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Original Article |

Prenatal Smoking and Early Childhood Conduct Problems:  Testing Genetic and Environmental Explanations of the Association FREE

Barbara Maughan, PhD; Alan Taylor, MSc; Avshalom Caspi, PhD; Terrie E. Moffitt, PhD
[+] Author Affiliations

From the Medical Research Council Social, Genetic and DevelopmentalPsychiatry Centre, the Institute of Psychiatry, King's College London, London,England (Drs Maughan, Taylor, Caspi, and Moffitt); and the University of Wisconsin,Madison (Drs Caspi and Moffitt).


Arch Gen Psychiatry. 2004;61(8):836-843. doi:10.1001/archpsyc.61.8.836.
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Published online

Background  Extensive evidence now supports a statistical association between prenatal smoking and increased risk for antisocial outcomes in offspring. Though this statistical link may signal a causal association, commentators have urged caution in interpreting findings because of the likelihood of confounding.

Methods  We used data from the Environmental Risk Longitudinal Twin Study, a representative British sample of 1116 twin pairs studied at ages 5 and 7 years, to assess associations between prenatal smoking and early childhood conduct problems net of the effects of both heritable and environmental risks for child antisocial outcomes.

Results  Prenatal smoking showed a strong, dose-response relationship with child conduct problems at ages 5 and 7 years. Around half of this association was attributable to correlated genetic effects. Mothers who smoked during pregnancy differed from other mothers in a number of ways. They were more likely to be antisocial, had children with more antisocial men, were bringing up their children in more disadvantaged circumstances, and were more likely to have had depression. Controlling for antisocial behavior in both parents, depression in mothers, family disadvantage, and genetic influences, estimates for the effects of prenatal smoking were reduced by between 75% and the entire initial effects.

Conclusions  Observed associations between prenatal smoking and childhood conduct problems are likely to be heavily confounded with other known risks for children's behavioral development. As a result, tests of any causal influence of prenatal smoking must await findings from experimental studies.

Figures in this Article

Maternal smoking during pregnancy is an established risk for adversebirth, health, and developmental outcomes for children.1,2 Morerecently, a growing body of evidence has also highlighted an association betweenprenatal smoking and aggressive, antisocial behaviors in offspring. Predictionof antisocial outcomes has been reported in both clinical3 andepidemiologic samples4; in offspring rangingin age from preschoolers5 to adults6; and on measures as diverse as behavior rating scales,diagnostic interviews, and crime records. Studies have documented dose-responserelationships with prenatal smoking that appear specific to antisocial outcomesand that are possibly specific to males.7

Taken together, these findings suggest the possibility of an etiologicrole for prenatal smoking in the development of antisocial behavior, arguedto operate through influences on early brain development.7 Althoughanimal studies support the plausibility of such a model,8 commentatorshave urged caution in interpreting the human evidence7,9 becauseof 3 likely sources of confounding.

First, prenatal smoking is more common among young, less well-educatedmothers,10 among women in adverse social circumstances,11 and among those who are depressed.12 Allof these factors are known risks for the development of conduct problems inchildren.13 In general, past studies have shownthat controlling for such risks attenuates, but does not completely erode,links with maternal smoking. If the association between prenatal smoking andchildren's antisocial behavior is not simply a by-product of other socialand parental adversities, it should consistently survive controls for factorsof this kind.

Second, smoking is more common among women with antisocial traits,14 and smoking during pregnancy may be especially so.15 Antisocial behavior in parents increases the risksof antisocial behavior in children through multiple routes, both genetic (throughthe transmission of heritable traits) and environmental (through effects onthe prenatal environment and through later risks of child and partner abuse,16 harsh and coercive discipline,17 andcomorbid drug and alcohol problems18). As aresult, associations between prenatal smoking and child outcomes may be spurious,reflecting instead the operation of these correlated risks. Past studies controllingfor parental antisocial behavior have shown mixed results. Most have reportedresidual effects of prenatal smoking, but 2 studies—the first a smallsample of parents with alcohol problems19 andthe second, a large study predicting offspring smoking as well as antisocialbehavior20—showed that the effects ofprenatal smoking were reduced to nonsignificance after controls for parentalantisociality. In other studies, however, measures of parental behavior haveoften been restricted to relatively extreme indicators such as offending orantisocial personality, and by no means have all studies taken into accountthe antisocial traits of both mothers and fathers. Given the high level ofassortative mating on antisocial behaviors,21,22 thismay be an important lack. The presence of 2 antisocial parents may be especiallyharmful for children, and the joint effects of both parents' characteristicsneed to be unconfounded from the effects of prenatal smoking. If the associationbetween prenatal smoking and children's antisocial behavior is not spurious,it should survive after controls for both parents' antisocial behavior.

Finally, prenatal smoking may be a proxy measure indexing genetic riskfor antisocial behavior. Antisocial behavior is partly heritable,23 as is women's smoking initiation, nicotine dependence,24 and prenatal smoking,25 raisingthe possibility that children who are exposed to smoking in utero would beat risk for antisocial behavior regardless of whether their mothers smokedduring pregnancy. To our knowledge, no study has yet undertaken a direct testof this possibility. But if prenatal smoking is not simply a marker for geneticinfluences on children's antisocial behavior, its statistical effects mustsurvive after controlling for heritable influences.

In this study, we use data from a nationally representative twin designto assess the effects of prenatal smoking on early childhood conduct problems(assessed at ages 5 and 7 years) after controlling for all 3 types of confounding.Early childhood conduct problems put children at increased risk of later antisocialbehavior.26 In addition, if prenatal smokinginfluences early brain development, we reasoned that a focus on young childrenshould provide clear evidence of its effects.

PARTICIPANTS

Participants were members of the Environmental Risk (E-Risk) LongitudinalTwin Study, which investigates how genetic and environmental factors shapechildren's development. The study follows an epidemiological sample of familieswith young twins who were interviewed in the home when the twins were aged5 and 7 years. The E-Risk study sampling frame was 2 consecutive birth cohorts(1994 and 1995) in the Twins Early Development Study, a birth register oftwins born in England and Wales.27 The fullregister is administered by the government's Office for National Statistics,which invited parents of all twins born in 1994 and 1995 to enroll. Of the15 906 twin pairs born in these 2 years, 11 352 (71%) joined theregister. Our sampling frame excluded opposite-sex twin pairs and began withthe 8298 (73%) register families who had same-sex twins.

The E-Risk study sample was drawn using a high-risk stratification samplingframe. High-risk families were those in which the mother had her first birthwhen she was aged 20 years or younger. We used this sampling (1) to replacehigh-risk families selectively lost to the register via nonresponse and (2)to ensure sufficient base rates of problem behaviors in 5-year-old children.Early first childbearing was used as the risk-stratification variable becauseit was recorded for virtually all families in the register, is relativelyfree of measurement error, and is a known risk factor for children's problembehaviors.28,29 The sampling strategyresulted in a final sample in which two thirds of study mothers accuratelyrepresent all mothers (aged 15-48 years) in the general population in Englandand Wales in 1994 and 1995 (estimates derived from the General Household Survey).30 The other one third of study mothers (younger only)constitute a 160% oversample of mothers who were at high risk based on theiryoung age at first birth (15-20 years). To provide unbiased statistical estimatesthat can be generalized to the population of British families having childrenin the 1990s, the data reported in this article were corrected with weightingto represent the proportion of young mothers in that population.30

Of the 1203 families from the initial list who were eligible for inclusion,1116 (93%) participated in the home-visit assessments at age 5 years and formthe base sample for the study. Teachers returned questionnaires on the children'sbehavior for 1049 (94%) of these children. Zygosity was determined using astandard zygosity questionnaire that has been shown to have 95% accuracy.31 Ambiguous cases were zygosity-typed using DNA. Thesample included 622 monozygotic (56%) and 494 dizygotic (44%) twin pairs.Sex was evenly distributed within zygosity (546 male [49.1%]).

A follow-up home visit (which we refer to as the age-7 assessment) wasconducted 18 months after the age-5 assessment, when the children were aged6.5 years on average (range, 6.0-7.0 years). Follow-up data were collectedfor 1089 (98%) of the 1116 E-Risk study families, and teacher questionnaireswere obtained for 2026 (91%) of the 2232 E-Risk study children (93% of thosetaking part in the follow-up). In both the age-5 and age-7 assessments, familieswere given shopping vouchers for their participation and children were givencoloring books and stickers. All research workers had university degrees inbehavioral science and experience in psychology, anthropology, or nursing.

MEASURES
Maternal Smoking

Mothers were contacted 1 year after the twins' birth and asked to provideinformation about the pregnancy, including the number of cigarettes they hadsmoked. Around a fifth of mothers (836 [20.8%] of 1055) reported smoking duringpregnancy, similar to the 23% rate for England and Wales recorded in a nationalsurvey of mothers who gave birth in 1995.32 Ninetystudy mothers (8.6%) reported smoking 1 to 9 cigarettes per day, 73 (6.9%)reported smoking 10 to 14 cigarettes per day, and 56 (5.3%) were relativelyheavy smokers, smoking 15 or more cigarettes per day during their pregnancy.

Early Childhood Conduct Problems

Children's conduct problems at ages 5 and 7 years were assessed usingthe Achenbach family of instruments.33,34 TheConduct Problems scale was derived by summing items from mother and teacherreports, including items from the Delinquent Behavior (eg, lying or cheating,swearing or bad language) and Aggressive Behavior (eg, physically attackspeople, temper tantrums, or hot temper) scales of the Child Behavior Checklist33 and the Teacher's Report Form,34 supplementedwith DSM-IV35 itemsassessing conduct disorder and oppositional defiant disorder (eg, spiteful,tries to get revenge, uses force to take something from another child).

Correlations of mother and teacher reports of conduct problems were0.29 (P≤.001) and 0.38 (P≤.001)at ages 5 and 7 years, respectively, which is typical of interrater agreementabout behavioral problems.36 At age 5 years,scores ranged from 0 to 130 (mean ± SD, 21.17 ± 16.27) and atage 7 years, scores ranged from 0 to 132 (mean ± SD, 18.48 ±15.80). The internal consistency of the combined score was 0.94 at age 5 yearsand 0.95 at age 7 years. The Achenbach instruments have several strengthsthat make them appropriate for use with children of this age. They have strongand well-documented psychometric properties, have been used in large Europeanand North American epidemiological studies, are highly predictive of DSM disorders at later ages, and have been shown to besensitive to treatment effects.37 To ease interpretationof the findings, scale scores were standardized to a mean of 0 and an SD of1.

Covariates

Mothers' and fathers' prior history of antisocial behavior was reportedby the mothers at the study contact at age 5 years. Mothers were interviewedusing the Young Adult Behavior Checklist,38 modifiedto obtain lifetime data and supplemented with questions from the DiagnosticInterview Schedule39 that assessed the (lifetime)presence of the DSM-IV35 symptomsof antisocial personality disorder. Scores ranged from 0 to 60 (mean ±SD, 11.25 ± 9.71) for mothers and from 0 to 88 (mean ± SD, 14.76± 16.29) for fathers. The internal consistency reliabilities of the2 scales were 0.90 and 0.95, respectively. A methodological study of mother-fatheragreement about men's antisocial behavior in a representative subset of thesample (67 couples) showed that women can provide reliable information abouttheir children's father's behavior. The correlation between men's and women'sreports about men's antisocial behavior was 0.74 (95% confidence interval,0.53 to 0.95).40

Maternal depression since the twins' birth was assessed at each studycontact using the Diagnostic Interview Schedule,39 whichprovides measures of depressive episodes according to DSM-IV criteria.35 Two hundred ninety (26%)mothers had experienced an episode of depression by the twins' fifth birthday,and 333 (30%) by their seventh birthday.

Family socioeconomic status disadvantage was assessed at each studycontact. We created an index summing binary indicators of 7 aspects of socioeconomicstatus disadvantage: (1) head of household has no educational qualifications;(2) head of household is employed in an unskilled occupation or is not inthe labor force; (3) total household gross annual income is less than £10,000;(4) family receives at least 1 government benefit, excluding disability benefit;(5) family housing is government subsidized; (6) family has no access to avehicle, and (7) family lives in the poorest of 6 neighborhood categories,41 in an area dominated by government-subsidized housing,low incomes, high unemployment, and single-parent families. At age 5, 600(45%) families experienced at least 1 socioeconomic status disadvantage.

DATA ANALYSIS

First, we used ordinary least squares regression to test the associationbetween prenatal smoking and children's conduct problems. We compared womenwho did not smoke during pregnancy with light (1-9 cigarettes per day), moderate(10-14 cigarettes per day), and heavy (≥15 cigarettes per day) prenatalsmokers. Because levels of early childhood conduct problems are higher inboys than in girls, child sex was included as a covariate in this and allsubsequent analyses. Regression results are based on the sandwich or Huber/Whitevariance estimator,42 a method available inStata 7.0,43 which adjusts estimated standarderrors to account for the dependence in the data due to analyzing sets oftwins.

Second, we used DeFries-Fulker (DF) regression analyses to test thehypothesis that passive gene-environment correlations accounted for the associationbetween maternal prenatal smoking and children's conduct problems. DeFries-Fulkeranalysis uses kinship-pair data (eg, twin data) to separate genetic and environmentalinfluences in a regression framework.44 Thesandwich variance estimator was used to correct for the nonindependence oftwin observations.45 The equation for the basicDF regression model is

ASBtwin1 = β1 + β2(R)+ β3(ASBtwin2)+ β4(R* ASBtwin2)+e,

where ASBtwin1represents the conduct problems scorefor twin 1, β1represents the constant term, R representsthe coefficient of genetic relatedness (1.0 for monozygotic twins; 0.5 fordizygotic twins), and ASBtwin2representsthe conduct problems score for twin 2. β4represents the populationheritability estimate h2 because, when it is statistically significant,it demonstrates that twin 1 and twin 2's resemblance for conduct problemsis conditioned on their degree of genetic relatedness; β3 estimatesshared environmental variation because it represents the twins' resemblancefor conduct problems independent of genetic resemblance.46

The hypothesis that genetic transmission accounts for the associationbetween maternal smoking during pregnancy and children's conduct problemspredicts that the effect of maternal prenatal smoking will no longer be significantonce genetic influences on children's conduct problems are controlled. Thebasic DF model was expanded to test this prediction. Thus, the effect of maternalsmoking was estimated in an augmented model

ASBtwin1 = β1 + β2(R)+ β3(ASBtwin2)+ β4(R* ASBtwin2)+ ΣβsmZsm,+e,

where Zsm represents3 dummy-coded variables representing light, moderate, and heavy maternal prenatalsmoking, respectively, with nonsmoking during pregnancy as the reference category.

Third, we used a series of regression models to test whether the associationbetween maternal smoking during pregnancy and children's conduct problemswas accounted for by parents' history of antisocial behavior and by relatedfamily adversities. We began by testing the association between maternal smokingduring pregnancy and children's conduct problems, using ordinary least squaresregression model

ASB = β1(lightsmoker) + β2 (moderate smoker) + β3(heavy smoker) +e,

where ASB representsthe child's conduct problems and β1 through β3 represent the effectsof light, moderate, and heavy maternal smoking during pregnancy compared withmothers who did not smoke during pregnancy (the reference, or contrast, group).

We then tested whether the association between prenatal smoking andchildren's conduct problems was accounted for by the parents' prior historyof antisocial behavior by reestimating model 1 after entering continuous measuresindexing the mothers' and fathers' antisocial behavior history

ASB = β1(light smoker) + β2 (moderate smoker) + β3(heavy smoker) + β4(mother's ASB) + β5(father's ASB) +e.

Next,we tested whether familywide social adversities that are correlated both withmaternal smoking during pregnancy and with children's conduct problems accountedfor the effects of maternal prenatal smoking on their children's outcomes.We expanded the regression model,

ASB = β1(light smoker) + β2 (moderatesmoker) + β3(heavy smoker) + β4(maternal ASB) + β5(paternal ASB) + ΣβjZj,+e,

where Zj is a set of observed confounding factors (ie, maternaldepression and family socioeconomic disadvantage).

Finally, we tested whether the combination of genetic factors, parents'antisocial behavior, and family adversities accounted for the effects of maternalprenatal smoking by expanding the augmented DF regression as

ASBtwin1 = β1(light smoker) + β2 (moderate smoker) + β3(heavy smoker) + β4(ρ) + β5(ASBtwin2)+ β6(R* ASBtwin2)+ β7(maternal ASB)+ β8(paternal ASB)+ ΣβjZj,+e.

IS THERE AN ASSOCIATION BETWEEN PRENATAL SMOKING AND CHILDREN'S CONDUCTPROBLEMS?

Prenatal smoking predicted children's conduct problems at age 5 years(F3,1054 = 13.75; P<.001) and age 7years (F3,1030 = 13.92; P<.001). Asexpected, boys had higher levels of conduct problems than girls at both age5 years (t1,1115 = 7.18; P<.001) and age 7 years (t1,1088 =7.40; P<.001). Figure 1 shows a dose-response relation between the number of cigarettessmoked and the z-transformed measure of conduct problemsin both boys and girls. At age 5 years, controlling for sex, children of light,moderate, and heavy prenatal smokers scored 0.33, 0.39, and 0.57 standarddeviation units higher, respectively, on the Conduct Problems scale than childrenof women who did not smoke during pregnancy (Table 1, panel A, model 1). These differences persisted at age 7years, when children of light, moderate, and heavy prenatal smokers scored0.38, 0.34, and 0.67 standard deviation units higher, respectively, than childrenof women who did not smoke during pregnancy (Table 1, panel B, model 1). As Figure 1 suggests, these associations were as powerful for girlsas for boys. Tests for interactions with child sex were nonsignificant atboth age 5 years (F3,1054 = 0.25; P =.86) and age 7 years (F3,1030 = 0.52; P =.67).

