses. Mares that have repeatedly aborted or produced weak premature/dysmature or septic foals are
at higher risk for foetal or neonatal loss compared to mares with a normal breeding history. Repeated
ultrasound examinations at specified developmental milestones are a routine part of ante-natal care of
women. Women who have had previous preterm deliveries are at high risk for preterm labour and
poor foetal survival in subsequent pregnancies. Programs are being developed to identify the risk
factors, monitor the women intensively and provide early intervention with antibiotics and
progesterone. Early results from prospective studies using this type of management significantly
improve outcomes in specific groups of women29, 43-46.
Until recently, ultrasound examination of mares with high risk pregnancies required admission to an
equine hospital. This limited the number of examinations that were performed. In addition the detailed
4
ultrasound examination required to determine the biophysical profile took considerable time, further
limiting its use in the field. New technology has allowed development of powerful portable ultrasound
machines that are capable of excellent trans-abdominal examinations in the field. Thus it is now
possible to monitor the progress of pregnancy in a large number of pregnant mares. In order to use this
technology appropriately, it is essential that prospective clinical trials are undertaken to validate the
ultrasound parameters used. Because there are significant losses associated with high risk pregnancies
and treatment regimens are empirical, this study was conducted to determine whether ultrasound
monitoring of equine pregnancies in the field is possible and if treatment based on the findings
improved foetal and neonatal health.
5
Objectives
The primary objectives of this study are to document the development and consequences of placental
abnormalities occurring during the second half of gestation in thoroughbred broodmares and to
determine whether treatment based on these findings improves foetal and neonatal foal health.
Specific Objectives
•
To correlate placental changes detected in mares by ultrasound, with gross and histopathological
evidence of placentitis.
•
To determine the incidence of placentitis in normal thoroughbred mares and in "high risk" mares,
i.e. mares with histories of late term abortion, premature delivery or delivery of a foal with
intrauterine growth retardation.
•
To monitor the development and progression of placental abnormalities detected by ultrasound in
normal and high risk thoroughbred mares.
•
To determine whether equine foetal and neonatal weight and health are correlated with placental
abnormalities detected by ultrasound.
6
Methodology
Mare Selection
The project was a prospective longitudinal observational study of thoroughbred broodmares. Pregnant
thoroughbred mares resident at three breeding farms in the Hunter Valley were enrolled in the study.
The mares (106) were selected by the stud managers, so that there were approximately equal numbers
of mares with a normal breeding history and mares that were considered to be at high risk of late term
abortion or delivery of a premature foal. The investigators were unaware of the classification of the
individual mares during the study. Complete data was collected from 77 mares and used in the
analysis of the results. The control group was 30 normally fertile thoroughbred mares (normal) and
the study group was 47 mares (high risk) that have had repeated late term abortion, a stillbirth, a
premature or small-for-gestational age septic foals. The project was conducted over two breeding
seasons.
Ultrasound Examination
Each mare was examined by trans-rectal and trans-abdominal ultrasonography using a portable
Terason 2000 ultrasound machine with a 5-7 MHz linear probe for the trans-rectal examinations and a
2-4 MHz curved array probe for the trans-abdominal examinations. The ventral abdomen was cleaned
with a brush and soaked with methylated spirits. Mares were kept outdoors throughout winter,
therefore the stud farm personnel requested that the ventral abdomen not be clipped. The first
examination was conducted at 150-180 days of gestation and repeated at intervals of 28 days until the
mare foaled.
7
Figure 1
Mares were examined in the facilities used for normal reproductive examinations
The CUPT was measured in three separate areas during the trans-rectal examination and recorded
twice in three sites in the ventral midline of the abdomen as previously described20. The CUPT was
graded 0 if normal and 1 if wider than normal. Turbidity of the foetal fluids was assessed as 0=
normal, and 1= turbid. The placenta was examined for folding and separation from the endometrium
and was recorded as 0 if normal and 1 if present for each parameter. The foetus was examined and
8
foetal activity, aortic diameter and heart rate were recorded. Examinations were conducted on the stud
farms in the facilities used for normal reproductive examination of the mares and took approximately
20 minutes for each mare. Mares were not routinely sedated for the procedure and any mare that
required repeated sedation was excluded from the study.
