SS A 21-Year Longitudinal Analysis of the Effects of Prenatal Alcohol Exposure on Young Adult Drinking John S. Baer, PhD; Paul D. Sampson, PhD; Helen M. Barr, MA, MS; Paul D. Connor, PRD: Ann P. Streissguth, PhD Background: Prenatal alcohol exposure may be a risk factor for the development of alcohol problems in humans Methods: We use data beginning with interviews of women in prenatal cate at midpregnancy to predict al- cohol use and alcohol-related problems in their off- spring now aged 21 years, Maternal drinking during preg- nancy was assessed from November 4, 1974, through ‘October 2, 1975, along with measures of maternal smok- ing, use of caffeine and other drugs, and demographic factors. Family history of alcohol problems was as- sessed from interviews with patents when offspring were 14 yeats of age and updated when ollspring were 21 years ‘of age. Measures of parental use of alcohol and other drugs and many aspeets of the family environment we sessed at 7 different ages, prenatally through 21 years. Young adult offspring (age, 21 years [N=433]) pro- vided self-reports of drinking quantity and frequency and completed the Alcohol Dependence Seale as a measure of alcohol-related problems and dependence. Results: Univariate, partial least squares, and regres- sion analyses indicate that prenatal alcohol exposure is, significantly associated with alcohol problems at 21 years ol age. The relationship persists independent of the ef- fects of family history of alcohol problems, nicotine ex- posure, other prenatal exposures, and postnatal environ- mental factors including parental use of other drugs. Prenatal nicotine exposure was not associated with al- cohol problems by offspring at 21 years of age. Conelustons: Prenatal alcohol exposure is risk factor development of drinking problems in humans ential mechanisms for the role of fetal exposure and the development of alcohol problems deserve study Arch Gen Psychiatry. 2003;60:377-385 ONTEMPORARY accounts of the etiology ofalcohol- ism typically acknowl edge a range of determi- nants, including genetic, and reviewed historical adoption records for evidence of maternal drinking during pregnancy. Adult adoptees with fetal ex- posure to alcohol reported more symp- toms of alcohol, nicotine, and other drug, From the Departments of Psychology (Dr Baer) and Statistics (Dr Sampson) University of Washington, Veterans Afais Puget Sound Health Care System (Dr Bac), and the University of Washington Schoo of Medicine (Ms Barr and Drs Connor and Stretsguth), Seat, Wash biological, psychological, and social fac- ors.’ Consistently overlooked in these models is the exposure to Leratogenie agents during pregnaney.’ However, etal exposure (o alcohol has been associated specifically with attention problems, memory problems, impulsivity, and de cits in executive cognitive functioning? cach of which has been implicated asa risk factor for the development of alcahol use disorders.* Fetal exposure to alcohol may also result in specific drug sensitivity and drug preferences, as has been suggested in animal models "" Drug sensitivity has also been included in models of risk for aleo- hol problems in humans. Recent evidence has begun to link fe- tal exposures to adolescent and adult sub- stance use problems in humans. Yates et al” examined a sample of adult adoptees dependence compared with those not ex- posed. Unfortunately, in their study, rates fof maternal alcohol use were not avail- able, and the authors could not control for ‘maternal use of nicotine and other drugs. this study of adoptees stg- gests that fetal alcohol exposure isa likely confound for models of genetic and envi ronmental influences on substance use dis- rders. In other studies, prenatal nico- ine expostre has been associated with later conduct disorders in adolescents! and smoking!*and drug use among female adolescents." Nevertheles In an earlier study of data from the Seattle Longitudinal Study on Alcohol and Pregnancy,” the relationship between fe tal alcohol exposure and early experi- ences with alcohol among young adoles- cents was examined. Maternal drinking, (©2003 American Medical Association, All rights reserved. ‘Downloaded From: https:/jamanetwork.com/ on 04/09/2023as reported by mothers when interviewed during preg- nancy, predicted rates of alcohol use and alcohol- related problems in adolescent children undergoing as- sessment 14 years later. Fetal alcohol expostire was associated with alcohol problems in early adolescence, even after controlling for family history of alcoholism, prenatal nicotine exposure, parenting style, current pa- rental drinking, houschold stress, and self-esteem ‘Alcohol use at 14 years of age is only 1 early risk fac- tor forthedevelopment ofarange of alcohol use disorders experienced at different periods throughout life. For the present study, weexamined drinkingasan outcome 7 years later, when this sample was 21 years of age. Prom 140 21 yeats of age, alcohol use changes markedly. Results of US national surveys repor that, contrast to early adolescence, almostall