journal of Epidemiology and Community Health 1990; 44: 302-306

Alcohol use in pregnancy, craniofacial features, andfetal growth

Agnes Rostand, Monique Kaminski, Nathalie Lelong, Philippe Dehaene, Isabelle Delestret,Catherine Klein-Bertrand, Denis Querleu, Gilles Crepin

AbstractStudy objective-The aim was to study the

relationship between the level of alcoholconsumption in pregnancy and craniofacialcharacteristics of the neonate.Design-This was a prospective survey of

a sample of pregnant women, stratified onprepregnancy level ofalcohol consumption.Setting-The study was carried out at the

public antenatal clinic of Roubaixmaternity hospital.Participants-During an eight month

period, 684 women (89% of those eligible)were interviewed in a standardised way attheir first antenatal clinic visit. Of these, allwho were suspected of being alcoholic orheavy drinkers (at least 21 drinks per week)were selected for follow up, as was asubsample oflight (0-6 drinks per week) andmoderate (7-20 drinks per week) drinkers.Of 347 women selected in this way, 202 hadtheir infants assessed by a standardisedmorphological examination.Measurements and and main results-

Suggestive craniofacial characteristics ofthe infants, present either in isolation or inassociation with growth retardation ("fetalalcohol effects"), were compared in relationto maternal alcohol consumption (alcoholic12%; heavy drinking 24%; moderatedrinking 28%; light drinking 36%). Nodifferences were found between light andmoderate drinkers. Infants born toalcoholics had a greater number ofcraniofacial characteristics and theproportion with features compatible withfetal alcohol effects was higher. There was asimilar trend for infants of heavy drinkers.Infants of heavy drinkers who haddecreased their alcohol consumptionduring pregnancy had fewer craniofacialfeatures. Infants ofheavy smokers were alsofound to have increased numbers ofcraniofacial characteristics.Conclusions-Craniofacial morphology

could be a sensitive indicator of alcoholexposure in utero. Altered morphology isusually considered specific for alcoholexposure, but the relation observed withsmoking needs further exploration.

Since the first descriptions of the fetal alcoholsyndrome in 1968 by Lemoine et al' and in 1973by Jones et al,2 several hundreds of cases havebeen described from various countries, all born toalcoholic mothers. It is usually considered thatmaternal alcoholism is a causal factor for this

syndrome, which includes growth retardation,characteristic craniofacial morphology, andimpaired mental development.3

Partial forms of fetal alcohol syndrome,including one or several of the signs mentionedabove, at a more or less severe stage, are less wellknown. Numerous factors influencemorphogenesis, growth and development, and thedegree to which more moderate alcoholconsumption might be harmful is not clear;nonetheless experimental studies in animals giveweight to the hypothesis of a teratogenic role ofalcohol in pregnancy, though an embryolethaleffect, and effects on congenital malformations,growth, development, and behaviour.4

Since craniofacial morphology appears to bemost specific for alcohol exposure, the objective ofthis study was to look at craniofacialcharacteristics and intrauterine growth at variouslevels of alcohol consumption. From previousstudies5 6 our hypothesis was that no clinicaleffect of alcohol exposure in utero would bedetectable for light or moderate drinking, and thatsuch an effect would appear only for heavydrinkers (not necessarily alcoholics), the expectedeffect being a minor form of fetal alcoholsyndrome, with specific craniofacialcharacteristics, either isolated or combined withintrauterine growth retardation into featuressuggestive of fetal alcohol effect.

