Maternal migraine and offspring ADHD: triangulating the evidence.

Abstract

Migraine and attention deficit hyperactivity disorder (ADHD) co-occur more frequently than would be expected by chance. However, little is known about whether there are causal links between maternal migraine during pregnancy and offspring ADHD. Using data from the Avon Longitudinal Study of Parents and Children, we performed observational analyses to examine associations between first-trimester maternal migraine and offspring ADHD traits at age 7, with partners' migraine as a negative control. We complemented this with polygenic risk score (PRS) regression to assess the association of maternal genetic liability to migraine and offspring ADHD. Two-sample Mendelian randomization (MR) was employed to estimate potential causal effects. Maternal migraine during the first trimester of pregnancy was associated with elevated offspring ADHD traits (OR = 1.59 [1.22, 2.06]) while evidence was weak for partner's migraine (OR = 1.31 [0.95, 1.82]). Maternal PRS for migraine was associated with increased offspring ADHD traits at age 7 (OR = 1.21 [1.11, 1.32]). MR analyses provided limited evidence of a causal effect of migraine genetic liability on ADHD (OR_IVW = 0.96 [0.92, 1.01]). There was weak evidence suggesting a potential causal effect of ADHD genetic liability on migraine (OR_IVW = 1.08 [1.02, 1.13]). Our findings do not support a direct intrauterine causal effect of maternal migraine on offspring ADHD traits. Instead, the observed associations might reflect shared genetic overlap between migraine and ADHD. Future studies should characterize the shared genetic architecture underlying migraine-ADHD links, distinguishing pleiotropic effects from mediated pathways.