individuals aged 21 years (00%) have tied alco hol, and heavy drinking, defined as consumption of 5 or more drinks in a row, is common." Problems associated \withheavy drinkingby youngadultsincludeaecidental death Injuries, academic failure, vandalism, aggression, and fam- ily conflict" Individual differences often associated with the risk for alcohol dependence, such as family history of alcohol problems,are less predictive ofdrinkingratesdur- ing this developmental period.” Social and environmen- tal factors such as college attendance and residence in large: ‘group housing (eg, barracks, dormitories, fraternities) are strongly associated with heavy drinking for young adults andare likely tobe time limited." Despite apparently sits ‘tional and developmental factors that increase heavy drink ing during youngadulthood, personality factors of impul- sivity and disinhibition remain the strongest predictors of negative consequences.” In the present study, we tested the hypothesis that prenatal alcohol exposure affects alcohol-related prob- lems in young adults. We studied drinking ratesand prob- lems at 21 years of age, by which virtually all subjects have heen exposed to alcohol, and negative consequences are not uncommon, Included in ourstaistical models ate vari ables reflecting a range of demographic indicators, poten- tally teratogenic agents (eg, nicotine and other drugs) fam- ily history of alcohol problems, and family environmental factors including measures of parental postnatal use of al- ‘cohol and other drugs. —xkm™m—_dy__ OVERVIEW From November 4, 1974, through October 2, 1975, 1529 con- secutive women presentingat one or the other of 2 Seattle, Wash, prenatal clinics by the ith month of pregnancy underwent screen. Ing via personal interview regarding health habits. Most were mat ried (88.5%) and had graduated from high school (87.5%). Ap- proximately 500 of these generally low-risk families have been Followed up as part of a longitudinal prospective study of child development *= The follow-up cahort of 300 was chosen to in- ‘clude all ofthe heaviest drinkers identified fom the initial screen and to representa continuum of lower levels of alcohol use, in- ‘cluding abstinence, with straticaion on cigarette use. Twenty- two yeas after the initial prenatal interview, 433 families were againreinterviewed (March 1, 1996, through December 21,1998) For the present study, we used the original data from the moth- cers reports of use of alcohol and other drugs during pregnancy, (aepnnyrep) ARCH GEN RYCHINTRVNOL GD, APR TOT (©2003 American Med together with demographic measures and assessments ofthe post natal family environment, to predict alcohol-related outcomes a sessed in offspring aged 21 years, ‘MEASURES. Prenatal Alcohol Exposure Matera drinking was asesed midpregnancy by means of sll report in-a confidential quanity-frequency-varsbilty inter ties." Thien scores were computed nclding an overall Sépoint priory scale and o pats of arabes, Each pair of vai athes scored a drinking dimension for he ime before pregnancy Tecogniion and the time covering pregnancy. Two pars of ‘aribls reflected average quantity of coal consumpon (a rage absolute ounces per day and ocssons per month} wheres theother pais measured aspects of heavy epsodic drinking (a erage numberof drinks pr eccasion, maximum nuinber ofan onany occsion, 5 drinksonan occasion anda point quay frequency-varabliy scl), Table ¥ presents data on levels of drinking for mothers during pregnancy (astisBsed on drink- ersony). Welound that 78.9% ofthe sample drank alcohol dur ingpregnancy anim the mons bore they ke they were reg ta and 30 9% reported heavy episodic drinking (=5 dic on ‘moccasion) during pregnancy, Oflepring of subjects recived 2 dagnosis of fel alcohol syndrome at bith» Thiny-one of 453 offepring have ben identifi as having possible or prob- able eta alcholic or alcohol-related nexrodevclopmental disorder onthe sie of results of dysmorphology examinations of subset of the longitudinal sample at ith" year” andor 1 years” or om a sas analyse of neurobehavioral deficits through 7 yeas of age" ‘Other Prenatal Exposures Prenatal exposure toa variety of additional ingestants was also measured during pregnancy. Variables reflecting the frequency of use of nicotine, aspirin, caffeine, acetaminophen, antibiotics, diazepam (Valium), marijuana, and other illicit drugs were in- ‘luded in the 1974-1975 prenatal interviews with mothers" Family History of Alcohol Problems Family history of alcoho problems was assessed from the par ent report on first-and second-degree relatives using a famuly tree questionnaire when offspring were 14 yeas of age. The determination of alcool problems foreach relative was based onalistof 9 questions elcing slcohol-rlted social and mat talproblems employment ares, physical symptoms, and real- tment, When offpring underwent assessment at 2 years of age, penis weresked to update he fly history assesment rtm 1 years of age bya simple indication of alcohol abuse among firs and second-degret relatives. Five