the epidemiology of stillbirth

8/16/2019 The Epidemiology of Stillbirth

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T h e p i d e m i o l o g y o f S t illb ir thSven nat t in giu s an d Olof Stephansson

S t i ll b ir t h s a c c o u n t f o r a n i n c r e a s i n g p r o p o r t i o n o f f e t o - i n f a n t m o r t a l i ty. Ye t c a u s e s o f s t i ll b ir t h a rer a r e ly r e p o r t e d a n d t h e c a u s e s o f m o s t s t i ll b ir t h s r e m a i n u n k n o w n . F e w s t u d i e s f o c u s s p e c i f i c a ll y o nt h e e p i d e m i o l o g y o f s ti l lb i r th . M a j o r ri sk f a c t o r s i n c l u d e h i g h m a t e r n a l a g e s m o k i n g a n d o v e r w e i g h t .T h e p r e v a l e n c e o f d e l a y e d c h i ld b e a r i n g a n d e s p e c i a l l y o v e r w e i g h t a r e i n c r e a s i n g i n m o s t d e v e l o p e dc o u n t r i e s . T h e p r o p o r t i o n o f s t il lb i r th a t t r i b u ta b l e t o o v e r w e i g h t i s li k e l y t o i n c r e a s e .Copyr ight 9 2002 by W.B . Saunders

t i ll b i r th c u r r e n t l y a c c o u n t s f o r m o r e t h a no n e t h i r d o f al l f e t o - i n f a n t m o r t a l i t ya n d

m o r e t h a n 5 0 % o f a ll p e r i n a t a l d e a t h s i n d e v e l -

o p e d c o u n t ri e s . 1,2 A m o n g n o n m a l f o r m e d f e-t u s e s / i n f a n t s , s t il l b ir t h a t 28 c o m p l e t e d g e s ta -t i o n al w e e k s o r l a t e r a c c o u n t s f o r m o r e t h a n5 0 % o f a ll f e t o - i n f a n t m o r t a l i t y ) M o r e o v e r , t h ec a u s e s o f s ti l lb i r th d i f f e r f r o m t h o s e o f e a r l yn e o n a t a l m o r t a l it y, z,4 D e s p i t e t h e c l e a r i m p o r -t a n c e o f s t il l b ir t h a s a p u b l i c h e a l t h p r o b l e m , f e ws t u d i e s h a v e fo c u s e d s p e c i fi c a ll y o n t h e e p i d e m i -o t o g y a n d c a u s e o f s t i ll b i r th .

C a u s e s

I n c o n t r a s t t o i n f a n t m o r t a l i t y, c a u s e s o f s t i l l b i rt ha r e g e n e r a l l y n o t r e g i s t e r e d i n v i ta l s ta t is ti cs o rp o p u l a t i o n - b a s e d r e s e a r c h r e g i s t e r s . T h e r ea r ea l s o s u b s t a n t i a l d i f f i c u l t i e s i n d e t e r m i n i n g t h ec a u s e o f s t i ll b i r th . F i r st , w e i g h t a n d g e s t a t i o n a ll e n g t h a r e , i n t h e c a s e o f a s t i ll b i r th , e s t i m a t e d a td e l i v e ry a n d n o t a t t i m e o f d e a t h . T h i s l e a d s n o to n l y t o a n o v e r e s t i m a t i o n o f g e s t a t io n a l l e n g t h ,b u t t h e f e tu s m a y a l s o h a v e l o s t w e i g h ta f t e rd e a t h . T h u s , t h e i m p o r t a n c e o f l o w b i r t h w e i g h ti n r e l a ti o n t o g e st a t io n a l a g e m a y t h e r e f o r e b eo v e r e s t i m a t e d i n s t il lb i rt h . S e c o n d , e v e n i f d ia g -n o s t i c i n v e s t i g a t i o n s a r e p e r f o r m e d , t h e r e m a yb e d i f f ic u l t i e s i n a c h i e x 4 n g v a l id r e s u l ts . P a t h o -l o g i c a l i n v e s t i g a t i o n s m u s t c o n s i d e r p o s s i b l ec h a n g e s o c c u r r i n g b e t w e e n t h e o f t e n u n k n o w nt i m e o f d e a t h a n d t i m e o f i n v e st ig a t io n . W h e nl o o k i n g f o r a n i n f e c t i o u s c a u s e , i t m a y b e u n -k n o w n w h a t i n f e ct i o n s s h o u l d b e c o n s i d e r e d l e -t h a l , a n d i n f e c t i o n s m a y a l so o c c u r d u r i n g o ra f t e r de l ive ry.

