Gravid i Norge 2013 100 000 graviditeter i Norge Perinatal dødlighet

Transcription

16.01.2014
100 000 graviditeter i Norge
Gravid i Norge 2013
Spontan abort
15 000
Ekstrauterint svangerskap
1500
Fødsel
spontan abort
indusert abort
Fødsel
EX uterint60
ssk000+
Babill Stray-Pedersen
Indusert abort
Kvinneklinikken
Rikshospitalet
Oslo Universitetssykehus
og
Universitet i Oslo
Norge
15 000
Gravid i Norge
60 255
Fødsler 2012:
Gutt 51% / Pike 49%
Anall barn per kvinne:
1.95
52 fødeinstitusjoner
21 neonatal enheter
20 % født uten
neonatal service
30 år
1. gangs fødende:
25 - 30 år (27.3)
19 %
7%
>35 år:
4 eller flere barn:
Lav spebarns dødlighet < 7d:
> 28 uker:
>22 uker:
Alder:
3, 6 av 1000
4. 8 av 1000
Best i verden
Svangerskap/fød permisjon (49 uker)
Mor
må ta 14 uker( 6+8)
Far
må ta 12 uker
Amme permisjon: 2 t per dag
Komplikasjoner
I svangerskapet:
1 av 4, stiger med alder
Ved fødsel:
1 av 3 , stiger med alder
For tidlig fødsel:
1 av 15
Fjernkulturelle:
1 av 15 ( 7%)
Under 0.5-1.5 kg 1% (ca 600 barn)
( Oslo 1 av 4)
Eldre mor
Mødre og spebarnsdødlighet
I Norge
Antall fødsler
Mor død
Perinatal dødlighet i Norge
Fødsler
70 000
107
100
60 000
20
21
40 000
47
Mor død
1950
10
11
14
1960
50
Perinatal død
17
5
1940
perinatal
død
per 1000
8
5
1970
Fødsels
register
1980
1990
Perinatal
komite
64
4
2000
Retninglinjer
1
16.01.2014
Mor er eldre i Norge idag
Perinatale
dødlighet
Downs
syndrom
Mors
dødlighet
6 per 1000
4 per 10 000
40 år: 20 per 1000
100 per 10 000
20
45 år: 30 per 1000
400 per 10 000
100
RR
23 år:
2010
191 dødfødte
3 per 1000
Biologiske klokke tikker
Dødfødte etter 22 uke er halvert sident1999
Mødre dødlighet i Norge
Risk of Maternal Death during Lifetime
1 : 140
Per 1000
kvinner
1/ 7600
10
blødning
5
1/ 2400
1/ 11
barselsfeber
1
1
1/ 120
1/ 31
Keisersnitt
1/12000
1/ 190
1/240
1/ 7400
Penicillin
Blod overføring
0,1
Tidlig mobilisering
1750
1800 1850
1900
1950
2000
UN, 2008
År
Mødre dødlighet i Norge
Maternal Mortality 2005
B
e
t
y
d
n
i
n
g
e
n
a
v
m
o
r
s
a
l
d
e
r
Direct causes per 100 000
74.2
7
5
7
0
1971-80
19.0
2
0
1
5
10.3
1
0
Per10fødsler
Hungary
11.9
France
11.3
Finland
9.9
Denmark
9.8
Austria
9.4
Portugal
9.0
Netherlands 7.7
UK
6.9
Belgium
4.7
Norway
4.5
5
4.1 4.5
5.0
0
<
2
0
2
0
2
4
2
5
2
9
3
0
3
4
3
5
3
9
>
4
0
A
l
d
e
r
s
s
p
e
s
i
f
i
k
k
m
ø
d
r
e
d
ø
d
e
l
i
g
h
e
t
s
r
a
t
e
2
16.01.2014
Hva har skjedd de siste 40 år ?
Alvorlig syklighet hos mor ved fødsel
Fertilitet(barn perkvinne)
Oslo: 1-2 av 100 kvinner
1/3 kan velges ut på forhånd
2/3 kommer helt uventet
= 6 per 1000 fødsler
2007
3.0
1.8
Alder på førstegangsfødende 21
28.4 år
4 eller flere barn
15 %
9%
Svangerskaps permisjon
12
47 u
For tidlig fødsel
6.5 %
6.1 %
under 28 uker
= 1 per 150 fødsler
1967
0.7%
1.8 %
Keisersnitt
2.2
17 %
Spebarnsdødlighet
20
5
Den norske mor barn undersøkelsen
MoBa
Bekkenløsning
• 15 % mente de hadde bekkenleddsyndrom.
• 2,5 % mente å ha alvorlig grad
• 7,7 % av de gravide brukte krykker på grunn av smertene.
• Inkludert 100 000 svangerskap 2008.
Risikoen for BL økte med antall tidligere fødsler:
• 11 % av de førstegangsfødende
– 18 % av de andregangsfødende
• Mor, far , barn
• 21 % av de tredjegangsfødende.
• 100 subprosjekter
• Risikoen for alvorlig BL var
– 2 ganger økt for 2 gangsfødende og
• 3 ganger økt for 3 gangsfødende
– sammenlignet med førstegangsfødende, justert for andre faktorer.
Preterm fødsel
MFR:
USA
USA
Norge
IVF
12,5 %
900 000
barn født >23 uker 1967-1983
Sammenheng mellom avtagende svangerskapslengde
og økt forekomst av
6%
9
8
•
•
•
•
7
6
%
5
4
3
2
1
0
1980
1990
2000
Year
cerebral parese,
psykisk utviklingshemning
flere andre funksjonshemninger,
andel med uførepensjon som voksne.
7,6
7,5
7,4
Belgia:
7,3
7,6 %
7,2
7,1
Moster et al, N Eng J Med 2008
7
6,9
6,8
1995
2000
2002
2004
3
16.01.2014
Assistert befruktning 2.9% : 1800 / år
Flerfødsler I Norge
2%
6000 IVF fødsler
1,7%
Twins
24%
Triplets etc
3%
Barn: IVF - naturlig befruktning (2500 barn)
• 25 gram lavere fødselsvekt,
• 2 dager tidligere
• 31 % høyere risiko for dødfødsel
Romundstad, Lancet 2008
Fødsels fakta i Norge
Fødsel
• Økende alder på mor,
nå stagnert
• Økende diabetes
• Barnet vekt avtagende
• Dobling av tvillinger,
nå avtagende
Totalt
Hjemme:
• Økende keisersnitt
60 000
100 + 200
Transport 180
Induksjon12%
Keisersnitt: 10 000
Operativ vaginal fødsel 9 %
Epidural 23%
Keisersnitt i Norge 1967-2009
Vacuum 8 %
17,1%
Tang 1,5%
Episiotomi 16 %
Perineal rift 3- 4 2,5%
Norgeshelsa-FHI
4
16.01.2014
Keisersnitt i Norge 1967-2009
Mors alder
Indikasjon/årsak
> 35 yrs
Total
< 20 yrs
%
Fosterstress (tegn på oksygenmangel)
Langsom framgang
Tidligere keisersnitt
Seteleie etter 34. svangerskapsuke
Mors ønske
Svangerskapsforgiftning
Mislykket igangsetting av fødsel
Andre indikasjoner
Totalt
608
248
234
211
172
112
602
22
21
9
8
8
6
4
22
2778 100
Kolaas T
God morgen
Komplikasjons risikoen ved keisersnitt øker ved
•
ikke planlagt keisersnitt ( 18 versus 38%)
•
gest.alder < 30 uker
•
stort foster
•
generell anestesi
•
cervix dilatasjon
0 cm:
16%
9-10cm:
33%
Am J Ob Gyn. 2004;190:428-34.
Vaginal fødsel etter keisersnitt VABAC
•
Velykket opp til 85%
E.S.27.11.02
•
Ruptur :
0,5 - 1,5 % ( normal fødsel - induksjon)
Mange små og veldig store barn
1.2% < 1.5kg ,
Amming i Norge
21% > 4 kg,
3 % over 4.5 kg
Svangerskapsomsorgen i Norge
1984
Perinatal komiteer
1995
Jordmor i hver komune
2006
EB medisin
Kunnskapsbasert
5
16.01.2014
De nye retningslinjer
Risiko for foster
• Informasjon til kvinnen, velge selv
Velge lege/jordmor:
samme person
• Røyk
• Alt er tilbud. (syfilis, HIV, ultralyd)
• Alkohol
• Færre kontroller ( 7-8 )
– Ikke gyn us, kun på indikasjon
– Spør om liv – ikke alltid lytte på fosterlyd
– Ikke barsels 6 ukers kontroll
• Infeksjoner
Røyking
Mor røyker
1.svangerskapskontroll
Norway:
18% røker tidlig I svangerskapet  7% siste kontroll
< 20år:
45%
20%
Behandling i svangerskapet
Diskusjon i dag
Før svangerskapet –
Prekonsepsjonell undersøkelse og veiledning
• Medisinen skal være:
Kvinner > 38 år,
• sikker for fosteret
Kvinner med sykdom, bruker medikamenter
• effektiv
• anvendes i kortest mulig tid
• dosering: identisk eller høyere enn
normal dose
Tidligere født sykt barn
Risikofylt arbeid : reiser, tungt fysisk arbeid
Folinsyre 27%67% / livsstil /
• Kvinnens egne varianter:
• Myk fødsel hjemme , alternativ fødestue
Se Legemiddelhåndboken
FASS
• Keisersnitt på eget ønske
• Hindre for tidlig fødsel
6
Vi skal gjennomgå
forandringer i:
•
•
•
•
•
Svangerskapets fysiologi
Blod
Hjerte- kar
Respirasjon
Nyrer
Gastrointestinaltraktus
Britt-Ingjerd Nesheim
Grunnkurs i obstetrikk 19. januar 2015
Hvordan kan vi forstå de fysiologiske
forandringene i svangerskapet?
• Svangerskapet er en hyperterm tilstand
Plasmavolum
•
•
– Fosteret produserer varme, det må avgis via mor
• Svangerskapet preges av en arteriovenøs
shunt
– Nemlig sirkulasjonen i uterus og placenta
•
•
Normalt
plasmavolum
hos ikkegravid: 2600
ml
Økning 1200 –
1500 ml i løpet
av
svangerskapet
Økning ca. 50
%
Årsak: ukjent
• Svangerskapshormoner
– Kjente og ukjente
Hytten & Chamberlain 1980
Vi skal gjennomgå
forandringer i:
Erytrocytter
•
•
•
•
•
•
Blod
Hjerte- kar
Respirasjon
Nyrer
•
•
•
Volum hos ikkegravide: 1400
ml
Økning
avhengig av
jerntilskudd
Hvis
jerntilskudd: 400
ml
Hvis ikke: 240
ml
Hytten & Chamberlain 1980
•Plasmavolum øker mer enn
erytrocyttvolum
Hemostase
•Hemoglobin synker
• Fibrinogen øker
• De fleste andre koagulasjonsfaktorer øker
• Fibrinolytisk aktivitet nedsatt
•Hematokrit synker
•MCHC er uforandret
•MCV er uforandret
Normale laboratorieverdier hos gravide. Gjennomsnitt (SD)
Ikke gravid
1. trimester
Siste trimester
Ca. 6 uker post
partum
Hgb (kvinner
som ikke tar
jern)
13,3 (0,8)
12,0 (0,7)
11,1 (0,8)
12,7 (0,9)
Hematokrit
39 (2)
35 (2)
33 (2)
38 (2)
Erytrocytter
(x1012/l)
4,7 (0,3)
4,0 (0,2)
3,9 (0,3)
4,5 (0,3)
Leukocytter
(x109/l)
5,6 (1,0)
6,9 (1,7)
10,2 (3,4)
7,3 (2,4)
Serumjern
(Pmol/l)
11-31
(Referanseområ
de)
23
14
Ferritin (Pg/l)
10-110
96
13
Serumalbumin
(g/l)
40-51
32,2 (4,0)
27,5 (3,0)
LD
150 – 450 U/L
Opp til 700 U/L
Andre endringer i blod
Vi skal gjennomgå
forandringer i:
•
•
•
•
•
•
•
•
•
•
Kolesterol (LDL) dobles
HDL uforandret
Triglycerider tredobles
Alkalisk fosfatase betydelig øket
Trombocytter lett redusert mot termin
– Ca. 10 % har lett trombocytopeni (100- 150 x
109/l)
– Øket aktivering og øket nedbrytning (?)
• Kortere levetid (i hvert fall ved preeklampsi)
• CRP normal eller litt øket
Blod
Hjerte- kar
Respirasjon
Nyrer
33,9 (3,5)
Change in systemic vascular resistance
Forandringer i puls og blodtrykk
pp
pp
Puls
Blodtrykk
52
24
38
pp
12
32
24
8
16
85
84
83
82
81
80
79
78
77
76
75
Fø
rs
va
ng
er
sk
ap
80
70
60
50
40
30
20
10
0
Clapp AF III, Capeleas E: Am J Cardiol 1997; 80: 1469-73
85
84
83
82
81
80
79
78
77
76
75
pp
52
pp
24
Fø
rs
va
ng
e
12
pp
38
32
24
16
8
rs
ka
p
Gjennomsnittlig arterielt blodtrykk
Pulsfrekvens
75
70
65
60
55
pp
52
pp
24
pp
38
12
32
24
16
8
Fø
rs
va
ng
er
sk
ap
50
Økt trykk i bekkenvener og v. femoralis
Respirasjon
o varicer og hemorrhoider
Respirasjonsforandringer i svangerskapet
• Tidevolumet øker
ca. 40 %
• Skyldes økt utslag
av diafragma
• Minuttvolumet øker
• O2behovet øker 15
%
• Produksjonen av
CO2 øker
tilsvarende
---- gravid
___ ikke gravid
Vi skal gjennomgå forandringer i:
•
•
•
•
•
Blod
Hjerte- kar
Respirasjon
Nyrer
Lungefunksjon i
svangerskapet
PEF = peak expiratory flow
FVC = forced vital capacity
FEV1 = forced expiratory volume
in 1 second
Urinveier
• Anatomi
• Fysiologi
FVC hos para > 0, dvs.
forandringene vedvarer etter
svangerskapet
G Grindheim,K Toska,M-E Estensen,LA
Rosseland, BJOG 2011
Diameter av calyces i
svangerskapet
Ventilasjon
Merk: større diameter på
høyre enn på venstre side
• Ventilasjonen mer økt enn nødvendig på
grunn av økt metabolisme
• o fjerning av karbondioksid
• o kronisk respiratorisk alkalose – renalt
kompensert
• Arteriell pCO2 5,3 kPa o 4,0 kPa
• pH uforandret
• Respirasjonssenterets sensitivitet for CO2 n
Peake et al. Radiology 1983; 146:16770
Vi skal gjennomgå
forandringer i:
Fysiologi
•
•
•
•
•
•
•
•
•
•
Blod
Hjerte- kar
Respirasjon
Nyrer
Blodgjennomstrømning n 30 – 50 %
Glomerulusfiltrasjon øker
Tilbakeresorbsjon øker
Glukosuri – skyldes økt glomerulusfiltrasjon
Utskillelse av vannløselige vitaminer øker
Væskebalanse
• Osmolaliteten i plasma p
• Gravide kvinner er ”omkoblet” til denne nye
situasjonen – normalt ville overskuddsvæske
vært skilt ut
• Økning av ekstracellulært volum – derfor Naretensjon
• Svangerskapsødemer er av det gode
Vi skal gjennomgå forandringer i:
•
•
•
•
•
Blod
Hjerte- kar
Respirasjon
Nyrer
• Nedsatt tonus og motilitet
– Forlenget tømningstid av ventrikkel
– Obstipasjon
– Betyr det noe for svangerskapskvalmen?
Svangerskap
Ernæring og ernærings tilskudd i
svangerskapet
Maternell
Føtal
Ernæring
Ernæring
Janette Khoury MD, PhD
Spesialist i Kvinnesykdommer og Fødselshjelp
Post Doc Universitetet i Oslo
Privatpraktiserendespesialist Brynmedisinske Senter
E-mail: jakhoury@hotmail.com
Januar 2011
Umbilical artery
Carrying the fetal blood to the placenta
for exchange of gases and nutrients
Optimal forhold
Sunt og balansert
kosthold
for
føtal utvikling og tilvekst
Metabolske tilpassninger i svangerskapet
Metabolske tilpassninger i svangerskapet
Maternell hyperkolesterolemi
Maternell hypertriglyceridemi
Plasma
LDL
3
Cholesterol
(mmol/l)
HDL
mmol/L
6
7,5
7
6,5
6
5,5
5
4,5
4
3,5
3
2,5
2
1,5
1
0,5
wk 8
VLDL
nonpregnant
8
14
20
28
36
Trigly
wk 20
wk 30
wk 38
wk pregnancy
Lactation
Pregnancy weeks
Modified after Fåhraeus, MD et al. Obstetrics & Gynecology 1985; 66: 468.
Avgjørende faktorer som påvirker
føtal ernæring og føtal tilvekst
Endringer i spiral arterier
Maternal side
Gjennomblødning i
The placenta
uteroplacental årer
uavhengig av maternal
 Uteroplacental gjennomblødning
(placentær svikt)
kontrol mekanismer i
 Overføring av næringsstoffer
over placenta
åreveggen som styrer
utvidelse eller konstriksjon
Preeclampsia
Normal
Fetal side
av blodårene.
 Morens endokrine og
metabolsk faktorer
(f.eks maternal hypercholesterolemia)
(f.eks maternal hyperinsulinemia)
kan øke med 10%
Secretary fase
 Mors ernærings tilstand,
metabolsk kapasitet, og daglig inntak
 Fosterets evne til å nyttig seg
næringsstoffene (medfødte misdannelse,
kromosomfeil)
Tore Henriksen, Acta Pædiatrica Suppl 1999; Godfrey et al Am J Clin
Nutr,2000; Barker DJP Theriogenology 2000,
Ernæring og ernæringstilskudd i
svangerskapet - J. Khoury
Føtal tilvekst versus fødselsvekt
Growth
Normal
Flere føtal tilvekst mønstre men
samme fødselsvekt
Large
restricted
A Late growth restriction
B Early growth restriction
C Normal growth
D Late growth restriction
followed by catch up growth
Harding, International Journal of Epidemiology 2001; 30 (1): 15-23.
Trenger ikke å spise for to
300-400 kcal ekstra fra 2 trimester
Kost veiledning
Nøvendig at det startes før
svangerkapet
Vekt økning i svangerskapet
Amerikanske anbefalinger
Institute of Medicine (IOM) 2009:
BMI kg/m2
Før konsepsjon
Anbefalt vektøkning (kg)
pr uke 2dre og
Totalt /
3dje trimester
Lav < 18,5
12,5-18,0 /
≥ 0,5
Normal 18,5-24.9
11,5-16,0/
0,4
Høy 25,0-29.9
7,0-11,5 /
≤ 0,3
Fedme > 30,0
5-9 /
≤ 0,2
National academies press (US); 2009
- En ekstra liten mellom måltid (300-400 kcal)
• 1 tykk skive grovt brød med mager pålegg + grønnsak
• 1 glass skummet melk
• 1 eple
Kost råd i svangerskapet
Balansert sun kost
• Fisk 2 ganger i uken. Gjerne fet fisk.
• Skummet melk, ekstra lett melk, lett melk eller
lett yoghurt
• Lett margarin på brød. Flytende margarin eller
vegetabilsk olje til matlaging.
• Magert kjøtt, kylling, egg, bønner, linser / erter.
• Grøvt brød, poteter, ris, pasta. Gjerne
fullkornalternativer.
• Frukt og grønnsaker.
• Kutt ned på inntaket av sukker.
Kost råd i svangerskapet
Balansert sun kost
Total fett
30 E%
Mettet fet
Protein
Karboydrater
10 E%
15 E%
55 E%
Fisk 2 ganger i uken, frukt og grønnsaker daglig
(3 forskjellige grønnsaker og 2 forskjellige frukt)
Spesielle behov i svangerskapet
• Høyere energi fra midten av svangerskapet.
•Vitamin og mineral tilskudd?
• Kvinner med spesial behov (melk intolerance, vegetarianer,
malabsorption, anorexi, fedme)
Folate
Kosttilskudd
• Kosttilskudd kan ikke erstatte det mangfoldet av
stoffer som et sunt og variert kosthold gir. Tar
kvinnen kosttilkudd, kan hun få i seg for mye av
enkelte næringsstoffer.
• Ønske den gravide likevel å ta kosttilskudd, er
det viktig å følge doseringen som er angitt på
kosttilskuddet og ikke ta flere ulike typer
kosttilskudd som inneholder de samme
vitaminene og mineralene.
Generelle spesial behov
• Folate
• Long chain essential fatty acids (omega 3)
• Vitamin D
• Calcium
• Jern
Folate Meabolism
a donor of methyl group
Folate - 400µg/d (under planlegging og opptil 12 uker)
- 200µg/d (resten av svangerskapet) ?
Source: Cummings AM, Kavlock RJ. Crit Rev Toxicol 2004;34:461-85.
Drop in prevalence of spina bifida and
anencephaly after food fortification
with folic acid
Maternal Vitamin B12 status
og risiko for NTD
Befolkning
6,0
Spina bifida
5,0
Prevalence (per 10,000)
Anencephaly
Irland, high NTD prevalens uten folat tilsettinger.
4,0
Resultater:
3,0
Mødre i lavere B12 kvartiler sammenliknet med
mødre i høyeste kvartiler, hadde 2 to 3 økt odds
for å bære en foster med NTD
2,0
1,0
Pre-fortification
Optional Fortification
Mandatory Fortification
0,0
1995
1996
1997
198
1999
2000
2001
Molloy et al . Pediatrics 2008
Teratology 2002; 66:33-39. Updated 6/2004.
