Parental autoimmunity and offspring risks of rheumatic diseases: a nationwide population-based study

Abstract

Objective Familial aggregation of systemic autoimmune diseases is frequently reported, but little is known about how fathers and mothers differentially contribute to the development of autoimmune diseases in their offspring. This study aimed to investigate the impact of maternal and paternal autoimmunity on the risk of offspring rheumatic diseases. Methods We constructed a nationwide population-based cohort using data from the Maternal and Child Health Database and the Taiwan National Health Insurance Research Data (NHIRD) from 2004 to 2019. The outcome was an autoimmune disease in the offspring. Inverse probability of treatment-weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for autoimmune diseases. Results Births with a father or mother with an autoimmune disease demonstrated respective risks of 1.22 times and 1.38 times the risk of developing an autoimmune disease compared to their counterparts. Maternal autoimmunity substantially contributed to SLE (aHR = 5.46, 95% CI: 5.28∼5.66), and paternal autoimmunity contributed to JIA (aHR = 1.76, 95% CI: 1.71∼1.81), and type 1 DM (aHR = 1.59, 95% CI: 1.39∼1.81) of their offspring. The contribution of mothers to the development of SLE (HR = 8.55, 95% CI: 8.10∼9.02) and inflammatory myopathy (HR = 2.08, 95% CI: 1.72∼2.51) were exacerbated in boys. Births with both parents with an autoimmune disease showed a 1.39-fold risk of developing an autoimmune disease. The maternal effect is stronger in preterm than full term births. Conclusions This study demonstrated the landscape of how autoimmune diseases pass from parents to infants of both genders and quantified the maternal and paternal contribution to disease separately.