IMPORTANCE: Although acid-suppressive medications are commonly prescribed during pregnancy, comprehensive studies on their association with neuropsychiatric disorders in children are limited.
OBJECTIVE: To investigate potential associations between prenatal exposure to acid-suppressive medication (histamine 2 [H2] receptor antagonists and proton pump inhibitors [PPIs]) and neuropsychiatric disorders in children.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of mother-child pairs in the South Korean National Health Insurance Service database with births from January 2010 through December 2017, with follow-up of offspring through December 2023. Analyses were conducted using a propensity score-based overlap-weighted cohort and a sibling-matched cohort.
EXPOSURE: Prenatal exposure to at least 1 prescription for a PPI or H2 receptor antagonist.
MAIN OUTCOMES AND MEASURES: Offspring neuropsychiatric disorders identified via International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, severe neuropsychiatric disorder, and obsessive-compulsive disorder.
RESULTS: Of 3?012?992 mother-child pairs initially identified, 2?777?119 were included, with 507?845 pairs exposed to prenatal acid-suppressive medication and were followed up a mean of 10.3 (SD, 2.3) years. In the overlap-weighted cohort (403?658 mother-child pairs exposed and 403?659 pairs unexposed to an acid-suppressive medication), respective risks among offspring exposed vs not exposed were 4.85% vs 4.25% for ADHD, 1.45% vs 1.33% for ASD, 1.25% vs 1.09% for intellectual disability, 0.94% vs 0.81% for severe neuropsychiatric disorder, and 0.30% vs 0.27% for obsessive-compulsive disorder. In the overlap-weighted cohort, the adjusted hazard ratio (HR) following prenatal acid-suppressive medication exposure was 1.14 (95% CI, 1.12-1.17) for ADHD, 1.07 (95% CI, 1.03-1.11) for ASD, 1.13 (95% CI, 1.09-1.18) for intellectual disability, 1.16 (95% CI, 1.10-1.21) for severe neuropsychiatric disorder, and 1.12 (95% CI, 1.03-1.21) for obsessive-compulsive disorder. Sibling-control analyses that included 157?069 exposed and 164?669 unexposed offspring revealed no significant associations between prenatal exposure and offspring outcomes. The adjusted HR for ADHD was 0.98 (95% CI, 0.95-1.02); for 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); or obsessive-compulsive disorders, 0.95 (95% CI, 0.82-1.10).
CONCLUSIONS AND RELEVANCE: 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. Small associations were observed in overlap-weighted models; these may reflect confounding by shared familial factors.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Obstetrics | Coming Soon... |
| FM/GP/Obstetrics | Coming Soon... |
Very interesting and important analysis! The safety of drug use in pregnancy is of great importance, and the authors deal with the recently disputed acid-suppressive medication issues skillfully. However (although the statisical analysis is scrupulous) it is a retrospective analysis. A study with a prospective design should be undertaken.
Nice little reassuring study.
An interesting study providing data from a very large population regarding an interesting topic that was not well addressed until now. As obstetricians, we prescribe a lot of acid suppressive medications. This study provides proof they are safe for the neurodevelopment of offspring.