binary variables were conypted, each an indicator of a lest 2 symptoms of alcohol problems reported with respect to the mother, lathes grand Patenis siblings, and auntsand uncles By this measure 93 fa there (212%) an 46 mothers (11.08) were enti has hav ing a history of alcohol problems. Combining binary scores actors fist and second-degree relatives, 239failes (37 0%) identified at least 1 member wth a history of alcohol prob- lems (26 families [6-24] were lentified via the update at 21 ears of ge, and 8 ale [1.9% were identified solely on the Bsc of maternal history of alcohol problems). ‘Other Postnatal Environment Meastres Postnatal environment measures spanned the 21-year study, from measures of neonatal nursing and early mother-child in- 1 Association, All rights reserved.Table 1. Alcohol Scores fr 346 Nonabstinent Mothers by Time of Drinking onerseoes Tareinahons——Wean(60)—_Wnimum ——‘Wedlan—_Waxinom ‘tea Neo cmc abi eal a rare pgrangyreagaaen 220 ot (17) oot oss 258 Dug peoaney ato st (088 ont a6 a55 5 rn ona acing Prat pregsney eeagion 0 038 049 4 a 1 Dg pean) 0 ot 043) ‘ a 1 ‘erae keine protson rar tpeosne capstan x0 25115) 150 aie 1300 Dura meoaney ato 221120 130 in 1300 asus fk oot an ny aezasin rar tpegsne capson x0 405 269 150 350 1300 Dura pean ato 362268 130 30 1300 Menton ting rar tpregrney ecagson x0 72s) a0 oa 24000 Dug peganey ato ane) 030 tg i000 Ch ryt ratio psy ogo x0 352 (109 2 3 5 Dug peganey xo 305 005 2 3 5 Chel paced contig tng, dos, pte 4S 2129 i H i ‘conversion at: To convert ounces omit, mdb 20 ‘Number of represents the waren with 2 postive sore ante covresponding leo! coe In all 320 epartdiking pir pagrancyrecognton: 380, turing pregancy S46 nt aso the 2 porods and 31, dtng beth pera. Pr pregrany recognition during pregnancy, dung pegraey assesed ath ith mot “hverage ounces abso acl pr day ia coninucus arable with a score camtinaton The nt highest score was 9.14 ox {Slieatesadhotomaus varbe combining th volume varity scores 5, oro prepa) tecogtiton refers the month fs etre pagnacy of nih of regan. 01100, reaing an average 2 dink pr dy of wn, br, uo, oF ay 8, and 11 by Catalan t 9), [Summatzs 3 cmensins of inking (Cahn eta"). The arder has boon vets fr consistancy wth te cher inking scales, so that 5 coesponds a tamara rng, "incates ana prior code develop followup stud. Fur ctes tho hi Fecturtor dete se Segue al atthe ctst fh ty to dessa th prs teraction to cumilative indicators of household changes fr ea- sons suchas illness, separation, and foster care and later or cur- rent measures of family environment.” From the parent or the ‘caregiver interviews, we also assessed measures ofthe fraction ‘ofthe subjects lives spent with alcohol and/or other drug abus- cersand the drinking behavior (ie, frequency, maximum quan- tities) of either parent ofthe subject. Offspring Drinking Rates and Associated Problems Cfspring at 21 yeas of age were asked to rate how often they ATrancalcoil how often they drank Sor more drnksat one ime the usual numberof drinks consumed, the mos they consume onetime ae the numberof drinks consumed on atypical week- end evening during the past month, Summary scores quantified $Fdimensonsof drking behavior (hereater fered oa drink ing rats) as follows: monthly frequency of drinking (da), tmonthly reuency of heavy drinking (dys per month with =3 ‘rinks, total monthly drinking volume requency of sual drinking x average usual quantity plus frequency of heavy Alinkngaverageepende quant), at average drinks pr drink- ing day Cota monthly drink monthly frequency of drinking). ‘Youngadultslcool problems were assessed withthe Al- cohol Dependence Scale (ADS) widely used and reliable as- Semen forthe presence and severyof dining problems and dependence symptoms, Inthe 25m sale, subjects re- pored the fequency of range of negative consequences from cohol use (eg, blackouts) and symptoms of alcohol depen- dence (eg, tolerance), SUBJECTS Subjects fr the present study include 433 offspring of moth- crs who were first studied in 1974-1975, The ssimple consists (©2003 American Medical Ass ‘Downloaded From: https:/jamanetwork.com/ on 04/09/2023 presi (in 1974) isk ard ene epsdie dinars (= drinks on sumed sk th tus of diferent inking pats to nll women inthe occasion) ad those averaging =2 enslay 0 227 men (52.4%) and 200 women (47.6%) who ranged in age from 20.8 1023.4 years. The following racaVethnic iden- tity generally reflects the population in this geographic area at the time of the initial 1974-1975 study: white, 354 (81.8%): African American, 19 (44%):Native American, 3 (0.7%); Asian, 15 0%); and mixed, 44 (10.2%). ANALYTIC PROCEDURES lation, All rights reserved.