Maternal use of selective serotonin reuptake inhibitors during pregnancy is associated with Hirschsprung's disease in newborns - A nationwide cohort study

Abstract

Background: Hirschsprung's disease is a rare condition caused by congenital malformation of the gastrointestinal tract affecting 1:5000 children. Not much is known about risk factors for development of Hirschsprung's disease. Two clinical cases of hirschsprung's disease led to an investigation of the association between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and development of Hirschsprung's Disease in the newborn child. The study examined a nationwide, unselected cohort of children born in Denmark from 1 January 1996 until 12 March 2016 (n = 1,256,317). We applied multivariate models to register-based data to estimate the odds ratio of Hirschsprung's disease, adjusting for possible confounders. The studied exposure period for SSRIs were 30 days prior to conception to the end of the first trimester. Results: In the main exposed cohort the prevalence of Hirschsprung's disease was 16/19.807 (0.08%) compared to 584/1.236.510 (0.05%) in the unexposed cohort. In women who redeemed a minimum of one prescription of selective serotonin reuptake inhibitors, the adjusted odds ratio for development of Hirschsprung's disease was 1.76 (95%CI: 1.07-2.92). In women who redeemed a minimum of two prescriptions, the adjusted odds ratio for Hirschsprung's disease was 2.34 (95% CI: 1.21-4.55). Conclusions: Our data suggest that early maternal use of selective serotonin reuptake inhibitors is significantly associated with the development of Hirschsprung's disease in the newborn child. Treatment of depression during pregnancy always has to be weighed against the risks posed by untreated maternal depression. Our results have to be confirmed in other studies.