Maternal autoimmune diseases during pregnancy and mortality up to young adulthood in offspring: a register-based cohort study

Abstract

Summary Background The implications of maternal autoimmune diseases for offspring survival after infancy remain poorly understood. We aimed to examine the association between maternal autoimmune diseases during pregnancy and all-cause and cause-specific mortality in offspring from birth to early adulthood. Methods In this nationwide population-based cohort study, we included all live births in Sweden between 2001 and 2014 and followed individuals until death, emigration, or December 31, 2023. Cox proportional hazards models were used to analyze the association between maternal autoimmune diseases during pregnancy and risk of mortality in offspring. To control for familial factors, we conducted cousin and paternal negative control analyses. Mediation analyses were performed to quantify the contribution of adverse perinatal outcomes. Findings Among 1,455,645 offspring followed for a median of 15.3 years (interquartile range 11.9–19.0), maternal autoimmune diseases were associated with an increased risk of all-cause mortality in offspring (HR 1.22, 95% CI 1.10–1.36). Associations were evident during infancy and attenuated with higher age. No clear association was observed for paternal autoimmune diseases, and cousin analyses yielded attenuated but directionally consistent estimates. Preterm birth and small for gestational age explained a proportion of the observed associations. Interpretation Maternal autoimmune diseases are associated with increased offspring mortality risk, with the excess risk primarily concentrated in early life and driven by deaths related to perinatal conditions and congenital malformations. These findings are consistent with a contribution of intrauterine mechanisms to the observed associations, although other maternal pathways may also contribute. Funding The study was supported by grants from the Swedish Heart and Lung Foundation (20230493, 20241167), Karolinska Institutet Research Foundation (2024-02588) and the 10.13039/501100006636Swedish Research Council for Health, Working Life and Welfare (2015-00837).