Artlcle

Prenatal Alcohol Exposure and Risk of Birth Defects

1. &Rlleen M. O'Leury, MPH, PhD
u
,
b
,
2. Nutushu Nussur, MPH, PhD
u
,
3. Jennlfer J. Kurlnczuk, MSc, MD
c
,
4. NlchRlus de Klerk, MSc, PhD
u
,
5. Ellzubeth GeelhRed, MPH, PhD
d
,
6. Ellzubeth J. ElllRtt, MBBS, MD, FRA&P, FR&P, FR&P&H
e
,
f
,
7. &urRl BRZer, MBBS, PhD
u

+ AuthRr AfflllutlRns
1.
u
DlvlslRn Rf PRSulutlRn Sclences, TelethRn Instltute fRr &hlld Heulth Reseurch,
2.
b
&entre fRr &hlld Heulth Reseurch, und
3.
d
DeSurtment Rf Heulth EcRnRmlcs, SchRRl Rf PRSulutlRn Heulth, Unlverslty Rf Western Austrullu, Perth,
Austrullu;
4.
c
NutlRnul Perlnutul ESldemlRlRJy Unlt, DeSurtment Rf Publlc Heulth, Medlcul Sclences DlvlslRn, Unlverslty
Rf OxfRrd, OxfRrd, EnJlund;
5.
e
DlsclSllne Rf Puedlutrlcs und &hlld Heulth, &hlldren's HRsSltul ut Westmeud &llnlcul SchRRl, Unlverslty Rf
Sydney, Sydney, Austrullu; und
6.
f
Austrullun Puedlutrlc Survelllunce Unlt, &hlldren's HRsSltul ut Westmeud, Westmeud, Austrullu

Next SectlRn
Abstract
OBJE&TIVE: The JRul Zus tR exumlne the ussRclutlRns betZeen dRse, Suttern, und tlmlnJ Rf Srenutul ulcRhRl
exSRsure (PAE) und blrth defects.
METHODS: Dutu frRm u rundRmly selected, SRSulutlRn-bused cRhRrt Rf nRnlndlJenRus ZRmen ZhR Juve blrth tR u
llve lnfunt ln Western Austrullu (WA) betZeen 1995 und 1997 (N = 4714) Zere llnked tR WA MldZlves NRtlflcutlRn
System und WA Blrth Defects ReJlstry dutu. We ussessed the ussRclutlRns Rf PAE befRre SreJnuncy, ln the flrst
trlmester, und ln lute SreJnuncy Zlth uny blrth defect und Zlth blrth defects clusslfled us ulcRhRl-reluted blrth defects
(ARBDs) by the Instltute Rf Medlclne (IOM), by uslnJ lRJlstlc reJresslRn.
RESULTS: The Srevulence Rf blrth defects clusslfled us ARBDs by the IOM Zus lRZ. &RmSured Zlth ubstlnence,
heuvy PAE ln the flrst trlmester Zus ussRcluted Zlth lncreused Rdds Rf blrth defects clusslfled us ARBDs (ud|usted
Rdds rutlR: 4.6 [95% cRnfldence lntervul: 1.514.3]), Zlth slmllur flndlnJs ufter vulldutlRn thrRuJh bRRtstruS unulysls.
There Zus nR ussRclutlRn betZeen lRZ Rr mRderute PAE und blrth defects.
&ON&LUSIONS: A fRurfRld lncreused rlsk Rf blrth defects clusslfled us ARBDs Zus Rbserved ufter heuvy PAE ln
the flrst trlmester. Muny lndlvlduul blrth defects lncluded ln the IOM clusslflcutlRn fRr ARBDs elther Zere nRt Sresent
ln thls cRhRrt Rr Zere nRt ussRcluted Zlth PAE. LurJe, SRSulutlRn-bused studles ure needed tR strenJthen the
evldence buse fRr ARBDs.
Key WRrds:
Srenutul ulcRhRl exSRsure
fetul ulcRhRl sSectrum dlsRrder
fetul ulcRhRl syndrRme
ulcRhRl-reluted dlsRrders
cRnJenltul ubnRrmulltles
druJ-lnduced ubnRrmulltles
cRhRrt studles
WHAT'S KNOWN ON THIS SUBJECT:
The evldence suSSRrtlnJ the IOM clusslflcutlRn Rf ulcRhRl-reluted blrth defects (ARBDs) cRmes frRm studles Rf hlJh-
rlsk JrRuSs und unlmul studles. There ls u luck Rf SRSulutlRn-bused evldence fRr the ussRclutlRn betZeen PAE und
blrth defects.
WHAT THIS STUDY ADDS:
Muny Rf the blrth defects clusslfled by the IOM us ARBDs elther Zere nRt Sresent ln thls cRhRrt Rr Zere nRt reluted
tR PAE. These flndlnJs rulse questlRns ubRut the cllnlcul vulldlty Rf lubellnJ sSeclflc blrth defects us ARBDs.