MethodsSELECTION OF STUDY SAMPLEThe study population included all women ofFrench origin who had their first contact with thepublic maternity hospital in Roubaix between 15May 1985 and 15 January 1986. Women offoreignorigin were excluded, both because their alcoholconsumption is usually low and becausecraniofacial characteristics vary according toethnic origin.7 8Among the 782 women satisfyingthe above criteria, 698 were actually interviewed,the difference being mainly due to refusals or lackoftime ofthe interviewer; 684 were interviewed attheir first antenatal visit in hospital, and 14, whohad delivered in the hospital during this eightmonth period but had had no hospital antenatalcare, were interviewed during their postnatal stay.This latter group, although interviewedretrospectively, was entered in the study, as itusually includes a high proportion of heavydrinkers and is at high risk of adverse pregnancyoutcome. However, we checked that excludingthem did not modify the results of the analysis.The interviews were conducted using a structuredquestionnaire. Separate inquiry was made on theconsumption of cider, beer, wine, and stronger

INSERM Unit 149,EpidemiologicalResearch on Maternaland Child Health,16 av Paul VaillantCouturier, 94807Villejuif Cedex,FranceA RostandM KaminskiN LelongDepartment ofNeonatology, RoubaixHospital, Roubaix,FranceP DehaeneI DelestretDepartment ofObstetrics andGynaecology, RoubaixHospital, Roubaix,FranceC Klein-BertrandD QuerleuG Crepin

Correspondence to:Dr Kaminski

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Alcohol in pregnancy

alcohols, in the number ofglasses per day on weekdays and at weekends. One glass of each beveragewas assumed to contain the same quantity ofabsolute alcohol, an average of 10 g. The hospitalis located in an area ofhigher than average alcoholconsumption, and the alcohol consumed in thispopulation is mainly beer.Women were classified by their average weekly

drinking before pregnancy into "light drinkers",consuming 0-6 glasses a week (65%), "moderatedrinkers", 7-20 glasses a week (16%), "heavydrinkers", 21 glasses a week or more (12%); 7% ofwomen were identified as known or suspectedalcoholics, either by the interviewer, or from themedical record. They were considered as aseparate group, independent of the alcoholconsumption they had declared, in order to avoidclassifying some alcoholics as light or moderatedrinkers. A similar classification was used foralcohol consumption during the first trimester.Abstinent women were not considered separately,as most previous studies have not found anydifference in outcome between abstinents andlight drinkers.5 6A subsample was selected for a standardised

neonatal morphological examination consisting ofall alcoholics, all heavy drinkers, and for each suchheavy drinker, one light drinker and one moderatedrinker matched on the date of recruitment. Weselected 347 women by this process; 10 womendelivered elsewhere, four had an abortion, andfive who had a twin pregnancy were excluded; intwo cases, alcohol consumption in the firsttrimester was unknown; 124 infants were notassessed due to lack of time, early discharge fromthe hospital or, more rarely, transfer to anotherunit.There was no significant difference in the

percentage of infants examined according to thelevel of alcohol consumption: 66% of the lightdrinkers' infants, 58% of the moderate drinkers',59% of the heavy drinkers', and 63% of thealcoholic group. However, the mothers of infantswho were examined described an average beerconsumption lower than that of the mothers ofinfants not examined. In this latter group, theinfants also tended to have a lower gestational ageand birthweight; this trend was observed in allalcohol groups. The final sample for analysisconsisted of 202 mother-infant pairs.

Table I Incidence of craniofacial characteristics by drinking group in the firsttrimester. Values are percent affected

Light andmoderate Heavy

Craniofacial drinkers drinkers Alcoholicscharacteristics (n = 151) (n= 26) (n= 25)

Bulged forehead (profile) 40 46 52Synophris 0 0 4Short palpebral fissures (< 18 mm) 13 24 20Antimnongoloid slants 10 20 24Strabismus 3 8 4Epicanthic folds 5 8 4Eyelid ptosis 14 15 8Hypertelorism (>24 mm) 13 12 17Deep nasal bridge 42 50 60Upturned nose 34 61 60Short nose 5 0 20Longphiltrum(>12mm) 13 11 12Hypoplastic philtrum 5 4 12Indistinct cupid bow 11 27 40Thin upper lip 49 69 40Retrognathia 29 28 40Posterior rotation of ears (>20°) 7 5 12

