Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies

Background Maternal smoking during pregnancy is an established risk factor for low infant birth weight, but evidence on critical exposure windows and timing of fetal growth restriction is limited. Here we investigate the associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth by triangulating evidence from 3 analytical approaches to strengthen causal inference. Methods and findings We analysed data from 8,621 European liveborn singletons in 2 population-based pregnancy cohorts (the Generation R Study, the Netherlands 2002–2006 [n = 4,682]) and the Born in Bradford study, United Kingdom 2007–2010 [n = 3,939]) with fetal ultrasound and birth anthropometric measures, parental smoking during pregnancy, and maternal genetic data. Associations with trajectories of estimated fetal weight (EFW) and individual fetal parameters (head circumference, femur length [FL], and abdominal circumference [AC]) from 12–16 to 40 weeks’ gestation were analysed using multilevel fractional polynomial models. We compared results from