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Prenatal smoke exposure (PSE) is a risk factor for adverse outcomes in the offspring, including those affecting psychological development. However, it is uncertain whether these associations are the direct result of PSE or other confounding factors. The aim of this study was to examine the possible relationship between PSE and behavioral development in children at 7.5 years of age, considering several prenatal, neonatal and postnatal covariates. A cohort of 266 mother-child pairs was followed from the first trimester of pregnancy until the children reached 7.5 years of age. PSE was assessed using a questionnaire from prenatal clinical records and corroborated by plasma cotinine determinations in the first and second trimesters and in the cord. Mother-child pairs were classified into one of four groups: unexposed, exposed to passive smoking, first trimester active smoking only and active smoking throughout pregnancy. Child behavior was assessed using the Child Behavior Checklist for ages 6–18 and the Childhood Autism Spectrum Test. In multiple linear regression models, smoking during pregnancy was associated with higher scores in affective problems (β?=?0.298; p?=?0.004). No significant associations were found between smoking during pregnancy and externalizing problems. Findings indicate that PSE is negatively associated with behavioral development in childhood.

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