Adverse birth outcomes and early-life infections after in utero exposure to corticosteroids for inflammatory bowel disease: a Danish nationwide cohort study

Abstract

Background: Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring.

Methods: We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment.

Results: After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39).

Conclusions: This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased.

Keywords: Apgar score; Birth outcomes; Congenital malformations; Corticosteroids; In utero exposure; Infant infections; Inflammatory bowel disease; Preterm birth; Small for gestational age.