Place holder to copy figure label and caption

Prenatal smoking and childhood conduct problems, ages 5 and 7 years.

Graphic Jump Location
Table Graphic Jump LocationTable 1. Results of Regression Analysis of the Effects of MaternalSmoking During Pregnancy on Early Childhood Conduct Problems*
IS THE ASSOCIATION BETWEEN PRENATAL SMOKING AND CHILDREN'S CONDUCTPROBLEMS ACCOUNTED FOR BY GENETIC RISKS?

The results of the DF regression analyses are presented in Table 1 (model 2). Three findings are highlighted.First, approximately two thirds of the variation in children's conduct problemsat age 5 years (68%) and at age 7 years (73%) was accounted for by geneticfactors. Second, prenatal smoking continued to predict children's conductproblems even after controlling for genetic effects. Third, genetic factorsaccounted for approximately 50% of the effect of maternal prenatal smokingon child outcomes at both age 5 and 7 years (Table 1, model 1 vs model 2 in panel A and panel B). The sharedenvironment parameter was nonsignificant at both ages and is therefore notincluded in the models presented in Table1. These findings provide partial support for the genetic transmissionhypothesis, but they also document that prenatal smoking is associated withenvironmentally mediated effects on children's conduct problems beyond genetictransmission.

IS THE ASSOCIATION BETWEEN PRENATAL SMOKING AND CHILDREN'S CONDUCTPROBLEMS CONFOUNDED BY THE MOTHERS' (AND FATHERS') ANTISOCIAL BEHAVIOR HISTORY?

Women who smoked during pregnancy were likely to engage in higher levelsof antisocial behavior than nonsmokers (Table 2). To illustrate, high levels of maternal antisocial behavior(the top quartile of the maternal antisocial behavior distribution) were associatedwith a 3-fold increase in the odds of prenatal smoking (odds ratio, 3.1 [95%confidence interval, 2.3 to 4.3]). In addition, women who smoked during pregnancywere significantly more likely to have children with antisocial men (Table 2). Moreover, there was significantassortative mating for antisocial behavior; antisocial women were significantlymore likely to reproduce children with antisocial men (r = 0.53; P<.001).

Table Graphic Jump LocationTable 2. Maternal Smoking in Pregnancy Is Associated With ParentalAntisocial Behavior and With Family Adversities*

Prior antisocial behavior of both mothers and fathers predicted children'sconduct problems (Table 1, model3). Moreover, comparing model 3 with model 1 showed that parental antisocialbehavior accounted for more than 50% of the effect of prenatal smoking onchildren's behavioral outcomes. At age 5 years, controls for parental antisocialbehavior reduced the effects of light smoking during pregnancy to nonsignificanceand those of moderate and heavy smoking during pregnancy to just below conventional(5%) levels of statistical significance. At age 7 years, the effects of lightsmoking during pregnancy became nonsignificant and the effects of moderatesmoking during pregnancy became marginally significant, but the effects ofheavy maternal smoking during pregnancy remained significant when parentalantisocial behavior was controlled.

IS THE ASSOCIATION BETWEEN PRENATAL SMOKING AND CHILDREN'S CONDUCTPROBLEMS CONFOUNDED BY SOCIAL DEPRIVATION AND MATERNAL DEPRESSION?

Women who smoked during pregnancy were also more likely to have beendepressed during their children's lifetime than other mothers, and their householdswere significantly more socioeconomically disadvantaged (Table 2). Both of these risks were associated with higher levelsof child conduct problems. Maternal depression was significantly linked tochildren's conduct problems at ages 5 years (F2,1108 = 30.33; P<.001) and 7 years (F2,1081 = 31.03; P<.001), as was social disadvantage. The more severethe family's socioeconomic deprivation, the more conduct problems the childrenhad at ages 5 years (F1,1115 = 78.88; P<.001)and 7 years (F1,1088 = 79.12; P<.001).Controlling for these adversities further reduced the association betweenprenatal smoking and children's behavioral outcomes. On average, three quartersof the association between prenatal smoking and children's conduct problemswas accounted for by parental antisocial behavior and other maternal and familyadversities (Table 1, model 4).Controlling for all of these factors, no reliable effects of prenatal smokingon child outcomes could be detected.

DOES PRENATAL SMOKING HAVE AN EFFECT ON CHILDREN'S CONDUCT PROBLEMSAFTER CONTROLLING FOR GENETIC AND ENVIRONMENTAL RISKS?

The final models (Table 1,model 5 in panel A and panel B) present results of augmented DF regressionanalyses that control for parental antisocial behavior, maternal depression,and social deprivation while also controlling for genetic risk. Coefficientsfor the effects of prenatal smoking were further reduced in these models;together, the genetic and environmental risks accounted for between 75% andthe entire initial effect of prenatal smoking on children's conduct problems.To test the robustness of these findings, we repeated the analyses with maternalsmoking treated as a scalar rather than a categorical variable and using otherindicators of early childhood conduct problems (the separate Child BehaviorChecklist aggression and delinquency subscales and a measure drawing on teacherreports only). (Results of these additional analyses are available from thecorresponding author on request.) In each case, strong initial effects ofprenatal smoking were reduced by at least 75% by controlling for both geneticand environmental risks. No reliable effects of prenatal smoking could bedetected in any of these models on child outcomes at age 5 years. On outcomesat age 7 years, effects of all levels of prenatal smoking were reduced tononsignificance on the Child Behavior Checklist aggression subscale and theteacher-only reports. On the Child Behavior Checklist delinquency subscaleand in analyses treating maternal smoking as a scalar variable, the effectsof light and moderate prenatal smoking were reduced to nonsignificance; theeffects associated with heavy smoking during pregnancy could still be detected,though they were small in magnitude.

Childhood conduct problems arise in the context of multiple and oftenoverlapping risks. We used data from a large representative twin sample totest the extent to which associations with 1 specific risk factor—prenatalsmoking—were robust to controls for genetic and environmental confounds.