‘Table 2, Drinking Rates and ADS Summary Score for 359 Nonabstinent Ottspring at Interview at 21 Years of Age “indeste etdgrs else, mca paar and ings {itches Aaa Dependonce Scale sare of tat 10 [clea real epost aoa epsadic alah ‘Snes test 8 rk per month separations etc), mental health problems in the family, religi- ‘sity, and family characteristics such as cohesiveness, cach as- sessed at varying times by means of interviews with offspring and parents, ‘We represent all of these blocks of variables by compos: ite scores (linear combinations). Different methods were used to develop composite scores for outcome blocks, predictor blocks, and covariate blocks, Linear combinations for the 2 ot ccome blocks (21-year drinking rates and ADS) and the 2 pri- mary predictor blocks (prenatal alcohol exposure and family history) were computed using partial east squares (PLS) analy ses perlormed on matrices of cross creations between pais “of locks of variables, These analyses result insets of saliences| (weights forthe variables ofeach block) that provide a simple ‘characterization ofthe crose-black correlation structure an that serveas coefficients for the computation of latent variable (LV) scores a weighted linear combinations of the elements of each block. The measures of prenatal alcohol exposute first nder- ‘vent nonlinear transformation on the basis of previously pub- lished PLS analyses of other outcomes with this sample.” Analy- ses were then performed relating prenatal alcohol exposure to 21-year drinking rates and ADS scores. Corresponding analy- ses were performed to relate fsiily history to 21-year drink ing rates and ADS scores. Bootstrap analyses" showed that dif ferences in item saiences were not significantly different between men and women, so the data were pooled across sex. Addi- tional bootstrap analyses showed thatthe salience defining the LV summary scores for each ofthe 4 primary blocks (prenatal alcohol exposure, family history, 2-year drinking rates, and 2L-year ADS scores) did not dilfer significantly according to (©2003 American Med Drang na oe wa 0) amen ma = Dikig dyer 577 G26) om a0 70 Veet flr. wna? 224 209 ° os oto Toa ett conta! pr ren ax arom os is 159 bards pr tting sc 270,228) to a8 ‘a0 ADS ounary cote asta a 3 a ‘Btn: DS Anh Dede Sale ‘iets ust king ns po eth theblock with which twas pared. Therefore, each block was Table 3. eto Prenatal Aloha Exposure represented by osigle average composite score 1 Family History of labo Problems “alent computor suscgy was used to develop on 2-Year Act! Problems and Drinking Rates compost scores forth flloving 4 group of covariates: de tnoglphis ober prentalexpostrs tc postnatal cho and Ter oy other rug environment and she osinatalenronnca mer tna Pea? sures Astin alicratve othe moe conventional sicpise se ami | —_leclonet nominally sigueant coveraeswe computed com eee posite scores for each of these 4 covariate blocks by means of Bz si9) “univariate PLS regressions” predicting the 21-year drinking rates and ADS LV scot Incaci case the compostes were th pre Frame : dictonsol-or victor dimcason PLS regressions We ound 31 04 4 that this approach provided a more effective computation of ise ie “a he fe fa l if related bles (i so gat thot tt of aera eld ae Ge ex Se ee Ald collection of individual covariates elected bya stepvise 2a) 6 786 procedure. a ca ‘A sequence of maliple near rpesions was then com el o> & pleted tases the relative importance prenatal alcool ex posure and family history inthe prediction of 21-year drink {ng rates and ADS scores, fist alone, then in models adjusting sequentially for different covariate blocks. We used standard graphical diagnostic procedures to assess assumptions such as Tinearity (in the composite scores) and to look for outliers oF potentially influential cases™ —_ i mW! DRINKING HABITS OF OFFSPRING Of the sample of 433 offspring, 359 (82.0%) reported themselves as current drinkers and 74 (17.1%), as life- long or current alcohol abstainers at the 21-year follow- up. Fable 2 provides descriptive statistics for drinking. rates among subjects who considered themselves to be drinkers. Subjects reported drinking, on average, 5.77 times per month, with an average of 3.79 drinks per drink- ing occasion, Consistent with national survey samples, 36.5% reported drinking 5 or more drinks on at least 1 fccasion during the past month. Thirty-five (8.19) of 433 scored at or above 10 on the ADS, indicatingat least mild alcohol dependence on the basts of validity studies us- ing diagnostic interviews.” DESCRIPTIVE CROSS TABULATIONS We present in Fable 3 cross tabulations providing first simple view ofthe relationships of maternal alcohol con- sumption and family history of alcohol problems with 21-yearaleohol dependency and drinking rates. Approxi- ‘maiely 8% of our sample indicated at least mild alcohol dependence symptoms. For descriptive purposes, we simi- 1 Association, All rights reserved.larly identified the 8% scoring highest on (otal number of drinks per month (a cut point of =o4 drinks per month). To represent fetal exposure, we considered abi- nary indicator of any episodic drinking (=5 drinks on an occasion) before or during pregnancy. We repre- sented family history of alcohol problems using a bi- nary indicator of any history of problems reported by irt- degree relatives (parents, and/or siblings). Logistic regression analyses showed significant main effects of ma- ternal episodic drinking on the 