Supplementary Materials The impact of maternal smoking during pregnancy on depressive and anxiety symptoms in offspring Supplementary Methods MOBA Study Detailed information regarding the Norwegian Mother and Child Cohort (MoBa) can be found at (http://www.fhi.no/eway/default.aspx?pid=240&trg=Main_6664&Main_6664=6894:0:25,7372: 1:0:0:::0:0) and Magnus et al(1). For the included cohort, participation rates were 38.7% of those invited. In a comparison performed on data acquired in MoBa between 2000 - 2006 and data from the Norwegian Medical Birth Registry, maternal participants in MoBa were more likely to be older, less likely to be single, have lower parity, have lower rates of previous stillbirths and less likely to suffer maternal asthma(2). In addition, MoBa participants were more likely to be non-smokers, more likely to use folic acid, and less likely to suffer from gestational diabetes and placental abruption.(2) Study response rates in our cohort were 94.9% for questionnaire 1 (early pregnancy), 91.0% for questionnaire 3 (late pregnancy), 72.5% for questionnaire 5 (18 month follow up), 58.5% for questionnaire 6 (36 month follow up) and 53.0% for questionnaire 7. Instruments and Measures The administrating committee of MoBa provides detailed documentation explaining the rationale behind choice of all instruments used in the study. In regards to childhood behaviour assessment, mothers reported symptoms by answering questions taken from the Childhood Behaviour Checklist (CBCL)(3). The CBCL is a commonly used tool to assess child behaviour, and can be divided into subscales including “emotionally reactive”, “anxious/depressed”, “somatic complaints”, “withdrawn”, “sleep problems”, “attention problems” and “aggressive behaviour”, with the first 4 representing “internalising symptoms” and the last two categories representing “externalising symptoms”. The CBCL requires participants have a minimum fifth grade reading level. MOBA condensed the larger CBCL into a shorter 25-question version, of which the relevant questions for this study have been mentioned in the main text. At the 18-month questionnaire, internalising symptoms were assessed using 5 items from the CBCL internalising scale. At the 36-month questionnaire, internalising symptoms were assessed using 9 items from the CBCL internalising scale. At the 5-year questionnaire, internalising symptoms were assessed using 11 items from the CBCL internalising scale. Clark and Watson(4) argue the mean inter-item correlation as a useful index of internal consistency for such scales, and recommend that this should be in the range 0.15 to 0.20 for broad constructs. Mean inter-item correlation for the CBCL items was 0.14 at 18 months in the current sample, 0.13 at 36 months in the current sample, and 0.16 at 5 years in the current sample. Factor analysis of the scales demonstrated that scale items were best explained by one factor at each time point (results available on request). The CBCL has been shown to possess good predictive validity in the Norwegian population(5), with the Norwegian translation performed by Nøvik(5, 6) used in this study. Web Results Study Attrition and Missing Variable Analysis Attrition: Multivariate logistic regression showed that attrition at late pregnancy was predicted by low maternal educational level (OR = 0·93, p <·01), high levels of depression in early pregnancy (OR = 1·38, p <·01), parity (OR = 1·09, p <·01), and smoking in early pregnancy 1 (OR = 1·40, p <·01). Attrition at 18 months was related to low maternal educational level (OR = 0·87, p <·01), maternal depression in early pregnancy (OR = 1·28, p <·01), low maternal age (OR = 0·97, p <·01), parity (OR = 1·11, p <·01), low gestational age at birth (OR = 0·93, p <·01), and to smoking in early pregnancy (OR = 1·26, p <·01). Paternal smoking, maternal smoking in previous pregnancies, and maternal alcohol consumption in early pregnancy were not related to attrition in late pregnancy or 18 months. Attrition at 36 months was predicted by maternal education (OR = 0·86, p<·01), maternal depression in early pregnancy (OR = 1·25, p <·01), smoking in previous pregnancies (OR = 1·09, p <·01), low maternal age (OR = 0·98, p <·01), parity (OR = 1·13, p <·01), low gestational age at birth (OR = 0·95, p <·01), and to smoking in early pregnancy (OR = 1·19, p <·01). Paternal smoking and maternal alcohol consumption in early pregnancy did not predict attrition at 36 months. Further, in these multivariate analyses, internalizing problems at 18 months did not predict attrition at 36 months. Attrition at 5 years was predicted by low maternal educational level (OR = 0·94, p <·01), maternal depression in early pregnancy (OR = 1·22, p <·01), smoking in previous pregnancies (OR = 1·14, p <·01), low maternal age (OR = 0·99, p <·01), low levels of maternal alcohol consumption in early pregnancy (OR = 0·91, p <·01), low gestational age at birth (OR = 0·97, p <·01), and smoking in early pregnancy (OR = 1·49, p<·01). Internalizing symptoms at 36 months did not predict attrition at 5 years in these multivariate analyses. Missing information on internalizing symptoms and smoking: Missing information on maternal smoking in early pregnancy was related to high educational level (OR = 1·15, p <·01), low age (OR = 0·97, p<·01), high alcohol consumption (OR = 1·29, p <·01), and parity (OR = 1·16, p <·01). At 18 months, 5274 women returned the questionnaire with missing information on internalizing problems. Multivariate logistic regression showed that this was predicted by low maternal educational level (OR = 0·75, p <·01), high maternal alcohol consumption in early pregnancy (OR = 1·78, p <·01), and smoking in early pregnancy (OR = 1·91, p <·01). At 36 months, 407 women returned the questionnaire with missing information on internalizing symptoms, and 95 women did this at 5 years. This was not predicted by any of the aforementioned variables or by internalizing symptoms at the previous questionnaires in multivariate logistic regression analyses. Web Table 1: Descriptive statistics of internalising symptoms and confounding factors Internalising 18 months (Range 1-3) Internalising 36 months (Range 1-3) Internalising 5 years (Range 1-3) Maternal depression in early pregnancy (Range 1-4) Maternal age Gestational age at birth Mean (SD) 1.27 (0.25) N Available (%) 69946 (65.1%) N Missing (%) 37433 (34.9%) 1.25 (0.22) 57143 (53.2%) 1.16 (0.19) 19778 (18.4%) 1.26 (0.40) 99533 (92.7%) 50236 (46.8%) 87601 (81.6%) 7846 (7.3%) 29.8 (4.6) 39.34 (2.26) 101764 (94.8%) 106440 (99.1%) 5615 (5.2%) 939 (0.9%) Web Table 2: Descriptive statistics of potential confounding variables N (% total) Maternal Education ≤9 years education 2782 (2.6%) 2 1-2 years high schooling 3 years schooling 1-4 college/university >4 years college/university Missing data 4944 (4.6%) 26854 (25.0%) 39388 (36.7%) 22579 (21.0%) Never <1 episode per month 1-3 episodes per month <1 episode per week 2-3 episodes per week 4-5 episodes per week 6-7 episodes per week Missing data 74702 (69.6%) 8615 (8.0%) 1995 (1.9%) 429 (0.4%) 61 (0.1%) 7 (0.0%) 15 (0.0%) 21555 (20.1%) 0 1 2 3 4+ Missing data 47515 (44.2%) 38188 (35.6%) 16443 (15.3%) 3610 (3.4%) 1132 (1.1%) 492 (0.5%) Yes No Missing data 25039 (23.3%) 76079 (70.9%) 6261 (5.8%) 10832 (10.1%) Maternal Alcohol Consumption Maternal Parity Paternal Smoking (early pregnancy) Web References 1. 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