Long chain essential fatty acids
Kan omega-3 forebygge
preterm fødsel
(omega 3)
Fiske olje inntak - Få RCT
Daglig behovet av omega-3 (0,7-1,2g)
dekkes av:
Tran
5ml/d (barne skje)
eller (2 kapsler)
- 3 RCT inkludert i en metaanalyse hvor 10 studier var eksludert
da de ikke fylte kriteriene.
- Disse 3 RCT påvist 20-30% reduksjon i forekomst av prematur
fødsel. Dosen som ble brukt var 2,7g/d.
(Salvig JD et al. AOGS; 2011)
Kolesterol reduserende kosthold i regi av en balansert sun
kosthold (fetfisk x2 i uken) kan være lovende i risiko reduksjon
av prematur fødsel men trenger mer forskning
(CARRDIP STUDEIN).
(KHOURY et al. AOGS; 2005)
Vitamin D
7.5 – 10 µg/d
f.eks. Bruk en av følgende:
-2 kapsler møllers dobbel
- 5ml Tran
- 1 tablett a’10µg D-vitamin
- 10ml/d ‘Sanasol’
Calcium
Viktig å holde unna
• 500 – 1000 mg /d til de med lavt inntak
Grunnet bacteria eller dioksiner og PCB
e.g. milk intolerance, vegetarians if they do not drink soya milk
• Fisk lever
• Upastørisert melk og melkeprodukter
• Rå fisk og kjøtt produkter
• ’Innmat’ fra crabbe
• Hval kjøtt og stor tuna og andre stor fisk.
•
Anbefalt daglig inntak (900 mg)
- 3 glass skummet milk
- 2 skiver ost
- 1 porsjon yoghurt naturell
• Vegetabilske matvarer rik in Ca++ :
Mandler , Tørket fiken, Sesam frø, Grønn kål, Spinat.
Iron
• Daglig behov i kost 12-18mg/d (opptak 3-8g/d).
_Jern absorbsjon øker i andre og tredje trimester
Iron
Norske anbefalinger fra 2005
 Rutinemessig jerntilskudd anbefales ikke.
Tilskudd anbefales når:
• WHO råd hos kvinner i fertil alder
60 mg /d som tilskudd fra sv. Uke 20 hvis
- Serum ferritin < 20µg/l eller Hgb < 11g/100ml
WHO/CDC Technical consultation at the population level 2005
- Tilskudd i form av Fe2+:
Ferromax 65mg x1/Hemofer 27mg x2.
Drikke
 Hgb < 11g/100ml ved første kontroll og i uke 28.
 S-Ferritin < 20 g/l, jerntilskudd fra sv uke 20.
Anbefales målt før sv. uke 15.
Etter sv. uke 15, S-Ferritin ikke god indikator. Anbefales
da å måle S-Transferrinreseptor i tillegg.
Viktig å holde unna
Vann er den beste drikke
Grunnet bacteria eller dioksiner og PCB
• Kaffe 1-2 kopper pr dag
• Te 3 – 4 kopper pr dag
• Akohol avholdene
• Minst mulig ’brus’
• Fisk lever
• Upastørisert melk og melkeprodukter
• Rå fisk og kjøtt produkter
• ’Innmat’ fra crabbe
• Hval kjøtt og stor tuna og andre stor fisk.
Sammendrag
Grupper som trenger kost veiledning
• BMI < 19-20 or BMI > 30
• Kvinner som har gjennomgått fedme operasjon.
• Røykere
• Tenår svangerskap
• Lav socioeconomisk status
• Innvandrere
• Diabetes, anorexi, GI problemer
• Tidligere spinabifida (4 mg folate i første trimester)
• Tidligere svangerskaps komplikasjoner

Kostveiledning bør helst starte før svangerskapet.

Følge generelle råd for sunt og balansert kosthold.

Kvinner med BMI > 30 eller < 19 ved start av svangerskapet, og kvinner
med lav vekt økning under svangerskapet bør få kostveiledning.

Vitamin and mineral tilskudd ikke nødvendig med unntak av:
- Folat 400µg under planlegging og ut første trimester.
- D-vitamin for alle spesielt vinter halv året.
- Folate 200µg resten av svangerskapet, og Calcium tilskudd for de med
marginal og lav inntak.

Jern tilskudd ved indikasjon.

Kolesterol reduserende kosthold i regi av en balansert sunt kosthold
kan være lovende i risiko reduksjon av fortidlig fødsel men trenger mer
forskning.
Brosjyren ernæring i
svangerskapet
øv
Pr
THE CARRDIP STUDY
0
t3
ins
m
et
vit g
i
t
ak da
www.helsedirektoratet.no
isk ver
s
h
y
f
r
i
e
re utt
væ min
å
Cardiovascular risk
reduction diet in pregnancy
CARRDIP studien
THE CARRDIP STUDY
Kost Intervensjons gruppen
1.
Spise fisk x 2 i uken spesielt fet fisk, rent kjøtt og fjærkre,
olivenolje, rapsolje, frukt, grønnsaker,nøtter, belgfrukter,
lett melk og magre oster
Janette Khoury, Tore Henriksen, Bjørn Chrisophersen, Serena Tonstad. Effect
of a cholesterol lowering diet on maternal, cord, neonatal lipids and pregnancy
outcome. A randomized clinical trial. American Journal of Obstetrics and
Gynecology 2005;193:1292-30.
2.
Janette Khoury, Tore Henriksen, Ingebjørg Seljeflot, Lars Mørkrid, Kathrine Frey
Frøslie, Serena Tonstad. Effect of an antiatherogenic diet during pregnancy on
markers of maternal and fetal endothelial activation and inflammation: the
CARRDIP study. British Journal of Obstetrics and Gynecology Br J Obstet
Gynaecol 2007;114:279 – 288.
3.
Janette Khoury, Guttorm Haugen, Serena Tonstad , Kathrine Frey Frøslie, Tore
Henriksen Effect of a cholesterol-lowering diet during pregnancy on maternal
and fetal Doppler velocimetry: The CARRDIP study. American Journal of
Obstetrics and Gynecology 2007 Jun;196(6):549.e 1-7.
SH direktoratet link
for brosjyren ernæring i
svangerskapet
http://www.shdir.no/vp/multimedia/
archive/00012/IS-2184_12613a.pdf
PRENATAL DIAGNOSIS
Prenat Diagn 2004; 24: 1049–1059.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pd.1062
REVIEW
The fetal circulation
Torvid Kiserud1 * and Ganesh Acharya2
1
2
University of Bergen, Department of Obstetrics and Gynecology, Bergen, Norway
Department of Obstetrics and Gynecology, University Hospital of Northern Norway, Tromsø, Norway
Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology,
but with important differences. The human fetus seems to circulate less blood through the placenta, shunt
less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal
sheep. However, there are substantial individual variations and the pattern changes with gestational age. The
normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of
development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen
ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale
are functionally closely related and represent an important distributional unit for the venous return. The left
portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus,
the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased
afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies:
increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance
in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.
Copyright  2004 John Wiley & Sons, Ltd.
KEY WORDS: circulation; blood flow; vein; artery; shunt; fetus
INTRODUCTION
Percentage of total blood volume
Modern techniques, particularly ultrasound with its
Doppler modalities, have opened a new era of fetal circulation. One of the consequences is that physiological data
derived from human fetuses increasingly substitute reference values established on classical animal experiments.
Many of the mechanisms described in these experiments
have been shown to operate also in the human fetus, but
in its own version. The following review is preferentially
based on human data in the fetal period of development,
with clinicians’ priorities. The bibliographic references
only selectively reflect a field that is growing by the day.
100
Fetus
75
50
25
FETAL BLOOD VOLUME
Typically, the blood volume in the human fetus is 10 to
12% of the body weight compared to 7 to 8% in adults
(Brace, 1993). One of the reasons for this difference
is that the placenta contains a large pool of blood,
a volume that is gradually reduced with the progress
of gestation (Barcroft, 1946) (Figure 1). The calculated
blood volume of 90 to 105 mL/kg in fetuses undergoing
blood transfusion during the second half of pregnancy
(Nicolaides et al., 1987) is probably an underestimation,
and does not represent a physiologically normal group.
Other studies indicate a volume of 110 to 115 mL/kg,
which is more in line with experimental sheep studies
*Correspondence to: Prof Torvid Kiserud, Department of Obstetrics and Gynecology, Bergen University Hospital, N-5021 Bergen,
Norway. E-mail: torvid@online.no
Placenta
0
0.5
0.6
0.7
0.8
0.9
1.0
Gestational age
Figure 1—Distribution of blood volume between the placenta
and fetal body in fetal sheep. Based on data from Barcroft J.
1946. Researches on Pre-natal Life. Blackwell Scientific Publications: Oxford
(Brace, 1983; Yao et al., 1969). The estimated volume of
80 mL/kg contained within the fetal body is marginally
more than that in adults. Compared to adults, the fetus
is capable of a much faster regulation and restoration of
the blood volume owing to high diffusion rates between
fetal compartments (Brace, 1993).
1050
T. KISERUD AND G. ACHARYA
BLOOD PRESSURE
The mean arterial pressure in human fetuses was
reported to be 15 mm Hg at gestational weeks 19 to 21
(Castle and Mackenzie, 1986). Intrauterine recording of
the intraventricular pressure in the human fetus suggests
that the systemic systolic pressure increases from 15 to
20 mm Hg at 16 weeks to 30 to 40 at 28 weeks (Johnson et al., 2000). The results did not show any difference
between the two ventricles, but variation was substantial.
Similarly, there was no difference in diastolic ventricular
pressure, which was ≤ 5 mm Hg at 16 to 18 weeks and
showed a slight increase towards 5 to 15 mm Hg at 19
to 26 weeks. Umbilical venous pressure (after subtracting amniotic pressure) recorded during cordocentesis in
111 normal pregnancies undergoing prenatal diagnosis
showed that the mean pressure increased with gestation
from 4.5 mm Hg at 18 weeks to 6 mm Hg at term (Ville
et al., 1994), which confirms previous studies reasonably
well (Nicolini et al., 1989; Weiner et al., 1989).
CARDIAC FUNCTION
CARDIAC OUTPUT AND CENTRAL
DISTRIBUTION
(a) 3
(b) 1.5
Stroke volume (mL/kg)
In contrast to postnatal life, the systemic circulation
is fed from the left and right ventricle in parallel, but
with a small proportion of the right output being spared
for the lungs. At mid-gestation, the combined cardiac
output is 210 mL and increases to 1900 mL at 38 weeks
(Rasanen et al., 1996) (Table 1). Doppler studies of this
kind have shown that the right ventricular output is
slightly larger than the left, and that pulmonary flow
Stroke volume (mL/kg)
Once the structural details have been organised during
the embryonic period, the fetal heart continues to grow
in an adaptive interplay with the changing demands.
The myocardium grows by cell division until birth and
a continued growth thereafter comes with cell enlargement. The density of myofibrils increases particularly
in early pregnancy, but the contractility continues to
improve during the second half of pregnancy (Thornburg and Morton, 1994). The two ventricles seem to
be histologically different, and show a different performance (Figure 2a) both in pressure/volume curves and
with an intact peripheral vasculature (Reller et al., 1987;
Thornburg and Morton, 1986). Typically, the fetal heart
has very limited capacity to increase stroke volume by
increasing end-diastolic filling pressure, the right ventricle even less than the left (Figure 2b), as they are
already operating at the top of their function curves.
The Frank–Starling mechanism does operate in the fetal
heart, which is particularly apparent during fetal arrhythmias (Lingman et al., 1984). Adrenergic drive also shifts
the function curve to increase stroke volume. However,
increased heart rate may be the single most prominent
means of increasing cardiac output in the fetus.
With the two ventricles pumping in parallel to the
systemic circulation, the pressure difference between the
ventricles is minimal compared to postnatal life (Johnson
et al., 2000). Still, the difference in compliance of the
great arteries and down stream impedance (upper body
vs lower body and placenta) is visible in their pressure
and velocity profiles. Some of the ‘stiffness’ of the
fetal myocardium is attributed to the constraint of the
pericardium, lungs and chest wall (Grant and Walker,
1996; Grant et al., 2001), all with low compliance
since no air is introduced. However, with the shunts in
operation and a metabolism capable of extracting oxygen
at low saturation levels, the fetal heart appears to be a
very flexible, responsive and adaptive structure.
2
LV
1
RV
0
30
60
90
Fetal arterial pressure (mmHg)
RV
1.0
LV
0.5
0
5
10
15
Mean atrial pressure (mmHg)
Figure 2—Difference in stroke volume for left and right ventricle (LV and RV) with increasing systemic blood pressure in late pregnancy (a).
Difference between left and right ventricular stroke volume in relation to atrial pressure (b). Fetal ventricles work near the breaking point of
their function curves (thick rule), and increased atrial pressure has little effect on stroke volume. Based on Thornburg KL, Morton MJ. 1986.
Filling and atrial pressures as determinants of left ventricular stroke volume in unanaesthetized fetal lambs. Am J Physiol 251: H961–H968;
Thornburg KL, Morton MJ. 1994. Development of the cardiovascular system. In Textbook of Fetal Physiology, Thorburn GD, Harding R (eds).
Oxford University Press: Oxford; Reller MD, Morton MJ, Reid DL, Thornburg KL. 1987. Fetal lamb ventricles respond differently to filling and
arterial pressures and to in utero ventilation. Pediatr Res 22: 519–532
Prenat Diagn 2004; 24: 1049–1059.
1051
FETAL CIRCULATION
Table 1—The combined cardiac output and its distribution to the left and right ventricle,
foramen ovale, lungs and ductus arteriosus in normal human fetuses (Rasanen et al.,
1996)
% of combined cardiac output at gestational age
Combined cardiac output
Left ventricle
Right ventricle
Foramen ovale
Lungs
Ductus arteriosus
20 weeks
30 weeks
38 weeks
210 (mL/min)
47
53
34
13
40
960 (mL/min)
43
57
18
21
32
1900 (mL/min)
40
60
19
25
39
in the human fetus is larger (mean 13–25%) than in the
classical fetal lamb studies ( 10%). Interestingly, a
developmental transition in fetal haemodynamics seems
to occur at 28 to 32 weeks, when the pulmonary blood
flow reaches a maximum (Rasanen et al., 1996). In
another study, similar flow distribution was noted, but
with less blood distributed to the fetal lungs, 11%
(Mielke and Benda, 2001), which is more in line with
the previous experimental studies.
The three shunts, ductus venosus, ductus arteriosus
and foramen ovale, are essential distributional arrangements, making the fetal circulation a flexible and adaptive system for intrauterine life. Their haemodynamic
properties and functional ranges constitute important
determinants for the development of the fetal heart and
circulation during the second and third trimester. The
classical via dextra and sinistra continues to be a useful
concept of blood flow distribution in the fetus (Figure 3).
In addition to the fetal shunts, the isthmus aorta has
received increasing attention since it forms a watershed
between the circulation of the upper body (including the
brain) and that of the lower body (including the placenta)
(Fouron et al., 1994; Makikallio et al., 2002; Teyssier
et al., 1993). Another watershed is the section of the
left portal vein situated between the main portal stem
and the ductus venosus (Figure 3). This venous section
normally directs umbilical blood to the right lobe of the
liver. Under abnormal conditions, the flow may cease
or be reversed, resulting in an increased admixture of
splanchnic blood in the ductus venosus (Kiserud et al.,
2003).
Oxygen saturation gives a picture of distribution
and blending of flows in the central fetal circulation
(Figure 3). The lowest saturation is found in the abdominal inferior vena cava (IVC), and the highest in the
umbilical vein (Rudolph, 1985). Interestingly, the difference between the left and right ventricle is only 10%,
increasing to 12% during hypoxaemia.
DUCTUS VENOSUS
The fetal ductus venosus is a slender trumpet-like shunt,
connecting the intra-abdominal umbilical vein to the
IVC at its inlet to the heart. The inlet, the isthmus, is the
restrictive area with a mean diameter of 0.5 mm at midgestation and hardly ever exceeds 2 mm for the rest of a
normal pregnancy (Kiserud et al., 1994b; Kiserud et al.,
2000b). An umbilical venous pressure ranging from 2
to 9 mmHg (Ville et al., 1994), or rather: the portocaval
pressure gradient, causes the blood to accelerate from
mean 10 to 22 cm/s to 60 to 85 cm/s as it enters the
ductus venosus and flows towards the IVC and foramen
ovale (Bahlmann et al., 2000; Huisman et al., 1992;
Kiserud et al., 1991). Since the well-oxygenated blood
from the ductus venosus is loaded with the highest
kinetic energy in the IVC, it will predominantly be this
blood that presses open the foramen ovale valve to enter
the left atrium, thus forming the ‘preferential streaming’
of the via sinistra.
While 30% of the umbilical blood is shunted through
the ductus venosus at mid-gestation, the fraction is
reduced to 20% at 30 weeks and remains so for the
rest of the pregnancy, but with wide variations (Kiserud
et al., 2000b) (Table 2). Interestingly, these results,
which have been confirmed in another study (Bellotti
Table 2—The fraction of umbilical blood shunted through the ductus venosus during
the second half of the human pregnancy (Kiserud et al., 2000b)
Degree of ductus venosus shunting (%)
Gestational age (weeks)
N
50th percentile
(10th; 90th percentiles)
18–19
20–24
25–28
29–32
33–36
37–41
34
45
34
32
21
27
28
25
22
19
20
23
(14;65)
(10;44)
(10;44)
(9;46)
(10;31)
(7;38)
Prenat Diagn 2004; 24: 1049–1059.
1052
Figure 3—Pathways of the fetal heart and representative oxygen saturation values (in numbers). The via sinistra (red) directs well oxygenated
blood from the umbilical vein (UV) through the ductus venosus (DV) (or left half of the liver) across the inferior vena cava (IVC), through
the foramen ovale (FO), left atrium (LA) and ventricle (LV) and up the ascending aorta (AO) to join the via dextra (blue) in the descending
AO. Deoxygenated blood from the superior vena cava (SVC) and IVC forms the via dextra through the right atrium (RA) and ventricle (RV),
pulmonary trunk (PA) and ductus arteriosus (DA). The isthmus aortae (arrow) and the section of the left portal vein between the main stem
(P) and the DV (striped area) represent watershed areas during hemodynamic compromise. CCA, common carotid arteries; FOV, foramen ovale
valve; LHV, left hepatic vein; MHV, medial hepatic vein; PV, pulmonary vein; RHV, right hepatic vein
et al., 2000), are at variance with the experimental
animal studies showing roughly 50% to be shunted
through the ductus venosus (Behrman et al., 1970;
Edelstone et al., 1978). The redistributional mechanisms
of increased shunting during hypoxaemia found in
animal experiments seem to operate in the human fetus
as well (Kiserud et al., 2000a; Tchirikov et al., 1998).
The diameter in the ductus venosus is under tonic
adrenergic control, and distends under the influence
of nitroxide and prostaglandins (Adeagbo et al., 1982;
Coceani et al., 1984; Kiserud et al., 2000a). The most
pronounced response is seen during hypoxaemia, which
causes a 60% increase of the diameter in fetal sheep
(Kiserud et al., 2000a). Interestingly, the changes in
diameter are not restricted to the isthmus, but include
the entire length of the vessel, which makes a far
greater impact on resistance (Kiserud et al., 2000a;
Momma et al., 1984). Normally, the shunt is obliterated
1 to 3 weeks after birth, but a little later in premature
neonates and cases with persistent pulmonary hypertension or cardiac malformation (Fugelseth et al., 1997,
1998; Fugelseth et al., 1999; Loberant et al., 1992). In
contrast to the ductus arteriosus where oxygen triggers
the closure, no trigger has been found for the ductus
venosus (Coceani and Olley, 1988).
An equally important regulatory mechanism is that of
fluid dynamics, that is, viscosity and pressure (Figure 4)
(Edelstone, 1980; Kiserud et al., 1997). Since blood
velocity in the ductus venosus is high, the blood has
Newtonian properties with low viscosity (similar to
water). In contrast, the liver tissue represents a huge
capillary cross section with a low blood velocity. At
low velocities, the blood is non-Newtonian with a
correspondingly high viscosity (and resistance) and a
Prenat Diagn 2004; 24: 1049–1059.
1053
FETAL CIRCULATION
Flow (mL/min)
30
Liver
Hct0%
(b) 50
Flow (mL/min)
Liver + DV
(a) 50
Hct26%
30
10
10
0
2
4
6
8
Pressure (mmHg)
Hct42%
0
2
4
6
8
10
Pressure (mmHg)
Figure 4—The umbilical flow distribution to the liver and ductus venosus (DV) varies with the umbilical pressure because viscosity plays a
more prominent role at low blood velocity in the liver than in the ductus venosus (a). At 7 mm Hg the liver and ductus venosus receive 50%
each of the umbilical flow, but at 3.5 mm Hg the distribution is 15 and 85%, respectively (stippled arrows). Note that the liver has an opening
pressure of 2 mm Hg. Viscosity, that is, haematocrit (Hct), is a major contributor to resistance in the vascular bed of the liver (b). To perfuse
the liver with 7 mL/min of blood with Hct 0, 26 or 42%, 1.4, 4.3 and 9 mm Hg is needed respectively (stippled arrows). Note the increasing
opening (closing) pressure with increasing Hct. Based on data from Kiserud T, Stratford L, Hanson MA. 1997. Umbilical flow distribution to
the liver and ductus venosus: an in vitro investigation of the fluid dynamic mechanisms in the fetal sheep. Am J Obstet Gynecol 177: 86–90
closing pressure of 1 to 4 mm Hg. Accordingly, an
increase in viscosity (i.e. haematocrit) causes a more
pronounced reduction of the umbilical venous liver flow
compared to that of the ductus venosus, thus increasing
the fraction directed through the ductus venosus. Along
the same line, variation in the umbilical venous pressure
affects the two pathways differently. A reduction in
venous pressure affects the liver perfusion more than the
ductus venosus, resulting in a higher degree of shunting.