OUTCOME MEASURESA standardised morphological examination wasadministered by one of three paediatricians whohad no knowledge of maternal alcoholconsumption or any other maternal charac-teristics; 92% of examinations were conductedon the first week of life.A list of 17 craniofacial characteristics

described in previous reports on fetal alcoholsyndrome9 was selected by a paediatrician (PD).Table I shows the frequency of each item bydrinking group in the first trimester. The numberof craniofacial characteristics was calculated foreach infant. Infants were considered to havefeatures compatible with fetal alcohol effects ifthey had at least four craniofacial characteristics,and if their birthweight, length, or headcircumference was below the 10th centileaccording to sex and gestation, using Largo et al'scurves as a reference.'0

CONFOUNDING VARIABLESVery little is known about the relation betweenmaternal characteristics (other than alcoholconsumption) and craniofacial characteristics.Thus we have considered as potentialconfounders the classical risk factors ofintrauterine growth retardation or pretermdelivery. 1 Considering the differences in thecharacteristics of heavy drinkers in differentpopulations,12 we selected those which werefound significantly associated with alcoholconsumption in our sample: age, educationallevel, weight gain during pregnancy, number ofprevious pregnancies, previous preterm delivery,and number of cigarettes smoked per day duringpregnancy (table II). Among these, three werefound to be associated with the number ofcraniofacial characteristics in the light ormoderate drinkers: number of cigarettes per dayduring pregnancy, number of previouspregnancies, and level of education. These werecontrolled for in the analysis. Neither gestationalage nor age at examination were found to berelated to the number of craniofacial anomalies.

ANALYSISFor each maternal or neonatal characteristic, thefollowing comparisons have been made: heavyversus light and moderate drinkers, alcoholicversus light and moderate drinkers, and alcoholicsversus heavy drinkers. Light and moderatedrinkers were grouped together after havingverified the assumption that there was nodifference in outcome ofpregnancy between thesetwo groups.The analysis was conducted both on the groups

defined from alcohol consumption beforepregnancy and on those based on alcohol use inthe first trimester. Results reported in this paperare limited to alcohol consumption in the firsttrimester. Nonetheless, in order to see if areduction in alcohol consumption in the firsttrimester was associated with differences inneonatal characteristics, further analysis was doneon the subsample of women who were heavydrinkers before pregnancy: the women whoremained heavy drinkers in the first trimesterwere compared to those who had become light ormoderate drinkers.

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Pearson's X2 test and one way analysis ofvariance were used in the univariate comparisons.Mantel Haenszel test and two way analysis ofvariance with interaction were used in thebivariate analysis, taking smoking status intoaccount. The relation between the number ofcraniofacial characteristics and indices of growthas dependent variables, and drinking groups andthe confounding variables as independentvariables, was investigated by multiple regressionanalysis. Risk of fetal alcohol effect was assessedby the use of logistic regression analysis.Confidence limits for the relative risk of fetalalcohol effect were estimated using the methoddescribed by Katz et al.13

ResultsAmong the 202 studied women, 120% were

included in the alcoholic group. Beforepregnancy, heavy drinking was reported by 24%,moderate drinking by 28%, and light drinking by36%. During the first trimester, theseproportions were respectively 13%, 28%, and470%; 450% of the original heavy drinkers becamelight or moderate drinkers in the first trimester.

NUMBER OF CRANIOFACIAL CHARACTERISTICSOffspring of alcoholics and heavy drinkers in thefirst trimester had significantly more craniofacial

characteristics than those of moderate or lightdrinkers (table III). Children of alcoholics hadmore characteristics than those of heavy drinkers,but the difference was not significant. The resultswere the same when we examined the proportionof children having at least four characteristics.However, a two way analysis of variance showed a

significant interaction (p = 0-02) between alcoholand tobacco (table IV): in heavy smokers, theaverage number of craniofacial characteristics didnot differ between drinking groups; in non-

smokers or light smokers, the number was

significantly related to alcohol exposure, even

when adjusted for number of previouspregnancies and level of education in a multipleregression.

INTRAUTERINE GROWTH

Infants of alcoholic women and of heavy drinkershad a shorter gestation than those ofmoderate andlight drinkers, the difference being significantonly for the alcoholics (table III). Afteradjustment for gestational age, there was no

significant difference in birth weight, birthlength, or head circumference. The trend,however, was for children of alcoholics to besmaller in weight and size. Adjustment for theconfounding variables listed above did not modifythe results.

