Prenatal SSRI Exposure Increases Risk of Functional Constipation: Study

Prenatal selective serotonin reuptake inhibitors (SSRIs) have been related to an increased risk of functional constipation in children, according to researchers. A recent Danish study was conducted by Kildegaard and colleagues which was published in the journal Molecular Psychiatry.

Previous preclinical data suggested that serotonin is critical for the development of the gut because it regulates gut innervation and colonic motility. The objective of this population-based study conducted by using Danish registries was to investigate the relationship between maternal SSRI use during pregnancy and disorders of gut-brain interaction (DGBI) in offspring.

All single-birth children from Denmark born between 1997 and 2015 were included in the study with follow-up until a diagnosis of DGBI, 15 years of age, death, emigration, or to the end of December 2018. The cohort was divided into two: the SSRI-exposed group and the unexposed group.

  • SSRI-exposed group: Children whose mothers took SSRI during pregnancy.

  • The unexposed group: Children whose mothers stopped taking SSRI before their pregnancy.

Cox regression analysis was used to estimate the risk of developing DGBI, including functional nausea and vomiting, abdominal pain disorders, functional diarrhea, and functional constipation. Laxative use prescribed by physicians was also included as an indicator of functional constipation.

Key Findings

The study analyzed a total of 1,158,560 children, of whom:

  • 21,969 children (1.9%) were exposed to SSRIs prenatally.

  • 30,174 children (2.6%) were born to mothers who discontinued SSRIs before pregnancy.

The 15-year cumulative incidence of any DGBI was:

  • 15.5% (95% CI, 14.9–16.2%) in the SSRI-exposed group.

  • 14.7% (95% CI, 14.0–15.3%) in the unexposed group.

  • SSRI-exposed children had an 8% higher overall risk of DGBI (HR: 1.08, 95% CI: 1.02–1.14).

  • SSRI-exposed children had a 19% higher risk of functional constipation (HR: 1.19, 95% CI: 1.10–1.28).

No significant associations were found for other DGBIs:

  • Functional nausea and vomiting: HR 0.97 (95% CI: 0.83–1.13).

  • Functional abdominal pain disorders: HR 0.90 (95% CI: 0.81–1.00).

In conclusion, this large population-based study demonstrated an association between prenatal exposure to SSRIs and an increased risk of functional constipation in children. These results support preclinical evidence emphasizing the role of serotonin in gut development and function. These findings underscore the importance of further research into long-term consequences of maternal SSRI use on offspring gastrointestinal health.

Reference:

Kildegaard, H., Bliddal, M., Ernst, M.T. et al. Prenatal exposure to selective serotonin reuptake inhibitors and risk of disorders of gut-brain interaction in children. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02848-3

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