Prenatal Exposure to Acid Suppressants and Kids’ IBD Risk: No Need to Worry?

Prenatal exposure to acid-suppressive drugs did not have a clear association with the development of inflammatory bowel disease (IBD) in childhood, a South Korean cohort study suggested.

While prenatal exposure to acid-suppressive medications — including proton pump inhibitors (PPIs) and H2 receptor antagonists — was associated with an elevated risk of IBD (HR 1.08, 95% CI 1.01-1.15), and specifically Crohn’s disease (HR 1.10, 95% CI 1.02-1.19), there was no association with ulcerative colitis (HR 1.04, 95% CI 0.93-1.17).

Furthermore, there was no significant increase in absolute risk differences for IBD (0.41 per 1,000 children, 95% CI -0.97 to 1.79), Crohn’s (0.51, 95% CI -0.98 to 2.00), or ulcerative colitis (0.21, 95% CI -1.56 to 1.97) with acid-suppressive medications, reported Hayeon Lee, PhD, of Kyung Hee University in Yongin, South Korea, and colleagues.

“We found no consistent evidence supporting an association between prenatal exposure to acid-suppressive medications and the risk of developing IBD in childhood,” they wrote in JAMA Network Open. “While continued caution in the use of medications during pregnancy remains warranted, these results provide reassurance that any potential impact of prenatal acid-suppressive medication exposure on childhood-onset IBD is likely to be small.”

Acid-suppressive drugs are often prescribed during pregnancy, with gastroesophageal reflux symptoms frequently occurring in over one-third of pregnant women, Lee and team noted. While mostly considered safe for use in pregnancy, research has suggested potential adverse health outcomes in children, including increased risks of serious infections and cardiac birth defects. However, results from a population-based study in Denmark showed that PPIs don’t appear to be a major cause of birth defects when used early in pregnancy.

Lee and colleagues also conducted a sibling comparison analysis in order to address possible bias from unmeasured confounding factors. This showed no significant association with IBD (HR 1.06, 95% CI 0.88-1.27), Crohn’s (HR 1.03, 95% CI 0.84-1.27), or ulcerative colitis (HR 1.10, 95% CI 0.78-1.55).

Although the initial propensity score-matched analyses suggested a modest relative increase in IBD and Crohn’s, “including a more pronounced association in subgroup analyses stratified by medication type (PPIs) and by timing of exposure (first trimester), the corresponding absolute excess risks were minimal,” Lee and colleagues pointed out. “In this context, the null findings observed in sibling comparison analyses of overall exposure underscore the need for caution in attributing these subgroup-specific signals to a direct causal effect.”

This nationwide population-based cohort study included all mother-child pairs from the National Health Insurance Service of South Korea identified from January 2009 through December 2017, with follow-up through December 2023.

A total of 2,631,880 mother-child pairs with a mean follow-up of 10.2 years were included. Among them, 17.6% were exposed to acid-suppressive medications and matched 1:3 to those who were unexposed.

Mean maternal age was 32 in both the exposed and unexposed groups, and 49.7% of offspring were female. Across both groups, a similar proportion of infants were born preterm (4.3% and 3.5%, respectively) and had low birth weight (3.1% and 2.5%).

The authors acknowledged that the study had limitations, including the possibility that IBD was underdiagnosed in pediatric patients because the young age of patients can lead some clinicians to overlook IBD in the differential diagnosis, as well as the difficulty in distinguishing it from several other common conditions seen in pediatric clinics.