Foal Health and Placental Assessment
All aborted foetuses and dead foals were collected and a post mortem examination was conducted.
Foals born alive were weighed 12-18 hours after birth, foal health recorded by the stud farm and blood
samples obtained for a complete blood count, plasma fibrinogen, and serum creatinine concentrations.
The exact length of gestation was recorded. Placentas from all mares in the study were examined by
an equine veterinarian unaware of the group assignment of each mare and any pathology of the
placenta was recorded. Two samples of the placenta, one adjacent to the cervical star and one from the
body of the placenta close to the umbilical insertion, were obtained for histological examination. The
histological examination was performed by a specialist pathologist who was unaware of the group
assignment, treatment history or pregnancy outcome of the mare.
Mare Treatment
Due to the value of mares and foetuses in the study, all mares with abnormalities detected by
ultrasound examination were treated with antibiotics and different combinations of anti-inflammatory
drugs and altrenogest. Treatment of the mares was decided by the veterinarian responsible for the
reproductive management of the farm. Because initiation of treatment was based on abnormal
ultrasound parameters and was continued until the parameters became normal, associations of
ultrasound parameters with neonatal foal health or with placental pathology were expected to be
affected by treatment. Variability in the value and previous breeding history of the mares in this study
and multiple veterinarians deciding treatment regimes, resulted in differences in timing of initiation
and drug combinations used for each mare. In addition, the study was not designed to investigate
treatment effects therefore precise details of treatments were not recorded and could not be analysed
in detail.
Statistical Analysis
The data was entered from an excel spreadsheet to statistics program for analysis (JMP 7, SAS
Institute Inc, Cary NC, USA). Descriptive analysis was calculated, data summarised and distribution
of continuous data was evaluated for normality. Indicators of neonatal health were the length of
gestation, death or admission to intensive care unit, foal’s complete blood count, neutrophil count,
plasma fibrinogen, serum creatinine concentration, foal weight, placental weight, and time to stand
and number of foals that took longer than 60 minutes to stand. Indicators of placental pathology were
presence of pathology at any site in the foetal membranes; presence of pathology at the cervical star of
the chorioallantois and presence of pathology at the body of the chorioallantois near the umbilical
insertion: 0 = normal, 1= pathology and total pathology score.
The relationship between mare risk group and foal health parameters or placental pathologypatholgy
was determined using Wilcoxin rank score tests. The relationship between gestational age at data
collection or mare treatment with ultrasound parameters was tested by multivariable analysis of
variance or logistic regression as appropriate. Means were compared using a Tukey-Kramer HSD,
Wilcoxin Ranks Sum or Fishers Exact test. The relationship between ultrasound detected placental
abnormality and neonatal foal health or placental pathology was determined using the dependent
variables listed above respectively. The independent variables were gestational age at each ultrasound
examination, mare treatment, and ultrasound parameters of rectal CUPT, rectal placental separation
and folding, abdominal CUPT, abdominal placental separation and folding, foetal heart rate, foetal
9
aortic diameter, and fluid turbidity score. Forward stepwise regression was used to determine which
parameters to include in the model. Gestational age at data collection and mare treatment was always
included. A probability of 0.25 was used for inclusion. Associations between ultrasound parameters
and foetal health or placental pathology were determined using multivariable analysis of variance or
logistic regression as appropriate with a p< 0.05 considered significant. An ultrasound index was
derived using the parameters that were found to have a significant association with foetal health or
placental pathology.
10
Results
Mare Treatment
Mares in the high risk group were more likely to be treated with antibiotics but both groups received
similar amounts of altrenogest. All of the mares in the high risk group and 27 of the 30 (90%) mares
in the normal group were treated with antibiotics at least once during this study. The 47 high risk
mares were examined 282 times during the study and it was decided to treat the mare after 80% of
these examinations. The 30 mares in the normal group were examined 180 times during the study and
it was decided to treat these mares after 57% of these examinations. In contrast, the expected
incidence of placental abnormality in a group of normally fertile thoroughbred mares is approximately
10 to 20%3-5.. There is no previous data available about the incidence of placental abnormalities
detected by ultrasound examination; however this project indicates that ultrasound examination
detects abnormalities at a far higher incidence than the published rate of placental pathology. This
may be due to an unexpectedly high rate of placental pathology in the normal group of mares during
the study; however, after the study was completed and the mares returned to normal management, they
were able to maintain normal pregnancy rates. This did not occur in those high risk mares that
returned to normal management after the study was completed (see below). It is more likely that the
ultrasound parameters that are currently used as normal values do not adequately discriminate a
normal pregnancy from one that is at risk of premature delivery. Further research is necessary to better
define parameters that can distinguish high risk pregnancies from normal.