On top of these fluid dynamic determinants comes the
neural and endocrine regulation of the hepatic vascular
bed, which has been difficult to demonstrate (Paulick
et al., 1990, 1991).
The physiological significance of the ductus venosus
function is unresolved. The low degree of shunting
through the ductus venosus implies that 70 to 80%
of the umbilical blood perfuses the liver, suggesting
a higher developmental priority of the liver than the
preferential streaming through the ductus venosus and
foramen ovale (Kiserud et al., 2000b). Although there is
a growing number of case reports connecting agenesis
of the ductus venosus to chromosomal abnormalities,
malformations, non-immune hydrops and intrauterine
death (Contratti et al., 2001; Hofstaetter et al., 2000;
Sivén et al., 1995; Volpe et al., 2002), agenesis is
also found in normally grown fetuses (Kiserud et al.,
2000b). Experimental obliteration of the vessel seems to
have little haemodynamic effect (Amoroso et al., 1955;
Rudolph et al., 1991), but causes an increase in insulinlike growth factor 2 and an increased growth of fetal
organs (Tchirikov et al., 2001). It should also be borne
in mind that the oxygen extraction in the liver is modest,
10 to 15% reduction in oxygen saturation (Bristow
et al., 1981; Townsend et al., 1989), which makes the
blood coming from the median and left hepatic vein an
important contributor of oxygenated blood. Actually, the
position and direction of the left hepatic venous blood
under the Eustachian valve (inferior vena cava valve)
favours this blood to be delivered at the foramen ovale
(Kiserud et al., 1992). However, while the liver seems to
have a high developmental priority, receiving most of the
umbilical venous return, an increased shunting through
the ductus venosus plays an important compensatory role
during acute hypoxaemia and hypovolaemia (Behrman
et al., 1970; Edelstone et al., 1980; Itskovitz et al., 1983,
1987; Meyers et al., 1991), and, probably, a prolonged
adaptational role during chronic placental compromise.
The Doppler examination of the ductus venosus is
increasingly used to identify hypoxaemia, acidosis, cardiac decompensation and placental compromise, and is
a promising tool for timing the delivery of critically
ill fetuses (Baschat et al., 2001; Ferrazzi et al., 2002;
Gudmundsson et al., 1997; Hecher et al., 1995a; Hecher
et al., 2001; Kiserud et al., 1993; Kiserud et al., 1994a;
Rizzo et al., 1994). An increased pulsatility, mostly
caused by the augmented atrial contraction wave, signifies increased atrial contraction and end-diastolic filling
pressure (Figure 5). Since the absolute blood velocity
at the isthmus reflects the portocaval pressure gradient
(Kiserud et al., 1994b), it is also a promising tool in
the evaluation of fetal liver diseases, anaemia and conditions with increased venous return such as twin–twin
transfusion syndrome (Hecher et al., 1995b).
FORAMEN OVALE
In neonatal and adult life, an atrial septum defect
is commonly associated with a left-right or right-left
shunting. It is conceivable that, even today, this concept
is used to describe the function of the foramen ovale
(Atkins et al., 1982; Wilson et al., 1989), but it is not a
fair representation of the actual haemodynamics. Rather,
it is a vertical blood flow that enters between the two
atria from below (Barclay et al., 1944; Kiserud et al.,
1991, 1992; Kiserud, 1999; Lind and Wegelius, 1949).
This blood flow ends as a fountain as it hits the interatrial
Prenat Diagn 2004; 24: 1049–1059.
1054
(a)
(b)
(c)
(d)
Figure 5—The blood velocity in the ductus venosus reflects the normal cyclic cardiac events (a) with a peak during ventricular systole (S), a
peak during passive diastolic filling (D) and a deflection during atrial contraction (A). A general increase in velocities (b) reflects an increased
portocaval pressure gradient (e.g. liver disease, anaemia). An additionally augmented atrial contraction wave (c) reflects increased end-diastolic
pressure (e.g. increased preload, adrenergic drive) commonly seen in placental compromise. A further deterioration (d) would be a reversed
A-wave. With increasing myocardial hypoxia and acidosis, the muscle is less compliant, causing a dichotomy of the S- and D-wave (e.g.
preterminal placental compromise)
ridge, the crista dividens, and is divided into a left
and right arm (Figures 6 and 7). The left arm fills the
‘windsock’, formed by the foramen ovale valve and the
atrial septum, to enter the left atrium. The right arm is
directed towards the tricuspid valve and joins the flow
from the superior vena cava and coronary sinus to form
the via dextra.
It is a delicate equilibrium easily influenced by
changes in pressure on the two sides. An increased
resistance and diastolic pressure of the left side is
instantaneously reflected in an increased diversion of
blood to the right side of the interatrial septum. In
contrast to the hypertrophy of the left ventricle seen in
Figure 7—Ultrasound scan (a) showing that the fetal atrial septum
(AS), at the level of the foramen ovale, is situated more towards
the right atrium (RA) than in postnatal life, opposing the inferior
vena cava (IVC). The entrance to the left atrium (LA) is formed as
a ‘windsock’, delineated by the foramen ovale valve (FOV) towards
the left, and the AS towards the right. M-mode (b) shows the changes
in diameter of this ‘windsock’ (FO) during the heart cycle. From
Kiserud T, Rasmussen S. 2001. Ultrasound assessment of the fetal
foramen ovale. Ultrasound Obstet Gynecol 17: 119–124
Figure 6—Flow distribution at the foramen ovale. The edge of the
atrial septum (crista dividens) divides the ascending flow in two
arms, to the right and left atrium (RA and LA). The horizontal
diameter between the foramen ovale valve and the atrium (broken
line) represents the restricting area into the LA. Position, direction
and kinetic energy of the flow from the ductus venosus makes it
predominantly enter the left atrium (dark gray). Conversely, blood
from the inferior vena cava (IVC) enters the RA (light gray). Ao, aorta;
PA, pulmonary trunk; PV, stem of the portal vein (From Kiserud and
Rasmussen, 2001)
aortic stenosis in adults, the fetal stenosis commonly
leads to a shift of blood volume from left to right at
the level of the foramen ovale with a corresponding
development of the fetal heart, left hypoplasia and a
compensatory growth of the right ventricle.
The developing ventricle responds to the demands of
the afterload and is stimulated by the blood volume of
the preload. However, for the left side of the heart, the
Prenat Diagn 2004; 24: 1049–1059.
1055
FETAL CIRCULATION
foramen ovale is an important limiting factor, particularly in cases of a maldeveloped foramen or a premature
closure (Lenz et al., 2002). Under physiological conditions, it is not the area of the ovally shaped hole of the
septum that constitutes the restricting area for the flow
to the left atrium, but rather the horizontal area between
the foramen ovale valve and the atrial septum above
the foramen ovale (Figure 5) (Kiserud and Rasmussen,
2001). Interestingly, the growth of this area is somehow blunted after 28 to 30 weeks of gestation compared
to the cross section of the IVC (Figure 8). The effect
coincides with changes in fetal lung perfusion (Rasanen et al., 1996) and ductus venosus shunting (Kiserud
et al., 2000b), and may signify a transition into a more
mature circulatory physiology.
DUCTUS ARTERIOSUS
This shunt is a wide muscular vessel connecting the pulmonary arterial trunk to the descending aorta (Figure 3).
During the second trimester, 40% or less of the combined cardiac output is directed through the ductus arteriosus (Mielke and Benda, 2001; Rasanen et al., 1996)
(Table 1). Normally, the shunt closes 2 days after birth
(Huhta et al., 1984), but a patent duct is a common clinical problem. The vessel is under the general influence
of circulating substances, particularly prostaglandin E2 ,
which is crucial in maintaining patency (Clyman et al.,
1978). The sensitivity to prostaglandin antagonists is at
its highest in the third trimester and is enhanced by glucocorticoids or fetal stress (Clyman, 1987; Moise et al.,
1988). Nitric oxide has a relaxing effect also before the
third trimester.
The ductus arteriosus bypasses the pulmonary circuit,
but the distribution between these two pathways depends
(a) 12
heavily on the impedance of the pulmonary vasculature,
which is under Prostaglandin I2 control in addition to a
series of substances (Coceani et al., 1980). In an elegant
study, Rasanen et al. showed how the reactivity in the
pulmonary vascular bed increased in the third trimester
(Rasanen et al., 1998). While fetuses at gestational age
20 to 26 weeks showed no changes during maternal
hyperoxygenation, fetuses at 31 to 36 weeks had a lower
impedance in the pulmonary arteries assessed by the pulsatility index, and an increased pulmonary blood flow.
Correspondingly, the blood flow in the ductus arteriosus
was reduced.
The increased reactivity of the ductus arteriosus in the
third trimester makes it vulnerable to prostaglandin synthase inhibitors such as indomethacin, which may cause
a severe and long-lasting constriction, resulting in a congestive heart failure (Huhta et al., 1987; Moise et al.,
1988).
ISTHMUS AORTAE
Fetal sheep studies have shown that roughly 10% of
the combined cardiac output in the fetus passes through
the isthmus aortae (Rudolph, 1985). The flexibility of
the central fetal circulation is particularly visible in the
isthmus aortae. In cases of reduced output from the left
ventricle (e.g. critical aorta stenosis and hypoplastic left
heart syndrome), the aortic arch is fed by blood from
the ductus arteriosus in a reversed fashion through the
isthmus.
Recent studies have highlighted the isthmus aortae
as a watershed between the aortic arch and the ductus
arteriosus–descending aorta (Figure 3) (Fouron et al.,
1994; Makikallio et al., 2002; Sonesson and Fouron,
(b) 2.0
1.8
1.6
1.4
8
FO/IVC ratio
FO outlet diameter (mm)
10
6
4
1.2
1.0
0.8
0.6
0.4
2
0.2
0.0
0
17
22
27
32
37
42
17
22
27
32
37
42
Figure 8—The horizontal diameter of the foramen ovale (FO) hardly grows after 30 weeks of gestation in normal pregnancies (a). The reduced
functional importance after 30 weeks of gestation is also reflected in the ration of the horizontal area of the foramen ovale (FO) and inferior
vena cava (IVC) (b). From Kiserud T, Rasmussen S. 2001. Ultrasound assessment of the fetal foramen ovale. Ultrasound Obstet Gynecol 17:
119–124
Prenat Diagn 2004; 24: 1049–1059.
1056
FETOPLACENTAL CIRCULATION
In the fetal sheep, 45% of the combined cardiac output
is directed to the umbilical arteries and placenta (Jensen
et al., 1991). In the exteriorised human fetus it is less,
but increases from 17% at 10 weeks to 33% at 20 weeks
of gestation (Rudolph et al., 1971). The results are
overestimating the placental fraction since the combined
cardiac output calculation was based on the systemic
venous return, not including the pulmonary venous
return. On the other hand, the measurements were not
performed under strict physiological conditions.
The introduction of Doppler ultrasound made it possible to assess umbilical venous blood flow (Eik-Nes
et al., 1980; Gill, 1979; Gill et al., 1981; Lingman
and Marsál, 1986), and, recently, also arterial flow
(Goldkrand et al., 2000) or a combination of arterial and venous flow(Lees et al., 1999) in the human
fetus in utero. Umbilical blood flow is 35 mL min−1 at
20 weeks and 240 at 40 weeks of gestation (Figure 9)
(Kiserud et al., 2000b). The corresponding normalised
flow is 115 mL min−1 kg−1 at 20 weeks and 64 at
40 weeks. These results have been confirmed in a similar
study (Boito et al., 2002) and are in accordance with earlier studies applying thermodilution at birth (Stembera
et al., 1965), but at some variance with others (Barbera
et al., 1999; Bellotti et al., 2000). The human umbilical
flow is considerably lower than that in the fetal sheep.
That is not disconcerting since the fetal sheep grows
at a higher rate, has a higher temperature and lower
haemoglobin.
At mid-gestation, as much as 50% of the total fetal
blood volume may be contained within the placenta, but
the fraction is reduced to 20 to 25% at term in fetal
sheep (Barcroft, 1946) (Figure 1). In the human at birth,
the fraction is 33% (Yao et al., 1969).
Resistance to flow is mainly determined by the peripheral vascular bed of the placenta. This vasculature has no
neural regulation and catecholamines have little effect
on the vasculature. Endothelin and prostanoid have a
constricting effect (Poston, 1997), nitric oxide vasodilates (Sand et al., 2002), but the exact role of humoral
regulation is not fully known (Poston et al., 1995).
The placental blood flow has been found to be fairly
stable and is chiefly determined by the arterial blood
pressure (Rudolph, 1985). The substantial increase in
vascularisation during late gestation accounts for a low
impedance and the corresponding high diastolic blood
velocity in the umbilical arteries, but placental vasculature is believed to account for 55% of the umbilical
500
450
400
350
Flow (mL/min)
1997; Teyssier et al., 1993). Since this watershed also
reflects the difference in impedance between the cerebral
circuit and that of the placenta and lower fetal body,
the blood velocity pattern across the isthmus has been
suggested as an indicator of placental compromise. With
increasing downstream impedance below the isthmus
aortae (and a reduced impedance in the cerebral circuit),
the orthograde blood velocity is changed to biphasic and
finally retrograde more or less during the entire cycle
(Bonnin et al., 1993).
300
250
200
150
100
50
0
17
21
25
29
33
37
41
Figure 9—Normal umbilical blood flow assessed in the intra-abdominal umbilical vein during the second half of pregnancy. From
Kiserud T, Rasmussen S, Skulstad SM 2000b. Blood flow and degree
of shunting through the ductus venosus in the human fetus. Am J
Obstet Gynecol 182 147–153
resistance (Adamson, 1999). The waveform recorded by
Doppler measurement in the umbilical artery reflects this
downstream impedance and is extensively used to identify placental compromise (Alfirevic and Neilson, 1995).
On the venous side, recent studies have shown that a
tightening of the umbilical ring at the level of the abdominal wall causes various degrees of venous stricture
after the period of umbilical herniation (7–12 weeks)
with venous blood velocity exceeding 100 cm/s in some
fetuses (Skulstad et al., 2001; Skulstad et al., 2002).
CIRCULATORY REGULATION
The regulation mechanisms and responses to hypoxaemia and hypovolaemia are particularly well studied in
animal experiments during the last third of pregnancy
(Iwamoto, 1993), but, even during mid-gestation and
earlier, there seem to be neural and endocrine responses
in addition to the prominent direct effect on cardiac
function caused by hypoxic insult (Iwamoto et al., 1989;
Kiserud et al., 2001). A hypoxic insult in late pregnancy
activates a chemoreflex mediated by the carotid bodies
(to a lesses extent the aortic bodies), causing an immediate vagal effect with reduced heart rate and a sympathetic
vasoconstriction (Giussani et al., 1993; Giussani et al.,
1996; Hanson, 1988; Hanson, 1997). This is followed by
endocrine responses (e.g. adrenalin and noradrenaline),
maintaining vasoconstriction (α-adrenergic), increasing
heart rate (β-adrenergic) and reducing blood volume
with renin release and increased angiotensin II concentration. The responses involve angiotensin–vasopressin
Prenat Diagn 2004; 24: 1049–1059.
FETAL CIRCULATION
300
Adrenal
% change of flow
200
Heart
Brain
100
Placenta
LIver
Fetus
Gut
Kidney
Carcass
Lung
0
−50
Figure 10—Redistribution of organ blood flow (% of control) during
fetal hypoxia caused by reduced uterine flow. Based on data from
Jensen A, Roman C, Rudolph AM. 1991. Effect of reduced uterine
flow on fetal blood flow distribution and oxygen delivery. J Dev
Physiol 15: 309–323
mechanisms, and an increased concentrations of ACTH,
cortisol, atrial natriuretic peptide, neuropeptide Y and
adrenomedullin are in play to orchestrate a circulatory redistributional pattern that maintains placental
circulation and gives priority to the adrenal glands,
myocardium and brain (Iwamoto, 1993) (Figure 10). In
clinical medicine, this translates into frequently visualised coronary circulation (Baschat et al., 1997; Baschat
et al., 2000; Chaoui, 1996; Gembruch and Baschat,
1996), shift in left-right ventricular distribution (Rizzo
et al., 1995), cerebral circulation with high diastolic flow
(Wladimiroff et al., 1987) and increased impedance in
the pulmonary circulation (Rizzo et al., 1996) during circulatory compromise.
A sustained hypoxia forces an adaptational shift to
less oxygen demand (Bocking et al., 1988; Bocking,
1993), reduced DNA synthesis (Hooper et al., 1991) and
growth, with a gradual return towards normal concentrations of blood gasses and endocrine status (Challis et al.,
1989), though with a residual deviation that may have a
long-lasting effect on the fetal and newborn life. There is
an increasing awareness that even subtle differences in
the development of autocrine, paracrine, endocrine and
metabolic functions induced by nutritional or circulatory
variations during pregnancy could have lasting effects
with increased risks of cardiovascular and endocrine diseases in adult life (Barker and Sultan, 1995).
REFERENCES
Adamson SL. 1999. Arterial pressure, vascular input impedance, and
resistance as determinants of pulsatile blood flow in the umbilical
artery. Eur J Obstet Gynecol Reprod Biol 84: 119–125.
Adeagbo ASO, Coceani F, Olley PM. 1982. The response of the lamb
ductus venosus to prostaglandins and inhibitors of prostaglandin and
thromboxane synthesis. Circ Res 51: 580–586.
1057
Alfirevic Z, Neilson JP. 1995. Doppler ultrasonography in high-risk
pregnancies: systematic review with meta-analysis. Am J Obstet
Gynecol 172: 1379–1387.
Amoroso EC, Dawes GS, Mott JC, Rennick BR. 1955. Occlusion of
the ductus venosus in the mature foetal lamb. J Physiol 129:
P64–P65.
Bahlmann F, Wellek S, Reinhardt I, Merz E, Welter C. 2000.
Reference values of ductus venosus flow velocities and calculated
waveform indices. Prenat Diagn 20: 623–634.
Barbera A, Galan HL, Ferrazzi E, Rigano S, Józwik M, Pardi G.
1999. Relationship of umbilical vein blood flow to growth
parameters in the human fetus. Am J Obstet Gynecol 181: 174–179.
Barclay DM, Franklin KJ, Prichard MML. 1944. The Foetal
Circulation and Cardiovascular System, and the Changes that they
Undergo at Birth. Blackwell Scientific Publications: Oxford.
Barcroft J. 1946. Researches on Pre-natal Life. Blackwell Scientific
Publications: Oxford.
Barker DJP, Sultan HY. 1995. Fetal programming of human disease.
In Fetal and Neonatal: Physiology and Clinical Application, Hanson MA, Spencer JAD, Rodeck CH (eds). Cambridge University
Press: Cambridge, MA; 255–274.
Baschat AA, Gembruch U, Gortner L, Reiss I, Weiner CP, Harman CR. 2000. Coronary artery blood flow visualization signifies
hemodynamic deterioration in growth-restricted fetuses. Ultrasound
Obstet Gynecol 16: 425–431.
Baschat AA, Gembruch U, Harman CR. 2001. The sequence of
changes in Doppler and biophysical parameters as severe fetal
growth restriction worsen. Ultrasound Obstet Gynecol 18: 571–577.
Baschat AA, Gembruch U, Reiss I, Gortner L, Diedrich K. 1997.
Demonstration of fetal coronary blood flow by Doppler ultrasound
in relation to arterial and venous flow velocity waveforms and
perinatal outcome—the ‘heart-sparing effect’. Ultrasound Obstet
Gynecol 9: 162–172.
Behrman RE, Lees MH, Peterson EN, de Lannoy CW, Seeds AE.
1970. Distribution of the circulation in the normal and asphyxiated
fetal primate. Am J Obstet Gynecol 108: 956–969.
Bellotti M, Pennati G, De Gasperi C, Battaglia FC, Ferrazzi E. 2000.
Role of ductus venosus in distribution of umbilical flow in human
fetuses during second half of pregnancy. Am J Physiol 279:
H1256–H1263.
Bocking AD. 1993. Effect of chronic hypoxaemia on circulation
control. In Fetus and Neonate. Physiology and Clinical Application.
Volume 1: the Circulation. Hanson MA, Spencer JAD, Rodeck CH
(eds). Cambridge University Press: Cambridge; 215–224.
Bocking AD, Gagnon R, White SE, Homan J, Milne KM, Richardson B. 1988. Circulatory responses to prolonged hypoxemia in fetal
sheep. Am J Obstet Gynecol 159: 1418–1424.
Boito S, Struijk PC, Ursem NTC, Stijnen T, Wladimiroff JW. 2002.
Umbilical venous volume flow in the normally developing and
growth-restricted human fetus. Ultrasound Obstet Gynecol 19:
344–349.
Bonnin P, Fouron JC, Teyssier G, Sonesson SE, Skoll A. 1993.
Quantitative assessment of circulatory changes in the fetal aortic
isthmus during progressive increase of resistance to umbilical blood
flow. Circulation 88: 216–222.
Brace RA. 1983. Fetal blood volume response to intravenous saline
solution and dextrane. Am J Obstet Gynecol 143: 777–781.
Brace RA. 1993. Regulation of blood volum in utero. In Fetus
and Neonate. Physiology and Clinical Application, Hanson MA,
Spencer JAD, Rodeck CH (eds). Cambridge University Press:
Cambridge, MA; 75–99.
