A large observational study reiterates the safety of taking acid-suppressive medications during pregnancy, finding no link to gastrointestinal disease in children.

The study, published in JAMA Network Open, found the relative risk for inflammatory bowel disease (IBD) was about 8% higher in kids whose mothers took prescription proton pump inhibitors (PPI) or H2 receptor antagonists (H2RAs) during pregnancy, while the risk for Crohn’s disease was 10% higher than in unexposed offspring.

However, when the researchers adjusted for confounding factors, they found no difference in risk for pediatric IBD, Crohn’s disease, or ulcerative colitis. A sibling pair analysis backed up these findings.

“It’s always nice to say we thought things were safe, and they are,” said Kara Rood, MD, maternal-fetal medicine physician at The Ohio State University Wexner Medical Center in Columbus, Ohio. “The absolute risk was extremely, extremely low, and the sibling analysis was very reassuring because there was no risk.”

The medications are widely prescribed and are considered very safe during pregnancy and breastfeeding, Rood said. Still, researchers continue to rule out any possibility of long-term health effects, including asthma and wheezing, allergies, and neuropsychiatric disorders, in babies born to people who took acid suppressants during pregnancy.

Researchers analyzed more than 2.6 million mother-child pairs between 2009 and 2023 whose medical records were included in the National Health Insurance Service of South Korea, which includes 98% of the Koreans. About 18% of the children were exposed to acid suppressants in utero, and all babies were followed for about 10 years after birth.

Pairs in which the mother was prescribed a PPI or H2RA during pregnancy were matched with three unexposed pairs. The study did not account for over-the-counter products, which in South Korea include H2RAs.

Nearly 200,000 children were included in a sibling comparison, which found no statistically significant differences in risk for IBD (hazard ratio [HR], 1.06; 95% CI, 0.88-1.27), Crohn’s disease (1.03; 95% CI, 0.84-1.27), or ulcerative colitis (1.10; 95% CI, 0.78-1.55).

The researchers concluded instances of IBD were no higher in kids whose mothers took prescription acid suppressants during pregnancy than in those whose mothers did not.

“This is largely reassuring,” said Laura Goetzl, MD, maternal-fetal medicine specialist at McGovern Medical School at UTHealth Houston.

The American College of Obstetricians and Gynecologists does not have official guidelines for treating heartburn or gastroesophageal reflux disease during pregnancy. Clinicians typically follow a step-up approach when treating these patients, starting with lifestyle changes such as eating smaller meals, elevating the head during sleep, and taking antacids such as Tums, Rood said. H2RAs such as Pepcid are recommended as second-line treatment.

“PPIs are added on for more severe or resistant symptoms,” Rood said. “Sometimes the lifestyle interventions work well early on in pregnancy, but then they need medication later on.”

PPI such as Prilosec are third-line treatments, not because the medications are dangerous for pregnant people but because long-term use of the drugs can hinder the stomach’s ability to absorb nutrients, according to observational studies.

“There’s really not a pathophysiological reason that taking these medications during pregnancy would cause any type of autoimmune disorder or gastrointestinal conditions in the fetus,” Rood said.

Because the fetal gut is sterile, there is no gut microbiome to alter with these medications, Goetzl said.

Rood said in her practice, the first question her pregnant patients usually ask about any medication is not regarding efficacy but safety for the fetus. Although clinicians are generally not concerned that acid-suppressive medications could be dangerous, affirming studies are helpful to discuss with patients, she said.

Rood said patients should not have to tolerate symptoms of acid reflux and gastroesophageal reflux disease during pregnancy.

“Ten months is a long time to not feel well, and people don’t have to suffer in silence just because heartburn is to be expected during pregnancy,” Rood said.

Rood and Goetzl both reported having no disclosures.

Kaitlin Sullivan is a journalist living in Colorado.