Prenutul ulcRhRl exSRsure (PAE) ls reSRrted tR lncreuse the rlsk Rf u runJe Rf blrth defects, neurRdevelRSmentul
dlsRrders, und fetul ulcRhRl syndrRme (FAS),
1
Zhlch ure ull lncluded under the umbrellu term Rf fetul ulcRhRl
sSectrum dlsRrders.
2
The Instltute Rf Medlclne (IOM) dluJnRstlc Juldellnes lnclude u Zlde runJe Rf blrth defects
Zlthln the term ulcRhRl-reluted blrth defects (ARBDs), Zlth the evldence suSSRrtlnJ thelr lncluslRn belnJ derlved
frRm reseurch Rn hlJh-rlsk SRSulutlRns Rr unlmul studles.
1,3

Muny Rf the blrth defects ussRcluted Zlth PAE ure nRt unlque tR PAE und huve Rther SRtentlul cuuses.
4
TherefRre, ln
the ubsence Rf fuclul dysmRrShRlRJlc feutures, uttrlbutlnJ u sSeclflc blrth defect tR PAE cun be dlfflcult. Severul Rf
the blrth defects lncluded by the IOM us ARBDs Rccur rurely, und lt ls Jenerully ucceSted thut the extent Rf the blrth
Srevulence Rf dlsRrders ussRcluted Zlth PAE ls nRt knRZn.
5
Other fuctRrs llmltlnJ Rur ublllty tR flnd evldence Rf the
ussRclutlRn betZeen PAE und blrth defects ut u SRSulutlRn level lnclude the ubsence Rf u murker Rf ulcRhRl
exSRsure, the luck Rf rRutlne screenlnJ fRr ulcRhRl use durlnJ SreJnuncy,
6
lnudequute dRcumentutlRn Rf muternul
ulcRhRl use ln medlcul recRrds,
7
und u luck Rf heulth cure SrRfesslRnuls' knRZledJe und uZureness Rf the fetul effects
ussRcluted Zlth ulcRhRl use ln SreJnuncy.
6
In uddltlRn, recent reseurch evldence lndlcuted the lmSRrtunce Rf
exumlnlnJ the effects Rf dRse, Suttern, und tlmlnJ Rf exSRsure Rn fetul RutcRmes.
8
We used u lurJe, Zell-deflned,
Zell-descrlbed, SRSulutlRn-bused cRhRrt Rf nRnlndlJenRus ZRmen ZhR dellvered u llve lnfunt ln Western Austrullu
(WA) tR exumlne the ussRclutlRn betZeen dRse, Suttern, und tlmlnJ Rf PAE befRre SreJnuncy, ln the flrst trlmester,
und ln lute SreJnuncy fRr (1) uny blrth defect und (2) blrth defects lncluded ln the IOM clusslflcutlRns fRr ARBDs.
PrevlRus SectlRnNext SectlRn
METHODS
Sample Selection
The detulls Rf thls study Zere descrlbed SrevlRusly.
8
BetZeen 1995 und 1997, u 10% rundRm sumSle Rf ull
nRnlndlJenRus ZRmen ZhR Juve blrth tR u llve lnfunt ln WA Zere lnvlted by letter ut 3 mRnths ufter blrth tR
SurtlclSute ln the RundRmly Ascertulned SumSle Rf &hlldren bRrn ln Austrullu's LurJest Stute (RAS&ALS) study.
The RAS&ALS study Zus deslJned tR survey heulth-reluted behuvlRrs und events befRre und durlnJ SreJnuncy und
eurly lnfuncy. &hlldren Jlven uS fRr udRStlRn (n = 5) Zere excluded. InfRrmutlRn fRr euch lndlvlduul cRmSletlnJ the
questlRnnulre (N = 4860; resSRnse rute: 81%) Zus llnked tR the cRrresSRndlnJ blrth lnfRrmutlRn recRrded ln the WA
MldZlves' NRtlflcutlRn System, u stututRry, SRSulutlRn-bused, survelllunce system Rf ull blrths ln WA. The
Srevulences Rf lRZ blrth ZelJht lnfunts und teen mRthers Zere sllJhtly lRZer thun thRse Rf the ZhRle SRSulutlRn ln
WA.
9
The unulyses reSRrted here Zere restrlcted tR ZRmen Zlth slnJletRn blrths (multlSle blrths excluded [n = 66])
und nRnlndlJenRus chlldren (lndlJenRus futhers excluded [n = 75]), Zhlch ylelded u sumSle slze Rf 4714.
Maternal Alcohol Consumption
InfRrmutlRn ubRut muternul ulcRhRl cRnsumStlRn Zus cRllected retrRsSectlvely ut 3 mRnths ufter blrth fRr the 3-mRnth
SerlRd befRre SreJnuncy und fRr euch trlmester seSurutely. Survey questlRns und cRdlnJ Rf PAE Zlth u cRmSRslte
methRd Rf clusslflcutlRn Zere reSRrted SrevlRusly.