Bristow J, Rudolph AM, Itskovitz J. 1981. A preparation for studying
liver blood flow, oxygen consumption, and metabolism in the fetal
lamb in utero. J Dev Physiol 3: 255–266.
Castle B, Mackenzie IZ. 1986. In vivo observations on intravascular
blood pressure in the fetus during mid-pregnancy. In Fetal
Physiological Measurements, Rolfe P (ed.). Butterworths: London,
Boston, Durban, Singapore, Toronto, Wellington; 65–69.
Challis JRG, Fraher L, Oosterhuis J, White SE, Bocking AD. 1989.
Fetal and maternal endocrine responses to prolonged reductions in
uterine blood flow in pregnant sheep. Am J Obstet Gynecol 160:
926–932.
Chaoui R. 1996. The fetal ‘heart-sparing effect’ detected by the
assessment of coronary blood flow: a further ominous sign of fetal
compromise. Ultrasound Obstet Gynecol 7: 5–9.
Prenat Diagn 2004; 24: 1049–1059.
1058
Clyman RI. 1987. Ductus arteriosus: current theories of prenatal and
postnatal regulation. Semin Perinatol 11: 64–71.
Clyman RI, Mauray F, Roman C, Rudolph AM. 1978. PGE2 is a
more potent vasodilator of the fetal lamb ductus arteriosus than
is either PGI2 or 6 keto PGF1alpha. Prostaglandins 16: 259–264.
Coceani F, Adeagbo ASO, Cutz E, Olley PM. 1984. Autonomic
mechanisms in the ductus venosus of the lamb. Am J Physiol 247:
H17–H24.
Coceani F, Olley PM. 1988. The control of cardiovascular shunts in
the fetal and perinatal period. Can J Pharmacol 66: 1129–1134.
Coceani F, Olley PM, Lock JE. 1980. Prostaglandins, ductus
arteriosus, pulmonary circulation: current concepts and clinical
potential. Eur J Clin Pharmacol 18: 75–81.
Contratti G, Banzi C, Ghi T, Perolo A, Pilu G, Visenti A. 2001.
Absence of the ductus venosus: report of 10 new cases and review
of the literature. Ultrasound Obstet Gynecol 18: 605–609.
Edelstone DI. 1980. Regulation of blood flow through the ductus
venosus. J Dev Physiol 2: 219–238.
Edelstone DI, Rudolph AM, Heymann MA. 1978. Liver and ductus
venosus blood flows in fetal lambs in utero. Circ Res 42: 426–433.
Edelstone DI, Rudolph AM, Heymann MA. 1980. Effect of hypoxemia and decreasing umbilical flow on liver and ductus venosus
blood flows in fetal lambs. Am J Physiol 238: H656–H663.
Eik-Nes SH, Brubakk AO, Ulstein MK. 1980. Measurement of human
fetal blood flow. Br Med J 280: 283–284.
Ferrazzi E, Bozzo M, Rigano S, et al. 2002. Temporal sequence of
abnormal Doppler changes in peripheral and central circulatory
systems of the severely growth-restricted fetus. Ultrasound Obstet
Gynecol 19: 140–146.
Fouron JC, Zarelli M, Drblik P, Lessard M. 1994. Flow velocity
profile of the fetal aortic isthmus through normal gestation. Am
J Cardiol 74: 483–486.
Fugelseth D, Kiserud T, Liestøl K, Langslet A, Lindemann R. 1999.
Ductus venosus blood velocity in persistent pulmonary hypertension
of the newborn. Arch Dis Child 81: F35–F39.
Fugelseth D, Lindemann R, Liestøl K, Kiserud T, Langslet A. 1997.
Ultrasonographic study of ductus venosus in healthy neonates. Arch
Dis Child 77: F131–F134.
Fugelseth D, Lindemann R, Liestøl K, Kiserud T, Langslet A. 1998.
Postnatal closure of ductus venosus in preterm infants ≤ 32 weeks.
An ultrasonographic study. Early Hum Dev 53: 163–169.
Gembruch U, Baschat AA. 1996. Demonstration of fetal coronary
blood flow by color-coded and pulsed wave Doppler sonography:
a possible indicator of severe compromise and impending demise
in intrauterine growth retardation. Ultrasound Obstet Gynecol 7:
10–16.
Gill RW. 1979. Pulsed Doppler with B-mode imaging for quantitative
blood flow measurement. Ultrasound Med Biol 5: 223–235.
Gill RW, Trudinger BJ, Garrett WJ, Kossoff G, Warren PS. 1981.
Fetal umbilical venous flow measured in utero by pulsed Doppler
and B-mode ultrasound. Am J Obstet Gynecol 139: 720–725.
Giussani DA, Riquelme RA, Moraga FA, et al. 1996. Chemoreflex
and endocrine components of cardiovascular responses to acute
hypoxemia in the llama fetus. Am J Physiol 271: R73–R83.
Giussani DA, Spencer JAD, Moor PD, Bennet L, Hanson MA. 1993.
Afferent and efferent components of the cardiovascular response to
acute hypoxia in term fetal sheep. J Physiol 461: 431–449.
Goldkrand JW, Morre DH, Lenz SU, Clements SP, Turner AD,
Bryant JL. 2000. Volumetric flow in the umbilical artery: normative
data. J Matern Fetal Med 9: 224–228.
Grant DA, Fauchére JCJEK, Tyberg JV, Walker AM. 2001. Left
ventricular stroke volume in the fetal sheep is limited by
extracardiac constraint and arterial pressure. J Physiol 535:
231–239.
Grant DA, Walker AM. 1996. Pleural and pericardial pressures limit
fetal right ventricular output. Circulation 94: 555–561.
Gudmundsson S, Tulzer G, Huhta J, Marsál K. 1997. Venous Doppler
in the fetus with absent end-diastolicflow in the umbilical artery.
Ultrasound Obstet Gynecol 7: 262–267.
Hanson MA. 1988. The importance of baro- and chemoreflexes in
the control of the fetal cardiovascular system. J Dev Physiol 10:
491–511.
Hanson MA. 1997. Do we now understand the control of the fetal
circulation? Eur J Obstet Gynecol Reprod Biol 75: 55–61.
Hecher K, Bilardo CM, Stigter RH, Ville Y, Hackelöer BJ, Kok HJ.
2001. Monitoring of fetuses with intrauterine growth restriction: a
longitudinal study. Ultrasound Obstet Gynecol 18: 564–570.
Hecher K, Snijders R, Campbell S, Nicolaides K. 1995a. Fetal
venous, intracardiac, and arterial blood flow measurements in
intrauterine growth retardation: relationship with fetal blood gases.
Am J Obstet Gynecol 173: 10–15.
Hecher K, Ville Y, Snijders R, Nicolaides K. 1995b. Doppler studies
of the fetal circulation in twin-twin transfusion syndrome.
Ultrasound Obstet Gynecol 5: 318–324.
Hofstaetter C, Plath H, Hansmann M. 2000. Prenatal diagnosis of
abnormalities of the fetal venous system. Ultrasound Obstet
Gynecol 15: 231–241.
Hooper SB, Bocking AD, White SE, Challis JRG, Han VKM. 1991.
DNA synthesis is reduced in selected fetal tissues during prolonged
hypoxemia. Am J Physiol 261: R508–R518.
Huhta J, Cohen M, Gutgesell HP. 1984. Patency of the ductus
arteriosus in normal neonates: two-dimensional echocardiography
versus Doppler assessment. J Am Coll Cardiol 4: 561–564.
Huhta JC, Moise KJ, Fisher DJ, Sharif DS, Wasserstrum N, Martin C. 1987. Detection and quantitation of constriction of fetal
ductus arteriosus by Doppler echocardiography. Circulation 75:
406–427.
Huisman TWA, Stewart PA, Wladimiroff JW. 1992. Ductus venosus
blood flow velocity waveforms in the human fetus—a doppler
study. Ultrasound Med Biol 18: 33–37.
Itskovitz J, LaGamma EF, Rudolph AM. 1983. The effect of reducing
umbilical blood flow on fetal oxygenation. Am J Obstet Gynecol
145: 813–818.
Itskovitz J, LaGamma EF, Rudolph AM. 1987. Effects of cord
compression on fetal blood flow distribution and O2 delivery. Am
J Physiol 252: H100–H109.
Iwamoto HS, Kaufman T, Keil LC, Rudolph AM. 1989. Responses to
acute hypoxemia in fetal sheep at 0.6–0.7 gestation. Am J Physiol
256: H613–H620.
Iwamoto HS. 1993. Cardiovascular effects of acute hypoxia and
asphyxia. In Fetus and Neonate. Physiology and Clinical
Application. Volume 1: the Circulation. Hanson MA, Spencer JAD,
Rodeck CH (eds). Cambridge University Press: Cambridge;
197–214.
Jensen A, Roman C, Rudolph AM. 1991. Effect of reduced uterine
flow on fetal blood flow distribution and oxygen delivery. J Dev
Physiol 15: 309–323.
Johnson P, Maxwell DJ, Tynan MJ, Allan LD. 2000. Intracardiac
pressures in the human fetus. Heart 84: 59–63.
Kiserud T, Eik-Nes SH, Blaas H-G, Hellevik LR. 1991. Ultrasonographic velocimetry of the fetal ductus venosus. Lancet 338:
1412–1414.
Kiserud T, Eik-Nes SH, Blaas H-G, Hellevik LR. 1992. Foramen
ovale: an ultrasonographic study of its relation to the inferior vena
cava, ductus venosus and hepatic veins. Ultrasound Obstet Gynecol
2: 389–396.
Kiserud T, Eik-Nes SH, Hellevik LR, Blaas H-G. 1993. Ductus
venosus blood velocity changes in fetal cardiac diseases. J Matern
Fetal Invest 3: 15–20.
Kiserud T, Eik-Nes SH, Blaas H-G, Hellevik LR, Simensen B.
1994a. Ductus venosus blood velocity and the umbilical circulation
in the seriously growth retarded fetus. Ultrasound Obstet Gynecol
4: 109–114.
Kiserud T, Hellevik LR, Eik-Nes SH, Angelsen BAJ, Blaas H-G.
1994b. Estimation of the pressure gradient across the fetal ductus
venosus based on Doppler velocimetry. Ultrasound Med Biol 20:
225–232.
Kiserud T, Stratford L, Hanson MA. 1997. Umbilical flow distribution to the liver and ductus venosus: an in vitro investigation of the
fluid dynamic mechanisms in the fetal sheep. Am J Obstet Gynecol
177: 86–90.
Kiserud T. 1999. Hemodynamics of the ductus venosus. Eur J Obstet
Gynecol Reprod Biol 84: 139–147.
Kiserud T, Jauniaux E, West D, Ozturk O, Hanson MA. 2001.
Circulatory responses to acute maternal hyperoxaemia and
hypoxaemia assessed non-invasively by ultrasound in fetal sheep
at 0.3–0.5 gestation. Br J Obstet Gynaecol 108: 359–364.
Kiserud T, Ozaki T, Nishina H, Rodeck C, Hanson MA. 2000a.
Effect of NO, phenylephrine and hypoxemia on the ductus venosus
diameter in the fetal sheep. Am J Physiol 279: H1166–H1171.
Prenat Diagn 2004; 24: 1049–1059.
FETAL CIRCULATION
Kiserud T, Rasmussen S, Skulstad SM. 2000b. Blood flow and degree
of shunting through the ductus venosus in the human fetus. Am J
Kiserud T, Rasmussen S. 2001. Ultrasound assessment of the fetal
foramen ovale. Ultrasound Obstet Gynecol 17: 119–124.
Kiserud T, Kilavuz O, Hellevik LR. 2003. Venous pulsation in the left
portal branch—the effect of pulse and flow direction. Ultrasound
Obstet Gynecol 21(4): 359–694.
Lees C, Albaiges G, Deane C, Parra M, Nicolaides KH. 1999.
Assessment of umbilical arterial and venous flow using color
Doppler. Ultrasound Obstet Gynecol 14: 250–255.
Lenz F, Machlitt A, Hartung J, Bollmann R, Chaoui R. 2002. Fetal
pulmonary venous flow pattern is determined by left atrial pressure:
report of two cases of left heart hypoplasia, one with patent and
the other with closed interatrial communication. Ultrasound Obstet
Gynecol 19: 392–395.
Lind J, Wegelius C. 1949. Angiocardiographic studies on the human
foetal circulation. Pediatrics 4: 391–400.
Lingman G, Dahlström JA, Eik-Nes SH, Marsál K, Ohlin P, Ohrlander S. 1984. Hemodynamic evaluation of fetal heart arrhythmias.
Br J Obstet Gynecol 91: 647–652.
Lingman G, Marsál K. 1986. Fetal central blood circulation in the
third trimester of normal pregnancy. Longitudinal study. I. Aortic
and umbilical flow. Early Hum Dev 13: 137–150.
Loberant N, Barak M, Gaitini D, Herkovits M, Ben-Elisha M,
Roguin N. 1992. Closure of the ductus venosus in neonates: findings
on real-time gray-scale, color-flow Doppler, and duplex Doppler
sonography. Am J Roentgenol 159: 1083–1085.
Makikallio K, Jouppila P, Rasanen J. 2002. Retrograde net blood flow
in the aortic isthmus in relation to human fetal arterial and venous
circulations. Ultrasound Obstet Gynecol 19: 147–152.
Meyers RL, Paulick RP, Rudolph CD, Rudolph AM. 1991. Cardiovascular responses to acute, severe haemorrhage in fetal sheep. J
Dev Physiol 15: 189–197.
Mielke G, Benda N. 2001. Cardiac output and central distribution of
blood flow in the human fetus. Circulation 103: 1662–1668.
Moise KJ, Huhta JC, Sharif DS, et al. 1988. Indomethacin in the
treatment of premature labor. Effect on the fetal ductus arteriosus.
N Engl J Med 319: 327–331.
Momma K, Takeuchi H, Hagiwara H. 1984. Pharmacological constriction of the ductus arteriosus and ductus venosus in fetal rats. In
Congenital Heart Disease. Causes and Processes, Nora J, Takao A
(eds). Futura: Mount Kisco; 313–327.
Nicolaides KH, Clewell WH, Rodeck CH. 1987. Measurement of
fetoplacental blood volume in erythroblastosis fetalis. Am J Obstet
Gynecol 157: 50–53.
Nicolini U, Fisk NM, Talbert DG, Rodeck CH, Kochenour NK.
1989. Intrauterine manometry: technique and application to fetal
pathology. Prenat Diagn 9: 243–254.
Paulick RP, Meyers RL, Rudolph CD, Rudolph AM. 1990. Venous
and hepatic vascular responses to indomethacin and prostaglandin
E1 in the fetal lamb. Am J Obstet Gynecol 163: 1357–1363.
Paulick RP, Meyers RL, Rudolph CD, Rudolph AM. 1991. Umbilical
and hepatic venous responses to circulating vasoconstrictive
hormones in fetal lamb. Am J Physiol 260: H1205–H1213.
Poston L. 1997. The control of bloodflow to the placenta. Exp Physiol
82: 377–387.
Poston L, McCarthy AL, Ritter JM. 1995. Control of vascular
resistance in the maternal and feto-placental arterial beds. Pharmac
Ther 65: 215–239.
Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC.
1998. Reactivity of the human fetal pulmonary circulation to
maternal hyperoxygenation increases during the second half of
pregnancy. Circulation 97: 257–262.
Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. 1996. Role
of the pulmonary circulation in the distribution of human fetal
cardiac output during the second half of pregnancy. Circulation
94: 1068–1073.
Reller MD, Morton MJ, Reid DL, Thornburg KL. 1987. Fetal lamb
ventricles respond differently to filling and arterial pressures and to
in utero ventilation. Pediatr Res 22: 519–532.
Rizzo G, Capponi A, Arduini D, Romanini C. 1994. Ductus venosus
velocity waveforms in appropriate and small for gestational age
fetuses. Early Hum Dev 39: 15–26.
1059
Rizzo G, Capponi A, Chaoui R, Taddei F, Arduini D, Romanini C.
1996. Blood flow velocity waveforms from peripheral pulmonary
arteries in normally grown and growth-retarded fetuses. Ultrasound
Rizzo G, Capponi A, Rinaldo D, Arduini D, Romanini C. 1995.
Ventricular ejection force in growth-retarded fetuses. Ultrasound
Rudolph AM. 1985. Distribution and regulation of blood flow in the
fetal and neonatal lamb. Circ Res 57: 811–821.
Rudolph AM, Heymann MA, Teramo K, Barrett C, Räihä N. 1971.
Studies on the circulation of the previable human fetus. Pediatr
Res 5: 452–465.
Rudolph CD, Meyers RL, Paulick RP, Rudolph AM. 1991. Effects of
ductus venosus obstruction on liver and regional blood flows in the
fetal lamb. Pediatr Res 29: 347–352.
Sand AE, Andersson E, Fried G. 2002. Effect of nitric oxide donors
and inhibitors of nitric oxide signalling on endothelin- and
serotonin-induced contractions in human placental arteries. Acta
Physiol Scand 174: 217–223.
Sivén M, Ley D, Hägerstrand I, Svenningsen N. 1995. Agenesis of
the ductus venosus and its correlation to hydrops fetalis and the
fetal hepatic circulation. Pediatr Pathol Lab Med 15: 39–50.
Skulstad SM, Kiserud T, Rasmussen S. 2002. Degree of fetal
umbilical venous constriction at the abdominal wall in a low
risk population at 20–40 weeks of gestation. Prenat Diagn 22:
1022–1027.
Skulstad SM, Rasmussen S, Iversen O-E, Kiserud T. 2001. The
development of high venous velocity at the fetal umbilical ring
during gestational weeks 11–19. Br J Obstet Gynaecol 108:
248–253.
Sonesson S-E, Fouron J-C. 1997. Doppler velocimetry of the aortic
isthmus in human fetuses with abnormal velocity waveforms in the
umbilical artery. Ultrasound Obstet Gynecol 10: 107–111.
Stembera ZK, Hodr J, Janda J. 1965. Umbilical blood flow in healthy
newborn infants during the first minutes after birth. Am J Obstet
Gynecol 91: 568–574.
Tchirikov M, Kertschanska S, Schroder HJ. 2001. Obstruction of
ductus venosus stimulates cell proliferation in organs of fetal sheep.
Placenta 22: 24–31.
Tchirikov M, Rybakowski C, Hünecke B, Schröder HJ. 1998. Blood
flow through the ductus venosus in singleton and multifetal
pregnancies and in fetuses with intrauterine growth retardation. Am
J Obstet Gynecol 178: 943–949.
Teyssier G, Fouron JC, Maroto E, Sonesson SE, Bonnin P. 1993.
Blood flow velocity profile in the fetal aortic isthmus: a
sensitive indicator of changes in systemic peripheral resistance. I.
Experimental studies. J Matern Fetal Invest 3: 213–218.
Thornburg KL, Morton MJ. 1986. Filling and atrial pressures as
determinants of left ventricular stroke volume in unanaesthetized
fetal lambs. Am J Physiol 251: H961–H968.
Thornburg KL, Morton MJ. 1994. Development of the cardiovascular
system. In Textbook of Fetal Physiology, Thorburn GD, Harding R
(eds). Oxford University Press: Oxford.
Townsend SF, Rudolph CD, Rudolph AM. 1989. Changes in ovine
hepatic circulation and oxygen consumption at birth. Pediatr Res
25: 300–304.
Ville Y, Sideris I, Hecher K, Snijders RJM, Nicolaides KH. 1994.
Umbilical venous pressure in normal, growth-retarded, and anemic
fetuses. Am J Obstet Gynecol 170: 487–494.
Volpe P, Marasini M, Caruso G, et al. 2002. Prenatal diagnosis
of ductus venosus agenesis and its association with cytogenetic/congenital anomalies. Prenat Diagn 22: 995–1000.
Weiner CP, Heilskov JRN, Pelzer GRN, Grant SRN. 1989. Normal
values for human umbilical venous and amniotic fluid pressure and
their alteration by fetal disease. Am J Obstet Gynecol 161: 714–717.
Wilson AD, Rao PS, Aeschlimann S. 1989. Normal fetal foramen
ovale flap and transatrial Doppler velocity pattern. J Am Soc
Echocardiogr 3: 491–494.
Wladimiroff JW, Wijngaard JA, Degani S, Noordam MJ, van Eyck J,
Tonge HM. 1987. Cerebral and umbilical arterial blood flow
waveforms in normal and growth-retarded pregnancies. Obstet
Gynecol 69: 705–709.
Yao AC, Moinian M, Lind J. 1969. Distribution of blood between
infant and placenta after birth. Lancet 2: 871–873.
Prenat Diagn 2004; 24: 1049–1059.
Ultrasound Obstet Gynecol 2006; 28: 126–136
Published online 6 July 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.2832
Fetal cardiac output, distribution to the placenta and impact
of placental compromise
T. KISERUD*†, C. EBBING*†, J. KESSLER*† and S. RASMUSSEN*†‡
*Department of Clinical Medicine, Section of Obstetrics and Gynaecology, University of Bergen, †Department of Obstetrics and
Gynecology, Haukeland University Hospital and ‡Locus of Registry Based Epidemiology, Norwegian Birth Registry, Bergen, Norway
K E Y W O R D S: blood flow; cardiac output; circulation; echocardiography; fetus; growth restriction; placenta; ultrasound
ABSTRACT
Objectives Intrauterine growth restriction is a common
clinical problem, but the underlying hemodynamic
changes are not well known. Our aim was to determine
the normal distribution of fetal cardiac output to the
placenta during the second half of pregnancy, and to
assess the changes imposed by growth restriction with
various degrees of placental compromise.