A n u m b e r o f m e t h o d s o f g r o u p i n g c a us e s o fd e a t h i n s t i l l b i r t h a n d n e o n a t a l d e a t h s h a v eb e e n u s e d . 5,6 T h e c a u s e o f s t i l l b i rt h d i f f e r s i nm a n y c a se s f r o m t h e c a u se o f n e o n a t a l d e a t h s,

w h i c h n e c e s s i t a t e s a s p e c i f i c c l a ss i f i c a ti o n s y s t e mf o r s t i l l b i r t h . M o r e i m p o r t a n t l y, d i a g n o s t i c r o u -t i n e s g e n e r a l l y d i f f e r s u b s t a n t i a l l y b e t w e e n h o s -

p i t a ls , a n d a s u c c e s s f u l c l a s s if i c a t io n o f c a u s e s o fs t il l bi r th i s h i g h l y d e p e n d e n t o n a s t a n d a r d i z e da n d s y s te m a t i c c l i n ic a l p r o c e d u r e . A s m o r e t h a n1 f a c t o r m a y c o n t r i b u t e t o f e ta l d e a th , m a n yc l a ss i fi c a ti o n s h a v e r e c o g n i z e d t h e n e e d f o r ah i e r a r c h i c a l c l a s s i f i c a t i o n s y s t e m , i n w h i c h p o -t e n t ia l ly l e t h a l a n o m a l i e s t a k e p r e c e d e n c e o v e ro t h e r c o n d i t i o n s . 5,6 Tw o o t h e r i m p o r t a n t c a u s e so f s t il l b ir t h a r e p r e n a t a l i n f e c t io n s , a n d a b o v ea l l , f e t a l g r o w t h r e t a r d a t i o n . O t h e r c a u s e s i n -c l u d e i s o i m m u n i z a t i o n , a b r u p t i o p l a c e n t a , m a -t e r n a l c h r o n i c d i s e a s e s, p r e g n a n c y - r e l a t e d d i s o r-

d e r s ( s u c h as p r e e c l a m p s i a a n d g e s t a t i o n a ld i a b e t e s ) , a n d u m b i l i c a l c o r d a c c i d e n t s . Ye t, d e -s p i t e a ll t h e s e p o s s i b l e c a u s e s o f s t i ll b i r th , as u b s t a n t i a l p r o p o r t i o n o f s t il l b ir t h s r e m a i nu n e x p l a i n e d . H o w e v e r , w i t h i n t h e g r o u p o f u n -e x p l a i n e d s t i ll b i r th s , t h e r e i s p r o b a b l y a r e l a -t iv e ly l a r g e g r o u p o f f e t u s e s w i t h u n d i a g n o s e df e ta l m a l n u t r i t i o n , c h r o m o s o m a l a b e r ra t i o n s, o ri n f e c t i o n s .