Like past investigators, we found a strong, dose-response relationshipbetween prenatal smoking and childhood conduct problems, replicated at 2 agesand as powerful for girls as for boys. Controlling for possible confoundsof this relationship, our findings yield 2 main conclusions. First, to ourknowledge, the present study provides the most direct test yet of the possibilitythat prenatal smoking may be a proxy measure indexing genetic risk for antisocialbehavior. Our twin analysis, which controlled for the heritability of conductproblems, confirmed that genetic confounds are important. Around half of theobserved association between prenatal smoking and young children's conductproblems was attributable to correlated genetic effects. But the results werealso clear in showing that, even after controlling for genetic influences,prenatal smoking continued to be significantly linked to children's behavioraloutcomes.

Second, our results documented that women who smoke during pregnancyare different from those who do not. They are more antisocial, they bear childrenwith more antisocial men, they are more likely to rear their children in disadvantagedenvironments, and they are more likely to be depressed. With these factorsand genetic risk controlled, estimates of the effects of prenatal smokingwere greatly reduced. In tandem, these 2 sets of findings suggest that (1)prenatal smoking is not simply a proxy indexing genetic risk for antisocialbehavior but that (2) it is also unlikely to be a unique cause of early childhoodbehavior problems.

These findings must be interpreted in light of 4 potential limitations.First, like most other studies in this field, our measures of prenatal smokingrelied on maternal reports. Although these have adequate reliability, directassessment of maternal cotinine levels would undoubtedly have been desirable.47 Second, the main measures of child outcomes and parentalantisocial behavior also came from maternal interviews, raising queries overthe possibility of reporter effects. Analyses of teacher-only reports of childbehavior, however, were clear cut. Using these independent reports of earlychildhood behavior problems, no significant effects of prenatal smoking weredetectable once genetic and environmental confounds were controlled.

Third, though our study was based on a twin sample, we assume that ourfindings can be generalized to the population of singletons. This assumptionis probably defensible because twin-singleton comparisons find no notabledifferences in rates of children's behavior problems,4852 becausethe rate of smoking during pregnancy in our sample is comparable with nationalrates of smoking among pregnant women32 andbecause the association between prenatal smoking and children's behavioraloutcomes is similar to that reported in samples of singletons.7 Finally,though nationally representative, our sample was confined to young childrenand to 1 historical period. If prenatal smoking influences early brain development,we reasoned that effects should be most evident early in childhood; it remainspossible, however, that older samples would highlight different patterns ofeffects. Our study also focused on a recent cohort, whereas some past researchhas used data from cohorts established many years ago. Historically, ratesof prenatal smoking have fallen in many Western countries in recent decades.10,32 As a result, prenatal smoking mayhave become more concentrated in families with other adversities, and theextent of confounding with other risks may have become more marked. Past cohortsmay not have experienced this level of confounding. For the future, however,our findings should provide a good guide to the extent of overlapping risk.

Given these caveats, the core conclusion of our analyses is that observedassociations between prenatal smoking and early childhood conduct problemsare highly confounded with other known risks for children's behavioral development.With few exceptions, past studies have found residual effects of prenatalsmoking after controls for other risks. We suspect that much of the powerof our analyses lay in our assessments of parental antisocial traits. Whereasmany past studies have focused on criminality or diagnosed psychiatric/personalitydisorders in parents, our dimensional measures of parental antisociality includeda broad spectrum of markers of antisocial behaviors that showed associationswith prenatal smoking and with risks for childhood conduct problems acrossthe range. Whereas some past studies have controlled for antisocial behaviorin just 1 parent, we found that both maternal and paternal characteristicsaccounted for independent variance in child outcomes. Because parents' antisocialbehavior indexes both heritable and environmental risks for children's behavioraldevelopment and because of the high degree of assortative mating for antisocialbehavior,21,22 we conclude thatcomprehensive assessments of parental traits are key to evaluating the independenteffect of other postulated risks.

Though our findings do not preclude an independent causal role for prenatalsmoking in the genesis of child conduct problems, they do imply that strategiesother than observational studies will be needed to detect it. Interventionsto reduce prenatal smoking offer perhaps the best tests here, though theseare known to face challenges. "Best practice" current programs are only successfulwith some 20% of pregnant smokers and least effective with those who smokeheavily.53 Studies of pregnant smokers15 concur with our findings to suggest that for manyof these women, prenatal smoking forms part of a wider spectrum of adjustmentproblems that may put both mothers and their children at risk. Reducing levelsof prenatal smoking remains a key target for public policy because of thedamaging effects of smoking during pregnancy on other aspects of fetal andearly child development.1,2 Forchild behavioral outcomes, our findings argue that while we await furtherevidence on the causal role of prenatal smoking, the many other risks facedby women who smoke during pregnancy constitute equally important targets forintervention and research.

Submitted for publication August 4, 2003; final revision received February16, 2004; accepted February 18, 2004.

The E-Risk Longitudinal Twin Study is funded by the UK Medical ResearchCouncil, London, England. Dr Maughan is supported by the UK Medical ResearchCouncil.

We thank the study mothers and fathers, the twins, and the twins' teachersfor their participation. We also thank Michael Rutter, MD, and Robert Plomin,PhD; Thomas Achenbach, PhD, for permission to adapt the Child Behavior Checklist;Hallmark Cards, Kansas City, Mo; and members of the E-risk team for theirdedication, hard work, and insights.

Dr Moffitt is a Royal Society Wolfson Research Merit Award holder.

Correspondence: Barbara Maughan, PhD, Box P046, Social, Genetic andDevelopmental Psychiatry Research Centre, Institute of Psychiatry, King'sCollege London, De Crespigny Park, Denmark Hill, London SE5 8AF, England(b.maughan@iop.kcl.ac.uk).

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Hill  J Biological, psychological and social processes in the conduct disorders. J Child Psychol Psychiatry. 2002;43133- 164
PubMed Link to Article
Bardone  AMMoffitt  TECaspi  ADickson  NStanton  WRSilva  PA Adult physical health outcomes of adolescent girls with conduct disorder,depression, and anxiety. J Am Acad Child Adolesc Psychiatry. 1998;37594- 601
PubMed Link to Article
Wakschlag  LSPickett  KEMiddlecamp  MKWalton  LLTenzer  PLeventhal  BL Pregnant smokers who quit, pregnant smokers who don't: does historyof problem behavior make a difference? Soc Sci Med. 2003;562449- 2460
PubMed Link to Article
Margolin  GGordis  EB The effects of family and community violence on children. Annu Rev Psychol. 2000;51445- 479
PubMed Link to Article
Fagot  BIPears  KCCapaldi  DMCrosby  LLeve  CS Becoming an adolescent father: precursors and parenting. Dev Psychol. 1998;341209- 1219
PubMed Link to Article
Robins  LN The intimate connection between antisocial personality and substanceabuse. Soc Psychiatry Psychiatr Epidemiol. 1998;33393- 399
PubMed Link to Article
Hill  SYLowers  LLocke-Wellman  JShen  SA Maternal smoking and drinking during pregnancy and the risk for childand adolescent psychiatric disorders. J Stud Alcohol. 2000;61661- 668
PubMed
Silberg  JLParr  TNeale  MCRutter  MAngold  AEaves  LJ Maternal smoking during pregnancy and risk to boys' conduct disturbance:an examination of the causal hypothesis. Biol Psychiat. 2003;53130- 135
PubMed Link to Article
Du Fort  GGBoothroyd  LJBland  RCNewman  SCKakuma  R Spouse similarity for antisocial behaviour in the general population. Psychol Med. 2002;321407- 1416
PubMed
Krueger  RCaspi  AMoffitt  TEBleske  ASilva  PA Assortative mating for antisocial behavior: developmental and methodologicalimplications. Behav Genet. 1998;28173- 186
PubMed Link to Article
Rhee  SHWaldman  ID Genetic and environmental influences on antisocial behavior: a meta-analysisof twin and adoption studies. Psychol Bull. 2002;128490- 529
PubMed Link to Article
Kendler  KSNeale  MCSullivan  PCorey  LAGardner  COPrescott  CA A population-based twin study in women of smoking initiation and nicotinedependence. Psychol Med. 1999;29299- 308
Link to Article
D'Onofrio  BMTurkheimer  ENEaves  LJCorey  LA The role of the children of twins design in elucidating causal relationshipsbetween parent characteristics and child outcomes. J Child Psychol Psychiatry. 2003;441130- 1144
PubMed Link to Article
Rutter  MGiller  HHagell  A Antisocial Behavior by Young People.  New York, NY Cambridge University Press1998;
Trouton  ASpinath  FMPlomin  R Twins Early Development Study (TEDS): a multivariate, longitudinalgenetic investigation of language, cognition, and behavior problems in childhood. Twin Res. 2002;5444- 448
PubMed Link to Article
Maynard  RA Kids Having Kids: Economic Costs and Social Consequencesof Teen Pregnancy.  Washington, DC Urban Institute Press1997;
Moffitt  TEand the E-Risk Study Team, Teen-aged mothers in contemporary Britain. J Child Psychol Psychiatry. 2002;43727- 742
PubMed Link to Article
Bennett  NJarvis  LRowlands  OSingleton  NHaselden  L Living in Britain: Results from the General HouseholdSurvey.  London, England Her Majesty's Stationery Office1996;
Price  TSFreeman  BCraig  IPetrill  SAEbersole  LPlomin  R Infant zygosity can be assigned by parental report questionnaire data. Twin Res. 2000;3129- 133
PubMed Link to Article
Foster  KLader  DCheesbrough  Sand the Office for National Statistics, Infant Feeding Survey 1995.  London, England Her Majesty's Stationery Office1997;
Achenbach  TM Manual for the Child Behavior Checklist/4-18 and1991 Profile.  Burlington University of Vermont Department of Psychiatry1991;
Achenbach  TM Manual for the Teacher's Report Form and 1991 Profile.  Burlington University of Vermont Department of Psychiatry1991;
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition.  Washington, DC American Psychiatric Association1994;
Achenbach  TMMcConaughy  SHHowell  CT Child/adolescent behavioral and emotional problems: implications ofcross-informant correlations for situational specificity. Psychol Bull. 1987;101213- 232
PubMed Link to Article
Greenhill  LLMalcolm  Jeds. Child and adolescent measures for diagnosis and screening. Task Force for the Handbook of Psychiatric MeasuresHandbook of Psychiatric Measures. Washington, DC AmericanPsychiatric Association2000;
Achenbach  TM Manual for the Young Adult Self-report and YoungAdult Behavior Checklist.  Burlington University of Vermont Department of Psychiatry1997;
Robins  LNCottler  LBucholz  KCompton  W Diagnostic Interview Schedule for DSM-IV.  St Louis, Mo Washington University Press1995;
Caspi  ATaylor  ASmart  MJackson  JTagami  SMoffitt  TE Can women provide reliable information about their children's fathers? cross-informantagreement about men's lifetime antisocial behaviour. J Child Psychol Psychiatry. 2001;42915- 920
PubMed Link to Article
CACI Information Services, ACORN User Guide.  London, England CACI Limited1993;
Gould  WSribney  W Maximum Likelihood Estimation With Stata.  College Station Tex: Stata Press1999;
Stata Corporation, Stata Statistical Software: Release 7.0.  College Station Tex: Stata Corp2001;
DeFries  JCFulker  DW Multiple regression analysis of twin data. Behav Genet. 1985;15467- 473
PubMed Link to Article
Kohler  HPRodgers  JL DF-analyses of heritability with double-entry twin data: asymptoticstandard errors and efficient estimation. Behav Genet. 2001;31179- 191
PubMed Link to Article
Rodgers  JLMcGue  M A simple algebraic demonstration of the validity of DeFries-Fulkeranalysis in unselected samples with multiple kinship levels. Behav Genet. 1994;24259- 262
PubMed Link to Article
Klebanoff  MALevine  RJClemens  JDDerSimonian  RWilkins  DG Serum cotinine concentration and self-reported smoking during pregnancy. Am J Epidemiol. 1998;148259- 262
PubMed Link to Article
Moilanen  ILinna  SLEbeling  HKumpulainen  KTamminen  TPiha  JAlmqvist  F Are twins' behavioural/emotional problems different from singletons'? Eur Child Adolesc Psychiatry. 1999;8(suppl 4)62- 67
PubMed Link to Article
Gjone  HNovik  TS Parental ratings of behavioural problems: a twin and general populationcomparison. J Child Psychol Psychiatry. 1995;361213- 1224
PubMed Link to Article
Levy  FHay  DMcLaughlin  MWood  CWaldman  I Twin-sibling differences in parental reports of ADHD, speech, reading,and behavioural problems. J Child Psychol Psychiatry. 1996;37569- 578
PubMed Link to Article
Simonoff  EPickles  AMeyer  JSilberg  JLMaes  HHLoeber  RRutter  MHewitt  JKEaves  L The Virginia Twin Study of Adolescent Behavioral Development. Arch Gen Psychiatry. 1997;54801- 808
PubMed Link to Article
van den Oord  EJCGKoot  HMBoomsma  DIVerhulst  FCOrleveke  JF A twin-singleton comparison of problem behaviour in 2-3 year olds. J Child Psychol Psychiatry. 1995;36449- 458
PubMed Link to Article
Orleans  CTBarker  DCKaufman  NJMarx  JF Helping pregnant smokers quit: meeting the challenge in the next decade. Tob Control. 2000;9(suppl 3)III6- 11
PubMed Link to Article

