Tobacco smoke exposure and behavioral problems the complexity of the central nervous system, the pattern of SDQ changes—namely, the higher hyperactivity/inattention and conduct problems scores—is suggestive: Continuous patterns of higher nicotine levels can alter noradrenalin and dopamine response (Sharma and Brody 2009); the current physiological hypothesis on ADHD is a relative shortage of noradrenalin and dopamine (Brennan and Arnsten 2008). Animals exposed to prena- tal nicotine and carbon monoxide showed hyperactivity and deficits in arousal modula- tion (Ajarem and Ahmad 1998; Thomas et al. 2000; Tizabi et al. 1997). Another possible explanation is the potential indirect effects of tobacco exposure. Smoking is associated with lower birth weight and perinatal problems, all of which increase the risk for later antisocial behavior. Given the sample of participants analyzed, healthy full-term births, these fac- tors should not play an important role in the investigated sample. Strengths and limitations. The SDQ is not a diagnostic instrument but only a screening test. However, we feel that this is a strength Table 3. Unadjusted and adjusted RRs for the association between intensity of prenatal tobacco smoke exposure and abnormal SDQ values at 10 years of age. Behavioral problem Total difficulties score Tobacco smoke exposure Never (72) Low prenatal (3) High prenatal (3) Hyperactivity Tobacco smoke exposure Never (97) Low prenatal (1) High prenatal (3) Emotional symptoms Tobacco smoke exposure Never (140) Low prenatal (3) High prenatal (6) Peer problems Tobacco smoke exposure Never (119) Low prenatal (3) High prenatal (2) Conduct problems Tobacco smoke exposure Never (158) Low prenatal (5) High prenatal (4) Crude RR (95%CI) Adjusted RRa (95%CI) 1 2.0 (0.7–6.0) 3.0 (1.0–8.8) 1 1.4 (0.4–4.8) 2.6 (1.0–7.1) 1 0.5 (0.1–3.4) 2.2 (0.8–6.5) 1 0.4 (0.1–3.0) 1.9 (0.6–6.0) 1 1.0 (0.3–3.0) 3.1 (1.6–6.2) 1 0.8 (0.3–2.7) 2.9 (1.4–5.9) 1 1.2 (0.4–3.6) 1.2 (0.3–4.6) 1 0.9 (0.3–3.1) 1.1 (0.3–3.7) 1 1.5 (0.7–3.4) 1.8 (0.8–4.5) 1 1.3 (0.5–3.0) 1.6 (0.7–3.8) Numbers in parentheses after the smoke exposure cat- egories indicate the number of children in each category who had abnormal SDQ values. Children never exposed serve as a reference category. The numbers of chil- dren with prenatal exposure only and abnormal SDQ values may not sum to the respective number in Table 2 because of missing information on numbers of cigarettes smoked. Low exposure, < 5 cigarettes/day; high expo- sure, > 5 cigarettes/day. aAdjusted for for sex, study center, intervention group, parental education, father’s employment, age of mother at birth, child’s time in front of screen, and being single father/mother. of our study. Children of parents with low socioeconomic status are more likely to have ADHD but are less likely to be diagnosed and treated as having ADHD (Froehlich et al. 2007). The SDQ relies only on perceptions of the parents and not on potential differential access to health care. We have combined postnatal exposure into one single variable (postnatal tobacco exposure, yes/no). However, there may be more and less relevant postnatal time peri- ods for the impact of tobacco smoke. Unfortunately the numbers in our analyses were not large enough to accurately compare, for example, children with only early post- natal exposure or only late postnatal expo- sure. However, we feel that the approach of disentangling the prenatal from the postnatal tobacco exposure should not be affected by this limitation. We used self-reports of smoking which might underestimate the true exposure to tobacco smoke. Furthermore, prenatal expo- sure relates only to active smoking of the mother. However, these limitations should not significantly affect the interpretations of our results. For example, it may be plausible that women who have children with behav- ioral problems tend to conceal smoking. This could lead to an underestimation of the asso- ciation between smoke exposure and behavio- ral problems. If the mother’s passive exposure to environmental tobacco smoke in pregnancy is associated with behavioral problems, this would also lead to an underestimation of the effects. Therefore, regarding potential expo- sure misclassification, we believe that underes- timation of the effects is possible. Because of incomplete information or loss to follow-up, a high number of cases had to be excluded from the analyses, [n = 3,129 (52.2%)] which may be associated with poten- tial bias. Children of young mothers and less- educated parents and children exposed to tobacco smoke were more likely to be excluded. Although children of mothers who smoked were more likely to be lost to follow-up, we do not feel that this influenced the association between smoke exposure and behavioral prob- lems. If “difficult” children of mothers who smoked had been less likely to be followed up, this would account for an underestimation of the observed association. When we confined the analysis to children of parents with at least 10 years of education, the results were compa- rable to those in the total sample. The association we found could not be explained by confounding by parental educa- tion, father’s employment, or age of mother. Adjusting for these factors should warrant a relatively reliable consideration of socio- economic status of the parents. Because socio- economic status is both likely associated with smoking and with behavioral problems, this Environmental Health Perspectives • volume 118 | number 1 | January 2010 is crucial. Nevertheless, residual confound- ing cannot be excluded. However, the study group was relatively homogeneous in socio- economic status because of the sample design, which included only healthy newborns of German nationality. The majority of parents were relatively highly educated, and more than half of fathers worked in highly quali- fied jobs. Therefore we feel that confounding by socioeconomic status is unlikely to explain our results. However, potential confounding by parental psychological problems could not be addressed and cannot be excluded. Conclusions In a prospective cohort study of considerable size we were able to demonstrate a strong asso- ciation of in utero exposure to smoking with several dimensions of abnormal behavioral development as assessed by the SDQ, an estab- lished and standardized test. Our data gave no indication for similarly strong associations with only postnatal exposure to tobacco smoke. Ref Rencs Ajarem JS, Ahmad M. 1998. Prenatal nicotine exposure modifies behavior of mice through early development. Pharmacol Biochem Behav 59(2):313–318. Batstra L, Hadders-Algra M, Neeleman J. 2003. Effect of antenatal exposure to maternal smoking on behavioural problems and academic achievement in childhood: pro- spective evidence from a Dutch birth cohort. Early Hum Dev 75(1–2):21–33. Braun JM, Froehlich TE, Daniels JL, Dietrich KN, Hornung R, Auinger P, et al. 2008. Association of environmental toxi- cants and conduct disorder in U.S. children: NHANES 2001–2004. Environ Health Perspect 116:956–962. Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904–1909. Brennan AR, Arnsten AF. 2008. Neuronal mechanisms underly- ing attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function. Ann NY Acad Sci 1129:236–245. DiFranza JR, Aligne CA, Weitzman M. 2004. Prenatal and post- natal environmental tobacco smoke exposure and chil- dren‘s health. Pediatrics 113(4 suppl):1007–1015. Ernst M, Moolchan ET, Robinson ML. 2001. Behavioral and neural consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc Psychiatry 40(6):630–641. Eskenazi B, Castorina R. 1999. Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in chil- dren. Environ Health Perspect 107:991–1000. Fergusson DM, Horwood LJ, Lynskey MT. 1993. Maternal smok- ing before and after pregnancy: effects on behavioral out- comes in middle childhood. Pediatrics 92(6):815–822. Filipiak B, Zutavern A, Koletzko S, von Berg A, Brockow I, Grubl A, et al. 2007. Solid food introduction in relation to eczema: results from a four-year prospective birth cohort study. J Pediatr 151(4):352–358. Froehlich TE, Lanphear BP, Epstein JN, Barbaresi WJ, Katusic SK, Kahn RS. 2007. Prevalence, recognition, and treatment of attention-deficit/hyperactivity disorder in a national sample of US children. Arch Pediatr Adolesc Med 161(9):857–864. Gatzke-Kopp LM, Beauchaine TP. 2007. Direct and passive prenatal nicotine exposure and the development of exter- nalizing psychopathology. Child Psychiatry Hum Dev 38(4):255–269. Gehring U, Leaderer BP, Heinrich J, Oldenwening M, Giovannangelo ME, Nordling E, et al. 2006. Comparison of parental reports of smoking and residential air nicotine con- centrations in children. Occup Environ Med 63(11):766–772. 153