Foal Health Outcomes from High Risk and Normal Mares
During the three years prior to the start of the study, high risk mares had a foaling rate of 38 % and
normal mares had a foaling rate of 84 % (Figure 2). During this period the mares were not examined
closely and received minimal treatment. However, during the study when mares were examined
regularly and treated intensively, the high risk mares had a foaling rate of 90% and the normal mares
had a foaling rate of 91%. After the study finished 16 mares from the high risk group were continued
in a similar program and produced 27 foals from 31 pregnancies, 11 mares died or were retired and
the remaining17 mares produced 13 foals from 32 pregnancies (41%) There were four mares from the
normal group that were continued in a similar program and all produced foals each year, one mare
from the normal group died and the remaining 25 mares produced 39 foals from 46 pregnancies in two
years (82%) (Figure 2). This indicates that mares the stud managers identify as poor breeders have a
lower foaling rate than mares identified as normal, and without intervention these mares will continue
to have a lower foaling rate than normal mares. Ultrasound directed treatment of high risk mares from
mid-gestation, before there are precocious signs of imminent parturition, produced the same foaling
rate in these high risk mares as in normal mares. All mares in the study were treated based on the
ultrasound parameters; an unintended consequence was that numerous mares in the normal breeding
group with a normal reproductive history were treated.
11
100
90
Foaling Percentage
80
27/30
Normal Mares
42/47
74/88
High Risk Mares
38/46
70
60
50
40
13/32
53/138
30
20
10
0
Figure 2
2002, 2003 & 2004
2005 & 2006
2007 & 2008
Before Study
No Ultrasound
No Treatment
Study Years
Ultrasound
and Treatment
After Study
No Ultrasound
No Treatment
The foaling percentages for mares included in the study in the three years before
the study during which they received no treatment, the two years during the study
when they received treatment based on ultrasound parameters and the two years
after the study, when only mares that received no ultrasound directed treatment
were included. The numbers in the columns are the number of foals/number of
pregnancies
The mares in the high risk group had a similar gestational length and their placental weights were
similar to mares from the normal group. The foals from high risk mares weighed less, but took the
same time to stand and suck as foals from normal mares. The percentage of foals that died or required
intensive care were similar for the two groups of mares (Table 1). Foals from high risk mares had
similar white blood cell count, neutrophil count, band neutrophil count and serum creatinine
concentration but a lower fibrinogen than foals from normal mares. (Table 1)
12
Foal Health Parameter
Gestational Length (days)
Percentage of foals that died or
required intensive care
Foal Birth weight (kg) p=0.0421
Time to Stand (min)
White Blood Cell Count x 109
Neutrophil Count x 109
Band Neutrophil Count x 109
Fibrinogen g/L p= 0.0399
Creatinine mmol/L
High Risk
Mares
342
(328-365)
10.00
53.1
(45-62)
60
N
47
47
38
44
(30-120)
7.4
(4.6-10.0)
5.95
(3.1-7.8)
0
(0-0.2)
2
(1-4)
200
(128-293)
Table 1
(4.9-8.1)
342
(331-351)
12.77
56.0 *
(50-64)
60
N
30
23
23
28
(25-90)
42
42
42
42
32
6.5
Placenta weight (kg)
Normal Mares
7.2
(5.4-9.6)
5.84
(3.9-8.2)
0
(0-0.5)
3*
(2-3.4)
174
(122-258)
25
25
25
25
21
7.3
44
(5.0-8.5)
26
Foal health parameters in foals from high risk and normal mares. Numbers are
median with the numbers in parenthesis are the 90% quantile. The numbers in the
“N” columns are the number of data points analysed
These data indicate that ultrasound directed treatment of mares at high risk for foetal and neonatal loss
reduces the number of pregnancies lost and the foals produced are similar to normal foals. This study
has resulted in the use of ultrasound directed treatment in a large number of broodmares during the
past three years. In 2007, yearlings from these mares sold at the two premier yearling sales in
Australia had an average price that was 1.6 times higher than the overall sales average.