S t i l l b i r t h a n d G e s t a t i o n a l A g e

W h e n s t il l b ir th i s d e f i n e d a s a f et a l d e a t h o c c u r -r i n g a t 2 0 w e e k s o r l a t e r , 8 2 % o f a ll st i l lb i r t h sa r er e p o r t e d t o o c c u r i n t h e p r e t e r m p e r i o d . 7 A l so ,w h e n s t il l b ir t h i s d e f i n e d a s f e t al d e a t h a t 2 4w e e k s o r l a t e r o r e v e n a t 2 8 w e e k s o r l a t e r , t h e

From the Departme nt of Med ical Epidemiology, Karolinska Institu-ter, Stockholm.Address ~'eprint requests to Sven Cnattingius, MD , P hD, D epartmentof Medical Epidemiology, Karolinska Instituter, P O Box 281 , SE-171 77 StockhoZm; e-ma il: Sven. Cnattingius@m ep.ki.se.Copyright 9 200 2 by W .B. Saundev'sO146-0005/02/2601-0005535. 00/0doi: O. 1053/sper.2002.29841

Seminars in Perinatology,Vol 26 , No 1 (February) , 2002: pp 25-30 25


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2 6 Cnattingius and Stephansson

majo r i t y o f s t i l l b ir t h occu r p r e t e rm. 8,9 S ince t hem a j o r i t y o f s t il l bi r th s o c c u r p r e t e r m , i t m a y s e e mparado x ica l t ha t t he r i sk o f s t i l lb i r t h i nc rea se s

wi th ge s t a t i ona l age . Howev e r, as po in t ed o u t byYud kin e t a l , 1~ fe tuses a t r i sk of s t i l lb i r th a t aspec i f i c ge s t a t i ona l age mus t i nc lude a l l l i ve f e -t u se s a t t ha t ge s t a t i o na l age . By us ing t h i s ap -p roa ch , Y udk in e t aP ~ showe d a cons i s t en t i n -c r ea se i n r i sk o f s t i l lb i r t h by ges t a t i ona l age (F ig1 ) , a n o b s e r v a t i o n t h a t h a s b e e n c o n f i r m e d b yot he r inv es t iga tors , n ,12 Thu s , the r i sk of s t i l lb i r thm a y b e h i g h e s t in t h e p o s t t e r m p e r i o d , w h i c h t oa l a rg e e x t e n t c a n b e e x p l a i n e d b y i n c r e a s e dra t e s o f sma l l - fo r-ges t a t i ona l - age f e tu se s bo rnpos t te rm . 1~

R i s k F a c t o r s

Maternal Age

T h e r e i s g o o d e v i d e n c e t h a t i t i s b e c o m i n g i n -c r ea s in g l y c o m m o n a m o n g w o m e n t o c h o o s e t ode l ay ch i ldbea r ing . I n t he Un i t ed S t a t e s , t hep r o p o r t i o n o f f i rs t -t i m e m o t h e r s w h o w e r e a g e30 o r o lde r i nc rea sed f ro m 4 i n 1969 to 21 i n1994.14 -The t r en d o f de l ayed c h i ldb ea r ing haso c c u r r e d p r i m a r i l y a m o n g w o m e n w i t h a t l e a s t

h i g h s c h o o l e d u c a t i o n a n d i s a t t r i b u t e d t ow o m e n v o l u n t a r i l y p o s t p o n i n g p r e g n a n c i e s f o rpe r sona l o r p ro fe s s iona l r ea sons . Seve ra l l a rgee p i d e m i o l o g i c a l s t u d i e s h a v e r e p o r t e d t h a t h i g h

2,0

1s

1 e

o 1 4

1 2

~ 0 8

0 6

0,4

0,2

0,029 31 33 35 37 39 41

Gestati onel age weeks)

Figure l . Rate of st il lbir th by gestat ional age, per1,000 live fetuses at that gestational age. (Reprintedwith permiss ion. I~

Table 1. Odds Ratio (OR) and 95 Confiden ceIntervals (CI) for Stillbirth by Maternal Age

Age (years) OR (95 CI)


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Epidemiology of Stillbirth 2 7

m a y b e d u e t o i m p r o v e d a c ce s s t o m e d i c a l c a r ea n d c h a n g e s o f o b s te t r i c a l p r a c ti c e .

