Rückinger et al. for the impact of tobacco smoke exposure were comparable in the crude and adjusted analyses. For example, the relative risk for only prenatal tobacco exposure on total difficulties was 2.2 (95% CI, 1.1–4.6) in the crude analysis and 1.9 (95% CI, 0.9–4.0) in the adjusted analysis. These differences between the crude and the adjusted analyses were similarly small for other SDQ subscales (Table 2). To assess a potential dose effect, we com- pared children of mothers who smoked heavily (> 5 cigarettes/day) during pregnancy with chil- dren of mothers who smoked lightly (< 5 ciga- rettes/day) during pregnancy and children never being exposed to tobacco smoke (reference cat- egory). The median number of cigarettes per day among smokers was 5. Unadjusted and adjusted relative risks are shown in Table 3. Children with heavy prenatal tobacco smoke exposure had consistently higher risks of abnor- mal behavior than did children with light expo- sure and children with no exposure. As a sensitivity analysis, we also confined the multivariable analysis to children of parents with at least 10 years of education. In this anal- ysis, the relative risks were comparable to the analysis on the total sample (data not shown). Discussion In this prospective birth cohort with follow-up to 10 years of age, children who were exposed to tobacco smoke were found to be at increased risk for being classified as abnormal according to the SDQ relative to children with no tobacco exposure. The association seemed to be stronger for exposure during pregnancy. The association could not be explained by con- founders such as parental education, father’s employment, child’s time spent in front of computer or television screen, being single father/mother, or age of the mother. Interpretation of the results. Prenatal expo- sure to tobacco smoke seemed to be the most influential exposure whether combined with postnatal exposure or not. Postnatal exposure alone seemed to have a lower impact on the risk for later abnormal behavior according to the SDQ, although fetal/placental/maternal metabolism may play a role in the differences between pre- and postnatal effect. Although prenatal exposure involves smoking by the mother only, postnatal exposure also includes smoking of the father in the household, which may dilute the effect of postnatal compared to prenatal exposure. Maternal smoking is more likely associated with intensive expo- sure to tobacco smoke than paternal smoking (Jaakkola and Jaakkola 2002). A diluted effect of postnatal exposure may partially explain the higher impact of prenatal exposure. Among the SDQ subscales, one of the strongest associations of both prenatal and postnatal tobacco exposure was found for hyperactivity/inattention. This is in accord- ance with previous research from a cross sectional survey that used attention deficit Table 1. Characteristics of the GINI study population including 5,991 children born 1995–1998 in Wesel (North Rhine–Westfalia, Germany) and Munich (Bavaria, Germany) [no. (%)]. Study population No complete Characteristic analyzed (n = 2,862) follow-up (n = 3,129)a Sex Male 1,456 (50.9) 1,158 (52.5) Female 1,406 (49.1) 1,046 (47.5) Center Wesel 1,372 (47.9) 1,670 (53.4) Munich I 727 (25.4) 679 (21.7) Munich II 763 (26.7) 780 (24.9) Tobacco smoke exposure Never 1,569 (54.8) 435 (47.1) Only postnatal 900 (31.5) 329 (35.6) Only prenatal 69 (2.3) 26 (2.8) Pre- and postnatal 324 (11.3) 134 (14.5) Father’s employment Unemployed or not working 94 (3.3) 68 (4.1) Low to average level 1,263 (44.1) 788 (47.7) High level 1,505 (52.6) 795 (48.2) Mother’s age at birth (years) ≥ 30 1,955 (68.3) 1,747 (56.1) < 30 907 (31.7) 1,367 (43.9) Parental education (years) At least one with > 10 2,630 (91.9) 2,485 (82.8) No parent with >10 232 (8.1) 515 (17.2) Single mother/father Yes 293 (10.2) 73 (18.8) No 2,569 (89.8) 316 (81.2) Time in front of screen < 1 hr/day 1,895 (66.2) ≥ 1 hr/day 967 (33.8) aThese numbers may not sum to 3,129 because of missing data. 152 Pre- and postnatal (38) 1.6 (1.1–2.2) Pre- and postnatal (61) 1.9 (1.4–2.5) Numbers in parentheses after the smoke exposure cate- gories indicate the number of children in each category who had abnormal SDQ values. 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. 275 (65.8) 143 (34.2) ovlume 118 | number 1 | January 2010 • Environmental Health Perspectives hyperactivity disorder (ADHD) diagnosis as outcome measure (Braun et al. 2006). In that study, prenatal exposure to tobacco smoke was associated with later ADHD diagnosis, whereas postnatal exposure at home was not (Braun et al. 2006). Furthermore, studies on the effects of in utero tobacco exposure have shown more pronounced effects on external- izing problems than on internalizing prob- lems (Batstra et al. 2003; Gatzke-Kopp and Beauchaine 2007; Yolton et al. 2009). Possible biological mechanisms. Tobacco smoke contains various toxic substances, and there are several possible links to fetal neurotoxicity. Neurotoxicity is hypothesized to occur via a) hypoxic effects on the fetal– placental unit (reduction of fetal blood flow, toxic increase in carbon monoxide) and b) teratologic effects on the developing nerv- ous system (Wakschlag et al. 2002). The fetal brain is protected against many neurotoxi- cants—but not against nicotine, which crosses the placental barrier and acts as a neurotrans- mitter on nicotinic receptors (Koren 1995). Although specificity is problematic, given Table 2. Unadjusted and adjusted RRs for the association between pre- and postnatal tobacco smoke exposure and abnormal SDQ values at 10 years of age. Crude RR (95%CI) Adjusted RRa (95%CI) Behavioral problem Total difficulties score Tobacco smoke exposure Never (72) Only prenatal (7) Only postnatal (59) Hyperactivity Tobacco smoke exposure Never (97) Only prenatal (5) Only postnatal (74) Emotional symptoms Tobacco smoke exposure Never (140) Only prenatal (11) Only postnatal (83) Peer problems Tobacco smoke exposure Never (119) Only prenatal (6) Only postnatal (84) Conduct problems Tobacco smoke exposure Never (158) Only prenatal (12) Only postnatal (104) 2.2 (1.1–4.6) 1.4 (1.0–2.0) 1 1 1.2 (0.5–2.8) 1.3 (1.0–1.8) 1 1.8 (1.0–3.1) 1.0 (0.8–1.4) 1 1.1 (0.5–2.5) 1.2 (1.0–1.6) 1 1.7 (1.0–2.9) 1.2 (0.9–1.5) 1 1.9 (0.9–4.0) 1.3 (0.9–1.9) 2.0 (1.4–3.1) 1 1.1 (0.5–2.7) 1.2 (0.9–1.6) 1.8 (1.3–2.6) 1 1.5 (0.9–2.8) 1.0 (0.7–1.3) 1.4 (1.0–1.9) 1 1.1 (0.5–2.4) 1.2 (0.9–1.5) 1.4 (1.0–2.0) 1 1.6 (0.9–2.8) 1.1 (0.9–1.5) 1.8 (1.3–2.3) Pre- and postnatal (36) 2.5 (1.7–3.6) Pre- and postnatal (42) 2.1 (1.5–3.0) Pre- and postnatal (44) 1.5 (1.1–2.1)