Placental Pathology of High Risk and Normal Mares
Forty-one of the 77 placentas examined had pathology in the placenta, detected either by gross or
histological examination (Table 2). This is higher than would be expected based on the health of the
foals. There was no difference in the overall incidence of pathology detected in the placenta between
high risk and normal mares. Pathology in the body of the placenta was the only site that was
associated with the risk group of the mare. High risk mares were more likely to have pathology in the
body of the placenta than normal mares (p=0.156).
13
Total Mares
n=77
(%)
High Risk
Mares n=47
Normal
Mares n=33
Table 2
Gross
Pathology
at Cervical
Pole
Histopathology
present at
Cervical Pole
Gross
Pathology
in Body of
Placenta
Histopathology
in Body of
Placenta
Gross
Pathology
at other
Sites
Pathology
at any Site
in the
Placenta
22
27
13
14
15
41
(28%)
(34%)
(16%)
(17%)
(18%)
(53%)
14
17
11
11
10
26
(30%)
(36%)
(23%)
(23%)
(21%)
(55%)
7
9
1
2
4
15
(23%)
(30%)
(3%) *
(7%) *
(13%)
(50%)
The number of placentas with pathology present in the different regions of the
placenta in normal and high risk mares.
Placental Pathology and Neonatal Foal Health
The presence of pathology at any site in the placenta had no effect on the gestational length, size of
the foal, whether the foal died or required intensive care, the white blood cell count, neutrophil count,
band neutrophils count, serum fibrinogen level, serum creatinine concentration or the placental
weight. The time taken for the foal to stand was the only parameter that was related to the presence of
pathology at any site (Table 3).
14
Foal Health Parameters
Gestational Length
Percentage of foals that died or
required intensive care
Birth Weight (kg)
Time to Stand ( minutes)
White Blood Cell Count x 109/L
Neutrophil Count x 109/L
Fibrinogen g/L
Creatinine Umol/L
Placental Weight ( kg)
Table 3
No Pathology
N
342
36
(331-353)
8%
36
54
27
(47-62)
53
34
(22—68)
7.5
32
(5.1-10.0)
6
32
(3.9-8.0)
2.5
32
(1-4)
184
23
(137-280)
6.5
33
(5-8.5)
Pathology
342
(328-366)
15%
54
(42-64)
60*
(30-120)
6.7
(4.4-9.7)
5.6
(3.1-8.6)
2
(1-3)
196
(122-290)
7
(4.9-8)
N
41
41
34
38
35
35
35
30
37
Health parameters in foals from placentas with and without pathology. Numbers are
medians with the 90% quantile in parenthesis, * indicates significantly different from
foals produced by mares with placentas with no pathology.
Pathology at the cervical star reduced the white blood cell count and the neutrophil count (Figure3).
The cervix is a common route of infection for the placenta and foetus. Infection of the neonate
frequently is associated with reduced white cell count. Hence the association of reduced white cell
count in foals from mares with cervical pole pathology may be due to a higher rate of infection in
these foals. Unfortunately, there was no attempt to obtain blood cultures from the healthy foals or to
isolate bacteria from the placentas in this study.
15
White Blood Cell Count x 109
12
11
10
9
8
7
6
5
4
3
No Pathology
Pathology Present
Cervical Pole of the Placenta
Figure 3
The white blood cell count in foals from mare that had pathology at the cervical pole
of the placenta was lower than in foals from mare with no pathology at the cervical
pole. The box plots of the two populations are shown, the width of the box plot
represents the size of the population.
The presence of pathology in the body of the placenta was associated with reduced foal birth weight
and increased time taken for the foal to stand (Figure 4). The size of the foal is dependant on the size
of the placenta and the development of the chorionic surface.
16
160
65
140
60
120
Time to Stand (Minutes
Foal Size (Kg)
70
55
100
50
45
40
35
30
No Pathology
Pathology
Present
80
60
40
20
0
No Pathology
Pathology
Present
Pathology in the Body of the Placenta
Figure 4
Pathology present in the body of the placenta reduced the size of the foal and
increased the time taken for the foal to stand. Box plots of the two populations are
shown, the width of the box plot represents the number in each population.