21-year ADS score (14.1% vs 4.5%; 1=2.65; P=.008), no significant main effect of family history ((=1.08), and nominally a suggestion (11.97; P=.051) ofan interaction effect. Those with the highest rate of alcohol dependence symptoms (15.9%) ‘were subjects with episodic prenatal alcohol exposure and without first-degree family history of alcohol problems. We found no nominally significant effects in the logistic regression analysis for prediction of 21-year drinking rates. These descriptive analyses were, of course, greatly lim- lted by the a priori binary eategorization of prenatal ex- posure, family history, and outcome scores, and they did not evaluate of control for many possible covariates PLS ANALYSES AND COMPOSITE SCORES The PLS analyses provide a measure of overall associa tion between blocks of variables and provide indices (sa- liences) of the contributions of individual variables for the composite associations. For overall associations, the ‘composite prenatal alcohol exposure LV score had a cor- relation of 0.28 with the 21-year-old ADS LV score, and (0.18 with the drinking rate LV score. The composite famm- ily history LV score had a correlation of 0.22 with the ADS LV score and 0.11 with the drinking rate LV score. Thus, consistent with univariate analyses, prenatal alco- hol exposure was related to drinking problems among offspring aged 21 years and less related to drinking rates Correlations were larger for prenatal expostire than they were for family history of alcoholism, Saliences for the individual prenatal alcohol expo- sure scores, computed with respect tothe ADS items, were cevenly weighted across the binge-voluume measures and across both time periods reflected in the questions (range, (0.23-0.34). Thus, no specific measure of maternal drink- ing during pregnancy was specifically identified. The fam- ily history of alcohol problems LV score resulting from the PLS analyses with respect to ADS scores weighted ma- ternal and paternal alcohol problems most highly and ‘equally (0.60), with lesser weights for the following other indicators: grandparents (0.33), siblings (0.31), and aunts and uncles (0.29). Because of the relatively Weak asso- ‘lation of 21-year drinking rate with family history, we used only the drinking rate saliences with respect to pre- natal alcohol exposure. The PLS analysts of the drink- ing rate variables showed drinks per month (0.55) and average drinks per drinking day (0.56) to beslightly more salient than the 2 frequency indicators (0.44). Table 4 provides endorsement rates and saliences for ADS items as defined in relation to prenatal alcohol ex- posure, family history of alcohol problems, and their av- cerages, Saliences computed for these 2 different predictor blocks were not significantly different according toa boot- (aepnnyrep) ARCH GEN RYCHIRTRVNOU GD, APRON (©2003 American Med strap analysis, Hence, the average salience was used for the computation ofa single composite ADS LV score, Table 4 labels (with a dagger) those average saliences 0.24 and above, as this capturesall items of reasonably consistently high salience with respect to both predictor blocks. ems reflecting negative consequences of specific episodes of heavy drinking (eg, hangovers, blackouts, un- clear thinking, passing out, stumbling/staggering, and being physically sick) provided the strongest contribu- tion to correlational relationships. A number of ADS items were endorsed only rarely, and these items tended to con- tribute litle to the compostie scores. Nevertheless, the endorsement rate did not completely correspond to s3- lience in these analyses, Atleast 1 relatively rare item was, highly salient (e, hangovers), and some frequently en- dorsed items were not salient in these analyses (ie, gulp- ing drinks and feeling hot or sweaty) REGRESSION ANALYSES Table 5 presents results of 4 separate regression analy- ses predicting the ADS LV score at 21 years of age from prenatal alcohol exposure, family history of alcohol prob- lems, and other covariates. Each regression model adds evaluation of covariate blocks of variables, We fitstevalt- ated demographics and other prenatal exposures (model 2), next added postnatal alcohol and other drug use in the ollspring environment (model 3),and finally addedall other postnatal environmental factors (model 4). We provided { statistics only as an indicator of the relative strengths of| terms ina model; conventional rules for determining sta- Uistical significance (eg, (2 indicates significance at ap- proximately 2.05-level) should not be strictly applied, as they do not account for the fact that these predictors were explicitly constructed as composite scores predictive of the ADS LV score. As can be seen in Table 5, 4 substantial prenatal posure term in the simple model (t=4.97) was clearly t- tenuated but remained in the complete model ((=2.38).Par- tial correlations forthe prenatal alcohol exposure LV score in these models were 0.23, 0.18, 0.14, and 0.13, respet tively (data not shown). Family history of alcohol prob- lems clearly