Methods A cross-sectional study of 212 low-risk pregnancies with a gestational age of 18–41 weeks constituted the
reference population. A second group of 64 pregnancies
with an estimated fetal weight ≤ 2.5th percentile constituted the study group. Ultrasound measurements of inner
diameters and velocities at the fetal left and right ventricular outlets and intra-abdominal umbilical vein were
used to determine combined left and right cardiac output (CCO) and the fraction distributed to the placenta.
Placental compromise was graded according to umbilical
artery waveform: pulsatility index normal, > 97.5th percentile, or absent/reversed end-diastolic velocity. Regression analysis and Z-score (SD-score) statistics were used
to establish normal ranges and to compare groups.
Results During gestational weeks 18–41 the normal
CCO/kg was on average 400 mL/min/kg and the fraction
directed to the placenta was on average 32%, while after
32 weeks it was 21%. In intrauterine growth restriction
the CCO/kg was not significantly different, but the
fraction to the placenta was lower (P < 0.001). This effect
was more pronounced in severe placental compromise
(P < 0.001).
Conclusions Normally, one third of the fetal CCO is
distributed to the placenta in most of the second half
of pregnancy, and one fifth near term. In placental
compromise this fraction is reduced while CCO/kg is
maintained at normal levels, signifying an increased
recirculation of umbilical blood in the fetal body.
Copyright  2006 ISUOG. Published by John Wiley
& Sons, Ltd.
INTRODUCTION
Intrauterine growth restriction (IUGR) is one of the
major challenges in antenatal care and an important
determinant for perinatal mortality and morbidity1 . Low
birth weight has also been associated with increased risk
of cardiovascular diseases and Type 2 diabetes in adult
life2 . Although impaired maternal nutrition may influence
birth weight and health in later life, the effect on birth
weight is rather modest. This suggests that additional
powerful mechanisms, of which placental compromise
is probably the most common, are involved in the
clinically important group of growth-restricted fetuses
seen during the second and third trimesters. Experimental
data suggest that restriction in placentation leads to
impaired fetal growth3 , and a sustained reduction in
oxygen delivery imposed by a restriction in the maternal or
fetal circulation of the placenta leads to down-regulation
of DNA synthesis and fetal growth4 . In the human fetus,
IUGR and compromised placenta are commonly linked
to an augmented pulsatility of the umbilical artery. The
extreme finding of absent or reversed end-diastolic flow
(ARED) in the umbilical arteries is associated with a
perinatal mortality rate of 36%5 . These fetuses show signs
of increased afterload6 and circulatory redistribution7 .
Thus, the circulatory pattern of these fetuses is emerging,
but some fundamental pieces of information on the
underlying hemodynamics are still lacking. One of these
is the proportion of fetal cardiac output distributed to
the placenta. In 1971, Abraham Rudolph et al.8 showed
Correspondence to: Prof. T. Kiserud, Department of Clinical Medicine, Section of Obstetrics and Gynaecology, Haukeland University
Hospital, N-5021 Bergen, Norway (e-mail: torvid.kiserud@kk.uib.no)
Accepted: 29 November 2005
Copyright  2006 ISUOG. Published by John Wiley & Sons, Ltd.
ORIGINAL PAPER
Placental fraction of CCO
that, under experimental conditions, roughly one third
of the combined left and right cardiac output (CCO)
was directed towards the umbilical circulation at midgestation in human pregnancies, and a later Doppler
study9 , under physiological conditions, points in the same
direction, although a low number of observations towards
the end of pregnancy made the statistics at this point
less reliable. As for compromised pregnancies causing
umbilical hemodynamic compromise and fetal growth
impairment, the fraction of fetal CCO directed to the
placenta is not known.
The aim of this study was to determine the fetal cardiac
output and its distribution to the placenta in normal
pregnancies during the second half of pregnancy, and to
assess the changes imposed by IUGR with various degrees
of placental compromise.
METHODS
Reference population
The reference population consisted of 212 women with
low-risk pregnancies recruited, after written consent, to
a cross-sectional study acknowledged by the Regional
Committee for Ethics in Medical Research. Excluded were
those with an obstetric history of previous hypertensive
complications, IUGR, placental abruption and history of
smoking, diabetes, hypertension or any general chronic
disease. Gestational age was assessed at the routine
ultrasound examination at 17–20 weeks of gestation.
Fetuses with malformations and known chromosomal
aberrations were not included. One participant withdrew
after cardiac malformation and trisomy 21 was identified
during the study examination, and another due to social
reasons. The median gestational age at birth was 40 + 3
(range, 34 + 3 to 42 + 2) weeks. The median birth
weight was 3665 (range, 1400–4900) g, and in terms
of percentiles for the Norwegian population, it was
50th percentile (range, 1–99th percentiles). The umbilical
venous flow in this group has been presented previously
and forms the reference ranges for the present study10 .
In this study, we established new reference ranges for the
blood flow in the cardiac outlets, left–right ventricular
output differences, CCO, CCO/kg and the placental
fraction of CCO in order to compare these with the
results of growth-restricted fetuses.
IUGR group
This group consisted of 66 women recruited into
the study when fetal biometry (biparietal diameter and
middle abdominal diameter) identified an estimated fetal
weight ≤ 2.5th percentile. Gestational age was determined
by crown–rump length before 12 weeks of gestation,
biparietal diameter at the routine scan at 17–20 weeks,
or certain information of a regular last menstrual period
(LMP). In cases of a discrepancy of ≥ 10 days between
the gestational age determined by the second-trimester
scan and that calculated from a certain LMP, we relied
127
on LMP because growth impairment was assumed to
start early, affecting size at the 17–20-week scan. Twins,
chromosomal aberrations, malformations and infections
in the present pregnancy excluded participation.
Those with a birth weight > 10th percentile were
excluded, leaving 64 for statistical analysis. These 64
had been examined at a median gestational age of
34 + 1 weeks (range, 23 + 5 to 39 + 5) weeks, and
delivered at a median gestational age of 35 + 6 (range,
25 + 0 to 40 + 6) weeks. The median lag between
examination and delivery was 3 (interquartile range
(IQR), 1–7; range, 0–85) days. The majority of neonates
were delivered by Cesarean section (47/64). In total there
were 29 girls and 35 boys, with a median birth weight
of 1870 (range, 270–3040) g. Of these, 51 were < 2.5th
percentile, seven were between 2.5th and 5th percentiles,
and six were between 5th and 10th percentiles according
to gender-specific birth-weight charts11 . Three deaths
occurred at delivery or in the delivery room (birth weights
of 270, 280 and 350 g). Of the remaining 61, seven had
an Apgar score of < 7 at 1 min and two had a score of
< 7 at 5 min, 31 were admitted to the neonatal intensive
care unit, and 19 required respiratory support.
Sonography
The participants were examined during a 45-min
session using a Vingmed CFM 800 (GE Vingmed,
Horten, Norway) ultrasound machine equipped with
a multifrequency mechanical sector transducer (center
frequency, 5 MHz) with color Doppler and pulsed
Doppler facilities (4 MHz). The spatial peak temporal
intensity was set at 45 mW/cm2 for pulsed Doppler.
The inner diameter (D) of the aorta and the pulmonary
artery was measured at an insonation angle perpendicular
to the vessel wall, between the open semilunar valves,
in a zoomed image (Figure 1). The optimal frame for
measurement was searched in the memory buffer. For the
aorta, the procedure was repeated three times or more
in 163/174 cases, and an average of 5.2 (median, 5;
IQR, 4–6; range, 1–14) times. For the pulmonary artery
the measurement was repeated three times or more in
168/177 cases, and an average of 5.5 (median, 5; IQR,
4–7; range, 1–13) times. The calculated mean diameters
were used in the statistical analysis. In a separate axial
insonation, the sample volume was placed at the ostia
of the aorta and pulmonary artery and the maximum
velocity during systole was recorded for 2–4 s during
fetal quiescence. The angle of insonation was kept as low
as possible; for the aorta it was 0◦ in 153 recordings and
the median was 10 (IQR, 2–18)◦ in the 27 remaining
recordings, while for the pulmonary artery it was 0◦ in
153 recordings and the median was 14 (IQR, 8–33)◦ in
the remaining 24. The systolic time-velocity integral (TVI)
and heart rate (HR) were calculated as an average of four
to six cardiac cycles. Left and right ventricular output
were calculated as π · (D/2)2 · TVI · HR. The CCO was
calculated as the sum of the two, and the normalized CCO
was calculated by dividing this by the fetal weight. The
Ultrasound Obstet Gynecol 2006; 28: 126–136.
Kiserud et al.
128
the 95% CI of the mean to half or less, depending on the
diameter12 . The same approach was used for the umbilical
venous flow assessment.
Statistical analysis
Figure 1 Doppler recording (a,c) and diameter measurement (b,d)
at the level of the aortic ostium (a,b) and at the pulmonary arterial
ostium (c,d) in a fetus at 30 weeks of gestation.
difference between left and right ventricular output was
calculated as a percentage of the CCO.
For the intra-abdominal umbilical vein the D was
determined as an average of four or more measurements
made before the first portal branches with an angle
of insonation perpendicular to the vessel wall10 . The
weighted mean blood velocity (Vwmean ) was recorded
during 2–4 s in a separate insonation along the axis
of the vessel with an expanded sample volume. The angle
of insonation was 0◦ in 56 recordings and the median was
16 (IQR, 10–24)◦ in the remaining 141. The fetoplacental
blood flow was calculated as π · (D/2)2 · Vwmean , and its
fraction of the CCO was calculated as a percentage.
In all fetuses, the fetal weight at the time of examination
was estimated on the basis of the weight percentile at
birth10 . In addition, the umbilical artery blood velocity
was recorded in the free loop, the pulsatility index (PIua )
was calculated from five to six waveforms, and ARED
was noted. Increasing waveform alteration was taken as
increasing hemodynamic compromise of the placenta and
the participants were grouped accordingly into those with
normal PIua , those with PIua > 97.5th percentile, and those
with ARED.
Measures were taken to restrict random error. One
person did all measurements (T.K.) in both groups. The
intraobserver variation, calculated as the coefficient of
variation for the diameter measurement, was 8.4% (95%
CI, 7.8–9.0) for the aorta and 7.7% (95% CI, 7.2–8.3)
for the pulmonary artery. The corresponding intraclass
correlations were 94% (95% CI, 92–95) and 97% (95%
CI, 96–97), respectively. In order to further control error,
the diameters were determined as a mean of three or more
repeat measurements, which we have shown to reduce
To produce means, fractional polynomial regression
models were fitted to the ln-transformed data and
SDs were modeled by the method of scaled absolute
residuals13 . The 10th percentile was calculated as
mean − 1.282 SD and the 90th percentile as mean +
1.282 SD using back-transformed values. To achieve
a normal distribution, the outcome measures of the
growth-restricted fetuses were ln-transformed and SD
scores (Z-scores) were calculated based on ln-transformed
mean and SD values of the normally grown fetuses.
Analysis of variance and 95% CIs were used to
assess differences. P ≤ 0.05 was regarded as statistically
significant.
The intraobserver coefficient of variation for repeated
diameter measurements of the aorta and pulmonary artery
was studied in 141 and 145 participants of the reference
group with four or more observations, respectively. The
intraobserver variation was also analyzed as the intraclass
correlation. The SPSS statistical package (SPSS, Chicago,
IL, USA) was used except for the intraobserver coefficient
of variation, which was carried out according to the
‘logarithmic method’ of Bland14 .
RESULTS
Of the 210 examined successfully in the reference group,
we obtained measurements of the umbilical flow in 195
and measurements from the cardiac outlets in 181, with
complete sets in 170. Fetal movements, unfavorable
position, maternal obesity and time constraints were
the reasons for incomplete data. Of the 64 growthrestricted fetuses included, we obtained umbilical flow
measurements in 62 and measurements in the heart in
32, with complete sets for output calculation in 29. In
addition to the reasons for missing data mentioned for
the low-risk group, fetuses with IUGR were examined for
a shorter time, and priority was given to the umbilical
circulation.
Figures 2 and 3 show the diameters of the aorta
and pulmonary artery measured at the ostia between
open valves at gestational ages of 18–41 weeks. The
relationship is almost linear. In fetuses with IUGR these
diameters tended to be less than they were in the reference
group (Figures 2 and 3, Table 1). The pulmonary arterial
diameter was significantly smaller in fetuses with IUGR
and normal PIua compared with the reference group,
while the severely affected fetuses with ARED flow before
32 weeks of gestation maintained a normal pulmonary
arterial diameter (Table 1).
Normal left and right ventricular output and the results
for growth-restricted fetuses are shown in Figures 4 and 5.
Those with IUGR had lower output on both the left and
the right sides, but without significant differences between
129
9
9
8
8
7
7
Aortic diameter (mm)
(b) 10
Aortic diameter (mm)
(a) 10
6
5
4
6
5
4
3
3
2
2
1
1
0
17
22
27
32
37
Gestational age (completed weeks)
0
17
42
22
27
32
37
42
Figure 2 Diameter of the fetal aorta measured at the ostium between the open valvular leaflets in (a) 181 low-risk pregnancies and (b) 32
pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery
pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The
growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for
the regression line was y = 1.63336229 − 307.1038719 · GA−2 + 0.00000716359 · GA3 , and SD = 0.088581647 + 0.00122008 · GA, where
GA is gestational age in weeks. Data were ln-transformed.
10
10
Pulmonary arterial diameter (mm)
(b) 12
Pulmonary arterial diameter (mm)
(a) 12
8
6
4
2
0
17
8
6
4
2
22
27
32
37
42
0
17
22
27
32
37
42
Figure 3 Diameter of the fetal pulmonary artery measured at the ostium between valvular leaflets in (a) 179 low-risk pregnancies and (b) 32
pregnancies with intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery
pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The
growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for
the regression line was y = 1.687988793 − 259.8188528 · GA−2 + 0.00001134 · GA3 , and SD = 0.150728212 − 0.000965064 · GA, where
GA is gestational age in weeks. Data were ln-transformed.
Kiserud et al.
130
Table 1 Combined cardiac output (CCO) and its distribution in intrauterine growth restriction (IUGR) compared with normal fetuses using
Z-score (SD-score) statistics
Measurement/fetus
Aortic diameter
Normal
IUGR, PIua normal
IUGR, PIua > 97.5th p.
IUGR, ARED
Aortic flow
Normal
IUGR, PIua normal
IUGR, ARED
Pulmonary arterial diameter
Normal
IUGR, PIua normal
IUGR, ARED
Pulmonary arterial flow
Normal
IUGR, PIua normal
IUGR, ARED
CCO
Normal
IUGR, PIua normal
IUGR, ARED
CCO/kg
Normal
IUGR, PIua normal
IUGR, ARED
Left-right flow difference
Normal
IUGR, PIua normal
IUGR, ARED
Umbilical flow
Normal
IUGR, PIua normal
IUGR, ARED
Umbilical flow/kg
Normal
IUGR, PIua normal
IUGR, ARED
Placenta/CCO flow fraction
Normal
IUGR, PIua normal
IUGR, ARED
Mean
SE
95% CI
n
Overall P
0.00
−0.98
−1.06
−0.49
0.08
0.30
0.30
0.37
−0.16
−1.58
−1.66
−1.22
0.15
−0.38
−0.46
0.24
181
12
12
8
< 0.001
0.00
−0.91
−2.01
−1.03
0.08
0.29
0.31
0.39
−0.15
−1.49
−2.62
−1.79
0.15
−0.33
−1.41
−0.27
175
12
11
7
< 0.001
0.00
−1.49
−0.14
0.01
0.08
0.30
0.30
0.37
−0.15
−2.09
−0.73
−0.71
0.16
−0.90
0.45
0.74
179
12
12
8
< 0.001
0.00
−1.45
−0.70
−0.93
0.11
0.31
0.31
0.40
−0.22
−2.06
−1.30
−1.72
0.22
−0.84
−0.09
−0.13
173
12
12
7
< 0.001
0.00
−1.55
−1.75
−1.35
0.08
0.33
0.33
0.41
−0.17
−2.20
−2.40
−2.17
0.17
−0.90
−1.10
−0.53
170
11
11
7
< 0.001
0.00
0.11
−0.11
0.61
0.08
0.32
0.32
0.40
−0.16
−0.52
−0.74
−0.18
0.16
0.74
0.52
1.40
170
11
11
7
0.485
0.00
−0.32
1.07
0.23
0.08
0.31
0.31
0.39
−0.16
−0.93
0.46
−0.54
0.16
0.29
1.68
1.00
170
11
11
7
< 0.001
0.00
−1.74
−2.47
−3.88
0.08
0.24
0.24
0.30
−0.16
−2.20
−2.94
−4.46
0.16
−1.27
−1.99
−3.29
195
24
23
15
< 0.001
0.00
−0.94
−1.32
−2.00
0.09
0.25
0.26
0.32
−0.17
−1.44
−1.83
−2.63
0.17
−0.45
−0.82
−1.38
195
24
23
15
< 0.001
0.00
−0.70
−1.19
−2.68
0.08
0.31
0.31
0.39
−0.16
−1.32
−1.81
−3.45
0.16
−0.08
−0.57
−1.90
164
11
11
7
< 0.001
IUGR fetuses were grouped according to umbilical artery waveform, i.e. pulsatility index normal (PIua ), PIua > 97.5th percentile (p.), or
absent/reversed end-diastolic flow (ARED).
the three sub-groups classified according to the umbilical
artery waveform (Table 1).
Comparing left and right ventricular output (Figure 6),
there was a shift towards higher volume load in the right
ventricle, this effect being augmented during the last weeks
of pregnancy. The combined values before 32 weeks of
gestation showed a 13% greater load in the right than in
the left ventricle, and the corresponding difference after
32 weeks was 26%. In fetuses with IUGR there was a
significant overall shift towards greater load in the right
ventricle compared with the reference group (Figure 6 and
Table 1). However, when divided into subgroups, fetuses
with IUGR and normal PIua were not different from
the reference population. On the other hand, those with
IUGR and PIua > 97.5th percentile shifted the distribution
significantly to the right compared with the reference
131
900
900
800
800
700
700
Aortic flow (mL/min)
(b) 1000
Aortic flow (mL/min)
(a) 1000
600
500
400
600
500
400
300
300
200
200
100
100
0
17
22
27
32
37
0
17
42
22
27
32
37
42
Figure 4 Left ventricular output (aortic flow) in (a) 175 low-risk pregnancies and (b) 30 pregnancies with intrauterine growth restriction and
various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th
percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the
reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was
y = 6.252257178 − 974.1413866 · GA−2 + 0.00000808794 · GA3 , and SD = 0.257218688 + 0.001375273 · GA, where GA is gestational age
in weeks. Data were ln-transformed.
1800
(b) 1800
1600
1600
1400
1400
Pulmonary arterial flow (mL/min)
Pulmonary arterial flow (mL/min)
(a)
1200
1000
800
600
1200
1000
800
600
400
400
200
200
0
17
22
27
32
37
42
0
17
22
27
32
37
42
Figure 5 Right ventricular output (pulmonary arterial flow) in (a) 173 low-risk pregnancies and (b) 31 pregnancies with intrauterine growth
restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those with
PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different
from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was
y = 5.825881953 − 722.6681806 · GA−2 + 0.0000236 · GA3 . and SD = 0.27653547 − 0.000171845 · GA, where GA is gestational age in
weeks. Data were ln-transformed.
group (95% CI of the Z-scores, 0.46 to 1.68 vs. −0.16
to 0.16), but also compared with those with IUGR and
normal PIua (95% CI, −0.93 to 0.29) (Table 1). Fetuses
with IUGR and ARED in the umbilical artery showed
the same tendency but did not reach significance, their
numbers being small (Table 1).
Kiserud et al.
132
(b) 100
80
80
60
60
Left−right difference (%)
Left−right difference (%)
(a) 100
40
20
0
20
0
− 20
− 40
17
40
− 20
22
27
32
37
− 40
17
42
22
27
32
37
42
Figure 6 Difference between left and right ventricular output, calculated as the percentage of the combined left and right output, showing a
dominance of the right ventricle, in (a) 170 low-risk pregnancies and (b) 29 fetuses with intrauterine growth restriction. These fetuses were
subdivided to show those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with absent
or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were different from the reference group (P < 0.001). Lines indicate
10th , 50th and 90th percentiles. The equation for the regression line was y = 5.199715945 − 0.028088562 · GA + 0.000013103 · GA3 , and
SD = 0.133574716 + 0.000029348 · GA, where GA is gestational age in weeks. Left–right flow difference + 100 was ln-transformed.
1800
1800
1600
1600
1400
1400
1200
1200
CCO (mL/min)
(b) 2000
CCO (mL/min)
(a) 2000
1000
800
1000
800
600
600
400
400
200
200
0
17
22
27
32
37
42
0
17
22
27
32
37
42
Figure 7 Fetal combined left and right cardiac output (CCO) in (a) 170 low-risk pregnancies, and (b) 29 pregnancies with intrauterine
growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index (PI) ( ), those
with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted fetuses were
different from the reference group (P < 0.001). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was
y = 5.544717402 − 201.4738872 · GA−2 + 18.309430055 · GA−1 , and SD = 0.414476269 − 0.005064894 · GA, where GA is gestational age
in weeks. Data were ln-transformed.
The mean fetal CCO was 80 mL/min at 18 weeks
and 1370 mL/min at 40 weeks (Figure 7). In fetuses
with IUGR the CCO was less (Figure 7 and Table 1).
The CCO/kg was on average 400 mL/min/kg during the
entire second half of the normal pregnancy and this
was no different from that in the group with IUGR,
133
(b)
1200
1000
1000
800
800
CCO/kg (mL/min/kg)
CCO/kg (mL/min/kg)
(a) 1200
600
400
200
0
17
600
400
200
22
27
32
37
0
17
42
22
27
32
37
42
Figure 8 Fetal normalized combined cardiac output (CCO/kg) in mL/min/kg for (a) 170 low-risk pregnancies and (b) 29 pregnancies with
intrauterine growth restriction and various degrees of placental compromise, showing those with normal umbilical artery pulsatility index
(PI) ( ), those with PI > 97.5th percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). The growth-restricted
fetuses were not different from the normal group (P = 0.485). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression
line was y = −3.137255228 + 1.794387574 · GA0.5 − 0.000015527 · GA3 , and SD = 0.205635425 + 0.000295948 · GA, where GA is
gestational age in weeks. Data were ln-transformed.
(b) 250
(a) 450
Umbilical venous flow/kg (mL/min/kg)
Umbilical venous flow (mL/min)
400
350
300
250
200
150
100
200
150
100
50
50
0
17
22
27
32
37
42
0
17
22
27
32
37
42
Figure 9 (a) Umbilical venous flow in 62 growth-restricted fetuses was lower than that in the reference group (P < 0.001). (b) The effect was
also present when flow was normalized for fetal weight (UV flow/kg) (P < 0.001). Growth-restricted fetuses were divided into groups,
showing various degrees of placental compromise: those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th
percentile ( ) and those with absent or reversed end-diastolic blood velocity ( ). Lines indicate 10th , 50th and 90th percentiles. The equation
for the regression line for the UV flow was y = −10.08885345 + 4.68474999 · ln(GA) − 0.001042436 · GA2 , and SD = 0.337017961 −
0.000922071 · GA, and that for the regression line for the UV flow/kg was y = 4.90993362 − 27.62004561 · GA−2 − 0.000011856 · GA3 ,
and SD = 0.575534616 − 0.007815357 · GA, where GA is gestational age in weeks. All data were ln-transformed.
or any sub-group of placental compromise (Figure 8 and
Table 1).
Umbilical blood flow was less in growth-restricted
compared with normal fetuses (P < 0.001) (Figure 9), and
there was a significant effect of increasing hemodynamic
compromise of the placenta (Table 1). This effect was less
pronounced when umbilical flow was normalized for fetal
weight, but was still significant (Figure 9 and Table 1).
Kiserud et al.
134
70
70
60
60
Placenta/CCO flow fraction (%)
(b) 80
Placenta/CCO flow fraction (%)
(a) 80
50
40
30
20
40
30
20
10
10
0
17
50
22
27
32
37
42
0
17
22
27
32
37
42
Figure 10 The fraction of fetal combined cardiac output (CCO) directed to the placenta calculated as a percentage of CCO (a) in 164
low-risk pregnancies. (b) The 29 fetuses with intrauterine growth restriction directed a lower proportion of CCO to the placenta
(P < 0.001), particularly in extreme degrees of compromise. Growth-restricted fetuses were divided into groups, showing various degrees of
placental compromise: those with normal umbilical artery pulsatility index (PI) ( ), those with PI > 97.5th percentile ( ) and those with
absent or reversed end-diastolic blood velocity ( ). Lines indicate 10th , 50th and 90th percentiles. The equation for the regression line was
y = 3.35420863 + 0.000060601 · GA3 − 0.000018693 · GA3 · ln(GA), and SD = 0.377370102 − 0.000755215 · GA, where GA is gestational
age in weeks. Data were ln-transformed.
The fraction of CCO directed to the placenta in
normally grown fetuses was on average 32% before
32 weeks, and 21% beyond 32 weeks (Figure 10). In
general, growth-restricted fetuses distributed less of
the CCO to the placenta (P < 0.001) (Figure 10 and
Table 1). While growth-restricted fetuses with normal
PIua distributed a similar fraction of the CCO to the
placenta compared with their normal peers, this was not
the case for those that had hemodynamic compromise.
Those with PIua > 97.5th percentile and particularly those
with ARED flow in the umbilical artery had a reduced
fraction of CCO distributed to the placenta (Table 1),
implying an increased recirculation of umbilical blood in
the fetal body.
DISCUSSION
In this study we showed that fetuses normally direct one
third of their cardiac output to the placenta during the
second half of pregnancy and one fifth during the last
couple of months. Interestingly, this implies an increase
in recirculation of umbilical blood in the fetal body
towards the end of pregnancy. Furthermore, this effect
is augmented in placental compromise. Growth-restricted
fetuses direct a reduced volume of blood towards the
placenta, both in absolute and in relative terms, while
maintaining a relatively normal cardiac output. The effect
seems to increase with the degree of placental compromise
and signifies a more extensive recirculation of umbilical
blood within the fetal body.
The distribution of volume load within the fetal heart
also seems to be affected. Although experimental data15,16
and some studies in humans17 suggest that the normal
dominance of the right ventricle is cancelled during
challenge, our study supports that in fetuses with increased
pulsatility of the umbilical artery the right ventricle
actually takes an increased proportion of the load18,19 .
This is in keeping with other mechanisms seen in such
fetuses: reduced size of and shunting through the foramen
ovale7,20 , increased resistance in the pulmonary circuit21 ,
with correspondingly less venous return to the left heart,
and retrograde blood flow at the aortic isthmus7,22 to
further supply the aortic arch and carotid arteries with
right ventricular blood via the ductus arteriosus. A shift
to the left of the watershed area between portal and
umbilical venous supply to the liver23,24 and an augmented
blood velocity in the hepatic artery25 will change the fetal
circulation in the same direction. These are mechanisms
of redistribution but also of increased recirculation of
umbilical blood in the fetal body, which correspond to
more extensive oxygen extraction. On average, the oxygen
concentration in the umbilical vein measured in the IUGR
fetus during cordocentesis is lower than that in their
normal peers26 .
The fraction of fetal CCO directed to the placenta
found in this study is in line with the two previous
studies that examined this issue in humans, but with
an important difference: the placental fraction was less
(one fifth) near term. The study of Rudolph et al.8
using the microsphere technique found an average 33%
distribution of the CCO to the placenta at mid-gestation,
but did not include higher gestational ages. Due to the
method of calculating CCO (pulmonary venous return
was not included) and the conditions not being strictly
physiological (the fetuses were exteriorized), the results
have awaited verification. Our study, applying a different
technique, presents very similar results indeed; 32% of
the CCO was directed to the placenta during gestational
weeks 18–32. In the second study, Sutton et al.9 used
Doppler ultrasound in physiological pregnancies to show
that the placental fraction of the CCO is one third
for the second half of pregnancy. Fewer numbers
included and calculation of umbilical venous flow using
maximum velocity (which tends to overestimate flow
if not corrected for the parabolic velocity profile) may
explain some of the differences from our study in late
pregnancy.
The normal fetal CCO found in our study had a
similar pattern during the second half of pregnancy to
that described in previous studies27 – 30 . Compared with
those using leading edges (inner–outer diameter) for the
vessel cross-section measurement, our results of CCO
are lower (1300 vs. 1900 mL/min at 38 weeks)29 ; our
results are more in agreement with those using inner
diameters in their calculation, as they are for CCO/kg
(400 vs. 425 mL/min/kg)30 . The 6% difference may be
ascribed to technique (this study measured between valves
at the ostium), or to chance. Knowing the variability of such measurements in the fetus31,32 , particularly
diameter measurements, we restricted error by repeating measurements12,33 and by using a single operator.
Coefficients of variation of 8.4 and 7.7%, and intraclass correlations of 94 and 97% for the diameter of the
aorta and pulmonary artery, respectively, ensured that the
study gave a fair representation of normal and abnormal
flows.
We acknowledge that having cardiac outflow measurements in less than half of the IUGR group might
represent a limitation of the study, with a possible
selection bias. A successful examination is least likely
in small fetuses with oligohydramnios in overweight
mothers; in our setting we believed that time constraints for such mothers and fetuses (which, due to
clinical reasons, tended to be examined for a shorter
period than did the low-risk group) were the main
reason for the low success rate. The fact that umbilical venous flow was obtained successfully in 62/64
cases underscores the point that due to time limitation,
the lower priority of cardiac measurements gave fewer
results.
In short, one third to one fifth of the fetal CCO
circulates the normal placenta; in comparison, the
compromised placenta shrinks this fraction, both in
absolute and in relative terms, thus driving the circulation
towards increased recirculation of umbilical blood within
the fetal body. We believe this reflects an increased
vulnerability in much the same way as does the
low oxygen concentration found in growth-restricted
fetuses.
135
ACKNOWLEDGMENT
The study was supported by the Norwegian Research
Council.
REFERENCES
1. Kramer MS, Olivier M, McLean FH, Willis DM, Usher RH.
Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990; 86:
707–713.
2. Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K,
Clark PMS. Type 2 (non-insulin-dependent) diabetes mellitus,
hypertension and hyperlipidaemia (syndrome X): relation to
reduced fetal growth. Diabetologia 1993; 36: 62–67.
3. Robinson JS, Kingston EJ, Jones CT, Thorburn GD. Studies on
experimental growth retardation in sheep. The effect of removal
of endometrial caruncles on fetal size and metabolism. J Dev
Physiol 1979; 1: 379–398.
4. Bocking AD. Effect of chronic hypoxaemia on circulation
control. Fetus and Neonate Physiology and Clinical Application,
Vol. 1, The Circulation, Hanson MA, Spencer JAD, Rodeck CH
(eds). Cambridge University Press: Cambridge, 1993; 215–224.
5. Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk
pregnancies: Systematic review with meta-analysis. Am J Obstet
Gynecol 1995; 172: 1379–1387.
6. Hecher K, Campbell S, Doyle P, Harrington K, Nicolaides K.
Assessment of fetal compromise by Doppler ultrasound
investigation of the fetal circulation. Circulation 1995; 91:
129–138.
7. Mäkikallio K, Jouppila P, Räsänen J. Retrograde aortic isthmus
net blood flow and human fetal cardiac function in placental
insufficiency. Ultrasound Obstet Gynecol 2003; 22: 351–357.
8. Rudolph AM, Heymann MA, Teramo K, Barrett C, Räihä N.
Studies on the circulation of the previable human fetus. Pediatr
Res 1971; 5: 452–465.
9. Sutton MSJ, Plappert T, Doubilet P. Relationship between
placental blood flow and combined ventricular output with
gestational age in normal fetuses. Cardiovasc Res 1991; 25:
603–608.
10. Kiserud T, Rasmussen S, Skulstad SM. Blood flow and degree
of shunting through the ductus venosus in the human fetus. Am
J Obstet Gynecol 2000; 182: 147–153.
11. Skjaerven R, Gjessing HK, Bakketeig LS. Birthweight by gestational age in Norway. Acta Obstet Gynecol Scand 2000; 79:
440–449.
12. Kiserud T, Saito T, Ozaki T, Rasmussen S, Hanson M. Validation of diameter measurements by ultrasound. Intra-observer
and inter-observer variation assessed in vitro and in the fetal
sheep. Ultrasound Obstet Gynecol 1999; 13: 52–57.
13. Royston P, Wright EM. How to construct ‘‘normal ranges’’ for
fetal variables. Ultrasound Obstet Gynecol 1998; 11: 30–38.
14. Bland JM. How should I calculate a within-subject coefficient
of variation? http://www-users.york.ac.uk/∼mb55/meas/cv.htm
[Accessed 22 September 2005].
15. Thornburg KL, Morton MJ. Filling and arterial pressures as
determinants of RV stroke volume in the sheep fetus. Am J
Physiol 1983; 244: H656–H663.
16. Rudolph AM. Distribution and regulation of blood flow in the
fetal and neonatal lamb. Circ Res 1985; 57: 811–821.
17. al-Ghazali W, Chita SK, Chapman MG, Allan LD. Evidence
of redistribution of cardiac output in asymmetrical growth
retardation. Br J Obstet Gynaecol 1989; 96: 697–704.
18. Reed KL, Anderson CF, Shenker L. Changes of intra-cardiac
Doppler blood flow velocities in fetuses with absent umbilical
artery diastolic flow. Am J Obstet Gynecol 1987; 157: 774–779.
19. Weiner Z, Farmakides G, Schulman H, Penny B. Central and
peripheral hemodynamic changes in fetuses with absent
end-diastolic velocity in umbilical artery: Correlation with
136
20.
21.
22.
23.
24.
25.
26.
computerized fetal heart rate pattern. Am J Obstet Gynecol
1994; 170: 509–515.
Kiserud T, Chedid G, Rasmussen S. Foramen ovale changes in
growth-restricted fetuses. Ultrasound Obstet Gynecol 2004; 24:
141–146.
Rizzo G, Capponi A, Chaoui R, Taddei F, Arduini D, Romanini C. Blood flow velocity waveforms from peripheral
pulmonary arteries in normally grown and growth-retarded
fetuses. Ultrasound Obstet Gynecol 1996; 8: 87–92.
Sonesson S-E, Fouron J-C. Doppler velocimetry of the aortic
isthmus in human fetuses with abnormal velocity waveforms
in the umbilical artery. Ultrasound Obstet Gynecol 1997; 10:
107–111.
Kiserud T, Kilavuz Ö, Hellevik LR. Venous pulsation in the
left portal branch – the effect of pulse and flow direction.
Kilavuz Ö, Vetter K, Kiserud T, Vetter P. The left portal vein is
the watershed of the fetal venous system. J Perinat Med 2003;
31: 184–187.
Kilavuz Ö, Vetter K. Is the liver of the fetus the 4th preferential
organ for arterial blood supply besides brain, heart, and adrenal
glands. J Perinat Med 1999; 27: 103–106.
Soothill PW, Nicolaides KH, Campbell S. Prenatal asphyxia,
hyperlactaemia and erythroblastosis in growth retarded fetuses.
Kiserud et al.
BMJ (Clin Res Ed) 1987; 294: 1051–1053.
27. Kenny JF, Plappert T, Saltzman DH, St John Sutton MG.
Changes in intracardiac blood flow velocities and right and left
ventricular stroke volumes with gestational age in the normal
fetus. Circulation 1986; 74: 1208–1216.
28. De Smedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac
output estimated by Doppler echocardiography during midand late gestation. Am J Cardiol 1987; 60: 338–342.
29. Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. Role
of the pulmonary circulation in the distribution of human fetal
cardiac output during the second half of pregnancy. Circulation
1996; 94: 1068–1073.
30. Mielke G, Benda N. Cardiac output and central distribution
of blood flow in the human fetus. Circulation 2001; 103:
1662–1668.
31. Beeby AR, Dunlop W, Heads A, Hunter S. Reproducibility of
ultrasonic measurement of fetal cardiac haemodynamics. Br J
Obstet Gynaecol 1991; 98: 807–814.
32. Simpson JM, Cook A. Repeatability of echocardiographic
measurements in the human fetus. Ultrasound Obstet Gynecol
2002; 20: 332–339.
33. Kiserud T, Rasmussen S. How repeat measurements affect
mean diameter of the umbilical vein and the ductus venosus.
Diabetes
i svangerskapet
Hva er diabetes?
En tilstand der blodsukkeret i fastende og/eller
ikke-fastende tilstand er over et definert nivå
Grunnkurs i Obstetrikk
2015
Tore Henriksen
Fødeseksjonen, Rikshospitalet
Hvorfor blir blodsukkeret for høyt?
Blodglukosens kilde nr 1: Tarm
Etter måltid
Kort om omsetningen (metabolismen) av
glukose
Blodglucose
Tarm
Kilde nr 2: Lever
De kvantitativt viktigste forbrukere av glukose
I fastende tilstand
Lever
Glykogen!
Insulin?
Glukoneogenese
(ved faste)
Blodglucose
Blodglucose
Hjerne
Tarm
Fettvev
Tarm
Muskel
Muskulatur og fettvev sammen med lever er sentrale
i regulering av blodsukkeret
Opptaket av glukose i muskel og fettvev er
avhengig av at Insulin-systemet virker
Glykogen!
Glykolyse
Glukoneogenese
Insulin
Insulin
Glukose
Glukose
Blodglucose
Blodglucose
Insulin
Insulin
Hjerne
Fettvev
Muskel
Tarm
Insulin-systemet kan svikte på to måter
Fettvev
Tarm
Muskel
Insulin
1. Svikt i pancreas’øyceller
Glykolyse
Glukoneogenese
Glykolyse
Glukoneogenese
Insulin
Glukose
Glukose
Blodglucose
Fettvev
Blodglucose
Muskel
Tarm
Fettvev
Tarm
Muskel
Type 1 diabetes: for lite insulin
1. Svikt i pancreas’øyceller
Glykolyse
Glukoneogenese
Glykolyse
Glukoneogenese
Insulin
Insulin
Glukose
Glukose
Blodglucose
Blodglucose
2. Insulinet virker ikke på
cellenivå (insulinresistens)
Fettvev
Tarm
Muskel
Fettvev
Tarm
Muskel
Type 2 diabetes:
Ofte høyt insulin, men insulin resistens,
gjerne kombinert med en relativ
svikt i øycellene
Øycelleinsuffisiens
Glykolyse
Glukoneogenese
Klassifikasjon av diabetes/glukoseintoleranse
i svangerskapet
Insulin
Glukose
Blodglucose
2. Insulinet virker ikke på
cellenivå (insulinresistens)
Fettvev
Tarm
 Pregestasjonell diabetes,
(“kjent diabetes”)
•
•
 Diabetes/glukoseintoleranse) oppdaget
første gang i svangerskapet
•
Type 1 diabetes. (IDDM)
Type 2 diabetes (økende!)
Nyoppdaget Type 1 diabetes (sjelden men
farlig !).
•
Svangerskaps-(gestasjonell) diabetes:
a) Nyoppdaget type 2 (vedvarer etter
fødselen)
b) “Ekte svangerskapsdiabetes”
(blir borte etter fødselen, dvs normal
glukosetoleranse-test post partum,
MEN gir økt risiko for diabetes senere.
Muskel
Diabetes/glukoseintoleranse: Definisjoner
(WHO/kriterier, 1999, men NYE ER PÅ VEI!)
PREGESTASJONELL
DIABETES
Forekomst/epidemiologi.
Plasma glukose nivå
mmol/l
Manifest Diabetes Mellitus:
Fastende
2 t etter 75g glukose oralt
250 -300 kvinner med Type 1 diabetes
og
ca 150-200 med Type 2
gjennomfører et svangerskap per år i Norge.
 7.0*
eller
 11.1**
”Nedsatt glukosetoleranse”
(hos gravide det samme som svangerskapsdiabetes (GDM:
Fastende
< 7.0
og
2 t etter 75 g glukose oralt
 7.8 men <11.1
*Kapillært fullblod: ≥ 6.1 . **Kapillærblod ≥ 10.0 .
Pregestasjonell diabetes
•
•
•
Nyoppdaget Type 1 diabetes (sjelden men
farlig !).
•
fødselen)
Gravide med pregestasjonell diabetes
(Type 1 eller Type 2)
1. Godt regulert diabetes før de blir gravide!!,
eventuell prekonsepsjonell veiledning. Komorbiditet?
Kost, vekt og mosjon!
HbA1c <7 før svangerskapet
Folat fra det tidspunkt en kvinne ønsker å bli gravid
Hvis antihypertensiva: Bruk (skift til) labetolol (event nifedipin
eller metyldopa)
Oppgave for primær og spesialisthelsetjenesten
glukosetoleranse-test post partum).
Spesialisthelsetjenesten: Vurdering (prekonsepsjonelt) av dem
som bruker metformin (event insulinanaloger)
Metformin ved type 2 diabetes?
• Synes ikke teratogent
• Men: usikkerhet m h p metabolsk langtidseffekt på barnet
Brukes i praksis når det er klar indikasjon der fordeler
og usikkerhet er vektet.
Komplikasjoner:
Gravide med pregestasjonell diabetes
(type 1 eller type 2)
(eller nyoppdaget insulinkrevende
gestasjonell diabetes):
1. Misdannelser (både type 1 og type 2!)
(HbA1c >8: tidlig/utvidet ultralyd)
2. Preeklampsi
3. Føtale vekstavvik (intrauterin veksthemning/makrosomi)
4. Økt perinatal mortalitet
Oppfølging av pregestasjonell (type 1 og 2)
diabetes i svangerskapet, forts.
7. Blodglukosemåling før og etter hovedmåltidene og ved sengetid.
Behandlingsmål:
Blodglukose 3,5 – 5,5 mmol/l før måltid og under 7,0 mmol/l målt 1½-2 timer etter måltid.
HbA1c < 6.0 % i 2. og 3. trimester.
8. Hvis skifte fra metformin til insulin tidlig i svangerskapet: Obs hyperglykemi!
9. Ved kostregulert Type 2: Blodsukkermåling fastende og ca 1.5 timer post-prandialt
hver annen dag. Medisinsk behandling foreslås hvis pasienten i løpet av en uke har til
sammen flere enn 2 målinger av enten fastende blodsukker > 5.5mmol/l eller
> 7mmol/l postprandialt.
11. Kostråd og mosjonståd. Se www.helsedirektoratet.no for generelle kostråd,
for diabetes og for gravide.
Pregestasjonell diabetes
Oppfølging i svangerskapet:
Spesialistoppgave
Oppfølging av pregestasjonell (type 1 og 2)
diabetes i svangerskapet
Henvises til fødepoliklinikk så raskt som mulig etter at graviditeten er bekreftet.