Table II Maternal characteristics by drinking group in the first trimester

1. Light andmoderate 2. Heavy p valuedrinkers drinkers 3. Alcoholics

Maternal characteristics (n=151) (n=26) (n=25) 2vl 3vl 3v2

Age (years)* 25 6 (5 3) 27 8 (5 6) 31 0 (5-6) <0 05 <0 001 <0 05Low educational statust (°) 45 58 79 NS <0 01 <0 01Weightgain(kg)* 112(51) 119(49) 87(40) NS <005 <005One or more previous pregnancies (%) 68 85 100 NS <0 001 <0 05Previous preterm delivery (%) 5 19 20 <0 01 <0 01 NSNo of cigarettes/day during pregnancy (%/0)

0 71 62 521-9 18 15 8 NS <0001 NS>10 11 23 40

* Mean (SD)t Limited to primary school

Table III Number of craniofacial characteristics and growth indices by drinking group in the first trimester

1. Light andmoderate 2. Heavy p valuedrinkers drinkers 3. Alcoholics

Infant characteristics (n= 151) (n= 26) (n= 25) 2vl 3vl 3v2

No craniofacial characteristics* 2 9 (1 7) 3 8 (1 5) 4 3 (1-9) <0 01 <0 001 NSNo craniofacial characteristics 4 (¾/0) 31 65 72 <0-01 <0-001 NSGestational age (weeks)* 39-9 (1 4) 39 4 (1 6) 39 1 (2 0) NS <0 05 NSWeight (g)* 3301 (496) 3368 (525) 3014 (669) NS NS NSLength (cm)* 49 9 (2-1) 50-0 (2 4) 48 7 (2 6) NS NS NSHead circumference (cm)* 34 3 (1 5) 34 6 (1-3) 33 6 (1 5) NS NS NSAt least one growth measurement < 10th centile (°) 28 23 40 NS NS NSFeatures suggestive of FAEt (%) 7 19 36 <0-05 <0 001 NS

* Mean (SD)t FAE =fetal alcohol effect. At least four craniofacial characteristics and at least one growth measurement below the 10th centile for gestational age

Table IV Number of craniofacial characteristics by drinking group in the first trimesster and by smoking status during pregnancy. Values are

means (SD)1. Light and p valuemoderate 2. Heavy --drinkers drinkers 3. Alcoholics 2vl 3vl 3v2

No of cigarettes/day:0-9 28(17) 39(14) 47(16) <001 <0001 (01)n 135 20 15

10 3 6 (1 4) 3-5 (1 9) 3 6 (2 1) NS NS NSn 16 6 10

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305Alcohol in pregnancy

FEATURES SUGGESTIVE OF FETAL ALCOHOL EFFECT

The proportion of children with featuressuggestive of fetal alcohol effect was significantlyhigher among heavy diinkers and alcoholicwomen than among light and moderate drinkers(table III). The relative risk was 5-4 for alcoholicscompared to light and moderate drinkers (95%confidence interval: 2-5-12-0), and 2-9 for heavydrinkers (95% confidence interval: 1-1-7-8).When controlling for tobacco, number of

previous pregnancies, and level of education in a

multiple logistic regression, the relative risk ofheavy drinkers was only at the limit ofsignificance.

REDUCTION IN ALCOHOL CONSUMPTION IN THE

FIRST TRIMESTER

Among the women who were heavy drinkersbefore pregnancy, there was no difference ingrowth indices, whether the women had remainedheavy drinkers in the first trimester or hadbecome light or moderate drinkers. In contrast,the children in the latter group had fewer(p < 005) craniofacial characteristics (2-8) thanthose of the women who had remained heavydrinkers (3 8), and were similar to children oflightand moderate drinkers before pregnancy. Asimilar trend was observed for the proportion ofchildren with features suggestive of fetal alcoholeffect.Although the women who remained heavy

drinkers in the first trimester were also more oftenheavy smokers, these relationships were not

explained by tobacco. There was no difference inaverage prepregnancy alcohol consumption,whether the women remained heavy drinkers or

had decreased their alcohol consumption in thefirst trimester.

