Abstract
BACKGROUND: Neurodevelopmental disorders affect a substantial proportion of children and often persist into adulthood, with lifelong consequences. We investigated the association between maternal smoking and neurodevelopmental disorders in offspring. METHODS: We performed a nationwide population-based mother-child cohort study of infants born between 2009 and 2018. Maternal smoking status was obtained from the closest NHIS general health examination conducted within 2 years prior to delivery and categorized as never, former, or current smokers. Offspring were followed up until 2021 for diagnoses of intellectual disability, autism spectrum disorder (ASD) (ascertained through governmental disability registration), and attention-deficit/hyperactivity disorder (ADHD) (ascertained through insurance records). RESULTS: Among the 861,876 offspring (51.4% boys; median follow-up 8.3 years), 790,728 (91.7%) were born to never-smoking mothers, 36,046 (4.2%) to former smokers, and 35,102 (4.1%) to current smokers. Offspring of women with any history of smoking had a higher cumulative incidence of all neurodevelopmental disorders than those of never smokers (all log-rank P < 0.001). After multivariate adjustment, maternal smoking was associated with a significantly increased risk of each outcome. Compared with offspring of never smokers, offspring of former smokers had hazard ratios (HRs) of 1.21 (95% confidence interval [CI] 1.04-1.41) for intellectual disability, 1.29 (95% CI 1.10-1.51) for ASD, and 1.18 (95% CI 1.12-1.26) for ADHD. Compared with offspring of never smokers, offspring of current smokers had higher risks (HR 1.44, 95% CI 1.25-1.66 for intellectual disability; HR 1.52, 95% CI 1.31-1.76 for ASD; HR 1.35, 95% CI 1.27-1.42 for ADHD). HR varied across pack-year tertiles among both former and current smokers; elevated risk estimates were observed even in the lowest tertile, particularly among current smokers across outcomes and among former smokers for intellectual disability and ADHD, without a strictly monotonic gradient. CONCLUSIONS: Maternal smoking status as assessed from pre-birth health examinations was associated with increased risks of intellectual disability, ASD, and ADHD in their offspring. These findings support public health efforts to reduce smoking in women of reproductive age.