Figures

Place holder to copy figure label and caption

Prenatal smoking and childhood conduct problems, ages 5 and 7 years.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Results of Regression Analysis of the Effects of MaternalSmoking During Pregnancy on Early Childhood Conduct Problems*
Table Graphic Jump LocationTable 2. Maternal Smoking in Pregnancy Is Associated With ParentalAntisocial Behavior and With Family Adversities*

References

Royal College of Physicians, Smoking and the Young.  London, England Royal College of Physicians1992;
Olds  D Tobacco exposure and impaired development: a review of the evidence. Ment Retard Dev Disabil Res Rev. 1997;3257- 269
Link to Article
Wakschlag  LSLahey  BBLoeber  RGreen  SMGordon  RLeventhal  BL Maternal smoking during pregnancy and the risk of conduct disorderin boys. Arch Gen Psychiatry. 1997;54670- 676
PubMed Link to Article
Fergusson  DMWoodward  LJHorwood  J Maternal smoking during pregnancy and psychiatric adjustment in lateadolescence. Arch Gen Psychiatry. 1998;55721- 727
PubMed Link to Article
Day  NLRichardson  GAGoldschmidt  LCornelius  MD Effects of prenatal tobacco exposure on preschoolers' behavior. J Dev Behav Pediatr. 2000;21180- 188
PubMed
Brennan  PAGrekin  ERMednick  SA Maternal smoking during pregnancy and adult male criminal outcomes. Arch Gen Psychiatry. 1999;56215- 219
PubMed Link to Article
Wakschlag  LSPickett  KECook  EBenowitz  NLLeventhal  BL Maternal smoking during pregnancy and severe antisocial behavior inoffspring: a review. Am J Public Health. 2002;92966- 974
PubMed Link to Article
Ernst  MMoolchan  ETRobinson  ML Behavioral and neural consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc Psychiatry. 2001;40630- 641
PubMed Link to Article
Fergusson  DM Prenatal smoking and antisocial behavior. Arch Gen Psychiatry. 1999;56223- 224
PubMed Link to Article
Matthews  T J Smoking During Pregnancy in the 1990s.  Hyattsville, Md National Center for Health Statistics2001;49
Ventura  SMathews  JCurtin  SMathews  TPark  M Births: Final Data for 1998.  Hyattsville, Md National Center for Health Statistics2000;Report48
Breslau  NKilbey  MAndreski  P Nicotine dependence and major depression: new evidence from a prospectiveinvestigation. Arch Gen Psychiatry. 1993;5031- 35
PubMed Link to Article
Hill  J Biological, psychological and social processes in the conduct disorders. J Child Psychol Psychiatry. 2002;43133- 164
PubMed Link to Article
Bardone  AMMoffitt  TECaspi  ADickson  NStanton  WRSilva  PA Adult physical health outcomes of adolescent girls with conduct disorder,depression, and anxiety. J Am Acad Child Adolesc Psychiatry. 1998;37594- 601
PubMed Link to Article
Wakschlag  LSPickett  KEMiddlecamp  MKWalton  LLTenzer  PLeventhal  BL Pregnant smokers who quit, pregnant smokers who don't: does historyof problem behavior make a difference? Soc Sci Med. 2003;562449- 2460
PubMed Link to Article
Margolin  GGordis  EB The effects of family and community violence on children. Annu Rev Psychol. 2000;51445- 479
PubMed Link to Article
Fagot  BIPears  KCCapaldi  DMCrosby  LLeve  CS Becoming an adolescent father: precursors and parenting. Dev Psychol. 1998;341209- 1219
PubMed Link to Article
Robins  LN The intimate connection between antisocial personality and substanceabuse. Soc Psychiatry Psychiatr Epidemiol. 1998;33393- 399
PubMed Link to Article
Hill  SYLowers  LLocke-Wellman  JShen  SA Maternal smoking and drinking during pregnancy and the risk for childand adolescent psychiatric disorders. J Stud Alcohol. 2000;61661- 668
PubMed
Silberg  JLParr  TNeale  MCRutter  MAngold  AEaves  LJ Maternal smoking during pregnancy and risk to boys' conduct disturbance:an examination of the causal hypothesis. Biol Psychiat. 2003;53130- 135
PubMed Link to Article
Du Fort  GGBoothroyd  LJBland  RCNewman  SCKakuma  R Spouse similarity for antisocial behaviour in the general population. Psychol Med. 2002;321407- 1416
PubMed
Krueger  RCaspi  AMoffitt  TEBleske  ASilva  PA Assortative mating for antisocial behavior: developmental and methodologicalimplications. Behav Genet. 1998;28173- 186
PubMed Link to Article
Rhee  SHWaldman  ID Genetic and environmental influences on antisocial behavior: a meta-analysisof twin and adoption studies. Psychol Bull. 2002;128490- 529
PubMed Link to Article
Kendler  KSNeale  MCSullivan  PCorey  LAGardner  COPrescott  CA A population-based twin study in women of smoking initiation and nicotinedependence. Psychol Med. 1999;29299- 308
Link to Article
D'Onofrio  BMTurkheimer  ENEaves  LJCorey  LA The role of the children of twins design in elucidating causal relationshipsbetween parent characteristics and child outcomes. J Child Psychol Psychiatry. 2003;441130- 1144
