Association of Offspring congenital heart disease with Maternal
Autoimmune Diseases: A Retrospective Cohort Study with Real-world
Evidence
Abstract
Objectives Very few investigations have explored the
association between CHDs in offspring and mothers with autoimmune
disease. In this study, we aimed to explore whether maternal autoimmune
disease increases the risk of CHDs in newborns. Methods We
analyzed 4780 offspring with maternal autoimmune disease and 9416
offspring without maternal autoimmune disease matching 1:2 with age and
sex between 2009 and 2016 from databases including the National Health
Insurance program, birth certificate applications, cause of death data,
and Maternal and Child Health Database, which is managed by the Health
and Welfare Data Science Center (HWDC) in Taiwan. Birth year, birth
weight, gestational age, the children’s sex, mode of delivery,
congenital defects, urbanization, insurance unit, maternal and paternal
comorbidities, child or parents died within one year after birth and
medication exposure during pregnancy were selected as covariates for
further multivariate analysis. Also, multiple Cox regression analysis
was performed to evaluate the adjusted hazard ratio (aHR) of CHDs.
Results The incidence of CHDs was 5.35 per 10000 person-months
in autoimmune mothers. The result of the multivariate Cox regression
showed that the children whose mothers had autoimmune disease had a
1.57-fold risk of CHDs compared to children whose mothers did not have
an autoimmune disease (crude hazard ratio: 1.57; 95% CI, 1.29-1.90,
aHR: 1.51; 95% CI, 1.24-1.85). Conclusion Maternal autoimmune
disease might be a risk factor for developing CHDs in offspring,
especially in mothers with systemic lupus erythematosus or Sjogren’s
syndrome. Further research is warranted to investigate the possible
pathogenesis mechanisms of this association.