Haan E, Sallis HM, Zuccolo L, et al. - Associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms were estimated accounting for shared familial factors.

• A negative control design comparing maternal and paternal substance use was used.

• Negative control analyses were conducted using three models: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner's substance use).

• Meta-analysis of the results was done across the cohorts.

• Thereafter, polygenic risk scores (PRS) were used as proxies for exposures.

• Regression of maternal PRS for smoking, alcohol and coffee consumption was done against ADHD symptoms.

• To infer causality, the results were triangulated across the two approaches.

• The following three longitudinal pregnancy cohorts were used to retrieve data for the analyses: Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway.

• Per findings, maternal prenatal substance use did not appear to have any causal intrauterine effect on offspring attention deficit hyperactivity disorder symptoms.