På Fødepoliklinikken:
1. Generell gjennomgang (som ved pregestasjonell veiledning) + tidligere svangerskap
2. HbA1c ≥ 8 % (nå eller rett før graviditeten): tilbys ekstra «utvidet ultralyd» i uke 15-16,
i tillegg til den ordinære ultralydscreeningen noen uker senere
3. Urin dyrkning ved 1. kontroll?
4. HbA1c måles hver 4. uke.
5. BT og stix; protein/ kreatinin ratio i urin med 4-6 ukers intervall.
6. Diabetes > 5 år: obs øyelege
Obetetriske momenter i oppfølgingen av pregetasjonell
• Reperterte tilvekstmålinger (ca hver 4. uke) fra ca uke 24.
• Tegn til avtakende tilvekst (vektmessig) eller tegn
til begynnende assymetri er alltid alvorlig selv om barnet er
er ”normalt stort”. Snikende placentasvikt kan sees hos store barn!
• Fostervannsmengde i nedre normalområde eller tegn til avtakende
fostervannsmengde, selv om det er innenfor refranseverdiene.
skal alltid vektlegges.
• Doppler: Sentralisering? (arteria cerebri media)
• CTG vektlegges: Obs: Basalfrekvens (endring?), kortidsvariabilitet
(Oxford 8002), reaktivitet (akselerasjoner).
• Bevegelser?!
• Preeklampsi-utvikling ved pregestasjonell diabetes alltid alvorlig
(placentasvikt slev om barnet er normal eller stort).
Dato
Svanger-
Indremed.
Jordmor
Gynekolog CTG
skapsuke
Kontrollhyppighet,
Insulinkrevende diabetes
6
X
Truende preterm fødsel ved insulinkrevende diabetes.
7
8
X
X
X
9
10
Absolutt risiko ca 15 %.
Rihemmende behandling ved diabetes i svangerskapet
Atosiban (Tractocile) Blodsukkeret skal følges, da atosiban kan gi
blodsukkerstigning.
X
11
12
X
14
X
16
X
18
X
20
X
22
X
24
X
26
X
28
X
30
X
X
Evt. UL
fosterm
Scr. v/jordmor
X
X
X
X
X
X
X
X
X
X
X
X
31
32
X
33
34
X
35
36
37
38
X
X
X
39
40
X
X
X Vurdering
X
X
X
X
Celeston
i to doser med (12-)24 timers intervall. Økt behov for
insulin Økningen gjelder både hurtig og langsomtvirkende insulin.
Forslag til dosering av insulin økes fra dag 2:
Dag 1 (Dagen etter første dose Celeston). Ingen endring av insulindose
Dag 2 30 % økning av den opprinnelige insulindosen
Dag 6 Vanlig insulindose
Ved blodsukker over 8 mmol/l gis ekstra hurtigvirkende insulin (4-6 enheter).
X
X Vurdering
X
Induksjon av fødsel ved pregestasjonell diabetes:
Induksjon vurderes fortløpende fra 38 fulle uker. Anbefales ikke å gå over termin.
Keisersnitt: Vanlige obstetriske indikasjoner. Ved alvorlige vaskulære, nyre eller
øyekomplikasjoner etter individuell vurdering. Keisersnitt vurderes ved
mistanke om vekt over 4500g*.
Ved tidligere skulderdystoci keisersnitt vurderes mistanke om vekt over 4000g*
Aktiv fødsel, Insulinkrevende diabetes
Blodsukkermåling ca hver time, eventuetl oftere, individuell vurdering.
Mål blodglukose: 4-8 mmol/l.
Insulin:
Pasientens egen erfaring med insulin!
*OBS! Vektestimering usikker business! Flere målinger over flere uker for å øke
sannsynligheten for riktigere estimat. Se på AC-målet!
Aktiv fødsel, insulinkrevende diabetes
Tiltak ved ulike blodsukkernivåer:
LAVT blodsukker:
Pasienten er bevisstløs eller kraftig føling: Glucose 200 mg/ml 40 ml i.v. i støt.
Dosen gjentas hvis pasienten ikke kommer til bevissthet i løpet av 10.
Blodsukker er under 4,0 mmol/l: Gi glucose 50 mg/ml i.v. infusjon etter kroppsvekt:
60 kg: 180 ml/t
80 kg: 250 ml/t
100 kg: 300 ml/t
HØYT blodsukker:
Blodsukker 8,0-10,0 mmol/l: 2- 4 E hurtigvirkende insulin s.c.
Gjentas etter 2 timer hvis fortatt er for høyt:
Blodsukker over 10,0 mmol/l : 4-8 E hurtigvirkende insulin s.c.
Eventuelt gjentas etter 2 timer.
Svangerskapsdiabetes (GDM)
•
•
•
Nyoppdaget manifest diabetes, nesten
alltid Type 1 diabetes (sjelden men farlig !).
•
fødselen)
glukosetoleranse-test post partum).
Antall med diabetes i svangerskapet per år
Svangerskapsdiabetes 1988-2012 (Kilde: Fødselsregisteret)
Denne økningen er ikke betinget i nye gener,
men i
1500
Miljø/livsstil
1000
500
1988
1998
2011
2012
Tore Henriksen 2010
Tore Henriksen 2014
Hvis kriteriene nedenfor oppfylles
første gang i svangerskapet: svangerskapsdiabetes (gestajonell
diabetes, GDM).
Plasma glukose nivå
mmol/l
Manifest Diabetes Mellitus:
Fastende
eller
 7.0*
Disse kriteriene er under revisjon,
11.1**
nye kommer!
2 t etter 75g glukose oralt
Svangerskapsdiabetes (GDM):
Fastende
Men:
2 t etter 75 g glukose oralt
< 7.0
Hva er grunnlaget for definisjonen av
svangerskapsdiabetes (GDM)?
Definisjonen hadde opprinnelig som mål å identifisere
gravide som hadde risiko for å utvikle diabetes senere i livet
(O’Sullivan 1964).
WHO-definisjonen (som vi har brukt i Norge) er overført rett fra
definisjoner for ikke-gravide, og antar at blodsukker over
disse verdiene gir en risiko for mor og barn, som det er verd å
bruke resurser på.
Nye kriterier er basert på perinatale utfall
(beregnet ut fra HAPO-studien)
 7.8 men <11.1
*Kapillært fullblod: ≥ 6.1 . **Kapillærblod ≥ 10.0 .
Nye definisjoner av GDM basert på IADPSG-kriterier
Disse er basert på risikoen for perinatale utfall:
IADPSG sier at de glukoseverdiene som medfører risiko (odds ratio 1.75) for:
Store barn (>90 percentilen), og/eller høy prosent kroppsfett (> 90 percentilen),
og/eller føtal hyperinsulinemi ( C-peptid >90 percentilen )
gir kvinnen diagnosen GDM.
Glukosegrense for GDM
(plasma eller serum)
Fastende
1-times verdien
2-timers verdien
5.1 mmol/l
10.0 mmol/l
8.5 mmol/l
Andel med GDM (%)*
8.3
14.0
16.1#
*Prosenten er akkumulativ d v s at én, to eller alle tre verdiene er til stede.
# I tillegg kommer 1.7 prosent med manifest diabetes oppdaget i svangerskapet
d v s fastende glukose  7.0 eller 2-timers verdi  11.1
Hva er prevalensen av GDM
i den gravide befolkningen?
HELT avhengig av:
1.Definisjonen (WHO, de nye IADPSG kriteriene eller andre)
2.Hvilken (sub)populsjon som undersøkes (etnisitet, sosial klasse etc)
3.Hvordan den undersøkelsen gjøres, d v s selektiv eller generell
screening
4.Screening-metoden i seg selv ( bare fastende blodsukker,
glukosebelastning eller tidlig HBA1c).
Noen prevalenser
Medisinsk fødselsregister , WHO, (2012) Selektiv screening: 2.5 %
Er det noen klinisk nytte av å oppdage og behandle
GDM?
STORK-Rikshsopitalet, skandinavisk populasjon, WHO,
(generell screening): %
STORK-Rikshospitalet etter IADPSG:
Sykeliggjør vi mange og forebygger lite?
%
STORK Grorud-dalen, WHO, generelle screening, mye innvandrere:
: %
STORK Grorud-dalen etter IADPSG:
Indikasjon insulinbehandling av diabetes i svangerskapet
Ca 70% av de med GDM trenger ikke insulin
• Pregestasjonell
diabetes
(kjent diabetes)
• Diabetes/glukoseintoleranse) oppdaget
første gang I
svangerskapet
Insulin
behandling
• Type 1 diabetes. (IDDM)
• Type 2 diabetes
• Nyoppdaget Type 1 diabetes
(sjelden men farlig !).
Helsdirekoratets arbeidsgruppe har konkludert med at det er av
klinisk nytte å oppdage og behandle GDM.
(basert på WHO og liknende definisjoner av GDM)
• Pregestasjonell
diabetes
(kjent diabetes)
• Type 1 diabetes. (IDDM)
• Type 2 diabetes
Det som avgjør om GDM
30 %
• Gestasjonell glukose-intoleranse/
ekte svangerskapsdiabetes/
type 2 diabetes
kostregulert
Insulinbehandling
• Nyoppdaget Type 1 diabetes
• Diabetes/glukosekrever
insulin er pre- og postintoleranse) oppdaget
prandiale
blodsukkerverdier
første gang i
• Svangerskapsdiabetes (GDM).
svangerskapet
(”døgnkurver”):
a Nyoppdaget type 2
3.5-5.5.
og <7 1.5-2 timer
<7 Fastende
og
b) Ekte svangerskaps2t:postprandialt
7.8-11.1: diabetes
Manifest
Diabetes.
Insulinavhengig
GDM
Kostregulert
70 %
Indikasjon for glukosebelastning
På denne bakgrunn bør vi fortsette å screene
for svangerskapsdiabetes
Men :
Hvem skal vi screene (risikogrupper eller alle)?
Hvordan skal vi screene ? (glukosebelastning, fastende glukose,
HBA1c)?
Når i svangerskapet 12-14 uker eller 26-30 eller begge deler?
Helsedirektoratets anbefaling:
1.Påvist glukosuri i morgenurin uansett når i sv. skapet.
Event gjentas ved ny glukosuri
2. Tidligere svangerskapsdiabetes
Under
revisjon!
3. Arvelig
disposisjon,
type 1 og type 2 hos foreldre/søsken
4. Innvandrere fra land utenfor Europa med høy forekomst
av diabetes, spesielt fra Nord-Afrika og det indiske
subkontinent, andre etter vurdering.
4. Alder ( >38år)
5. Overvekt/fedme (BMI > 27 kg/m2)
Når skal glukosebelasningen foretas?
Norsk gynekologisk forenings
Veileder i fødselshjelp:
Glukosebelastning vurderes også ved:
1. Utvikling av polyhydramnion og/eller
rask fostertilvekst i aktuelle
svangerskap.
2. Tidligere stort barn (>4500 g),
3. Tilfeldig påvist fastende blodsukker
mellom 6.1 og 7.0 mmol/l.
.
Komplikasjoner knyttet til tidlig og sent innsettende
glukoseintoleranse/svangerskapsdiabetes
Bartha et al Am J Obstet Gynecol 2000
Tidlig diabetes
18± 6.6 uker
n=65
Hypertensjon (%)
Preeklampsi (n)
Behov for insulin (%)
Neonatal hypogkykemi (n)
Neonatal død (n)
18.5
2
34
4
3
Sen diabetes
33 ±3.9 uker
n=170
5.9
0
7
0
0
Gjeldende retningslinjer
Tiltak i forhold til svar på glukosebelastning
< 7.8 mol/l:
Ikke glukoseintoleranse. Ingen spesiell tiltak men generelle kost
og mosjonsråd. Prøven gjentas etter 6 uker hvis ny glukosuri.
Under revisjon!
7.8-9 mmol/l:
Grundig kost- og mosjonsråd. Pasienten bør lære å måle
blodsukker. Prøven gjentas etter 4-6 uker.
Behandlingsmål: Bl sukker < 7 mmol/l ca 2 timer etter måltid
Hvis stadig > 7, henvisning (insulin).
Primærhelsetjenesten
Helsdirektoratet:
Under revisjon!
Uke 26-28, tidligere ved eventuell glukosuri eller
diabetes i tidligere svangerskap.
Norsk gyekologisk forening:
Så tidlig som mulig (der det er indikasjon)
Det nye rentingslinjene fra HD går i renting av
1.Generell screening
2.Screening med tidlig med HBA1c
3.Diagnosen GDM: Fastende over 5.2 eller 2-timersverdi
over 8.7
Konsekvens: økt forekomst av GDM.
Tiltak i forhold til svar på glukosebelastning
>9 mmol/l: Henvises til spesialavdeling.
Ofte kan de med 2-timers verdi mellom 9-11 mmol/l følges av
Under
revisjon!
primærlege, i samarbeid
med spesialist.
Pasienten læres opp i
blodsukker-måling. Behandlingen er også her grundig kost-og
mosjonsråd.
Mål: Blodglukose 3,5 – 5,5 mmol/l før måltid og under 7,0 mmol/l
målt 1½-2 timer etter måltid. Ved verdier over dette vurderes
insulin.
HbA1c < 6.0 % i 2. og 3. trimester
Forløsning ved svangerskapsdiabetes (GDM).
Induksjon:
Gravide med insulin-krevende svangerskapsdiabetes:
som pregestasjonelle diabetes
De øvrige vurderes individuelt, men skal henvises før termin.
Mål for glukose nvå under fødselen:
Insulinkrevende diabetes: som for pregestasjonell diabetes
(4-7 mmol/l)
Takk for oppmerksomheten !
Kvinner som har hatt svangerskapsdiabetes (GDM)
Har økt risko for diabetes senere .
Hvor fort skal det kontrolleres (glukosebelastning)?
Momenter:
Famileanamnese
Overvekt/fedme
Stort barn?
Overvekt/fedme i historisk perspektiv
Overvekt, Fysiologi
I løpet av1-2 generasjoner har det vært en økning i
forekomsten av fedme som er historisk uovertroffen.
Mennesket har levd på jorden i 7000-10000 generasjoner!
19.1. 2015
Tore Henriksen
Oslo University Hospital
University of Oslo
Oslo, Norway
Fedme og svangerskap:
Konsekvenser på kort og lang sikt.
For mor og barn
Short term
Consequences
(this pregnancy)
Maternal
overweight/
obesity
Long term
Consequences
(future life)
• Miscarriage
• Preeclampsia
• Gestational diabetes
• Thromboembolism
• Congential malformations
• Intrauterine fetal death
• Delivery complications
(Prolonged labour, Fetal
distress, Vacuum/forceps,
Cesarean section)
• Neonate injuries
• Maternal injuries/infections
• Need for neonatal
intensive care
• Less breast feeding
Det å studere fedme(epidemien) har tre perspektiver:
Årsakene til at fedme
utvikler seg i en befokning
Hva skjer fysiologisk
når fedme utvikles
• Maternal
Overweight
Diabetes
Anal dysf.
• Child
Diabetes
Overweight
Cancer
Cardiovascular?
Grunnleggende fakta om
overvekt/fedme
Overvekt/fedme er et resultat av samspill mellom
gener og miljø. Genene forandrer seg ikke på 1-2
generasjoner.
Miljøet må derfor ha spilt avgjørende rolle for den
overvektsepidemien vi har.
Gener spiller derimot en rolle for hvordan fedmen
fordeler seg i en befolkning på et gitt tidspunkt
Hvilke helsemessige
konsekvenser
har fedme
Årsaker til en fedmepidemi.
Regulering av energi-inntak, gener
og miljø
Miljø:
•Fosterliv
•(Mors) Ernæring
•Miljøgifter
•Fysisk aktivitet
•Psykologiske forhold
•Samfunsmessige forhold
•Klimaforhold?
Reguleringen av mat- (energi-)inntaket
består i komplekst samspill mellom
en rekke organer
Gener,
og geners aktivitet
(epigenetikk)
Fedme, gener og miljø, forenklet modell
Er tarmens bakteriesammensetning
viktig for utviklingen av fedme?
Miljø dominerende
betydning
Healthy
diet
Unhealthy
diet
Healthy
diet
Unhealthy
diet
Healthy
diet
Unhealthy
diet
Ref: Tilg H et al JCI
2011
Gener dominerende
betydning
Tore Henriksen 2012
Hva skjer fysiologisk (“i kroppen”) når fedme utvikles
Summary: Adipose tissue is a metabolically and hormonally
very active!
Triglyserider
Adipocytes
Adipocytes
Frie fettsyrer
Tore Henriksen 2011
Adipose tissue has major effects on (interacts with)
other organs
Liver
Adipose tissue has major effects on (interacts with)
other organs
Liver
Adipose tissue
Adipose tissue
Systemic vessels
Systemic vessels
Placenta
Striated muscles
Tore Henriksen 2011
Striated muscles
Tore Henriksen 2011
Free fatty acids are continuously
released from adipose tissue
Adipose tissue,
peripheral or
omental
Liver
In Liver: Free fatty acids are
synthesized “back” to triglycerides
and secreted to circulation (as VLDL),
and transported to adipose tissue
and striated muscles (etc)
Adipose tissue,
peripheral or
omental
lipolysis
Liver
FFA
FFA
Triglycerides FFA
TG
(VLDL)
TG
(VLDL)
Systemic vessels
with endothelial cells
Systemic vessels
FFA
FFA
Striated muscles
Tore Henriksen 2011
Thus: Fatty acids are continuously being
turned over in a loop
Adipose tissue,
peripheral or
omental
Striated muscles
Tore Henriksen 2011
In obesity there is an increased size and number
of adipocytes:
lipolysis
Liver
Triglycerides FFA
FFA
TG
(VLDL)
TG
(VLDL)
Systemic vessels
FFA
Striated muscles
Tore Henriksen 2011
With increasing amount mass of adipose tissue
there is an increasing presence of immune cells, like
Macrophages
Tore Henriksen 2011
Macrophages
With increasing adiposity there is and increasing
inflammation
macrophages
macrophages
Tore Henriksen 2011
When macrophages and (other immune cells) come:
Adiposity inflammation leads to
increased flux of FFA in the circulation:
Adipose tissue,
peripheral or
omental
Portal vein
Lipolysis
and
inflammation
FFA
Liver
FFA
Triglycerides
FFA
TG
(VLDL)
Free Fatty acids
Inflammatory
(FFA) response in
Toll like
Receptors
(TLR4)
adipose tissue
Release of pro-inflammatory
Cytokines, like TNF, IL-1β, etc
TG
(VLDL)
Systemic vessels
MCP-1
FFA
Recruitment of macrophages
Tore Henriksen 2012
Increased flux of fatty acids:
Fat deposition in liver:
Adipose tissue,
peripheral or
omental
Striated muscles
Fat deposition in liver leads to
2. inflammation
Portal vein
In the liver:
Fatty liver!
Tore Henriksen 2011
Adipose tissue,
peripheral or
omental
Portal vein
Lipolysis
and
inflammation
FFA
FFA
Triglycerides
Fatty liver,
Inflammation!
Lipolysis
and
inflammation
FFA
FFA
Triglycerides
FFA
FFA
TG
(VLDL)
TG
(VLDL)
TG
(VLDL)
TG
(VLDL)
Systemic vessels
Systemic vessels
FFA
FFA
Striated muscles
Tore Henriksen 2011
Striated muscles
Tore Henriksen 2011
Overall consequence: Increased circulation of inflammatory
cytokines etc, both from liver and adipose tissue
In the liver:
1: Fatty liver!
2. Inflammation!
Triglycerides
FFA
Lipolysis
and
Inflammation!
FFA
In the liver:
1: Fatty liver!
2. Inflammation!
FFA
Lipolysis
and
Inflammation!
FFA
Triglycerides
FFA
FFA
TG
(VLDL)
Adopose tissue
Cytokines, etc
Liver TG
(VLDL)
Cytokines,
etc
FFA
TG
(VLDL)
Resulting
in
systemic
inflammatory response
TG
(VLDL)
FFA
Tore Henriksen 2011
Tore Henriksen 2011
Consequences of an
adiposity induced inflammatory
responses in preganncy
Placenta
Systemic inflammatory response
Systemic nflammatory
response
Cytokines
Endothelial
Insulin resistance/
activation
diabetes
Cytokines
Insulin resistance/
diabetes
Consequences of an
adiposity induced inflammatory
responses in preganncy
Endothelial
activation
Glucose
Preeclampsia
Glucose
Preeclampsia
Insulin
receptor
Insulin FFA
receptor
FFA
Tore Henriksen 2012
Placental
inflammatory
reaction
Increased fatty acid
transport?
Glucose transport?
Tore Henriksen 2012
Hepatic steatosis in neonates
Case:
32 år. Nullipara. BMI 35. Tidligere frisk Gestasjonell diabetes diagnostisert ved 31 uker. Diett. Induksjon ved 39 uker p g a mistanke om stort barn og diabetes
Vektestimat 4100‐4400g. God fremgang I fødselen m h p mormunn, men hodet sto ved/rett
under spinae ved full åpning
Deretter liten fremgang, forsøk på å trykke uten fremgang. Det ble bestemt å forsøke vakumforløsning.
Det tilkom en betydelig skulderdystoci, asfyski og barnet døde. 4850 g
Obduksjonen viste betydelig fettavleiring i barnets lever(!)
(fettlever)
Maternal high fat diet in non‐human primates and fetal liver lipotoxicity
McCurdy CE et al 2009
Patel KR et al 2014 J Pediatric Gastroenerology and Nutrition:
Hepatic steatosis was highly correlated with birth weight (r=0.6, p=0,0007). But not with maternal BMI. The five stillborns of the 5 women with normal range BMI and AGA
infants, had steatosis. In the fetus the liver appear to be the primary
site of of the response to overnutrition/energy
surplus
(McCurdy CE 2009, Brumbaugh DE 2014)
Maternal supply of energy providing nutrients
(glucose, fatty acids and amino acids) seems
Essential for development of steatosis-promoting
changes in liver metabolism
Liver fat deposition
and inflammation
T. Kiserud
Similar findings: Bruce KD et al 2009: Maternal high fat diet primes steatohepatitis
in adult mice offspring , involving mitochondrial dysfunction and lipogenesis gen expression.
