Tobacco smoke exposure and behavioral problems Materials and Methods Study design. The GINI-plus study is an ongo- ing birth cohort study, initiated to prospec- tively investigate the influence of nutrition intervention during infancy plus the associ- ation of air pollution and genetics with the development of allergies. Between September 1995 and July 1998, a total of 5,991 healthy full-term newborns were recruited in obstet- ric clinics in Munich and Wesel, Germany. The number of mothers initially contacted was approximately 10,700, so the participa- tion rate was 56%. The exclusion criteria of the study were severe acquired or congenital diseases, pregnancy of < 37 gestational weeks, birth weight < 2,500 g, or parents unable to complete the questionnaire. Children were followed up at the ages of 1, 2, 3, 4, 6, and 10 years. The cohort of children is composed of an intervention (n = 2,252) and a nonin- tervention group (n = 3,739). Group assign- ment was based on family history of allergy and willingness to participate in a randomized clinical trial. The intervention group received nutritional advice promoting breast-feeding for at least 4 months and participated in a ran- domized trial on the effect of hydrolyzed for- mula versus conventional cow’s-milk formula in preventing allergies (in the control group). The study protocol was approved by the local ethics committees (Bavarian General Medical Council, Medical Council of North Rhine Westphalia), and written consent was obtained from all participating families. Details on the study design are described elsewhere (Filipiak et al. 2007; von Berg et al. 2007). Definition of tobacco smoke exposure. Parents were asked for details on use of tobacco (“Have you smoked during preg- nancy?”) at birth and at follow-up examina- tions when the child was 1, 2, 3, 4, 6, and 10 years of age. At each visit parents were asked about tobacco use over the preced- ing year (“In the last 12 months have you smoked in your home?”). If they had smoked, they were asked for the average number of cigarettes per day (or week). At the 10-year follow-up, parents were interviewed regard- ing exposure to smoking during the 7th, 8th, 9th, and 10th year of life of the child. Children were included in the analyses if their parents had participated and answered ques- tions on smoking for at least 5 of 9 possible years. Children were defined as “never” being exposed to tobacco when the mother reported not smoking during pregnancy, and no smok- ing in the home was reported at follow-up. Children were classified as being only post- natally exposed to tobacco smoke when the parents reported that they had smoked in the home in at least one follow-up but the mother had not smoked during pregnancy. Pre- and postnatal exposure was defined for children whose mothers had smoked during pregnancy and smoking in the home was reported in at least one follow-up. Outcome measure. At the 10-year follow- up examination, the SDQ was completed by the parents (Goodman 1997; Goodman et al. 1998). The SDQ is an internationally applied and validated screening questionnaire (SDQ 2001). It assesses mental and behavioral dif- ficulties and strengths of 3- to 16-year-old children along the following dimensions: “emotional symptoms,” “conduct problems,” “hyperactivity/inattention,” “peer-relationship problems,” and a “prosocial scale.” Each scale consists of five items, each rated on a three- point scale (“not true,” “somewhat true,” “certainly true”). Higher scores indicate more problems and/or more serious problems. In the present study, we used the German par- ent-reported version of the SDQ with the German cutoff points (Woerner et al. 2004). According to these cutoff points, children are classified as ”normal,” “borderline,” or “abnormal” on each scale and on the total dif- ficulties score. These cutoff points were estab- lished in a representative sample of German children in order to classify about 10% of children as borderline and 10% as abnormal (Woerner et al. 2004). Statistical analysis. We dichotomized the results for the SDQ subscales, compar- ing children with abnormal SDQ scores with borderline and normal children. Results from each subscale and the total difficulties score were analyzed separately. We calculated Poisson regression models to obtain relative risk (RR) estimates. In these models age of mother at birth (< 30 years vs. ≥ 30 years), father’s employment [unemployed, not work- ing, low to average-level work (such as clerk, craftsman, or public servant in intermediate service), high-level work (such as public serv- ant in higher service, officer, or chief executive officer of a company)], and parental education (at least one parent with > 10 years of school education vs. both parents with < 10 years of school education), child’s time spent in front of computer or television screen (≥ 1 hr/ day vs. < 1 hr/day), and being single father/ mother were included as potential confound- ers. Furthermore the Poisson models included sex, study center, and intervention or non- intervention group as covariates. To obtain confidence intervals (CIs) for the RR esti- mates, we calculated robust error variance estimates as proposed by Zou (2004) using the GENMOD procedure with REPEATED statement in SAS (version 9.1; SAS Institute Inc., Cary, NC, USA). Potential dose effect. We assessed inten- sity of tobacco smoke exposure for the pre- natal exposure in order to evaluate potential dose effects based on number of cigarettes smoked per day (“How many cigarettes were smoked in your home per day on average?”). Environmental Health Perspectives • volume 118 | number 1 | January 2010 Mothers were categorized as heavy smokers if they smoked > 5 cigarettes/day (median, 5 cigarettes/day) and as light smokers if they smoked < 5 cigarettes/day. In separate mul- tivariable Poisson regression models, we cal- culated relative risks for being classified as abnormal in order to compare children of mothers who were heavy smokers with chil- dren of mothers who were light smokers and children who were never exposed to tobacco smoke (reference category). Results A total of 2,862 children had complete infor- mation on smoking exposure at least at five follow-up time points plus SDQ assessment at 10 years of age. The dropout rate was con- siderably higher for children of young moth- ers and for children of parents with low level of education (Table 1). More than 90% of parents were classified as being highly edu- cated, and > 50% of fathers worked in highly qualified jobs (Table 1). Because only very few fathers were unemployed or not work- ing (e.g., still attending school), we excluded this group from the multivariable analyses and defined low- to average-level work as the reference category. The analyzed study popu- lation showed a higher proportion of subjects never exposed to tobacco smoke than subjects excluded from the study (Table 1). At the 10-year follow-up, 6.3% (n = 181) of children were classified as having abnormal behavior and 5.8% (n = 167) were classified as borderline regarding the SDQ total diffi- culties score. The highest prevalence of abnor- mal and borderline behavior was observed for the subscale “conduct problems” (e.g., “Often lies or cheats” or “Steals from home, school or elsewhere”) where every fourth child (25.5%, n = 730) was outside the range of normal behavior. The lowest prevalence of abnormal or borderline behavior was observed for the SDQ subscale “hyperactivity/inatten- tion” (e.g., “Easily distracted, concentration wanders” or “Restless, overactive, cannot stay still for long”); 5% (n = 143) were classified as borderline and 7.9% (n = 227) were classified as abnormal. In multivariable Poisson regression models adjusting for potential confounders, exposure to tobacco smoke (both pre- and postnatal) was associated with behavioral problems measured by the SDQ (Table 2). The strength of the effect was dependent on the timing of tobacco smoke exposure. Children who were prenatally exposed to tobacco smoke had considerably higher risk of behavioral problems at 10 years of age, whereas postnatal exposure seemed to have only slight additional potential to cause problems. Postnatal exposure alone was also associated with abnormal behavior, but this association was weaker for most subscales of the SDQ (Table 2). The relative risk estimates 151