FETAL ALCOHOL SYNDROME AND CONGENITALMALFORMATIONSAfter the morphological assessment, two childrenwere diagnosed as having fetal alcohol syndromeby the examiner; the mother ofone ofthem was an

alcoholic, whereas the other was a moderatedrinker before pregnancy, classified as lightdrinker in the first trimester. Neither of themshowed any other congenital malformation.Congenital malformations were very few in thetotal sample.

DiscussionThis study has shown that infants of alcoholicsand women drinking heavily in the first trimesterof pregnancy (three drinks a day or more) on

average had more craniofacial characteristics andfeatures compatible with a possible fetal alcoholeffect than infants of light and moderate drinkers.A similar relation was found with heavy smokingduring pregnancy. An interaction betweenalcohol and tobacco was observed, therelationship with alcohol exposure being limitedto non-smokers or light smokers. However, theproportion of heavy smokers was low in our

population.These results were observed in spite of the fact

that the power of the study was limited for two

reasons: (1) the group of alcoholics may haveincluded a few more moderate drinkers, thus

reducing the contrast in comparison to the othergroups of women; however, in this group 3800 ofwomen had a gamma glutamyl transferase above18 U/litre, in comparison to 60o and 18°orespectively in the two other groups;'4 (2) amongthe subsample selected for morphologicalexamination, 380o were not examined. In view ofthe reasons for the absence of assessment, and theorganisation of the neonatal examination, there isno reason to suppose that the appearance of theinfants may have influenced whether or not theywere examined. As heavier drinking and lowbirthweight were slightly overrepresented amongthe infants who were not assessed, the study canlead only to an underestimation of the associationbetween alcohol consumption and infantcharacteristics. This might explain why nosignificant relationship was found in thissubsample between alcohol consumption andbirthweight (apart from the trend observed foralcoholic women), whereas such a relationship hasbeen observed in several previous studies.5 15-17

In this study, two infants were diagnosed ashaving fetal alcohol syndrome. This number is inagreement with a previous prevalence studycarried out in the same city,18 where theprevalence varied from 1 in 200 to 1 in 700,according to the degree of severity of the fetalalcohol syndrome. As mentioned earlier, thisstudy was done in an area characterised by a heavyalcohol consumption, and the samplingoverrepresented the heavier drinkers.The significant relationship found between the

quantity of alcohol consumed and the number ofcraniofacial characteristics, either isolated orassociated with intrauterine growth retardation, isconsistent with the results of the only other studywe know ofwhich had a similar approach.8 In thisstudy, the authors considered 15 craniofacialanomalies of the newborn baby, nine of whichwere also considered in our study.The other epidemiological studies which have

described anomalies in relation to alcoholconsumption have not separated craniofacialfeatures from other anomalies; they have analysedeither the total number of anomalies7 19-21 or anindex of characteristics consistent with the fetalalcohol syndrome.'9 22 23 Even though the resultsofthese studies are difficult to compare because ofthe differences in the anomalies they haveconsidered, they seem consistent with a non-linear dose-response relationship. A significantassociation between anomalies and alcohol wasfound in studies on alcoholics, or when the level ofdefinition or the proportion of heavier drinkerswas high.2023 At lower levels, no significantassociation was observed.7 lFor their score of anomalies, Ernhart et al8

showed a curvilinear dose-response relationship,with a really marked increase above three ouncesof alcohol (six drinks) per day. In our study, anincrease in the number of craniofacial anomalieswas detected for consumption of three drinks aday or more. These results do not rule out apossible effect on craniofacial morphogenesis atlower doses, but this effect might be too small tobe clinically detectable.Our results, as well as those of Ernhart and

colleagues, suggest that the effect of alcoholtoxicity on craniofacial morphogenesis might be

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mostly linked to first trimester alcohol exposure,as opposed to alcohol consumption beforepregnancy. This hypothesis is consistent withexperimental studies.24Among heavy drinkers inthe first trimester, most must have continuedduring the whole pregnancy; Rosett et al2" havefound that children of heavy drinkers had moreanomalies than children of moderate drinkers,whether or not they had modified their alcoholconsumption later in pregnancy.