S m o k m g

T h e a s s o c i a t i o n b e t w e e n s m o k i n g a n d s t i l l b i r t hr i s k i s w e l l k n o w n a n d t h e r e i s p r o b a b l y a c a u s a la s s o c i a t i o n . F i rs t, t h e r i s k o f s t i l lb i r t h i n c r e a s e sw i t h t h e a m o u n t s m o k e d . 2,2~ S e c o n d , t h e r e is as u p p o r t i v e b i o l o g i c a l h y p o t h e s i s . S m o k i n g d u r -i n g p r e g n a n c y i n c r e a s e s f e t a l c a r b o x i h e m o g l o -b i n c o n c e n t r a t i o n a n d i n c r e a s e s t h e v a s c u l a r r e -s i st a n c e , b e c a u s e o f t h e v a s o c o n s t r i c t i v e e f f e c t o fn i c o t i n e a n d t h e r e d u c e d p r o s t a cy c l i n sy n t h e-

s is . 2~-23 T h e s e t o x i c e f f e c t s o f t o b a c c o s m o k e m a yp a r t l y e x p l a i n t h e c a u s a l a s s o c i a t i o n b e t w e e ns m o k i n g a n d r e d u c e d f e ta l g r o w t h Y 4 T h e s e e f-f e c t s m a y a ls o c o n t r i b u t e t o t h e p l a c e n t a lc h a n g e s a m o n g s m o k e r s , s u c h a s d e c i d u a l n e -c r o si s , w h i c h i n t u r n m a y l e a d t o a b r u p t i o p l a -c e n t a . 25 26 I n a s t u d y o f M e y e r a n d To n a s c i a , 27t h e e l e v a t e d r i sk o f f e t a l d e a t h i n s m o k e r s w a sl a r g e l y b e c a u s e o f h i g h e r r a t e s o f p l a c e n t a l a b -r u p t i o n a n d p l a c e n t a p r e v ia . A n o t h e r s t u d yf o u n d a 4 0 % o v e r a l l i n c r e a s e d r i sk o f s t il l b ir t ha m o n g s m o k e r s , b u t s m o k e r s w h o d i d n o t s u f f e r

f r o m p l a c e n t al c o m p l i c a t i o n s o r d e l iv e r e dg r o w t h r e t a r d e d i n f an t s h a d n o i n c r e a s e d r i sk o fs t i ll b i r t h , t2 T h u s , i t a p p e a r s t h a t t h e a s s o c i a t i o nb e t w e e n s m o k i n g a n d s ti ll b ir t h is e x p l a i n e d b yt h e s m o k i n g - r e l a t e d r is k s o f f e t a l g r o w t h r e t a r -d a t i o n a n d p l a c e n t a l c o m p l i c a t i o n s . T h i r d , t h eh y p o t h e s i s o f a c a u s a l a s s o c i a ti o n b e t w e e n s m o k -i n g d u r i n g p r e g n a n c y a n d s ti ll b ir t h i s f u r t h e rs t r e n g t h e n e d b y a r e c e n t D a n i s h s t u dy, r e p o r t -i n g t h a t s m o k i n g c e s s a t i o n i n t h e f i r st t r i m e s t e rr e d u c e s t h e r i s k o f s t il l b ir t h c o r r e s p o n d i n g t ot h a t o f n o n s m o k e r s . 23 T h i s r e s u l t a l so i n d i c a t e s

t h a t s m o k i n g e x e r t s i ts i n f l u e n c e o n s t il l b ir t ha f t e r t h e f ir s t t r i m e s t e r . S m o k i n g h a s b e e n r e -p o r t e d t o p r im a r i l y i n f l u e n c e r is k o f p r e t e r ms t i l lb i r t h , ~2 a n d t h e s e r e s u l t s a r e i n t u r n s u p -p o r t e d b y a f i n d i n g t h a t i n t r a u t e r i n e g r o w t h r e -t a r d a t i o n is a s t r o n g e r r is k fa c t o r f o r p r e t e r mt h a n f o r t e r m s t i ll b i r th , s

A l t h o u g h t h e p r e v a le n c e o f s m o k i n g d u r i n gp r e g n a n c y h a s d e c l i n e d i n m a n y c o u n t r i e s , s ti llb e t w e e n 1 0 % to 3 0% o f t h e p r e g n a n t p o p u l a -t i o n i n t h e w e s t e r n w o r l d s m o k e . 23,29 T h u s ,s m o k i n g c o n t i n u e s t o b e o n e o f t h e m o s t i m p o r -

t a n t p r e v e n t a b l e r i sk f a c t o r s f o r s t i l lb i r th .

