Prenatal acid-suppressive medications not linked to neuropsychiatric disorders in offspring

A large population-based study published in JAMA Women’s Health found no evidence that prenatal exposure to acid-suppressive medications increases the risk of neuropsychiatric disorders in children when accounting for shared familial factors. While modest associations were observed in conventional models, no links in sibling-controlled analyses were observed, suggesting that unmeasured confounding rather than medication exposure may explain earlier concerns.

Acid-suppressing medications common, studies of association with offspring disorders limited

Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine 2 (H2) receptor antagonists, are commonly prescribed during pregnancy to manage gastroesophageal reflux and related conditions. Despite their widespread use, comprehensive evaluations of their potential long-term neurodevelopmental effects in offspring have been limited.

To address this gap, researchers conducted a large retrospective cohort study using data from the South Korean National Health Insurance Service, enabling long-term follow-up and the use of advanced analytic approaches to reduce confounding.

The study included births from January 2010 through December 2017, with offspring followed through December 2023. After exclusions, the final cohort consisted of 2,777,119 mother-child pairs, of whom 507,845 children were prenatally exposed to at least one prescription for a PPI or H2 receptor antagonist.

Key design features included:

• Use of a propensity score–based overlap-weighted cohort
• A sibling-matched cohort to control for shared genetic and environmental factors
• Mean follow-up of 10.3 years

Neuropsychiatric outcomes were identified using ICD-10 codes and included attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability, severe neuropsychiatric disorder, and obsessive-compulsive disorder.

Findings from conventional analyses

In the overlap-weighted cohort, children exposed to acid-suppressive medications during pregnancy showed slightly higher absolute risks of several neuropsychiatric outcomes compared with unexposed children.

Verbatim data points reported by the investigators included:

• ADHD: 4.85% in exposed children vs 4.25% in unexposed children
• ASD: 1.45% vs 1.33%
• Intellectual disability: 1.25% vs 1.09%
• Severe neuropsychiatric disorder: 0.94% vs 0.81%
• Obsessive-compulsive disorder: 0.30% vs 0.27%

Adjusted hazard ratios in these models ranged from 1.07 to 1.16 across outcomes.

Sibling-matched analyses show no association

When the researchers applied sibling-control analyses—comparing exposed and unexposed siblings within the same family—there were no significant associations between prenatal exposure and outcomes in the children.

Adjusted hazard ratios in sibling analyses were:

• ADHD: 0.98 (95% CI, 0.95–1.02)
• ASD: 0.98 (95% CI, 0.92–1.04)
• Intellectual disability: 1.02 (95% CI, 0.95–1.09)
• Severe neuropsychiatric disorder: 1.00 (95% CI, 0.93–1.08)
• Obsessive-compulsive disorder: 0.95 (95% CI, 0.82–1.10)

“Exposure to acid-suppressive medication during pregnancy was not associated with children’s risk of ADHD, severe neuropsychiatric disorder, obsessive-compulsive disorder, intellectual disability, or ASD in sibling-control analyses,” concluded the study authors. “Small associations were observed in overlap-weighted models; these may reflect confounding by shared familial factors.”

Reference:

Hong S, Lee S, Kim H, et al. Prenatal Exposure to Acid-Suppressive Medications and Risk of Neuropsychiatric Disorders in Children. JAMA. Published online January 07, 2026. doi:10.1001/jama.2025.23956