Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring

Background Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. Methods We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders. Results A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis. Conclusions Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.