Materna l Body mass Index

A n a s s oc i a ti o n b e t w e e n m a t e r n a l b o d y - m a ss in -

d e x ( B M I ) a n d s t i l l b i r t h ri s k , w i t h t h e h i g h e s tr is k a m o n g o v e r w e i g h t a n d o b e s e w o m e n w a sr e p o r t e d i n 1 9 9 3 . 2o A S w e d i s h r e g i s t e r - b a s e ds t u d y c o n f i r m e d t h i s a n d f o u n d t h a t t h e a ss o ci -a t i o n b e t w e e n i n c r e a s i n g B M I a n d s t i l l b i r t h r i s kw a s h i g h e s t a m o n g n u t l i p a r o u s w o m e n . 3~ A r e -c e n t S w e d i s h st u d y o n a n t e p a r t u m s t il l b ir t h sf o u n d t h a t t h e a s s o c i at i o n b e t w e e n e a r ly p r e g -n a n c y B M I a n d s t il l b ir t h r i s k w a s s tr o n g e s t f o rt e r m s t i l l b i r t h s , s u g g e s t i n g a n i n c r e a s i n g e f f e c to f a h i g h B M I b y g e s t a t i o n a l l e n g t h . 31 T h e m e c h -a n i s m s f o r t h e B M I - r e l a t e d i n c r e a s e s i n r i s k o f

s t il l b ir t h r e m a i n a m a t t e r o f s p e c u l a t i o n . O v e r -w e i g h t a n d o b e s e w o m e n a r e m o r e l i k el y t o h a v ea lo w s o c i o - e c o n o m i c s ta t us a n d a r e m o r e o f t e nc i g a r e t t e s m o k e r s . P r e g n a n c y c o m p l i c a t i o n s ,s u c h a s g e s t a t i o n a l d i a b e t e s , p r e e c l a m p s i a , a n de c la m p s ia , a r e m o r e c o m m o n a m o n g o v e r w ei g h ta n d o b e s e w o m e n . A f t e r e x c l u d i n g c a se s a n dc o n t r o ls w i t h w e i g h t - re l a t ed p r e g n a n c y c o m p l i -c a t io n s , t h e r i s k o f st i ll b i rt h r e m a i n e d i n c r e a s e da m o n g o v e r w e i g h t w o m e n , b u t w a s a t t e n u a t e da m o n g o b e s e w o m e n ( Ta b l e 2 ). 3~ T h e p r e v a -l e n c e o f o v e r w e i g h t a n d o b e s i t y i s r i s in g r a p i d l y

i n d e v e l o p e d c o u n t r i e s ( F ig 2 ) , 32 a n d i n t h eU n i t e d S t at es a t h i r d o f t h e p r e g n a n t p o p u l a t i o na r e o v e r w e i g h t ( B M I > 2 5 ) . a s I f c au s a l , o v e r -w e i g h t m a y f r o m a p u b l i c h e a l t h p e r s p e c ti v e b et h e m o s t i m p o r t a n t r i s k f a c t o r f o r s t i l l b i r t h .

Tab le 2 . Odds Ra t io (OR) and 95% Conf idenceInterva ls (CI) for An tep ar tu m St i llb i r th by Body-m a s s I n d e x ( BM I ) A m o n g N u l l ip a r o u s Wo m e n

Excluding Casesand Controls With

GestationalAl l Cases and Diabetes andControls Preeclampsia

( n = 6 1 3 / 6 6 0 ) * ( n = 4 6 1 / 5 4 6 ) *

BM I OR~ (95 CI) OR~ (95 CI)

-30.0 2.1 (1.2-3.6) 1.5 (0.7-3.0)

* Number of cases/controls.t A djusted for ag e, height, occupation, and cigarette smok-ing.++Re feren ce g rou p.Data from reference 31.