8
The cRmSRslte methRd cuteJRrlzes the level Rf ulcRhRl
cRnsumStlRn lntR 4 mutuully excluslve JrRuSs, thut ls, nRne (ubstlnent thrRuJhRut SreJnuncy), lRZ drlnklnJ,
mRderute drlnklnJ (lncludlnJ blnJe drlnklnJ less thun Zeekly), und heuvy drlnklnJ (lncludlnJ blnJe drlnklnJ Zeekly
Rr mRre frequently) (Tuble 1). One stundurd drlnk ln Austrullu ls equul tR 10 J Rf ulcRhRl. The lRZ cuteJRry Zus
deflned ln llne Zlth the 2001 recRmmendutlRn tR ZRmen ZhR ure SreJnunt Rr mlJht sRRn becRme SreJnunt set Rut
by the Austrullun NutlRnul Heulth und Medlcul Reseurch &Runcll ln ulcRhRl Juldellne 11, Zhlch recRmmended, If
ZRmen chRRse tR drlnk, Rver u Zeek, they shRuld huve less thun 7 stundurd drlnks, AND, Rn uny Rne duy, nR mRre
thun 2 stundurd drlnks.
10
The mRderute JrRuS lncluded ZRmen ZhR drunk 70 J Rf ulcRhRl Ser Zeek, Zlth the
mu|Rrlty cRnsumlnJ 21 tR 49 J Ser RccuslRn; therefRre, the quuntlty cRnsumed Ser RccuslRn dlscrlmlnuted mRderute
exSRsure frRm lRZ exSRsure. WRmen ZhR enJuJed ln blnJe drlnklnJ Rf 50 J Ser RccuslRn less thun Zeekly Zere
lncluded ln the mRderute JrRuS. Thls umRunt ls equlvulent tR 5 stundurd drlnks ln Austrullu, 4 stundurd drlnks ln the
Unlted Stutes, und 6 stundurd unlts ln the Unlted KlnJdRm, Zhere stundurd drlnks/unlts ure equul tR 10, 12, und 8 J
Rf ulcRhRl, resSectlvely. The heuvy JrRuS lncluded ZRmen ZhR enJuJed ln blnJe drlnklnJ 1 Rr 2 tlmes Ser Zeek Rr
mRre thun tZlce Ser Zeek und heuvy drlnkers ZhR cRnsumed <5 stundurd drlnks Ser RccuslRn (the mu|Rrlty
cRnsumed >20 J Rf ulcRhRl Ser RccuslRn) but >70 J Ser Zeek. TR Sresent mRre detull ubRut the dlstrlbutlRn Rf
exSRsure und RutcRmes, the heuvy JrRuS Zus dlvlded lntR 4 subJrRuSs, thut ls, blnJe drlnklnJ 1 Rr 2 tlmes Ser Zeek,
blnJe drlnklnJ mRre thun tZlce Ser Zeek, cRnsumStlRn Rf 70.1 tR 140 J Ser Zeek, und cRnsumStlRn Rf 140.1 J Ser
Zeek Zlth <5 stundurd drlnks cRnsumed Ser RccuslRn (Tuble 1).
VleZ thls tuble:
In thls ZlndRZ
In u neZ ZlndRZ
TABLE 1
Putterns Rf Muternul AlcRhRl &RnsumStlRn BefRre und DurlnJ PreJnuncy und Prevulence Rf Blrth Defects
Birth Defects
The WA Blrth Defects ReJlstry (WABDR) cRllects lnfRrmutlRn fRr the WA SRSulutlRn Rn blrth defects dluJnRsed fRr
stlllblrths, termlnuted SreJnuncles, und llve blrths (uS tR 6 yeurs Rf uJe), uslnJ multlSle sRurces Rf uscertulnment.
11,12

StrenJths Rf the WABDR dutu lnclude the use Rf cRnslstent deflnltlRns Rver tlme, cuse revleZ, clusslflcutlRn Rf
severlty, und lncluslRn Rf bRth mu|Rr und mlnRr cRnJenltul unRmulles dluJnRsed ln WA chlldren uS tR 6 yeurs Rf uJe.
All blrth defects ln the cRhRrt Zere ldentlfled, und then the descrlStlve text fRr euch cuse Zus revleZed by 1 Rf the
uuthRrs (Dr BRZer), ZhR Zus bllnded tR PAE. Only blrth defects thut cRuld nRt be uttrlbuted tR unRther syndrRme Rr
u Jenetlc Rr cRnJenltul cRndltlRn Zere clusslfled us ARBDs by uslnJ the IOM deflnltlRns. Blrth defects Zere JrRuSed
lntR 2 cuteJRrles, lrresSectlve Rf fuclul dysmRrShRlRJlc feutures, lntellectuul develRSment, und JrRZth.
3
The
cuteJRrles Zere (1) uny blrth defect und (2) ARBDs uccRrdlnJ tR IOM crlterlu
1,3
(Tuble 2). &hlldren Zere lncluded ln
u cuteJRry lf they hud 1 blrth defect ln the cuteJRry. We Zere unuble tR exumlne the relutlRnshlS betZeen euch
lndlvlduul blrth defect und PAE becuuse Rf the smull numbers Rf sRme blrth defects und the SRtentlul fRr
ldentlflcutlRn Rf lndlvlduuls. Dutu Rn 4 defects lncluded ln the IOM Juldellnes (strublsmus, refructlve errRrs, rullrRud
truck eurs, und hRckey stlck Sulmur creuses) ure nRt cRllected by the WABDR, und thRse defects Zere nRt lncluded
ln thls study.
