Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring

Background Maternal Smoking During Pregnancy (SDP) has consistently been associated with increased risk of attention‐deficit/hyperactivity disorder (ADHD) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding. Methods A total of 813,030 individuals born in Sweden between 1992 and 2000 were included in this nationwide population‐based cohort study. Data on maternal SDP and ADHD diagnosis were obtained from national registers and patients were followed up from the age of 3 to the end of 2009. Hazard Ratios (HRs) were estimated using stratified Cox regression models. Cousin and sibling data were used to control for unmeasured familial confounding. Results At the population level maternal SDP predicted ADHD in offspring (HRModerateSDP = 1.89; HRHighSDP = 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders (HRModerateSDP = 1.62; HRHighSDP = 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) (HRModerateSDP = 1.45; HRHighSDP = 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) (HRModerateSDP = 0.88; HRHighSDP = 0.84). Conclusions Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding.