Associations of prenatal exposure to maternal autoimmune disorders with a wide spectrum of psychiatric and neurodevelopmental disorders in offspring-a nationwide cohort study.

study questionAre children exposed SUMMARY ANSWER: Prenatal exposure to maternal ADs and AIDs, but for those of the nervous system, was at modest effect sizes associated with a number of primarily early onset neurodevelopmental disorders. WHAT IS KNOWN ALREADY: Prenatal exposure to maternal immune activation and certain ADs or AIDs has been associated with psychiatric and neurodevelopmental disorders in offspring. However, most studies examined only one specific maternal exposure, such as rheumatoid arthritis, in relation to one specific outcome, such as autism spectrum disorder (ASD). The potential impact of a broader range of maternal AD/AIDs on various mental outcomes remains largely unexplored. STUDY DESIGN SIZE DURATION: A nationwide, population-based cohort study of all live births in Finland from 1996 to 2014, with follow-up to 2021 (N = 1 107 802). Analyses were conducted from October 2023 to December 2025. PARTICIPANTS/MATERIALS SETTING

methodsMaternal diagnoses of AD/AIDs, recorded prior to and/or during pregnancy, were identified through Finnish National Health Registers (N = 34 033). Cox regression was used to estimate the hazard ratios (HRs) with 99% and 95% CIs of psychiatric and neurodevelopmental disorder diagnoses in offspring to AD/AIDs mothers. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 1 107 802 births, 3.2% were to mothers with an AD/AID. Offspring exposed to maternal AD/AIDs had a 15% higher risk of a major psychiatric disorder (HR, 1.15 [99% CI, 1.09-1.21]) and an 18% higher risk of a neurodevelopmental disorder (HR, 1.18 [99% CI, 1.14-1.22]).Combining AD/AIDs according to the main body system affected, associations with offspring's mental diagnoses were detected mainly for connective tissue AD/AIDs and endocrine AD/AIDs. Although most effect sizes were modest (HRs below 2), there were two notable exceptions with more than 2-fold risk: (i) ASD in autoimmune thyroiditis, and (ii) other behavioral or emotional disorders (F98) in pernicious anemia. A 70-99% higher risk for certain neurodevelopmental disorders or milder regulatory disturbances was observed in offspring exposed to systemic vasculitis, type 1 diabetes mellitus (T1DM), acute thyroiditis, Crohn's disease, and SIC (being polymyalgia rheumatica, Sjögren's syndrome, and hypermobility syndrome). The T1DM associations were not completely mediated by adverse birth factors. LIMITATIONS REASONS FOR CAUTION: The number of exposure-discordant siblings was insufficient to fully adjust for shared unmeasured familial confounding, and paternal information and breastfeeding data were unavailable. Second, some AD/AIDs were rare, limiting the statistical power. The numbers of exposed cases with outcome in the two associations with largest effect size was limited (n = 9 and 20). Third, rare prodromal AD/AID symptoms cannot be excluded, potentially causing misclassification. Fourth, some AD/AIDs recorded prior to pregnancy might have resolved before pregnancy, unknown to the study. Fifth, grouping AD/AIDs by the main affected body system implies a risk for not detecting true associations of individual AD/AIDs. Finally, the study is exploratory, and the observational design prevents causal inference. WIDER IMPLICATIONS OF THE

findingsThe findings may provide information for maternity care and family planning clinics potentially alleviating concerns among mothers with an AD/AID regarding offspring risk of neurodevelopmental and psychiatric disorder. STUDY FUNDING/COMPETING INTERESTS: This research was funded by Prima Child and Adult Psychiatry Stockholm AB (E.S.), the Swedish Research Council, Sweden (C.L., 2022-01188), the Swedish Brain Foundation, Sweden (C.L., FO2024-0194 and FO2025-0276-HK-192), Bo and Ulla Lundevall, Ulf Lundahl Memorial Fund, the regional agreement on medical training and clinical research (ALF) between Region Stockholm and Karolinska Institutet, Sweden (C.L., RS2021-0855 and 2023-0859) and China Scholarship Council (W.C.). The authors have no conflict to declare. TRIAL REGISTRATION NUMBER: N/A.