In this study, craniofacial characteristics weremore numerous among infants of heavy smokersin pregnancy. Although features compatible withfetal alcohol effects have been observed inmarijuana users in one study,"9 the associationwith tobacco has never been found.7 122n25though a few associations with congenital defectshave been observed, tobacco is not generallyconsidered to be a teratogen.4 26 It should benoted, however, that a recent paper27 hassuggested the possibility of identifying maternalsmoking through fetal appearance. As thecraniofacial characteristics analysed in this studyare commonly considered as specific of prenatalalcohol exposure, more investigations on theassociation with smoking are needed: tobacco is awell known factor causing intrauterine growthretardation, and as with alcohol, might play a rolein craniofacial morphogenesis. However, neitherthis study nor other published reports haveconsidered the craniofacial morphology of theparents as a potential confounding variable.

Features compatible with fetal alcohol effectsobserved at birth seem to be a good predictor ofdysmorphology evaluated at four years of age.25The results of the Seattle follow up study28 are infavour of a relationship between intrauterinealcohol exposure and later development, but thevalue of a specific craniofacial morphology as anindicator of future mental development remainslargely unknown. Nonetheless, this study, as wellas that of Ernhart et a18 21 suggests thatcraniofacial morphology could be a more sensitiveand specific indicator of prenatal alcohol effectthan other anomalies, growth indices, or neonatalbehaviour: the number of craniofacial anomaliescould be a useful outcome measure in evaluatingthe effectiveness of interventions aiming at

reducing the alcohol consumption of pregnantheavy drinkers.

We thank A Erramdani, S Hebbinckuys-Ovlaque, 0Klein, and D Subtil for their contribution to the datacollection; A Hennion and M Franczuk for theirtechnical assistance in the extraction of data from thecomputerised hospital records; the staff of the ObstetricDepartment for their help and support; and all thepregnant women who have participated in the study.The data were analysed at the INSERM computercentre SC5, and the manuscript was prepared with theassistance of M Corre.The study is part of the EC Concerted Action:

"Maternal alcohol consumption and its effect on

pregnancy and child development". The study was

partly funded by the Haut Comite d'Etudes et

d'Information sur l'Alcoolisme (re 1984/63). AgnesRostand was supported by a grant from the Fondationpour la Recherche Medicale.

1 Lemoine P, Harousseau H, Borteyru JP, Menuet JC. Lesenfants de parents alcooliques: anomalies observees. OuestMidical 1968; 21: 476-82.

2 Jones KL, Smith DW, Ulleland CN, Streissguth AP.Pattern of malformation in offspring of chronic alcoholicmothers. Lancet 1973; i: 1267-71.

3 Rosett HL. A clinical perspective of the fetal alcoholsyndrome. Alcoholism Clin Exp Res 1980; 4: 119-22.

4 Abel EL. Consumption of alcohol during pregnancy: areview of effects on growth and development of offspring.Human Biol 1982: 54: 421-53.

5 Kaminski M, Rumeau-Rouquette C, Schwartz D.Consommation d'alcool chez lesfemmes enceintes et issuede la grossesse. Rev Epidemiol Sante Publique 1976; 24:27-40.

6 Kaminski M, Franc M, Lebouvier M, du Mazaubrun C,Rumeau-Rouquette C. Moderate alcohol use andpregnancy outcome. Neurobehav Toxicol Teratol 1981; 3:173-81.

7 Tennes K, Blackard C. Maternal alcohol consumption,birthweight, and minor physical anomalies. Am J ObstetGynecol 1980; 138: 774-80.

8 Ernhart CB, Sokol RJ, Martier S, et al. Alcoholteratogenicity in the human: a detailed assessment ofspecificity, critical period, and threshold. Am J ObstetGynecol 1987; 156: 33-9.

