A Gut Risk for Kids: Prenatal Antidepressants?

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Research reveals new ways by which prenatal factors can influence lifelong health outcomes. Among these, selective serotonin reuptake inhibitors (SSRIs)—the most common class of antidepressants used during pregnancy—have drawn attention for their potential negative effects on the developing interactions between the gut and the brain. A study published in Molecular Psychiatry, by Helenie Kildegaard and a team of investigators from the University of Southern Denmark, sheds light on the connection between prenatal SSRI exposure and the risk of disorders of gut-brain interaction in children. These findings add to our understanding of how early life exposures may shape both gut and brain development.

The brain-gut system is a bidirectional communication system linking the central nervous system and the gut, including the millions of nerve cells sandwiched between the layers of the gut. These cells make up the enteric nervous system (ENS), often referred to as the “second brain.” The neurotransmitter serotonin plays an important role in this communication system: regulating many vital functions including sleep, pain sensitivity, and mood in the brain, and many essential gut functions including motility, peristalsis, and secretion. About 95% of the body’s serotonin is produced and stored in the gastrointestinal tract, highlighting the gut’s crucial role in overall health. Disruptions to this system can have significant consequences, with functional constipation—affecting approximately 10–15% of children—being one of the most common disorders of gut-brain interaction.

“Disruptions to this system, whether through genetic factors, maternal health conditions, or pharmacological interventions like SSRIs, can have lasting effects on gut function.”

During fetal development, serotonin plays a crucial role in forming neural circuits within the ENS. Disruptions to this system, whether through genetic factors, maternal health conditions, or pharmacological interventions like SSRIs, can have lasting effects on gut function. These disruptions are believed to contribute to several so-called functional GI disorders (now referred to as disorders of gut brain interactions of DGBI), a group of conditions noted by chronic gastrointestinal symptoms in the absence of structural abnormalities.

In their study, the researchers analyzed data from 1,158,560 Danish children born between 1997 and 2015. The study compared children whose mothers continued SSRIs during pregnancy (21,969 children) with those whose mothers discontinued SSRI use before pregnancy (30,174 children).

The results revealed a significant association between prenatal SSRI exposure and an increased risk of brain-gut disorders, specifically functional constipation. Chronic functional constipation presents as a long-term difficulty in passing stool, often caused by impairments in the gut’s ability to contract and move stool effectively. It can result in infrequent bowel movements, hard stools, and straining during defecation, which significantly impacts quality of life. This condition accounted for the majority of the increased risk, with SSRI-exposed children during pregnancy showing a 19% higher likelihood of developing chronic constipation compared to the unexposed group.

No significant associations were observed for functional nausea, vomiting, abdominal pain, or diarrhea, suggesting a specific link between SSRIs and constipation. The study didn’t explore whether the children developed mood or anxiety disorders, which is a limitation since these conditions could help provide a fuller picture of the effects of prenatal SSRI exposure. While the researchers adjusted for mothers’ psychiatric conditions, this might still leave some unanswered questions.

As for irritable bowel syndrome (IBS), another key brain-gut disorder often presenting with constipation, it wasn’t specifically addressed in the findings. The authors mention that national coding practices in Denmark did not routinely include pediatric IBS diagnoses during much of the study period, which likely led to an underrepresentation of IBS cases in their dataset. Instead, children meeting the criteria for IBS were often coded under defecation disorders or abdominal pain. The fact that IBS was not being fully accounted for represents another notable limitation of this study.

The study highlights several mechanisms that may explain the increased risk of functional constipation following prenatal SSRI exposure:

  • Disruption of ENS Development: SSRI exposure during critical periods of fetal development may impair the normal development of the ENS, leading to long-term abnormalities in the contractile, propulsive and secretory activity of the gut.
  • Chronicity of Symptoms: Functional constipation in this study persisted from infancy through adolescence, underscoring the long-term nature of these disruptions.
  • Interestingly, no similar associations were seen when paternal SSRI use during pregnancy was used as a control, strengthening the argument that exposure during pregnancy is likely the driving cause.

“This study does not advocate against SSRI use during pregnancy but rather calls for a nuanced approach.”

Balancing maternal mental health needs with potential risks to offspring remains a crucial aspect of prenatal care. Untreated maternal depression can have severe consequences, including preterm birth, low birth weight, and impaired maternal-infant bonding. As SSRIs are among the most commonly prescribed antidepressants during pregnancy, understanding their potential risks and benefits is essential. Beyond the risk of functional constipation, maternal SSRI use has been associated with other potential side effects in the fetus, including an increased risk of neonatal adaptation syndrome, which may cause symptoms like jitteriness, feeding difficulties, and respiratory distress shortly after birth.

This study does not advocate against SSRI use during pregnancy but rather calls for a nuanced approach, including individualized care, where the severity of the mother’s depression, her overall health, and potential alternatives to SSRIs are considered. It also involves close monitoring of both the mother and the child during and after pregnancy to identify and manage any complications, such as functional gastrointestinal issues in the child. Early intervention strategies, like behavioral, dietary, and psychological interventions for chronic constipation or support for maternal mental health should be included in this holistic approach.

While this study offers valuable insights, it is not without limitations. The reliance on registry-based data may underrepresent milder cases of brain-gut disorders that do not require hospitalization or prescription treatments. Additionally, while the study adjusts for maternal depression, confounding variables such as maternal nutrition, stress, or other medications may still influence the results.

The findings add to the growing evidence for the role of early life influences shaping gut-brain health and highlights functional constipation as a significant concern following prenatal SSRI exposure. Parents and caregivers can take actionable steps by monitoring their child for early signs of constipation, such as infrequent bowel movements, hard stools, or visible discomfort during defecation, and consulting a pediatrician if concerns arise. Ensuring a fiber-rich diet, maintaining proper hydration, and encouraging regular physical activity can also support healthy digestion. For expecting mothers, discussing the potential risks and benefits of antidepressants with their healthcare provider is crucial. By staying informed and proactive, families can help promote better health outcomes for their children.

Richard Tirado is a recent graduate from UCLA, where he majored in Biology and minored in Anthropology.

This article was reviewed and approved by Emeran Mayer, MD