contributed lessin the predictive equation than did prenatal alcohol exposure, and its correlation with the postnatal environmental factor lowered its estimated effect essentially 10 in the multiple regression models, Men had significantly higher ADS scores compared with wornen in all models. In contrast to univariate cross tabulations, re- gression analysis showed no evidence of interaction be- ‘ween prenatal alcohol exposure and family history ((=0.08 fora multiplicative interaction term added to mode! 4), and no interaction effects involving sex and prenatal alcohol exposure or family history (t=-0.14, (=1.38 for interac- tion terms added to model 4). We found no convincing evi dence of other demographic elfects of other prenatal e posures in the final model. In particular, we found no evidence of any effect of prenatal nicotine exposure on the ADS LV score marginally (simple correlation, ~0.08) or in ‘a muluiple regression model. Models 3 and 4 showed that the postnatal environment was an important predictor of the ADS scores (with the highest statistics), but did not fully account for the elfect of prenatal aleohol exposure. 1 Association, All rights reserved.‘Table 4. Endorsement Rates and Sallences Detinng the ADS LV Score With Respect {to Prenatal Alcohol Exposure, Family History of Alcohol Problems, and Their Average 08 tom Endorsement Rate average {OSH aunt drake ime 020 Dz ‘ADS02——_‘Hangovers on Suny Monday 006 028 ‘ADSI Shales, whan sobering up 08 ong ADSL Physically sick a8 24 ‘80805 alum tremens ons 001 ‘ADS0S Stumble about and tngerh ozs 026 ADS07 Fave hoes ozt 8 ‘D502 Saw things not tare os 08 ‘8DS09 Far oft ving dink o 0 DSO Alalou, oes of memart oz0 020 S0Si1 ——Carryatte om 010 ADS12——_Heay drinking postabtnance 015 og ADS! Passed uth. oz 020 ADS14——_Conisions oot oor ADSI5——_Drinktroughot th dy one 005, ‘ADS16 Thinking as boon unclear 04a 020 ‘ADS17 Hea betng raphy O09 a8 ‘ADSI8 Constantly thikng shout lech! oot 06 D519 Heard hinge nt hae on om 0520 Wied sensation oe oz ‘AD521 Cran tings nat there om 008 D822 Frequency of Blackouts ozs 031 80823 Tried nut down, fled on a7 0824 Gp dre ozt 020 019 020 ‘ADS25 Ability to stp erinking once stared one oa oz ong ‘Abbrovaions: ADS, Alcohol Dependence Seale; Len atl ‘Salences in coluns 2 and (uth gar to rena alcool exposure ard tay istry of aleoklpoblms,respctnel) are proportional othe caeltons a tho ADS ta sores with he pranatl alah exposure LV score (ampued using the salences in Tal) andthe corlations of the ADS om ‘Stores wih respect othe family stor LV seare(computd using he slurs roared Inthe ta). ‘rag saleces wera 0.24 of eanter, ‘Table, Resulls of 4 Regression Analyses ofthe ADS LV on Prenatal Alcohol Exposure LV, Famlly History LV, and Covariate LVs* (= 433) (W433) Coomelet 1 Gaamicent ——¢ | ‘entice '—Cootiernt Franatal aahoTemponare om 4a) 0 ~«Sa~S~COSCSC SSC Famiy history om 318 ote 005 © 0gs 0p} a2 Sox 42 4m 02 3m 09 45 09 9 4m Demographics ose 128 ot 195 078 (ter rental exposures too 268 8105 oT Postnatal aeoho and thr deg 128 at 1a Postnatal enirnment ue 8a Abbreviations: ADS, Alcohol Depndance Sale LY, tnt arable “ihe fttisice se proved ol ea noo he le strengths of em ina model conventional ts for dating tail sincance (9 1>2indeatig signieancs approximately 205 level) haul nat be appl because of th constuction of the predtas ax campositscree. Mol 1 and secamlated on th fl samp = £3) Becaise of mizing aes on measures of postnatal strnmen, madsle3ad fare vated or 32 eu Religious activity (206 of 378 homes had positive scores, with prenatal alcohol exposure or family history after ad- and 55 had missing scores) was the most important com- _justment for demographics, other exposures, and the post- ponent of the postnatal environment composite and had ‘natal environment the single highest simple correlation with the ADSLY score atr=-0.12, P comment | Similar regression models (not displayed) were com- pleted for the prediction of 21-year drinking rates. Inthese Prenatal aleohol exposure is significantly associated with models, drinking rates were not significantly associated __aleohol-related problems assessed in ollspring at 21 years (©2003 American Medical Association. AI rights reserved, iHjamanetwork.com/ on 04/09/2023of age. This relationship remains when we acount for sex, other demographic factors, family history of alco- hol problems, prenatal exposure to nicotine and other drugs, and other aspects of the family environment. With, the results from recent studies of adoptees," this study suggests that prenatal exposure o alcohol should be con- sidered within the matrix of etiologic factors for alcohol use disorders. This conclusion also suggests that fetal ex- posure to alcohol represents an uncontrolled confound for studies of the heritability of alcoholism. ‘Our analyses provide additional information about what aspects of young adult drinking might be most re lated to feta alcohol exposure. Drinking rates at 21 years ‘of age do not appear to be significantly related to maternal drinking during pregnancy alter adjustment