Overvekt/fedmne
Takk!
Kliniske konsekvenser:
I dette svangerskapet
Gener
Miljø:
Maternal
overweight/
obesity/
Systemic
inflammation
Inflammasjon:
Endothelial
activation
• Miscarriage
• Preeclampsia
• Thromboembolism
• Macrosomia
• Placental dysfunction
På sikt:
Insulin
resistance
• Maternal
Overweight
Diabetes
Cardiovascular.
• Child
Diabetes
Overweight
Cancer?
Cardiovascular?
Histological composition
of
Adipose tissue
Nerve endings
Histological composition
of
Adipose tissue
Nerve endings
Capillaries
Capillaries
Adipocyte (Fat cell)
Adipocyte (Fat cell):
Filled with triglycerides
Extracellular matrix
Extracellular matrix
Immune cell (macrophages,T-cells, etc)
Immune cell (macrophages,T-cells, etc)
Synthesis of Triglycerides
Glycerol
The “fundamental”
type of lipid:
Fatty acids:
Tore Henriksen 2006
Tore Henriksen 2006
3 free fatty acids
Triglycerides (Triacylglycerols)
In the adipocytes triglycerides are
synthesized continuously
Triglycerides
Glycerol
In the adipocytes triglycerides are
split into fatty acids and glycerol continuously
Free fatty acids
Basic principle of fat metabolism
in adipose tissue
Capillary
Fat cell
Triglycerides
Triglycerides
(TG)
Free Fatty acids
(FFA)
into blood
lipases
Lipolysis
(hormone
sens.lipase)
Triglycerides
(TG: VLDL),
from blood
Synthesis
Glycerol
Lipolysis
(Lipoprotein lipase)
Free Fatty acids
(FFA)
Glycerol
Free fatty acids
Macrophages
Tore Henriksen 2011
Increased amount of fatty acids and of macrophages,
how is it linked??
Why
Oxidized fatty acids
leads increasing adiposity increasing
Inflammation?
Toll like
Receptors
(TLR4)
Free Fatty acids
(FFA)
macrophages
Tore Henriksen 2011
Tore Henriksen 2011
Increased amount of fatty acids and of macrophages,
how is it linked??
Free Fatty acids
(FFA)
Toll like
Receptors
(TLR4)
MCP-1
Activation
of the
macrophages
Recruitment of macrophages
Tore Henriksen 2011
Fedme som obstetrisk risikofaktor
Tore Henriksen
Fødeseksjone
Rikshospitalet
Fedme er ingen ny ting
To hovedbudskap:
I: Overvekt gir økt risiko for komplikasjoner i
svangerskapet, fødsel og barseltid.
II: Det transgenerasjonelle perspektivet:
Effekten av det intrauterine miljø på neste
generasjon(er).
Aftenposten 1951
“Coming epidemic”
Henrik VIII. Av England
1491-1547
Fedme , USA
Fedme i USA
1995
1985
No Data
<10%
10%–14%
No Data
<10%
10%–14%
15%–19%
≥20%
Fedme i USA
2009
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data
<10%
10%–14%
15%–19%
20%–24%
25%–29%
≥30%
Fedme i Norge
Utvikling av kroppsmasseindex (BMI) i Nord-Trøndelag
HUNT 1, 2 og 3
1984-86
2
Særlig har økningen yngre aldersgrupper
vært stor
Prosent
Kvinner med BMI  30 kg/m
1995-97
25
2006-08
20
2001-05
15
MoBa STORK
10
5
0
20-29
2008
30-39
40-49
Alder (år)
Upubliserte data. HUNT forskningssenter, NTNU 03.11.09
The HUNT Study, Norway
K. Midthjell et al 2013
Årsaker til en fedmepidemi.
Regulering av energi-inntak, gener
og miljø
Denne økningen er ikke betinget i nye gener,
men i
Reguleringen av mat- (energi-)inntaket
består i komplekst samspill mellom
en rekke organer
Miljø/livsstil
Miljø:
•Fosterliv
•(Mors) Ernæring
•Miljøgifter
•Fysisk aktivitet
•Psykologiske forhold
•Samfunsmessige forhold
•Klimaforhold?
Tore Henriksen 2014
Gener,
og geners aktivitet
(epigenetikk)
Kortsiktige og langsiktige virkninger av maternell
overvekt/fedme, metabolsk syndrom og diabetes
På kort sikt
(svangerskapskomplikjoner)
Maternell
overvekt/
fedme, metabolsk
syndrom,
diabetes
Maternell
overvekt/
fedme, metabolsk
syndrom,
diabetes
På lang sikt
Overweight/obesity and pregnancy.
Short and long term outcomes
Mor
På kort sikt
(svangerskapskomplikjoner)
Maternell
overvekt/
fedme, metabolsk
syndrom,
diabetes
Short term
Consequences
(mother/child)
Barn
Mor
Maternal
overweight/
obesity/
Metabolic syndrome
Diabetes
Long term
consequences
På lang sikt
Barn
Short and long term outcomes
Short term
Consequences
(Mother/child)
Maternal
overweight/
obesity/
Metabolic syndrome
Diabetes
Long term
consequences
• Miscarriage
• Preeclampsia
• Thromboembolism
Cesarean section)
intensive care
• Maternal
Overweight
Diabetes
Anal dysf.
• Child
Diabetes
Overweight
Cancer
Cardiovascular?
• Miscarriage
• Preterm birth
• Preeclampsia
• Thromboembolism
Cesarean section)
intensive care
• Maternal
Overweight
Diabetes
Anal dysf.
• Child
Diabetes
Overweight
Cancer
Cardiovascular
disease
JAMA
April 16, 2014, Vol 311, No. 15
Maternal Body Mass Index and the Risk of Fetal Death,
Stillbirth, and Infant Death A Systematic Review and
Meta-analysis
Dagfinn Aune, MS ; Ola Didrik Saugstad, MD, PhD ;
Tore Henriksen, MD, PhD ; Serena Tonstad, MD, PhD
1,2,3
4
5
2,6
BMI og risiko for fosterdød
Overweight/obesity and
pregnancy outcomes Observational studies: Cesarean delivery
Overall Cesarean delivery: Obese versus ideal weight*
Heslehurst N et al Obes Rev 2008
100 % økt risiko for sectio ved BMI >30
* BMI >30kg/m2 versus BMI 20‐25
Elective Cesarean delivery: Obese versus ideal weight*
Emergency Cesarean delivery: Obese versus ideal weight*
60 % økt riiko for akutt keisersnitt
pregnancy outcomes Observational studies: Cesarean section: Dose‐response
Barau G et al BJOG 2006:
Instrumental vaginal delivery: Risk of Cesarean section (Odds Ratio, OR) according to
pre-pregnancy maternal BMI,
adjusted for fetal macrosomia.
Obese versus ideal weight*
17 % økning i bruk av vakum/tang ved fedme
Rode et al Obstet Gynecol 2005;105:527-42
Cesarean delivery
OR (95%CI)
BMI (kg/m2)
<25
1.0
25-29.9
1.5 (1.3-1.8)
≥ 30
1.7 (1.3-2.2)
BMI i seg selv, uavhengig av hvor stor barnet, er
øker risikoen for sectio
Mean length hospital stay Neonatal Intensive Care Unit.
Nesten tre dager lengre sykehusopphold ved fedme
Maternal haemorrhage: Obese versus ideal weight*
24 % økning i risikoen for post partum blødninger
35 % økt risko for opphold på Nyfødt hvis mor har fedme
Maternal infection Obese versus ideal weight*
3-4 ganger økning i risikoen for post partum infeksjoner
pregnancy outcomes Observational studies Obesity and progression of labor
Timing of dropout due to Cesarean Section
Vahratian A et al 2004
Preeclampsia
After You et al 2006
Groups with various
BMI
Women still in labor (%)
2-3 ganger økning i risikoen
for preeklampsi ved>29
fedme
*
20‐26
*
26‐35
>35
20‐26
*
26‐29
>29
25‐30
*
>30
20‐25
*
Normal
Obese
Overweight
Her er det flere som ikke lenger er i fødsel
fordi det ble gjort keisersnitt.
25‐30
>30
Cervical dilation (cm)
*BMI Ref group
Odds ratio
Macrosomia and maternal weight
Gestational diabetes and overweight/obesity
Risk (odds ratio, OR) of macrosomia (birth weight above 4500g)
according to 1. trimester maternal weight (n=2050 pregnancies)
(Clausen T, Henriksen T. 2005)
Maternal first trimester body mass index (BMI) and
risk (odds ratio, OR) gestational diabetes
(Clausen T, Henriksen T )
4 ganger økt risiko for
over 4500 g OR
ve (95%
fedme
ORbarn
(95%CI)
CI)
unadjusted
adjusted *
2-5 ganger økning i risikoen for svangerskapsdiabetes
ved fedme
BMI
OR (95 % CI)
1. Trimester BMI (kg/m2)
<20
1.0
1.0
20-25
1.3 (0.6-2.8)
0.9 (0.4-2.1)
25-30
3.5 (1.5-7.9)
2.5 (1.1-6.0)
>30
4.6 (1.8-11.7)
4.3 (1.5-12-1)
P-trend
<0.001
<0.001
< 20
20-25
25-30
>30
1.0
1.5 (0.7-3.2)
2.4 (1.0-5.7)
5.9 (2.4-14.6)
p trend
<0.0001
* Adjusted for age, parity, smoking, weight gain, placenta weight,
gestational diabetes
Risk of LGA (>90p) according to Maternal obesity,
Gestational diabetes (GDM) and
high Gestational Weight Gain (GWG)
Prevalence of Large Birth Weight by BMI groups and Gestational Weight Gain
Dietz PM et al AJOG 2009
Bowers K et al Diabetologia 2013
10
Risk of LGA
Odds ratio
I alle fire BMI gruppene øker prosent store barn
med økende vektøkning i svangerskapet
0
GDM GWG Obesity
GDM
+GWG
Obesity
+GWH
GDM
+obesity
GDM +obesity+ GWG
Birth weight and maternal injuries
at vaginal deliveries
Skader på mor ved
høy fødselsvket
Brachial plexus injury
% brachial plexus injuries
Percent brachial plexus injuries according to birth weight in Sweden
(Meeuwisse et al 1998)
(Meeuwisse et al 1998)
2-3 ganger økning i perinealskader ved store barn (<4500g)
Type of injury,
no/1000 deliveries
Birth weight,
grams
Perineal
laceration
Cervical
laceration
uterine
rupture
<3500
3500-3999
4000-4499
>4500
22
41
66
99
3
6
10
16
0.14
0.25
0.49
0.53
p for trend
<0.005
<0.01
<0.025
Long term outcomes
5
4
p for trend <0.0005
for both periods
Short term
consequences
3
Maternal
overweight/
obesity/
Metabolic syndrome
Neste generasjon!
2
1
2500-3499
4000-4499
50003500-3999
4500-5000
Birth weight
Other: Bassaw 1992; Lewis 1998; Nocon 1993; Hope 1998; Robinson 2003
Fosterliv og senere overvekt
i neste generasjon
Long term
consequences
• Miscarriage
• Preeclampsia
• Thromboembolism
• Newborn macrosomia
Cesarean section)
intensive care
• Maternal
Overweight
Diabetes
Anal dysf.
• Child
Diabetes
Overweight
Cancer
Cardiovascular
Aortic intima thickness in newborns according to
Maternal obesity/overweight
Begg LM et al Arch Dis Fetal Neonatal 2013
Risiko for overvekt
Birth weight and long term overweight risk
Schellong K et al 2012
Fødseslsvekt (g)
Other: Yu ZB et al; OR for obesity if BW > 4000g 2.07 comp to BW < 4000g
Obesity and risk of congenital anomalies
Birth weight and acute lymphoblastic leukemia (ALL)*
Stothard et al JAMA, 2009
Odd ratio(OR)
*
Spina bifida
2.24; CI, 1.86-2.69).
Cardiovascular anomalies
1.30; CI,1.12-1.51)
Cleft lip and palate
1.20; CI, 1.03-1.40).
Anorectal atresia
1.48; CI, 1.12-1.97).
Hydrocephaly
1.68; CI, 1.19-2.36).
Limb reduction anomalies
1.34; CI, 1.03-1.73).
Gastroschisis
0.17; CI, 0.10-0.30).
Risk (odds ratio) if birth weight > 90 percentile
compared to birth weight 10-90 perentile
Risk (odds ratio
Acute lymphoblastic leukemia 1.66 (95% CI 1.32-2.10)
* Sprehe et al. Pediatr Blood Cancer, 2009
* Reference OR=1: ”recommended weight”
Risk of Type 2 diabetes in siblings exposed or not exposed to diabetes
in utero (a sibling study)
Dabelea D et al Diabetes 2000, 49:2208‐11
Exposed In Utero
Diabetes i svangerskapet og risiko for diabetes hos barna:
Uavhengig av gener
Dabelea D et al Diabetes 2000, 49:2208-11
Første svangerskap:
Mor hadde ikke diabetes
Frisk sønn
Risk of Type 2 Diabetes
OR (95 % CI)
Andre svangerskap:
Mor fikk diabetes
No
1
Yes
3.7 (1.3‐11.3)
Age-adjusted adult body mass index (BMI) in women
according to birth weight.
Datter som fikk
diabetes
Risk of metabolic syndrome according to
birth weight in children of mothers with and without gestational diabetes
Boney wt al Pediatrics 2005;115:290.6)
(Drawn from Curhan et al. Circulation 1996a)
27.0
26.5
Large for gestational age
(>90th percentile)
Appropriate for gestational
Fødselsvekt over 90 percentilen gir
age
økt risiko for metabolsk
syndrom hos barnet,
Age at risk
særlig hvis mor hadde svangerskapsdiabetes
26.0
25.5
25.0
24.5
<2.3
2.3-2.49 2.5-3.19 3.2-3.89
3.9-4.5
>4.5
Birth weight (kg)
Cumulative hazard
Adult BMI
Birth weights:
Cumulative hazard
27.5
Tore Henriksen 2005
Age at risk
Aftenposten 1951
Cardiovascular events in offsprings of mothers
with obesity in pregnancy
Reynolds R et al, BMJ 2013
“Coming epidemic”
All cardiovascular events combined
Hazard ratio (95% CI)
Mother Underweight
0.80 (0.63-1.00)
Mother normal weight
Samlet vurdering av nytten av å intervenere hos gravide
med overvekt/fedme
for svangerskapsutfall
• Overvekt og fedme medfører generelt i befolkningen en betydelig helserisiko.
Svangerskap er en motiverende periode for informasjon om og oppfølging
av overvekt og fedme.
• Det er ingen holdepunkter for at råd om sunn kost og fysisk aktivitet hos
gravide gir uheldige svangerskapsutfall (aktive slankeprogrammer anbefales
ikke for gravide).
• Ovenfor er dokumentasjonsnivået angitt for de viktige kliniske
utfall, som det finnes data for. Dokumentasjonen er i stor grad basert på nye
meta-analyser av randomiserte studier, som viser gunstige effekter,
særlig av kostråd, på noen utfall, men ikke alle.
1
Mother overweight
1.15 (1.04-1.26)
Mother obese
1.29 (1.06-1,57)
Prekonsepsjonell veiledning.
Anbefales, hvis praktisk mulig, for alle med BMI over 30:
Grundig anamnese, medisinsk og om livsstil.
Klinisk erfaring og fysiologisk kunnskap taler for at:
Redusert BMI,
Godt fysisk aktivitetsnivå
Råd: Som under svangerskapet, vanligvis med unntak av de spesielle tilskuddene.
Mål: Etterfølgelse av rådene om kost og mosjon, vektreduksjon
(5-10% eller mer), bedret fysisk kondisjon. (se også Helsedirektoratets hefte
”Gravid”. eller www.helsedirektoratet.no
God kontroll på medfølgende sykdommer (co-morbiditet)
på konsepsjonstidspunktet spiller en viktig rolle for å redusere risikoen for
komplikasjoner.
• Den samlede vurderingen er at intervensjon med kost og tilpasset
fysisk aktivitet bør gis alle gravide og spesielt til dem med overvekt og fedme.
Ved første svangerskapskontroll kartlegges:
• En eller flere medfølgende sykdommer (co-morbiditet)* ?
• Familieanamnese
• Obstetrisk anamnese: tidligere preeklampsi, svangerskapsdiabetes,
tilveksthemning/placentasvikt, forløsning,
post partum blødning)
• Blodprøver i tillegg til vanlige blodprøver:
Glukosebelastning?
Tyreoideastatus vurderes
Andre relevante blodprøver ved co-morbiditet
Co-morbiditet:
• Diabetes/glukoseintoleranse (se Diabeteskapitlene)
• Hypertensjon
• Trombotiske sykdommer
• Autoimmune sykdommer (SLE, vaskulitter, nefropati)
• Maternell hjertesykdom,
• Meternell lungesykdom
• Fedmeopererte (bariatrisk kirurgi)
• Komplisert psykososiale anamnese
• Andre tilstander som kan gi økt risiko form svangerskaps og
fødselskomplikasjoner i kombinasjonen med fedme .
Weight control during pregnancy
Kvinner med overvekt og fedme uten relevant komorbiditet:
Følges i primærhelsetjenesten hvis BMI er under 35.
Ved BMI over 30 legges en plan for en tettere oppfølging med kost og andre
livsstilsråd enn for gravide generelt.
Ved BMI over 35-40* (fedme klasse II og III) henvises kvinnen til spesialist ved
ca 24 ukers svangerskap, med oppfølging spesialist ved ca 32 og ca 36 uker.
Oppfølgingen ved ca 32 uker bør være ved aktuelle fødepoliklinikk for
planlegging av fødselen.
*Grensen må vurderes ut fra lokale forhold (samhandling med
primærhelsetjenesten, kapasitetsvurderinger og kompetanse).
Institute of Medicine guidelines:
BMI
(<20):
12.5-18 kg
BMI
(20-25.9):
11.5-16 kg
BMI
26-29:
7-12 kg
BMI
>30:
>6 kg
Cedergren (2007):
BMI
(<20):
BMI
(20-24.9):
BMI
25-29.9:
BMI
>30
4-10 kg
2-10 kg
<9 kg
<6 kg
When controlled weight inrease is employed: a “balanced diet” is
essential.: http://www.helsedirektoratet.no
Adipol RH: fetometri at 24, 32 and 36 weeks
Fødselen ved fedme
Kvinner med relevant co-morbiditet
Aktuelle co-morbiditet vil avgjøre grad av oppfølging ved spesialist/fødepoliklinikk.
Ofte vil oppfølging i primærhelsetjenesten i samarbeid med spesialist
være det optimale.
Kost og andre livsstilsråd vil generelt være som for adipøse uten co-morbiditet,
men tilpasset aktuelle pasient.
Også denne gruppen må sikres minst en konsultasjon (ca 32 uker) ved
aktuelle fødepoliklinikk for planlegging av fødselen.
Planlegging av fødselen er vesentlig for adipøse gravide. Konsultasjon ved
fødepoliklinikken ved ca 32 uker anbefales ved BMI >35, der også
anestesilege bør orienteres.
Induksjon:
Ved BMI under 35 følges de generelle indikasjonene for induksjon
(spesifikke medisinske indikasjoner og overtid).
Ved BMI over 35 med ukomplisert svangerskap tas pasienten inn til
vurdering for induksjon i løpet av den første uken etter termindato.
Tidspunktet for induksjon vurderes da individuelt.
Ved innleggelse i fødeavdelingen (alle fedmekategoriene)
bør anestesilege og vakthavende gynekolog orienteres.
Fødselen ved fedme (BMI<30).
• Ved start av fødselen eller ved muligheten for akutt forløsning før fødselsstart
(f eks ikke-normalt CTG) legges to intravenøse tilganger.
Sectio
• Tidlig epiduralkateter
vurderes, for eventuelt senere aktivering.
• Ved avvik i fødselsforløpet informeres
gynekolog og anestesilege.
• Fosterovervåkning.
Kontinuerlig CTG, eventuelt STAN, med tidlig amniotomi og skalpelektrode.
Ved bruk av ekstern CTG-registrering kan U2-proben være best.
Kontroll mot mors puls anbefales.
• Regional anestesi der det er mulig
• Eventuell hengende buk kan trekkes opp med taping av abdomen, hvis det er tid.
• Hudsnitt: fortrinnsvis tverrsnitt
• Ved forløsning er det økt risiko for skulderdystoci både ved spontan og
instrumentell forløsning og beredskap for skulderdystoci anbefales.
• Operativ vaginal forløsning foreslås utført på operasjonsstue med
mulighet for godt forberedt omgjøring til sectio.
• Antibiotikaprofylakse: Anbefales både ved akutte og elektive keisersnitt.
• Post partum:
Økt risiko for post partum blødninger.
Økt risiko for trombose.
Rask mobilisering og støttestrømper anbefales.
Lavmolekylært heparin
Alle med BMI over 40 foreslås gitt tromboseprofylakse uansett forløsningsmåte.
Helse og sykdom i et utvidet perspektiv
Preconception
al
Nutrition
Metabolic state
Infections
Alcohol/drugs
Stress
Pollution
Tore Henriksen 2011
Cardiovasc.
Diabetes
Mental health
Next
Etc
Generation(s)
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Gravid i Norge 2013 100 000 graviditeter i Norge Perinatal dødlighet

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