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 (HR(ModerateSDP) = 1.89; HR(HighSDP)= 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders (HR(ModerateSDP)= 1.62; HR(HighSDP)= 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) (HR(ModerateSDP)= 1.45; HR(HighSDP)= 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) (HR(ModerateSDP)= 0.88; HR(HighSDP)= 0.84).

Conclusions: Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding.