505Maternal autoimmune disease and increased attention deficit/hyperactivity disorder among offspring: A cohort study and meta-analysis

Background Maternal autoimmune disease (AD) has been associated with increased neurodevelopmental disorders in the offspring, but few studies have assessed Attention Deficit/Hyperactivity Disorder (ADHD). Methods Population-based record linkage study of 831,718 singleton term births in New South Wales, Australia, 2000-2010. Any maternal AD and specific autoimmune conditions were identified from hospital admission data, and ADHD in children was ascertained from stimulant prescription data (up to 2014). The association between maternal AD and ADHD was examined using Cox regression analysis after propensity score matching (1:4) to control for maternal confounders. A systematic review and meta-analyses were conducted, and pooled hazard ratios (HR) were calculated using random-effects meta-analysis with inverse variance weights. Results Of 831,718 births, 12,767 (1.5%) women had AD. In a propensity score-matched cohort (n = 63,050) maternal AD was associated with ADHD in offspring: “any AD” (HR 1.30, 95%CI 1.15-1.46), type-1 diabetes (T1D) (HR 2.23, 95%CI 1.66-3.00), psoriasis (HR 1.66, 95%CI 1.02-2.70) and rheumatic fever/carditis (HR 1.75, 95%CI 1.06-2.89). Five studies including ours were identified and included in the meta-analysis. Any AD (2 studies: HR 1.20, 95%CI 1.03-1.38), T1D (4 studies: HR 1.53, 95%CI 1.27-1.85), hyperthyroidism (3 studies: HR 1.15, 95%CI 1.06-1.26), and psoriasis (2 studies: HR 1.31, 95%CI 1.10-1.56) were associated with ADHD. Conclusions Maternal ADs were associated with increased ADHD among offspring, suggesting shared underlying genetic vulnerability or a role for maternal immune activation in fetal neurodevelopment. Future studies are required to understand causal mechanisms and identify interventions. Key messages Maternal ADs are associated with increased ADHD among offspring.