BACKGROUND: Women with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short-term outcomes in children exposed in utero to these medicines is reassuring, long-term safety data are lacking.
AIM: To assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence.
METHODS: This nationwide cohort study was based on information using Danish registers and comprised all live-born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%-75% percentiles 5.5-12.4 years); children not exposed were followed for 13.9 years (25%-75% percentiles 8.7-19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease.
RESULTS: A total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow-up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35-1.73); for IBD, it was 1.45 (95% CI 0.64-3.27); for asthma 0.94 (95% CI 0.73-1.21), and for congenital malformations, it was 0.95 (95% CI 0.78-1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis.
CONCLUSION: We found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.