To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks gestation). The multicenter, prospective Extremely Low Gestational Age Newborn (ELGAN) Study enrolled newborns at birth between 2002-2004. Prenatal tobacco smoke included self-reported maternal (i.e., active) and passive smoking during pregnancy at study enrollment. Neurological impairment at 10 years of age included: epilepsy, cerebral palsy, and cognitive impairment. Poisson regression with generalized estimating equations was used to estimate adjusted risk ratios (aRRs), adjusted for mother’s age, race/ethnicity, education, insurance, multiple gestation, and infant’s sex; and separately, we adjusted for gestational age at delivery in sensitivity analysis, given its classification as an intermediate and not confounding variable. Secondarily, we assessed whether 1) the primary association varied by infant sex (male vs. female) given sexual epigenetic dimorphism in the placenta; and 2) postnatal inflammation in the child within 2 weeks after birth. Of 1,200 ELGAN study survivors, 886 were assessed at 10 years of age, of whom 14% (120/867) had been exposed to maternal tobacco use during pregnancy and 24% (210/863) to passive tobacco smoke. Compared to children who were not exposed prenatally to tobacco, children exposed to maternal tobacco use during pregnancy had a higher risk of epilepsy at 10 years of age (14% vs. 5%; aRR: 1.6, 95% CI: 1.6 to 1.7). This risk remained after adjustment for gestational age at delivery. Prenatal tobacco smoke exposure was not associated with cerebral palsy and cognitive impairment. Secondarily, the primary association held for female but not male infants; and tobacco smoke exposure did not influence the contribution of postnatal inflammation to impaired neurodevelopment. Among extremely preterm infants born <28 weeks, active maternal tobacco smoke during pregnancy increases the risk of epilepsy in the offspring at 10 years of life.View Large Image Figure ViewerDownload Hi-res image Download (PPT)