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2 8 nattingius and Stephansson

20

15

10

5

0

MI 25.0-29,9

[] BMI 30.0-34.9

[] BMI 35.0+

1960-62 1971-74 1976-80 1988-94

Figure 2. Prevalence of overweight and obesityamong women aged 20-29 years, United States 1960-1994. Data from refere nce 32.)

Maternal Weight Gain During Pregnancy

Few s tud i e s have i nves t i ga t ed t h e a s soc i a t i on be -

t w e e n w e i g h t g a i n d u r i n g p r e g n a n c y a n d s t i l l -b i r t h r i sk . We igh t ga in i s r e l a t ed t o p r ep reg -n a n c y B M I , a n d w o m e n w i t h a h i g h B M I g a i nl e s s w e i g h t d u r i n g p r e g n a n c y ?T T h e r e f o r e , i ti s i m p o r t a n t w h e n a n a l y z i n g t h e a s s o c i a t i o n b e -tween we ig h t ga in a nd r i sk o f s t i l lb i r t h t o con -s i d e r p r e p r e g n a n c y B M I a s a c o n f o u n d i n g f a c -to r. Ta ff e l e t a135 show ed an a s soc i a t i on b e twe enlow ma te rn a l we ig h t ga in an d s t i l l b i r th r i sk ,whe reas - th i s was no t fou nd by Rydhs t r6m e t a l . ~6H o w e v e r, n o n e o f t h e se s t u d i es s i m u l t a n e o u s l yinves t i ga t ed t he pos s ib l e i n f luences by o the r co -

va r i at e s . A r ece n t Swed i sh s tudy was ab l e t o t akes u c h c o n f o u n d e r s i n t o a c c o u n t a n d f o u n d n oa s s o c ia t i o n b e t w e e n p r e g n a n c y w e i g h t g a i n a n dan te pa r t um s t i l lb i r th r i sk . 31

Socio economic Factors

Al though i t i s gene ra l l y known tha t soc io -eco -no mi c s ta tus inf lue nce s s t i l lb i r th r i sk , 2~ the rea-s o n s r e m a i n e s s e n t i a l l y u n k n o w n . T h i s i s n o te n t i re l y b e c a u s e m o s t s t u d ie s h a v e i n c l u d e d f e wcova r i a t e s , bu t r e su l t s f rom a r ecen t s t udy sug -ges t t ha t t he r ea s ons fo r t he a s soc i a t i on may be

h a r d t o d i s e nt a n gl e . 9 T h e g r o u p o f w o m e n f r o mlow soc ia l c la s s was f avo red by a r e du ced p reva -l e n c e o f d e la y e d c h i l d b e a re r s , b u t , o n t h e o t h e rh a n d , t h e y w e r e m o r e o f t e n s m o k e r s a n d o v e r -we igh t . Thus , t he r i sk s o f s t i ll b i r th r e l a t ed t o l ows o c i o - e c o n o m i c s t a tu s , w e r e a f t e r a d j u s t m e n t f o rm a t e r n a l a g e , s m o k i n g a n d b o d y m a s s i n d e x ,e s sen ti a l l y t he s ame a s t he c rud e r isk s. Moreo ve r,f u r t h e r a d j u s t m e n t s f o r t i m e o f a d m i t t a n c e t oan t ena t a l c a r e , nu m be r o f v is it s t o p r ena t a l c a r e ,a n d a n u m b e r o f o t h e r c o v a r ia t es , d i d n o t e s s en -t i a ll y cha ng e t he se r i sk s , no r we re t he r i sk s