3

VleZ thls tuble:
In thls ZlndRZ
In u neZ ZlndRZ
TABLE 2
Prevulence Rf Blrth Defects &lusslfled by the IOM us ARBDs
Data Linkage
Dutu frRm the RAS&ALS cRhRrt Zere llnked by the WA Dutu LlnkuJe Brunch, thrRuJh SrRbublllstlc mutchlnJ,
13
tR 2
dutu sets, numely, the WA MldZlves NRtlflcutlRn System, Zhlch SrRvlded lnfRrmutlRn Rn muternul churucterlstlcs,
SreJnuncy und dellvery, und lnfunt RutcRmes, und the WABDR fRr cuses uscertulned uS tR the end Rf 2006.
14
After
the llnkuJe SrRcess, deldentlfled dutu flles Zere extructed by the dutu custRdluns, merJed Zlth the survey dutu frRm
the RAS&ALS cRhRrt, und SrRvlded tR the reseurchers.
Data Analyses
The effects Rf PAE ln sSeclflc SerlRds Rf SreJnuncy Zere exumlned by lnvestlJutlnJ the numbers und SrRSRrtlRns Rf
blrth defects ln the RffsSrlnJ Rf ZRmen ZhR drunk ln the SreSreJnuncy SerlRd, ln the flrst trlmester, und ln lute
SreJnuncy (deflned us the muxlmul cRnsumStlRn ln the secRnd und/Rr thlrd trlmester). Smull numbers Srevented
exumlnutlRn Rf euch cuteJRry seSurutely; therefRre, blnJe drlnklnJ Rnce Ser Zeek Rr mRre frequently und heuvy
ulcRhRl cRnsumStlRn Rf 70.1 J Ser Zeek Zere cRmblned fRr the unulyses. OccuslRnul blnJe drlnklnJ Zus cRmblned
Zlth the mRderute JrRuS becuuse the meun, medlun, und muxlmul lntukes fRr thls JrRuS Zere slmllur tR thRse fRr the
mRderute JrRuS.
8

Multlvurlute lRJlstlc reJresslRn unulyses Zere used tR ussess the ussRclutlRn betZeen PAE ln euch Rf these tlme
SerlRds und the 4 cuteJRrles Rf blrth defects descrlbed ubRve. The cRmSurlsRn JrRuS fRr the SreSreJnuncy unulysls
Zus deflned us ZRmen ZhR ubstulned durlnJ the SreSreJnuncy SerlRd und thut fRr unulysls durlnJ SreJnuncy Zus
deflned us ZRmen ZhR ubstulned thrRuJhRut SreJnuncy. All Rf the unulyses Zere ud|usted fRr Srenutul fuctRrs,
lncludlnJ muternul uJe, murltul stutus, Surlty, lncRme, smRklnJ durlnJ SreJnuncy, und use Rf druJs (lncludlnJ
trunqulllzers) durlnJ SreJnuncy. Dutu unulyses Zere cRnducted by uslnJ SPSS 15.0 (SPSS Inc, &hlcuJR, IL), und
results ure Sresented us Rdds rutlRs (ORs) Zlth 95% cRnfldence lntervuls (&Is). TR exumlne the rRbustness Rf the
estlmutes, Ze culculuted bRRtstruS 95% &Is by uslnJ Stutu 10.1 (Stutu, &RlleJe StutlRn, TX). We ulsR culculuted the
excess rlsk, thut ls, the rute (cuses Ser 1000 blrths) Rf the RutcRme (blrth defect Rr JrRuS Rf blrth defects) ln the
exSRsed SRSulutlRn mlnus the rute ln the unexSRsed SRSulutlRn.
15

Ethics
ASSrRvul fRr the cRnduct Rf thls study Zus Jrunted by the Prlncess MurJuret HRsSltul Reseurch Ethlcs &Rmmlttee
und the WA &Rnfldentlullty Rf Heulth InfRrmutlRn &Rmmlttee.
PrevlRus SectlRnNext SectlRn
RESULTS
The frequency Rf muternul ulcRhRl cRnsumStlRn ln the 3 mRnths befRre und durlnJ SreJnuncy ls shRZn ln Tuble 1.
The drlnklnJ Sutterns clusslfled us mRderute und heuvy fRr the unulyses ure shRZn dlvlded lntR subJrRuSs. FeZer
thun Rne-hulf (40.8%) Rf ZRmen ubstulned thrRuJhRut SreJnuncy; 8.1% Rf ZRmen ZhR drunk ln the flrst trlmester
ubstulned ln lute SreJnuncy, und 16.6% ZhR ubstulned ln the flrst trlmester drunk ln lute SreJnuncy. There Zus u
reductlRn ln the SrRSRrtlRn Rf ZRmen ZhR drunk frRm the SreSreJnuncy SerlRd tR the flrst trlmester, Zlth the Jreutest
reductlRn (75%) fRr ZRmen ZhR reSRrted drlnklnJ ut heuvy levels. Further decreuses Zere Rbserved fRr ull Sutterns
Rf drlnklnJ ln lute SreJnuncy, Zlth the exceStlRn Rf ZRmen ZhR drunk 70 tR 140 J Ser Zeek ZlthRut blnJe drlnklnJ.
