The risk of chronic diseases and congenital malformations during childhood and adolescence after in utero exposure to thiopurines

Abstract

Summary 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.

Schwangerschaft und Stillzeit bei Morbus Crohn

“…Hinweise auf vermehrte angeborene Fehlbildungen oder die Entwicklung chronischer Erkrankungen, wie z. B. Zöliakie, rheumatoide Arthritis oder Asthma, konnten nicht gefunden werden [20]. Diese Erkenntnisse konnten ebenfalls von einer retrospektiven Studie aus den Niederlanden gestützt werden, wobei die Nachbeobachtung hier nur 5 Jahre betrug [16].…”

The Effect of In Utero Exposure to Maternal Inflammatory Bowel Disease and Immunomodulators on Infant Immune System Development and Function

“…No increased risk of IBD (aHR, 1.45; 95% CI, 0.6‒3.3) or rheumatoid arthritis (aHR, 0.78; 95% CI, 0.4‒1.7) was identified. 168 Thus, such exposures in-utero may be less significant than previously postulated with regards to risk of autoimmunity.…”