Ultrasound Parameters of High Risk and Normal Mares
Consistent with the foal health data and placental pathology data, there was no difference in
ultrasound parameters, controlled for gestational age and treatment, between the high risk and normal
mares.
Ultrasound parameters changed significantly with gestational age. Rectal CUPT and abdominal CUPT
increased significantly as gestational age increased. The line of best fit for rectal CUPT was a
polynomial 2nd degree line (Figure 5). Whereas the best fit for the abdominal CUPT and gestational
age was linear (Figure 6). There was no difference in these parameters between the high risk mares
and the normal mares.
17
1.5
Rectal CUPT (cm)
1.3
1.1
0.9
0.7
0.5
0.3
0.1
150
180
210
240
270
300
Gestational Age (days)
330
High risk mares
Normal Mares
Abdominal
CUPT (cm)
Figure 5
The rectal CUPT increased with gestational age similarly in both normal and high
risk mares. Dotted lines represent 95% confidence intervals.
1.7
1.5
1.3
1.1
0.9
0.7
0.5
0.3
0.1
150 180 210 240 270 300 330
Gestational Age (Days)
High risk mares
Normal Mares
Figure 6
The abdominal CUPT increased with gestational age similarly in both normal and
high risk mares. Dotted lines represent 95% confidence interval.
The rectal and the abdominal CUPT were correlated with the best fit being linear. There was no
difference between normal and high risk mares (Figure 7).
18
Abdominal
CUPT (cm)
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.3 0.5 0.7 0.9 1.1 1.3 1.5
Rectal CUPT (cm)
High risk mares
Normal Mares
Figure 7
The rectal and abdominal CUPT were very well correlated. Dotted lines represent
95% confidence interval.
These data indicate that high risk and normal mares have similar changes in their placentas during
gestation and that when an abnormally wide placenta was detected by trans-rectal examination, there
was a high probability that trans-abdominal ultrasound examination would detect the CUPT wider
than normal.
Ultrasound Parameters Associated with Gestational Age and
Treatment
Rectal and abdominal CUPT, and foetal aortic diameter increased and foetal heart rate decreased with
gestational age (Figures 8&9). Foetal fluid turbidity did not change with gestational age. As
gestational age increased, wider than normal CUPT values and placental separation detected by transrectal ultrasound examination were more likely to occur. As gestational age increased, a wider than
normal CUPT and placental folding and separation detected during trans-abdominal ultrasound
examination was more likely to occur. The rectal CUPT was correlated with the presence of
separation and placental folding detected on the trans-rectal ultrasound. The abdominal CUPT was
correlated with the presence of separation and placental folding detected on the trans-abdominal
ultrasound. These findings indicate although there are changes in the ultrasound parameters with
gestational age, that there is close correlation in abnormal ultrasound parameters, and when one
parameter is abnormal other parameters are typically also abnormal.
19
Foetal Heart Rate (bpm)
160
140
120
100
80
60
150 180 210 240 270 300 330
Gestational Age (days)
Foetal Aortic Diameter (cm)
Figure 8
The foetal heart rate decreased with gestational age. Dotted lines indicate 95%
confidence interval.
2.8
2.4
2
1.6
1.2
0.8
Figure 9
150 180 210 240 270 300 330
Gestational Age (days)
The aortic diameter increased with gestational age. Dotted lines indicate 95%
confidence interval.
20
Rectal and abdominal CUPT and foetal aortic diameter were reduced and foetal heart rate was
increased in mares that were treated. Foetal fluids were more likely to be turbid in mares that were
treated (Figure 9). This result would be expected as mares were treated based on abnormal ultrasound
findings. Placental folding was more likely to be detected during trans-rectal and trans-abdominal
ultrasound in mares that were treated. However, placental separation detected during trans-rectal and
trans-abdominal ultrasound was not associated with the treatment of the mare.
Fluid Turbidity
1.00
Turbid
0.75
0.50
Clear
0.25
0.00
Not Treated
Treated Mares
Figure 10 Mosaic plot of amniotic and allantoic fluid turbidity in treated compared with
untreated mares.
Ultrasound Parameters Associated with Foal Health and Placental
Pathology
The mares were treated based on the ultrasound findings which resulted in an increase in foetal and
neonatal survival (Figure 2). The remarkably low incidence of disease in the neonatal foals in this
study restricted detection of any association between foal health and ultrasound parameters.