&Rnversely, the SrRSRrtlRn Rf ZRmen drlnklnJ ut lRZ levels lncreused frRm 28.1% ln the flrst trlmester tR 38.1% ln
lute SreJnuncy. The dlstrlbutlRn Rf uny blrth defects ln the RffsSrlnJ Rf ZRmen ZhR enJuJed ln blnJe drlnklnJ less
frequently thun Zeekly Zus sllJhtly lRZer thun thut Rbserved fRr the mRderute JrRuS, und there Zere nR ARBDs ufter
less-thun-Zeekly blnJe drlnklnJ ln the flrst trlmester. The SrRSRrtlRn Rf ARBDs ufter blnJe drlnklnJ Zeekly Rr mRre
frequently ln the flrst trlmester (3%) Zus slmllur tR the 4% Rbserved ufter heuvy drlnklnJ Zlth <5 stundurd drlnks Ser
RccuslRn und 70 tR 140 J Ser Zeek. NR ARBDs Zere Rbserved ln the very heuvy exSRsure JrRuS.
Any tySe Rf blrth defect Zus dluJnRsed fRr 306 chlldren (6.5%). Wlth the use Rf the IOM Juldellnes tR deflne Rur
cuteJRrles, 51 (1.1%) hud blrth defects Zlthln the ARBD cuteJRry, Rf ZhRm 47 (92%) hud 1 blrth defect und 4 (8%)
hud 2 blrth defects (Tuble 2). The mRst cRmmRnly dluJnRsed blrth defects Zere ventrlculur seStul defects (VSDs) (n
= 32 [10.5%]) und utrlul seStul defects (ASDs) (n = 7 [2.3%]). AlmRst tZR-thlrds (62.7%) Rf the blrth defects
clusslfled us ARBDs Zere VSDs, und 15.7% Zere ASDs.
The dlstrlbutlRn und rlsk Rf uny blrth defect und thRse ln the vurlRus IOM clusslflcutlRn cuteJRrles ure Sresented
uccRrdlnJ tR dRse, Suttern, und tlmlnJ Rf PAE ln Tubles 3 und 4. &RmSured Zlth the ubstlnent JrRuS, there Zus nR
ussRclutlRn betZeen lRZ Rr mRderute PAE befRre Rr durlnJ SreJnuncy und the Rccurrence Rf uny blrth defect (Tuble
3) Rr blrth defects Zlthln the cuteJRry Rf ARBDs (Tuble 4).
VleZ thls tuble:
In thls ZlndRZ
In u neZ ZlndRZ
TABLE 3
Prevulence und ORs Rf Any Blrth Defects AccRrdlnJ tR PAE
VleZ thls tuble:
In thls ZlndRZ
In u neZ ZlndRZ
TABLE 4
Prevulence und ORs Rf ARBDs AccRrdlnJ tR PAE
&RmSured Zlth the ubstlnent JrRuS, lncreused Rdds Rf huvlnJ u blrth defect clusslfled us un ARBD Zere fRund ufter
heuvy PAE ln the flrst trlmester (ud|usted OR [uOR]: 4.57 [95% &I: 1.4614.26]) (Tuble 4), und thls ussRclutlRn Zus
slmllur ufter bRRtstruS unulysls Zlth 50 bRRtstruS sumSles (uOR: 4.56 [95% &I: 1.6013.06]). Of the chlldren ZhR
hud blrth defects clusslfled us ARBDs und ZhR exSerlenced heuvy PAE ln the flrst trlmester, 80% hud curdluc seStul
defects. In thls JrRuS, the Rdds Rf huvlnJ u VSD Rr ASD Zere lncreused ulmRst threefRld (uOR: 2.67 [95% &I: 0.79
9.00]) but the estlmute Zus lmSreclse becuuse Rf smull numbers. The excess rlsk ufter heuvy PAE ln the flrst
trlmester Zus 1.7 cuses Ser 1000 fRr u blrth defect clusslfled us un ARBD by the IOM.
AlthRuJh numbers Rf cuses Zere tRR smull tR ullRZ unulysls Rf the JrRuS Zlth mRderute PAE ln the flrst trlmester,
there Zus u dRubllnJ Rf the Rdds Rf ARBDs ufter mRderute PAE ln lute SreJnuncy (uOR: 2.28 [95% &I: 0.985.30])
(Tuble 3). HRZever, 2 Rf the 5 chlldren ZhR hud blrth defects clusslfled us ARBDs und ZhR hud mRderute PAE ln
lute SreJnuncy (dutu nRt shRZn) ulsR hud heuvy PAE durlnJ the flrst trlmester.