e x p l a i n e d b y i n c r e a s e d r a t es o f s m al l -f o r -

g e s t a t i o n a l - a g e p r e g n a n c i e s o r p r e g n a n c y - r e -l a t e d d i s o r d e rs a m o n g w o m e n f r o m l o w s o c ia lc l as s 9 R e s id u a l c o n f o u n d i n g o f a l c o h o l a n d i l -

l i c i t d rug u se i s a pos s ib l e bu t no t p robab leexp la na t ion . S ince t he r i sk r e l a t ed t o l ow soc i alc l a s s was p r imar i l y i nc rea sed fo r t e rm s t i l l b i r t h ,o n e m a y h y p o t h e s i z e w h e t h e r t h e s e d i f f e r e n c e sa re due t o sub t l e d i f f e r ences i n ca r e .

Recurrent Stillbirth

T h e t e n d e n c y t o r e p e a t p r e g n a n c y o u t c o m e s i nsuccess ive b i r t h s i s we l l know n and a l so i nc ludesr i sk o f s ti l lb i r th . W om en wi th a p r ev ious s ti ll -b i r t h m a y, c o m p a r e d t o w o m e n w i t h n o p r e v i o u s

s t i l lb i r th , have a 6 to 10-fo ld increased r i sk ofs t i l l b ir t h i n n ex t p r egn ancy . 37,3s A l th oug h r ecu r-r e n c e o f s ti ll bi rt h is m o r e c o m m o n a m o n gw o m e n w i t h d i a b e t e s o r p r e g n a n c y - i n d u c e d h y -pe r t ens ive d i s ea ses , and m ay a lso be a s soc i a t edw i t h r e c u r r e n c e o f f e t al g ro w t h r e t a r d a t i o n , s u c hf a c t o rs p r o b a b l y o n l y p a r tl y e x p l a i n t h e r is k o fre pe at in g st i l lbir th, s7-~9

Maternal Hem oglobin Concentration

D u r i n g n o r m a l p r e g n a n cy, t h e h e m o g l o b i n c o n -cen t r a t i o n f a l ls un t i l t he 20 th week o f ge s t a t i on ,

r e m a i n s f a i rl y c o n s t a n t u p t o 3 0 w e e k s a n d t h e r e -a f t e r r i s e s s l i gh t ly. These changes i n hemog lob inc o n c e n t r a t i o n a r e m a i n l y d u e t o a n i n c r e a s e dp l a s m a v o l u m e . I n d e v e l o p e d c o u n t r i e s , b o t hh i g h a n d l o w h e m o g l o b i n c o n c e n t r a t i o n d u r i n gp r e g n a n c y h a v e b e e n a s s o c i a t e d w i t h s m a l l - f o r -g e s t a t i o n a l - a g e a n d p r e t e r m b i r t h s . Tw o s t u d i e sh a v e r e p o r t e d i n c r e a s e d r a t e s o f p e r i n a t a l d e a t hw i th b o t h l ow a n d h i g h h e m o g l o b i n c o n c e n t r a -t i o n d u r i n g p r e g n a n c y, 4~ a n d 1 s t u d y f o u n d as imi lar u- sha ped associa t ion fo r s t i l lb i r th ra tes . 42In a r ecen t ly pu b l i sh ed s tudy the r i sk o f st i l l b ir t h

was i nc rea s ed fo r bo t h l ow -- --1 46 g / L ) e a r ly p r e g n a n c y h e m o g l o b i n c o n -

cen t r a t i o n , 43 and a r e l a t ive ly l a rge d ec rea s e i nh e m o g l o b i n c o n c e n t r a t i o n d u r i n g p r e g n a n c yt e n d e d t o b e p r o te c t i v e. T h e r i sk re l a t e d t o h i g hh e m o g l o b i n v a lu e s w as c o n f i n e d t o a n t e p a r t u ms t i l l b i r t h s w i thou t ma l fo rma t ions , and e spec i a l l yp r o n o u n c e d i f t h e f e t u s a ls o wa s g ro w t h - r e -t a r d e d Ta b l e 3 ). T h e b i o l o g i ca l m e c h a n i s m f o rt h e i n c r e a s e d r i sk o f st i ll b ir t h f o r h i g h h e m o g l o -b i n c o n c e n t r a t i o n m a y b e t h at p l a s m a e x p a n s i o ne n h a n c e s f e t a l g r o w t h . T h e r e d u c e d b l o o d v is -

c o si ty m a y f a v o r b l o o d f lo w i n t h e m a t e r n a l i n-


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pidemiology of Stillbirth 2 9