Gestational length decreased in association with wider than normal rectal CUPT and abdominal
placental separation. The foal’s size was correlated with the aortic diameter and the foetal heart rate.
The number of foals that died or require intensive care was associated with the abdominal CUPT. An
increased time for the foal to stand was associated with abdominal placental separation and folding
and the foetal heart rate. The foal’s white blood cell count, neutrophil count, fibrinogen and creatinine
concentration and the placental weight were not correlated with any of the ultrasound parameters
(Table 4).
Placental pathology was associated with wider than normal CUPT, separation and folding detected
during the trans-abdominal examination only. No other ultrasound parameters were associated with
placental pathology. Further prospective investigation of ultrasound assessment of pregnant mares
needs to be completed to be able to determine the important discriminatory ultrasound parameters for
foetal survival and placental pathology (Table 4).
21
Foal Health
or Placental
Pathology
Parameter
Gestational
Length
(days)
Percentage
of foals that
died or
required
intensive
care
Placental parameters
detected during Rectal
Exam
CUPT
Separation
Folding
Placental parameters
detected during Abdominal
Exam
CUPT
p=.0003
Separation
Foetal
Heart Rate
Foetal Aortic
Diameter
p=.0232
p= .009
Folding
p=.0157
p=.0493
Foal Birth
weight (kg)
Time to
Stand (min)
Fluid
p=.0195
p=.0003
p=.0007
White Blood
Cell Count x
109
Neutrophil
Count x 109
Band
Neutrophil
Count x 109
Fibrinogen
g/L
Creatinine
mmol/L
Placenta
weight (kg)
p=.0227
p=.0499
Pathology at
Cervical
Pole
Pathology in
Body of
Placenta
p=.0147
Pathology at
any Site in
the Placenta
Table 4
Foal Health or Placental Pathology Variables that were correlated with ultrasound
parameters have highlighted boxes with p values in the box
22
Ultrasound parameters that were correlated with foetal health or placental pathology (rectal and
abdominal CUPT, placental separation and folding detected during the trans-abdominal ultrasound
examination, foetal aortic diameter and foetal heart rate) were used to derive a model ultrasound
index. This ultrasound index was positively correlated with the foal’s time to stand and with presence
of pathology in the placenta (Figure 11). Further prospective investigation of ultrasound assessment
of pregnant mares is necessary to determine the important discriminatory and ultrasound parameters
for foetal survival.
log time to stand
5
4
3
0
1
2
Ultrasound Index
3
4 5
Figure 11 The derived model ultrasound index was correlated with the time taken for the foal
to stand. Box plots for the time to stand at each index level are represented.
Incidence of Abnormal Scans and Placental Pathology
An abnormal ultrasound parameter was detected at 92% of examinations. The percentage of abnormal
ultrasound parameters did not vary with the origin of the ultrasound image (trans-rectal or transabdominal) or with the risk group of the mare (Table 5). This incidence is similar to that expected for
high risk mares but much higher than expected for normal mares and consequently, almost all the
mares were treated at least once during the study (see Results: Mare Treatment). These data indicate
that the current normal values, when used prospectively, over-estimate the incidence of placental
pathology in a population of mares. The created model ultrasound index was four or greater in only 8
% of examinations; in addition, utilisation of this parameter would have resulted in the treatment of 31
% of the mares. Further prospective clinical trials need to be conducted on mares that are not treated
so that the predictive value of ultrasound parameters to determine equine pregnancy outcome can be
accurately evaluated and excessive treatment avoided.
23
All Mares
Percentage
of
Ultrasound
Parameters
Table 5
Rectal
CUPT
wider
than
normal
Rectal
Placental
Separation
Rectal
Placental
Folding
Abdominal
CUPT
wider than
normal
Abdominal
Placental
separation
Abdominal
Placental
Folding
Model
Ultrasound
Score >4
46%
20%
38%
46%
36%
37%
17%
The percentage of ultrasound parameters that were abnormal in the entire study
population of mares.
