Article

Maternal Smoking During Pregnancy and Attention Deficit Hyperactivity Disorder Symptoms in Offspring Anita Thapar, M.B., Ph.D., M.R.C.Psych. Tom Fowler, B.Sc. Frances Rice, Ph.D. Jane Scourfield, M.R.C.Psych., Ph.D. Marianne van den Bree, Ph.D. Hollie Thomas, D.Phil. Gordon Harold, Ph.D.

Objective: The aim of this study was to examine whether smoking during pregnancy is associated with symptoms of attention deficit hyperactivity disorder (ADHD) in offspring and whether these effects are additional to genetic influences. Method: Children’s ADHD symptoms (parent- and teacher-rated), maternal smoking during pregnancy, conduct disorder symptoms, and family adversity were assessed with questionnaires for a population-based sample of twins (1,452 twin pairs 5–16 years of age).

Dale Hay, Ph.D.

Results: Although genetic influences accounted for most of the variance in offspring ADHD, maternal smoking during pregnancy was still found to show a significant environmentally mediated association. Maternal smoking remained a significant influence when other potential confounds were taken into account. Conclusions: Maternal smoking during pregnancy appears to show an association with offspring ADHD symptoms that is additional to the effects of genes and not attributable to shared rater effects, clinical referral biases, or covariation with antisocial behavior. (Am J Psychiatry 2003; 160:1985–1989)

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aternal smoking during pregnancy has been found to be associated with attention deficit hyperactivity disorder (ADHD) in several clinical studies (1–3). Confounding factors such as parental psychopathology, parent ADHD, alcohol and drug use, birth weight, IQ, and psychosocial adversity do not appear to account for the association. However, it has been difficult to draw conclusions about whether smoking during pregnancy has a real risk effect (4) for the following reasons. First, all of these studies of ADHD have been based on clinical samples. Although there have been many population-based studies of prenatal smoking and child behavior, these have focused on the association with conduct disorder (mainly early-onset, life course-persistent symptoms) or criminality (5–8). ADHD was not examined in these studies with the exception of one British study. Maughan and colleagues (8) found that maternally rated smoking during pregnancy was associated with conduct disorder but not ADHD symptoms in a prospective, population-based study. However, only three ADHD items (taken from the Rutter A scale) were available. Thus, it remains uncertain whether prenatal smoking is associated with ADHD symptoms in a nonreferred population, particularly when covariation with conduct disorder symptoms is taken into account. Second, most but not all of these studies used the same rater (the mother) to measure smoking during pregnancy and child behavior. Thus, as recently highlighted (9), the observed association between maternal smoking during pregnancy and ADHD could arise from shared rater effects. Am J Psychiatry 160:11, November 2003

Finally, despite the large number of studies demonstrating a relationship between maternal smoking during pregnancy and ADHD, none have been able to take into account the effects of genetic factors. Mothers and offspring share on average half of their genes in common, and both ADHD and smoking are highly heritable (10). Thus, we cannot rule out the possibility that the observed association between smoking during pregnancy and ADHD/antisocial behavior in the offspring is explained by a common set of genes influencing both the putative risk factor and the outcome. We set out to examine whether maternal smoking during pregnancy is associated with offspring ADHD symptoms by using a twin study design that allows us to establish the contribution of genetic influences on ADHD. We also used maternal reports of smoking during pregnancy and teacher reports of ADHD symptoms to avoid the problem of shared rater effects. We further tested whether the association remained after removing the effects on ADHD of conduct disorder symptoms, birth weight, and family and social adversity.

Method Families of all twins, 5–16 years of age, identified from the population-based Greater Manchester Twin Register were sent a package of questionnaires (11). Mothers were asked to complete a validated twin similarity questionnaire (12), the Rutter A scale (13), and the Family Environment Scale (14), and information was requested on the number of cigarettes smoked during pregnancy (0, 20 cigarettes per day) and birth weight of each twin (11). Data were obtained for 2,054 twin pairs (73% response rate). http://ajp.psychiatryonline.org

1985

MATERNAL SMOKING AND OFFSPRING ADHD TABLE 1. Relationship Between Maternal Smoking During Pregnancy and ADHD Symptom Scoresa in a PopulationBased Sample of Twins

scores attributable to social adversity (family size, social class, family conflict), birth weight, and antisocial symptom scores.

ADHD Symptom Maternal ADHD Symptom Ratings by Teacherb Smoking Ratings by Parentc During Score Score Pregnancy (cigarettes/day) N Meand 95% CI N Meand 95% CI None 1,017 3.18 2.87–3.52 1,454 7.33 6.93–7.80 1–10 151 4.81 3.69–6.20 221 9.18 7.92–10.56 11–20 239 5.36 4.44–6.48 325 10.02 9.00–11.33 >20 26 5.17 2.87–8.76 42 10.59 7.36–14.97

Results

a Obtained with the scale presented in Appendix b Significant within-group difference in symptom

1. scores (F=9.42, df=

3, 1432, p