Prenatal exposure to selective serotonin reuptake inhibitors and risk of disorders of gut-brain interaction in children.

Preclinical data suggest that gestational exposure to selective serotonin reuptake inhibitors (SSRI) alter gut innervation, and delays colonic motility. In this study we investigated associations between gestational SSRI exposure and offspring disorders of gut-brain interaction (DGBI). Using population-based registries, we included all single-birth Danish children born 1997-2015 with follow-up until outcome occurrence, age 15 years, death, emigration, or December 2018. Children to mothers who continued SSRIs during pregnancy and children to mothers who discontinued SSRI use before pregnancy were compared using Cox regression. Main outcomes were the first diagnosis of a childhood DGBI (functional nausea and vomiting, functional abdominal pain disorders, functional diarrhea, and functional constipation), or a physician-prescribed laxative. Among 1,158,560 children, 21,969 children (1.9%) were exposed to SSRIs prenatally and 30,174 children (2.6%) were born to mothers who discontinued SSRIs before pregnancy. Overall, the estimated 15-year cumulative incidence of any DGBI was 15.5% (95% CI, 14.9-16.2) in the SSRI-exposed group and 14.7% (14.0-15.3) in the unexposed group. SSRI-exposed children had an overall increased risk of DGBIs (HR 1.08, [1.02-1.14]), which was driven by functional constipation (HR 1.19, [1.10-1.28]) rather than functional nausea and vomiting (HR 0.97, [0.83-1.13]) or functional abdominal pain disorders (HR 0.90, [0.81-1.00]). These data suggest that prenatal SSRI exposure is associated with an increased risk of developing functional constipation. These findings are also consistent with extensive preclinical data supporting key roles for serotonin in gut development and function. Together findings support the need for further investigation of the long-term impact of maternal depression and SSRI exposure on development of common gastrointestinal disorders.