When the data from mares that received no treatment and produced a healthy foal was summarised,
the number of abnormal observations was reduced, but remained about 30%. (Table 6) However, only
3% of the examinations of these mares resulted in a total ultrasound score of 4 or greater, suggesting
that the derived ultrasound score maybe a better discriminatory variable than individual ultrasound
parameters for foetal survival and health. There were no mares in the study that were not treated and
aborted or delivered a critically ill foal, so comparisons based on foal outcome from untreated mares
could not be performed.
Untreated
Mares
Healthy
Foals
Percentage
of
Ultrasound
Parameters
Table 6
Rectal
CUPT
wider
than
normal
Rectal
Placental
Separation
Rectal
Placental
Folding
Abdominal
CUPT wider
than normal
Abdominal
Placental
Separation
Abdominal
Placental
Folding
Model
Ultrasound
Score >4
37%
23%
28%
49%
23%
21%
3%
The percentage of ultrasound parameters that were abnormal in untreated mares
that produced healthy foals.
The mean rectal and abdominal CUPT from mares that produced a normal foal and received no
treatment at each gestational age was similar to previously published data 20. In this group of mares
the maximum ultrasound score exceeded 4 on only 5 occasions and the median total ultrasound score
was 2 or less at all gestational ages examined (Table 7).
24
Mean Rectal
CUPT (cm)
Std Dev
(Rectal
CUPT)
Mean
Abdominal
CUPT (cm)
Std Dev
(Abdominal
CUPT)
Median
Ultrasound
Score
150-180
0.48
0.09
0.64
0.13
2
180-210
0.49
0.08
0.69
0.15
1
210-240
0.55
0.11
0.74
0.14
.5
240-270
0.66
0.10
0.87
0.14
1
270-300
0.79
0.10
0.98
0.11
2
300-330
0.98
0.17
1.06
0.13
2
Gestational
Age
Table 7
Mean rectal and abdominal CUPT and median ultrasound score in normal mares
that were not treated and produced a healthy foal.
This study has generated considerable clinical work examining pregnant mares that the owners value
highly. Unfortunately the current techniques have not been validated in a thorough prospective trial
using normal mares. This study shows clearly that the outcome of high risk pregnancies can be
improved using this technology, however an unacceptably high number of normally fertile mares were
treated because of the high rate that abnormalities were detected. One of the secondary aims of this
study was to reduce the indiscriminate use of antibiotics in broodmares; unfortunately this technology
has the opposite effect. It is critically important to conduct a prospective trial using these parameters,
particularly the total ultrasound score, in a large group of normal mares that are not treated so that the
positive and negative predictive values can be determined.
25
Discussion
Overall Objectives
The primary objective, to document the development and consequences of placental abnormalities
occurring during the second half of gestation in thoroughbred broodmares and determine whether
treatment based on these findings improves foetal and neonatal foal health was achieved. It is possible
to conduct a modified detailed placental and foetal ultrasound examination of broodmares in the field.
Utilisation of the data collected to direct treatment of the mares resulted in an increase in the number
of healthy foals produced by mares with a previous history of abortion or premature labor. The
technology detects subtle changes in the placenta and results in a large number of mares receiving
treatment during a monitored pregnancy. It is expected that many of the normally fertile mares would
control the mild placental pathology detected and deliver a normal foal without treatment. Therefore,
it is critically important that improved discriminatory parameters are developed so that treatment can
be more efficiently directed.
Specific Objectives
To correlate placental changes detected in mares by ultrasound, with gross and
histopathological evidence of placentitis.
To determine whether equine foetal and neonatal weight and health are
correlated with placental abnormalities detected by ultrasound.
These two objectives could not be adequately achieved because treatment of the mares was more
successful than expected. Treatment of the mares was determined by the ultrasound detected changes
in the placenta and significantly affected these parameters. In addition, treatment improved foetal and
neonatal foal health; hence there were significantly fewer cases of foetal loss or critically ill neonates
than expected. Consequently, the data available to determine correlations between ultrasound detected
placental abnormalities and foal health or placental pathology was insufficient for adequate statistical
analysis. The significant disadvantage of this failure to meet these objectives is that numerous
valuable mares now have regular ultrasound assessments of their pregnancies and a large number of
mares receive treatment that may be unnecessary because pregnancies with a high probability of a
poor outcome cannot be accurately discriminated from those that will have a normal outcome. Further
work to improve the predictive values of ultrasound examination is essential.