9 Clarren SK, Smith DW. The fetal alcohol syndrome. N EngJ Med 1978; 298: 1063-7.

10 Largo RH, Walli R, Duc G, Fanconi A, Prader A.Evaluation of perinatal growth. Helv Paediatr Acta 1980;35: 419-36.

11 Thomson AM. Fetal growth and size at birth. In: BarronSL, Thomson AM, eds. Obstetrical epidemiology. London:Academic Press, 1983: 89-142.

12 Walpole I, Zubrick S, Pontre J. Confounding variables instudying effects of maternal alcohol consumption beforeand during pregnancy. J Epidemiol Community Health1989; 43: 153-61.

13 Katz D, Baptista J, Azen SP, Pike MC. Obtainingconfidence intervals for the risk ratio in cohort studies.Biometrics 1978; 34: 469-74.

14 Kaminski M, Rostand A, Lelong N, et al. Consommationd'alcool pendant la grossesse et caracteristiques neonatales.Journal d'Alcoologie 1989; 1: 35-46.

15 Little RE. Moderate alcohol use during pregnancy anddecreased infant birthweight. AmJ7 Public Health 1977; 67:1154-6.

16 Wright JT, Waterson EJ, Barrison IG, et al. Alcoholconsumption, pregnancy, and low birthweight. Lancet1983; i: 663-5.

17 Mills JL, Graubard BI, Harley EE, Rhoads GG, BerendesHW. Maternal alcohol consumption and birth weight. Howmuch drinking during pregnancy is safe?JAMA 1984; 252:1875-9.

18 Dehaene P, Crepin G, Delahousse G, et al. Aspectsepidemiologiques du syndrome d'alcoolisme foetal.Nouvelle Presse Medicale 1981; 10: 2639-43.

19 Hingson R, Alpert JJ, Day N, et al. Effects of maternaldrinking and marijuana use on fetal growth anddevelopment. Pediatrics 1981; 70: 539-46.

20 Rosett HL, Weiner L, Lee A, Zuckerman B, Dooling E,Oppenheimer E. Patterns of alcohol consumption and fetaldevelopment. Obstet Gynecol 1983; 61: 539-45.

21 Ernhart CB, Wolf AW, Linn PL, Sokol RJ, Kennard MJ,Filipovich HF. Alcohol-related birth defects: syndromalanomalies, intrauterine growth retardation, and neonatalbehavioral assessment. Alcoholism Clin Exp Res 1985; 9:447-53.

22 Hanson JW, Streissguth AP, Smith DW. The effects ofmoderate alcohol consumption during pregnancy on fetalgrowth and morphogenesis. Pediatrics 1978; 92: 457-60.

23 Silva VA, Laranjeira RR, Dolnikoff M, Grinfeld H, MasurJ. Alcohol consumption during pregnancy and newbornoutcome: a study in Brazil. Neurobehav Toxicol Teratol1981; 3: 169-72.

24 Pratt OE. What do we know of the mechanisms of alcoholdamage in utero? In: Mechanisms ofalcohol damage in utero.

(CIBA Foundation Symposium No 105) London: Pitman,1984: 1-7.

25 Graham JM, Hanson JW, Darby BL, Barr HM, StreissguthAP. Independent dysmorphology evaluations at birth andfour years ofage for children exposed to varying amounts ofalcohol in utero. Pediatrics 1988; 81: 772-8.

26 Shiono PH, Klebanoff MA, Berendes HW. Congenitalmalformations and maternal smoking during pregnancy.Teratology 1986; 34: 65-71.

27 Stirling HF, Handley JE, Hobbs AW. Passive smoking inutero: its effects on neonatal appearance. Br Med J 1987;295: 627-8.

28 Streissguth AP, Barr HM, Martin DC. Alcohol exposure inutero and fonctional deficits in children during the first fouryears of life. In: Mechanisms of alcohol damage in utero.

(CIBA Foundation Symposium No 105) London: Pitman,1984: 176-96.

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