PrevlRus SectlRnNext SectlRn
DISCUSSION
TR Rur knRZledJe, thls ls the flrst study uslnJ SRSulutlRn dutu tR exumlne the ussRclutlRn betZeen the dRse, Suttern,
und tlmlnJ Rf PAE und blrth defects. Heuvy PAE ln the flrst trlmester Zus ussRcluted Zlth u mRre thun fRurfRld
lncreused rlsk Rf ARBDs, us deflned by the IOM, und u nRnslJnlflcunt 2.6-fRld lncreused rlsk Rf curdluc seStul
defects. NRt surSrlslnJly, the ussRclutlRn Zus sSeclflc tR PAE ln the flrst trlmester und, ulthRuJh there Zere Rnly
smull numbers Rf cuses, the results Zere suSSRrted by the bRRtstruS unulysls. The flndlnJ Rf tZRfRld lncreused Rdds
Rf ARBDs ufter mRderute levels Rf PAE durlnJ lute SreJnuncy ls llkely becuuse muny ZRmen ulsR hud heuvy flrst
trlmester exSRsure und reduced thelr ulcRhRl lntuke us SreJnuncy SrRJressed. Our flndlnJs ure cRnslstent Zlth the
fuct thut the flrst trlmester ls u SerlRd Rf ruSld fetul develRSment und the mRst vulneruble tlme fRr the Rccurrence Rf
structurul blrth defects.
16

Our results suSSRrt SrevlRus studles thut fRund PAE tR be ussRcluted Zlth VSDs und ASDs
17,,19
und u recent revleZ
thut fRund llmlted evldence Rf un ussRclutlRn betZeen PAE und renul defects.
20
In Rur study, the mRst frequently
RccurrlnJ blrth defects ln the ARBD cuteJRry Zere VSDs und ASDs, und there Zere cleur effects Rf dRse und tlmlnJ
Rn the exSresslRn Rf thRse defects. The evldence fRr lncluslRn Rf muny Rf the ARBDs ln the IOM crlterlu ls frRm
unlmul studles Rr hlJh-rlsk SRSulutlRns,
1
but the strenJth Rf the evldence relutlnJ PAE und muny Rf the lndlvlduul
defects ls nRt reSRrted. FRr exumSle, u recent systemutlc revleZ Rf the llteruture fRund llttle evldence Rf un
ussRclutlRn betZeen PAE und renul blrth defects.
20
AlthRuJh the flndlnJs Rf thls study suSSRrt thut revleZ, the
evldence ZRuld be strenJthened by SRSulutlRn-bused studles Zlth lurJer numbers Rf sub|ects Zlth heuvy exSRsure
levels.
AlthRuJh 59% Rf the ZRmen ln Rur cRhRrt drunk ulcRhRl ut sRme stuJe durlnJ SreJnuncy, muny ut heuvy levels, the
Srevulence Rf the lndlvlduul blrth defects Zlthln the cuteJRry Rf ARBDs Zus lRZ. Only 40% Rf the blrth defects
clusslfled us ARBDs by the IOM Zere Sresent ln the cRhRrt. Blrth defects deflned us ARBDs Rccurred ln euch PAE
JrRuS, Zlth ulmRst Rne-hulf (47%) RccurrlnJ ln lnfunts bRrn tR ZRmen ZhR hud ubstulned frRm ulcRhRl durlnJ the
flrst trlmester. Thls lndlcutes the dlfflculty Rf rellubly uttrlbutlnJ these blrth defects tR ulcRhRl ln cllnlcul settlnJs,
Surtlculurly becuuse the dRse, Suttern, und tlmlnJ Rf PAE ure nRt recRrded rRutlnely, Zhlch suJJests thut thls
lnfRrmutlRn ls nRt sRuJht rRutlnely.
It Zus suJJested recently thut uddlnJ fuclul unRmulles churucterlstlc Rf FAS, nRrmul JrRZth, und nRrmul lntelllJence
tR the dluJnRstlc crlterlu fRr ARBDs ZRuld muke the dluJnRstlc crlterlu mRre Sructlcul fRr cllnlcul und reseurch
settlnJs.
3
The recRmmended chunJes tR the IOM Juldellnes reSresent un uttemSt tR enhunce thelr utlllty ln cllnlcul
settlnJs, but uddltlRnul SRSulutlRn-bused evldence ls requlred tR demRnstrute thelr sultublllty fRr mRnltRrlnJ ARBDs
ln the Jenerul SRSulutlRn. We uJree Zlth the uuthRrs Rf the IOM Juldellnes
1
thut cllnlcluns must exclude Rther
SRsslble dluJnRses befRre uttrlbutlnJ u blrth defect tR PAE, us Ze dld ln thls study, but the neZ requlrements muy be
cRunterSrRductlve und need tR be vullduted befRre they ure lntrRduced lntR Sructlce.
AlcRhRl cRnsumStlRn
21
und rlsky drlnklnJ
22
ure hlJhly Srevulent ln ZRmen Rf chlldbeurlnJ uJe, und ulmRst Rne-hulf
(47%) Rf the SreJnuncles ln Rur cRhRrt Zere reSRrted tR be unSlunned.