To monitor the development and progression of placental abnormalities detected
by ultrasound in normal and high risk thoroughbred mares.
This objective was limited by the treatment of mares during the study, however abnormalities were
detected during both trans-rectal and trans-abdominal examination and changes in these abnormalities
over time were observed. When treatment was initiated, the changes in the ultrasound parameters
typically returned to normal. In many mares when treatment was discontinued, the ultrasound
parameters increased again to be outside the normal ranges. This was more noticeable in high risk
mares. Because the study was not designed to assess the effect of treatment, precise records of
treatment regimes are not available and further analysis of the changes noticed within mares as a
response to treatment unfortunately cannot be performed.
26
To determine the incidence of placental pathology in normal thoroughbred
mares and in mares at high risk for abortion or premature delivery.
Pathology was detected in the placenta of 53% of all the mares examined, although fewer normal
mares (47%) had some pathology detected in their placentas than high risk mares (55%); this
difference was not significant. These data are similar to previous reports from thoroughbred mares
where histopathology was found in 23/50 (46%) of the placentas examined 30. High risk mares were
more likely to have pathology in the body of the placenta than normal mares. The survival of foals
from placentas with histological abnormalities has previous been reported to be less than 10% (2/23)
(30). In contrast, in this study survival of foals from placentas with histological abnormalities was
greater than 80% (24/29). The histopathology in the placenta of mares in this study was assessed by
an experienced equine specialist pathologist completely unaware of the mare’s risk, treatment regime
or pregnancy outcome. Both studies included examination of similar numbers of placentas. It is
possible although pathology developed in the placenta, that treatment during pregnancy improved
foetal health and neonatal survival. This result is particularly encouraging for the horse breeding
industry; because it indicates that intensive monitoring and ultrasound directed treatment results in the
delivery of healthy foals from mares with suboptimal placental development. Assessment of the racing
performance of the foals from this study is currently underway and will be the final determinant of the
success of this intensive intervention.
27
Implications
The group of 47 high risk mares produced 43 healthy foals during this study. Based on previous
foaling records and foaling records in the two years subsequent to the study, these mares would
normally be expected to produce only19 foals. Adoption of this technology should be able to halve the
number of pregnancies lost after conception which could improve the average annual foaling rate by
up to 10%. Importantly, the size and health of these foals was similar to foals from the normal mares.
During the 2006, 2007 and 2008 breeding seasons, numerous thoroughbred breeding farms in the
Hunter Valley and in the Hawkesbury region have adopted the program to improve the productivity of
their mares. The program has been so successful in the region that there are now several other
veterinarians using the technology to monitor high risk pregnancies. In addition, the owners of
numerous valuable mares with normal breeding records have requested ultrasound monitoring during
pregnancy. The use of this technology in normal mares resulted in a large number receiving
unnecessary treatment; it is critically important that the ultrasound index derived in this project is
investigated in a prospective study in a large group of normal mares that receive no treatment.
28
Recommendations
This study has clearly demonstrated that ultrasound monitoring and treatment of high risk mares
improves foetal and neonatal viability. It is important that the technology is further validated by
prospective studies in untreated mares and refined to be more useful in evaluating normal equine
pregnancies. Preventive ante-natal monitoring programs similar to those used in women could then
be developed. Information derived from this study needs to be disseminated to equine veterinarians
throughout Australia and internationally by presentations at veterinary meetings, workshops and
publications in veterinary journals.
29
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32
Placentitis in Horses
by Joan Barbara Carrick
Publication No. 10/156
Placentitis or inflammation of the placenta is most often
caused by infection. Placentitis and placental abnormalities
are a major cause of reproductive loss, which costs the equine
industry a large amount of money each year due to lost foals
and the treatment of critically ill foals. Because clinical signs of
placental pathology are variable, typically the first indication of a
problem is abortion or still birth.
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Most of the information we produce can be downloaded for free
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Ultrasound examination can identify placental pathology before RIRDC books can also be purchased by phoning
abortion or premature delivery occurs. In this study, mares were 1300 634 313 for a local call fee.
treated based on abnormalities identified during the ultrasound
examinations. The regime of intensive examination and
treatment resulted in a foaling rate that was similar to the foaling
rate for normal mares.
Cover photo: Ultrasound examination on a pregnant mare to detect Placentitis and placental abnormalities
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