Table 3 . Odds Rat io (OR) and 95 Conf i denceIntervals (CI) for St i l lb i r th by Hemogl obi nConcentra t ion in Fi rs t Tr imester

An tepm r Stillbirth Witho utMalformations

A l l S G A - s t i l l b i r t h s( n = 5 1 9 / 6 1 0 ) * ( n = 1 3 7 / 3 9 0 ) *

Fi rs t Hb g /L O Rt (95 CI) O R? (95 CI)

--146 2.0 (1.1-3.8) 4.2 (1.3-1 3.9)

* Number of cases and controls.

t Adjusted for age, height, BMI, occupation, smoking, earlypregnanc y weekly change in Hb, and week of first Hb mea-surement.Source: Stephanssou et al. JAMA 2000;284:2611-7.

t e r v i l l o u s s p a c e a n d p r e v e n t t h r o m b o s i s i n t h eu t e r o p l a c e n t a l c i r c u l a t i o n .

Multiple irth

S i n c e t w i n s a re m o r e l ik e ly to b e g r o w t h - r e -t a r d e d a n d t o b e d e l iv e r e d p r e t e r m , t h e y h a v e a n

i n c r e a s e d r i s k o f s t il l b ir t h a n d a b o v e al l) n e o -n a t a l d e a t h . A p a r ti c u l a r c o n c e r n is m o n o z y g o t i ct w in s , w h o h a v e p o o r e r s u rv i v al t h a n d i z y g o t ictw ins . 44,45 I f 1 tw in d i e s i n u t e ro , t he co tw in i s no to n l y a t i n c r e a s e d r i sk o f f e t a l d e a t h , b u t a l so r u n sa n i n c r e a s e d r is k o f c e r e b r a l p a l sy a n d o t h e rc e r e b r a l i m p a i r m e n t s . 44 T h e r e la t iv e i m p o r t a n c eo f t w i n p r e g n a n c y a s a r is k f a c t o r f o r s t il l b ir t h i sl i k el y t o i n c r e a s e , a s t h e r a t e o f tw i n p r e g n a n c i e sa r e i n c r e a s i n g . 46

C o n c l u s i o n s

I n c o n t r a s t t o i n f a n t m o r t a l i ty, t h e d e c l i n e i ns t i l lb i r t h r a t e s h a v e , i n m o s t c o u n t r i e s , b e e n l e sso b v i o u s . T h e m a j o r i t y o f s ti l lb i r th s d i e s u n e x -p e c t e d l y p r e t e r m , w h e n p o s s i b il i ti e s t o d e t e c tw a r n i n g s ig n s , s u c h a s f e t a l g r o w t h r e s t r i c ti o n ,a r e l i m i t e d . M a j o r m a t e r n a l r i s k f a c t o r s i n c l u d em a t e r n a l s m o k i n g , h i g h m a t e r n a l a g e , a n d o v e r -w e i g h t, b u t w h y h i g h m a t e r n a l a g e a n d o v e r -w e i g h t i n f l u e n c e s t il l b ir t h r i sk r e m a i n s t o b ed e t e r m i n e d . I n c o n t r a s t to s m o k i n g , t h e p r e v a-l e n c e o f d e l a y e d c h i l d b e a r i n g a n d o v e r w e i g h t

a r e i n c r e a s i n g i n m o s t d e v e l o p e d c o u n t r i e s .

T h u s , t h e r e l at i v e i m p o r t a n c e o f th e s e f a c t o r s i sl i k e ly t o i n c r e a s e .

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the epidemiology of stillbirth

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