23
Thls lndlcutes thut u substuntlul SrRSRrtlRn
Rf SreJnuncles ure exSRsed tR ulcRhRl, muny ut heuvy levels, befRre the uZureness Rf SreJnuncy und ut u crltlcul
SerlRd Rf develRSment, Zhlch Sluces the fetus ut rlsk Rf u blrth defect cRnslstent Zlth u fetul ulcRhRl sSectrum
dlsRrder. Wlth the ussumStlRn thut Rur results lndlcute u cuusul ussRclutlRn, heuvy PAE ln the flrst trlmester ls u
slJnlflcunt cRntrlbutRr tR ARBD-clusslfled blrth defects, Zlth un excess rlsk cRmSuruble ln muJnltude tR thut Rf
neurul tube defects ln Austrullu (1.11.6 cuses Ser 1000).
14
A runJe Rf struteJles ure ln Sluce tR Srevent neurul tube
defects ln Austrullu.
24
In cRntrust, uSurt frRm nutlRnul Juldellnes Rn ulcRhRl use fRr ZRmen ZhR ure SreJnunt Rr
SlunnlnJ SreJnuncy, nutlRnul Rr even stuteZlde SreventlRn struteJles uddresslnJ muternul ulcRhRl cRnsumStlRn
durlnJ SreJnuncy huve nRt yet been reullzed. InterventlRns tR reduce the Srevulence Rf ARBDs Zlll need tR turJet
nRt Rnly SreJnunt ZRmen but ulsR rlsky drlnklnJ und unSlunned SreJnuncles umRnJ ull ZRmen Rf chlldbeurlnJ uJe.
25

It shRuld be recRJnlzed thut, ulthRuJh Ze dld nRt flnd uny ussRclutlRn betZeen mRderute levels Rf PAE und blrth
defects, there ls evldence suSSRrtlnJ un lncreused rlsk Rf chlld behuvlRrul SrRblems ufter thls level Rf exSRsure.
26
The
sufest chRlce fRr ZRmen ZhR ure SreJnunt Rr SlunnlnJ u SreJnuncy ls tR ubstuln frRm ulcRhRl.
StrenJths Rf thls study lnclude the llnkuJe Rf the cRhRrt dutu Zlth the WABDR dutu tR uscertuln lnfRrmutlRn Rn blrth
defects, Zhlch RvercRmes reSRrtlnJ bluses und lRss tR fRllRZ-uS. InfRrmutlRn Rn RutcRmes ls relluble und vulld,
becuuse blrth defects ure uscertulned lndeSendently by the WABDR und lnfRrmutlRn reJurdlnJ blrth defect
dluJnRses Zus llnked Zlth SreJnuncy lnfRrmutlRn thrRuJh recRrd llnkuJe. AlsR, the clusslflcutlRn Rf blrth defects fRr
thls study Zus undertuken by u blrth defects sSeclullst (Dr BRZer) ZhR, Zlth bllndlnJ tR exSRsure stutus, revleZed
the descrlStlve cuteJRrles fRr euch chlld Zlth u blrth defect. AlthRuJh chlldren ZhR mlJruted Rut Rf WA Zere nRt
lncluded, <1% Rf the SRSulutlRn deSurted Sermunently Rr fRr lRnJ SerlRds ln 1995,
27
und there Zere llkely feZ
deSurtures Zlthln the flrst yeur ufter blrth, Zhen >87.9% Rf blrth defects ure detected.
28
FurthermRre, Ze huve nR
reusRn tR suSSRse thut mlJrutlRn Rut Rf WA ZRuld be reluted tR muternul ulcRhRl cRnsumStlRn. The dutu Rn muternul
ulcRhRl cRnsumStlRn Zere cRllected ut 3 mRnths ufter blrth, und Ze cunnRt rule Rut the SRsslblllty Rf recull blus,
becuuse sRme Rf the blrth defects ulreudy ZRuld huve been recRJnlzed. HRZever, becuuse Ze fRund Rnly un
ussRclutlRn betZeen heuvy PAE und blrth defects, thls seems unllkely.
Glven thut muny Rf the blrth defects deflned us ARBDs ln the IOM Juldellnes ure rure, Rur llmlted sumSle slze und
strutlflcutlRn ucrRss PAE levels restrlcted the RSSRrtunlty tR Rbserve muny lndlvlduul blrth defects. The Srevulence Rf
blrth defects ln thls cRhRrt (6.5%) reflects the Srevulence fRr the ZhRle Rf WA (6.8%) durlnJ 19951997, und the
Srevulence Rf mRst Rf the lndlvlduul blrth defects ln Rur cRhRrt mlrrRred the reSRrted stute Srevulence.