for demo- ‘graphics and other prenatal exposures, Consistent with ex- tant etiologic data," rates of drinking in an episodic and heavy manner may be socially mediated and not related to individual-level differences i risk for alcohol-related dis- ‘orders. The negative consequences associated with heavy drinking, however, are related to prenatal aleohol expo- ‘sure, When examined witha simple dichotomization ofthe conventional ADS summary score (=10), maternal heavy episodic drinking during pregnancy, in contrast toall lower (nonepisodlic) drinking exposure, approximately triples the ‘odds that an offspring aged 21 years will indicate at least mild alcohol dependence (4.5% vs 14.1%). This relation- ship is attenuated, but nevertheless remains statistically sig nificant, when the ADS LV scores are evaluated in regres- sion analyses adjusting fora host of other predictive factors including the substance use of mothers postnatally. The [ADS items endorsed at 21 years of age that are most fe lated to prenatal exposure generally reflect negative con- ‘sequences from episodes of heavy drinking (eg, passing out, blackouts, and being physically sick) rather than symp- toms reflecting compulsive patterns of use (eg, carrying a bottle, drinking throughout the day, and inability to stop drinking once started), With respect to the association with drinking prob- lems in offspring aged 21 years, our measures of mater- nal prenatal drinking were relatively evenly weighted in PLS analyses, suggesting that no single indicator (eg, av- ‘erage number of drinks per day) accounts for the ob- served relationship. Descriptively, however, we can char- acterize, in part, the maternal drinking levels of the top 20% of the prenatal alcohol exposure LV scores by their median prenatal alcohol scores. This top 20% did not re port consumption typically associated with alcohol- related problems or alcoholism, but rather reported a pat- tern that could be described as frequent and moderate, ie, nearly 3.5 drinks per drinking occasion and almost 17 occasions per month prior to pregnancy recognition, and almost 3 drinks per drinking occasion and 9 occa sions per month during the first half of pregnancy (ap- proximately 2 drinking days per week). Before and dur- ing pregnancy, the median for the maximum drinks ‘consumed on an occasion was 6. The results reported here both complement and con- tradiet findings from recent studies of prenatal expo- sures and adolescent psychopathology. We observed no clfect of nicotine exposure on 21-year drinking out ‘comes, a result inconsistent with recent studies report (aepnnyrep) ARCH GEN RYCHIRTRVNOL GD, APR TOT (©2003 American Med ing relationships between fetal nicotine exposure and ado- lescent smoking and conduct problems." We also observed no effects for women only,” and did not find that family history accounts for the effects of fetal alco- hol exposure.” Our outcome, drinking problems at 21 years of age, may not be strongly related to other psy- chopathology assessed in younger adolescents in other studies. Predictive relationships between prenatal expo- sure to alcohol and drinking practices may emerge only alter ollspring are old enough so that much of the sample hhas experience with alcohol. However, the method of as- sessment of prenatal exposures may affect results. To our knowledge, no study of the effects of prenatal nicotine exposure of adolescent psychopathology has assessed the frequency and quantity of maternal drinking during preg- nancy. Course dichotomies of maternal drinking limit the power to observe statistical associations. Given that smok- ingand episodic drinking are highly comorbid, itis con- ceivable that relationships thought to be associated with prenatal smoking may reflect prenatal alcohol exposure Instead, or in combination. Interpretations about the relative predictive power of several constructs require comparable measurement accuracy. Por example, our assessment of prenatal aleo- hol use may be more reliable than out assessment of fam- tly history of alcoholism, which limits longitudinal pr ction. Thus, strong conclusions about the relative predictive relationships of these many factors should be cautioned owing to unknown reliability of the assess- ‘ment of different constructs. In fact, we raise this same concer about the assessment by previous studies of pre- natal nicotine and aleohol use. The results reported herein should be interpreted relative o other strengths and limitations inherent in our method, Its primary methodological strength ts the as- sessment of maternal drinking during pregnancy, more than 21 years before offspring underwent assessment as young adults. This design minimizes problems with ret- rospective assessment and allows analysis of specific as- pects of maternal drinking, Although unwillingness to Acknowledge alcohol use during pregnancy may now be abartier to accurate sell-report, the erain which thisstudy began was before general knowledge about the dangers associated with drinking during pregnancy. In fact, this hhabit