PubMed Link to Article
Rutter  MGiller  HHagell  A Antisocial Behavior by Young People.  New York, NY Cambridge University Press1998;
Trouton  ASpinath  FMPlomin  R Twins Early Development Study (TEDS): a multivariate, longitudinalgenetic investigation of language, cognition, and behavior problems in childhood. Twin Res. 2002;5444- 448
PubMed Link to Article
Maynard  RA Kids Having Kids: Economic Costs and Social Consequencesof Teen Pregnancy.  Washington, DC Urban Institute Press1997;
Moffitt  TEand the E-Risk Study Team, Teen-aged mothers in contemporary Britain. J Child Psychol Psychiatry. 2002;43727- 742
PubMed Link to Article
Bennett  NJarvis  LRowlands  OSingleton  NHaselden  L Living in Britain: Results from the General HouseholdSurvey.  London, England Her Majesty's Stationery Office1996;
Price  TSFreeman  BCraig  IPetrill  SAEbersole  LPlomin  R Infant zygosity can be assigned by parental report questionnaire data. Twin Res. 2000;3129- 133
PubMed Link to Article
Foster  KLader  DCheesbrough  Sand the Office for National Statistics, Infant Feeding Survey 1995.  London, England Her Majesty's Stationery Office1997;
Achenbach  TM Manual for the Child Behavior Checklist/4-18 and1991 Profile.  Burlington University of Vermont Department of Psychiatry1991;
Achenbach  TM Manual for the Teacher's Report Form and 1991 Profile.  Burlington University of Vermont Department of Psychiatry1991;
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition.  Washington, DC American Psychiatric Association1994;
Achenbach  TMMcConaughy  SHHowell  CT Child/adolescent behavioral and emotional problems: implications ofcross-informant correlations for situational specificity. Psychol Bull. 1987;101213- 232
PubMed Link to Article
Greenhill  LLMalcolm  Jeds. Child and adolescent measures for diagnosis and screening. Task Force for the Handbook of Psychiatric MeasuresHandbook of Psychiatric Measures. Washington, DC AmericanPsychiatric Association2000;
Achenbach  TM Manual for the Young Adult Self-report and YoungAdult Behavior Checklist.  Burlington University of Vermont Department of Psychiatry1997;
Robins  LNCottler  LBucholz  KCompton  W Diagnostic Interview Schedule for DSM-IV.  St Louis, Mo Washington University Press1995;
Caspi  ATaylor  ASmart  MJackson  JTagami  SMoffitt  TE Can women provide reliable information about their children's fathers? cross-informantagreement about men's lifetime antisocial behaviour. J Child Psychol Psychiatry. 2001;42915- 920
PubMed Link to Article
CACI Information Services, ACORN User Guide.  London, England CACI Limited1993;
Gould  WSribney  W Maximum Likelihood Estimation With Stata.  College Station Tex: Stata Press1999;
Stata Corporation, Stata Statistical Software: Release 7.0.  College Station Tex: Stata Corp2001;
DeFries  JCFulker  DW Multiple regression analysis of twin data. Behav Genet. 1985;15467- 473
PubMed Link to Article
Kohler  HPRodgers  JL DF-analyses of heritability with double-entry twin data: asymptoticstandard errors and efficient estimation. Behav Genet. 2001;31179- 191
PubMed Link to Article
Rodgers  JLMcGue  M A simple algebraic demonstration of the validity of DeFries-Fulkeranalysis in unselected samples with multiple kinship levels. Behav Genet. 1994;24259- 262
PubMed Link to Article
Klebanoff  MALevine  RJClemens  JDDerSimonian  RWilkins  DG Serum cotinine concentration and self-reported smoking during pregnancy. Am J Epidemiol. 1998;148259- 262
PubMed Link to Article
Moilanen  ILinna  SLEbeling  HKumpulainen  KTamminen  TPiha  JAlmqvist  F Are twins' behavioural/emotional problems different from singletons'? Eur Child Adolesc Psychiatry. 1999;8(suppl 4)62- 67
PubMed Link to Article
Gjone  HNovik  TS Parental ratings of behavioural problems: a twin and general populationcomparison. J Child Psychol Psychiatry. 1995;361213- 1224
PubMed Link to Article
Levy  FHay  DMcLaughlin  MWood  CWaldman  I Twin-sibling differences in parental reports of ADHD, speech, reading,and behavioural problems. J Child Psychol Psychiatry. 1996;37569- 578
PubMed Link to Article
Simonoff  EPickles  AMeyer  JSilberg  JLMaes  HHLoeber  RRutter  MHewitt  JKEaves  L The Virginia Twin Study of Adolescent Behavioral Development. Arch Gen Psychiatry. 1997;54801- 808
PubMed Link to Article
van den Oord  EJCGKoot  HMBoomsma  DIVerhulst  FCOrleveke  JF A twin-singleton comparison of problem behaviour in 2-3 year olds. J Child Psychol Psychiatry. 1995;36449- 458
PubMed Link to Article
Orleans  CTBarker  DCKaufman  NJMarx  JF Helping pregnant smokers quit: meeting the challenge in the next decade. Tob Control. 2000;9(suppl 3)III6- 11
PubMed Link to Article

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