14
HRZever, the
Srevulence Rf mlcrRceShuly ln thls study Zus 0.2 cuses Ser 1000, lRZer thun the WABDR Srevulence Rf 0.53 cuses
Ser 1000. AlthRuJh the Srevulence ls slmllur tR the 0.23 cuses Ser 1000 ln the EurRcut reJlstrles
29
und ls nRt
substuntlully lRZer thun the Srevulence Rf 0.37 cuses Ser 1000 reSRrted fRr Utuh ln 2006,
30
thls dlscreSuncy muy be
uttrlbutuble tR sumSle slze. TherefRre, lt ls lmSRrtunt thut the study be reSeuted Zlth u lurJer SRSulutlRn sumSle tR
cRnflrm the flndlnJs und tR SrRvlde mRre-detulled lnfRrmutlRn Rn the effects Rf PAE Rn sSeclflc blrth defects.
PrevlRus SectlRnNext SectlRn
CONCLUSIONS
AlthRuJh u lurJe SrRSRrtlRn Rf ZRmen ln thls cRhRrt cRnsumed ulcRhRl durlnJ SreJnuncy, the Srevulence Rf uny Rf
the blrth defects clusslfled us ARBDs by the IOM Zus lRZ (2.3%). A slJnlflcunt fRurfRld lncreuse ln blrth defects
fRllRZed heuvy PAE durlnJ the flrst trlmester, SredRmlnuntly uttrlbutuble tR VSDs und ASDs. ScreenlnJ und
dRcumentutlRn Rf ulcRhRl use by ZRmen Rf chlldbeurlnJ uJe und SreJnunt ZRmen ZRuld enhunce survelllunce
effRrts und lnfRrm SreventlRn.
PrevlRus SectlRnNext SectlRn
ACKNOWLEDGMENTS
Thls study Zus suSSRrted by Austrullun NutlRnul Heulth und Medlcul Reseurch &Runcll SrRJrum Jrunt 353514
(20052009), NutlRnul Heulth und Medlcul Reseurch &Runcll Reseurch FellRZshlS 353628 (Dr BRZer), NutlRnul
Heulth und Medlcul Reseurch &Runcll Publlc Heulth (Austrullu) FellRZshlS 404118 (Dr Nussur), NutlRnul Heulth und
Medlcul Reseurch &Runcll EnubllnJ Grunt 402784 (Austrullun Puedlutrlc Survelllunce Unlt), und NutlRnul Heulth und
Medlcul Reseurch &Runcll PructltlRner FellRZshlS 457084 (Dr ElllRtt). Dr Kurlnczuk Zus suSSRrted ln Surt by u
NutlRnul Publlc Heulth cureer sclentlst uZurd frRm the DeSurtment Rf Heulth und NutlRnul Heulth Servlces Reseurch
und DevelRSment (PH&S022) Zhen thls unulysls Zus belnJ cRnducted. The Western Austrullun Survey Rf Heulth-
Reluted BehuvlRurs und Events DurlnJ PreJnuncy und Eurly Infuncy Zus funded by Jrunts frRm HeulthZuy (the
Western Austrullun Heulth PrRmRtlRn FRundutlRn; Jrunts 94/2705, 96/49078, und 98/8016), tR Zhlch Ze ure mRst
Jruteful.
We thunk MurJuret WRRd und Peter &RsJrRve fRr mulntenunce Rf the dutubuses. We thunk the stuff members Rf the
WA Dutu LlnkuJe Unlt fRr uccess tR the WA Dutu LlnkuJe System und fRr thelr usslstunce ln RbtulnlnJ the dutu und
the WA Heulth Dutu &ustRdluns fRr uccess tR the cRre heulth dutu sets. We ure very Jruteful tR the Surents ZhR huve
SurtlclSuted ln the RAS&ALS study und fRr the suSSRrt Rf the TelethRn Instltute fRr &hlld Heulth Reseurch,
Surtlculurly the RAS&ALS study teum. We ulsR thunk the edltRrs und revleZers fRr thelr cRmments Rn the
munuscrlSt.
PrevlRus SectlRnNext SectlRn
Footnotes
o AcceSted July 8, 2010.
Address cRrresSRndence tR &Rlleen M. O'Leury, MPH, PhD, TelethRn Instltute fRr &hlld Heulth Reseurch,
PO BRx 855, West Perth, WA 6872, Austrullu. E-mull: cRlleenR#lchr.uZu.edu.uu
FINAN&IAL DIS&LOSURE: The uuthRrs huve lndlcuted they huve nR flnunclul relutlRnshlSs relevunt tR thls
urtlcle tR dlsclRse.
uOR =
ud|usted Rdds rutlR
ARBD =
ulcRhRl-reluted blrth defect
ASD =
utrlul seStul defect
FAS =
fetul ulcRhRl syndrRme
IOM =
Instltute Rf Medlclne
OR =
Rdds rutlR
&I =
cRnfldence lntervul
PAE =
Srenutul ulcRhRl exSRsure
RAS&ALS =
RundRmly Ascertulned SumSle Rf &hlldren bRrn ln Austrullu's LurJest Stute
VSD =
ventrlculur seStul defect
WABDR =
Western Austrullu Blrth Defects ReJlstry
WA =
Western Austrullu
PrevlRus SectlRn

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