was endorsed at midpregnancy by 80% of these pri- marily middle-class, married, well-educated mothers. In a longitudinal study of 500 consecutive births of chil- dren who were for the most part raised in the homes of their genetic parents, we eannot completely separate the effects of genetic, prenatal, and postnatal environments. (Our regression analyses, however, show that drinking rates during pregnancy, assessed during pregnancy, retain as- sociation with 21-year outcomes, even alter controlling, for maternal drinking historically and in the years after the offspring were born. Drinking rates and conse- quences at 21 years of age are based on self-report mea- sures, which could result in inaccurate or socially desir- able reporting. Fortunately, sell-report measures have been demonstrated as quite reliable and valid where no pen- alties exist for specific responses.” Finally, our out- comes are limited to rates of alcohol use and associated problems. Measures of other substance use, psychiatric 1 Association, All rights reserved.comorbidity, and adjustment in young adulthood may ‘or may not reflect the patterns of association noted with respect to alcohol use Mechanisms accounting for a relationship between. prenatal alcohol exposure and later problems with aleo- holuse deserve study. Prenatal expostiretoaleohol at vary- ing levels and at different periods during gestation is known to affect a variety of physical and functional de- vvelopmental processes, many of which could place an in- dividual atriskforalcohol use disorders. Our data do not suggest that those in this cohort identified as having fe- tal alcohol effects or alcohol-related neurodevelopmen- tal disorder contributed to the relationships observed. ‘Only 1 of the 24 cases clearly identified as fetal alcohol effects from the results of dysmorphology examinations or facial photographs:*"* and only 1 of 11 eases identified asa longitudinal pattern of neuropsychologi- cal deficits up to 7 years of age consistent with a diag- nosis of alcohol-related neurodevelopmental disorder ‘were among the eases with an ADS score at or above 10 a 21 years of age. Prenatal effects on executive cogni- tive functioning and temperament could account for ob- served differences in the management of drinking and dlrinking-related activities Individuals with impaired problem-solving skills orattention deficits" or who tend to respond impulsively may make especially risky choices before, during, or after drinking heavily. Prenatal aleo- hol exposure could also affect adult drinking problems via changes in aleohol preference and sensitivity to ale cohol effects. For example, in studies of rats, exposure to ethanol in utero has been found to increase infantile and adult preference for aleohol.°** Such changes could be due to processes involving catecholamines and stimulant effects of ethanol,” enhanced adult pituitary adrenal and analgesic responsiveness to stress and cdrugs,"*” or early associative learning with respect to gus- tatory cues The analyses reported herein provide evidence of the relationship, across more than 21 years, between prena~ tal aleohol exposure ane the degree of negative conse- ‘quences that result from heavy drinking in young adult- hood. Most individuals who drink heavily at 21 years of age do not go on to develop alcohol misuse disorders later in adulthood."”*** However, those with persistent alcohol problems in midlife typically began drinking in adolescence and young adulthood. Thus, a central chal- lenge for effective prevention with young people is to differentiate those with time-limited problems from those at risk for more persistent problems. *"* studies of the type reported herein are needed with samples at older ages. Future follow-up with this sample will assess the association of prenatal alcohol exposure with greater chro- nicity oF severity of drinking problems over time ‘Submitted for publication January 11, 2002; final revision received June 25, 2002; accepted June 27, 2002, This study was supported by grant R37 01455-01-25 {from the National Institute on Alcohol Abuse and Alcohol- sm, Bethesda, Md (Dr Strcissguth). This study was presented in part a the meeting of the Research Society on Alcoholism National Meeting, Mon- treal, Quebec, June 2001 (aerninreD) TECH GEN (©2003 American Medical Ass ‘Downloaded From: https:/jamanetwork.com/ on 04/09/2023 We thank Fred Bookstein, PRD, Juan Molina, PRD. Jen- nifer Ogden, Michael Hampton, and Kaylin Anderson for their technical and material assistance. Corresponding author and reprints: Ann P. Streiss- _guth, PRD, Fetal Alcohol and Drug Unit, 180 Nickerson St, Seattle, WA 98109 (e-mail: astreiss@u.washington-edu), ss} 1. Mesos Behera gente models of acho and dining Leona AE Blane, es Psetlogal Teor of Oring an Aol. 2nd No Yr WY air Pubes 1009372421 2. Wad. neon Sherk, Alaa and misuse: Bum A Revenon TA Sagar Es Handbot of Heath syeaogy Hl, Lanance A Erbsum Asoc, 2001281318 8 Ber J8 Ba HM, Boksten FL, Sarpson PD Suosgut AP. 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