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. 2025 Mar;48(3):265-277.
doi: 10.1007/s40264-024-01496-4. Epub 2024 Dec 4.

Prenatal Exposure to Proton Pump Inhibitors and Risk of Serious Infections in Offspring During the First Year of Life: A Nationwide Cohort Study

Mylène Tisseyre  1   2 , Mathis Collier  3   4 , Nathanaël Beeker  3   4 , Florentia Kaguelidou  3   5 , Jean-Marc Treluyer  6   3   4 , Laurent Chouchana  6   3
Affiliations

Prenatal Exposure to Proton Pump Inhibitors and Risk of Serious Infections in Offspring During the First Year of Life: A Nationwide Cohort Study

Mylène Tisseyre et al. Drug Saf. 2025 Mar.

Abstract

Introduction and objective: Proton pump inhibitor (PPI) use in children increases the risk of infections, prompting inquiry into the impact of prenatal PPIs exposure on serious infections in offspring. As a research gap in this area exists, this study aimed to address it by assessing the association between prenatal PPIs exposure and serious infections in infants during their first year of life.

Methods: Using the French health insurance data warehouse (SNDS) (2013-2018), we conducted a retrospective cohort study on singleton, full-term liveborn non-immunocompromised infants, stratified by PPI use during the first three months of life (early-life use). Proton pump inhibitor dispensing in ambulatory care settings during pregnancy defined exposure. Outcomes concerned any serious infections in offspring aged between 3 and 12 months. Adjusted odds ratios (aORs) were estimated using logistic regression with multivariable models to control for potential confounders.

Results: Of the 2,485,545 infants included, 497,060 (23.3%) were prenatally exposed to PPIs and 97,767 (4.6%) had PPI use during the first three months of life. Prenatal PPI exposure was associated with serious infections in offspring (aOR, 1.09 [95% CI, 1.07-1.10]) in infants without early-life PPIs use. No association was found for infants with early-life PPI use (aOR, 1.05 [95% CI, 1.00-1.11]). Gastrointestinal infections were the sole site with persistent significance.

Conclusion: Prenatal PPI exposure is common and is not associated with a major risk of serious infections in infants during their first year. However, even after adjusting for several confounding factors, a weak association remains, especially in infants without early-life PPI use. While offering reassurance, adherence to clinical guidelines is still crucial.

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Conflict of interest statement

Declarations. Funding: No funding was received for conducting this study. Conflicts of interest: Authors have no conflicts of interest to disclose. Availability of data and material: Data sharing is not applicable to this article, as the datasets used are based on pseudo-anonymized data that are protected by agreements with the CNIL (Commission Nationale de l’Informatique et Liberté (French Data Protection Commission)). Ethics approval: This study was approved by the CNIL (Commission Nationale de l’Informatique et Liberté (French Data Protection Commission)) (agreement DE-2015-192) and CERESS (Comité spécifique de Recherche sur les Données de Santé (French committee for the protection of health care data). In agreements with French regulations, observational studies conducted on anonymous medico-administrative data do not require an ethics committee approval. Consent to participate: Not applicable. Consent for publication: Not applicable. Code availability: Code is available upon reasonable request to the authors. Author contributions: M. Tisseyre conceptualized and designed the study, collected data, carried out the initial analyses, analyzed the results, drafted the initial manuscript, and critically revised the manuscript. M. Collier designed the data collection instruments, carried out the initial analyses, and critically reviewed the manuscript. N. Beeker designed the data collection instruments, and critically reviewed the manuscript. F. Kaguelidou and JM. Treluyer reviewed the study design, analyzed the results, and critically reviewed the manuscript for important intellectual content. L. Chouchana conceptualized and designed the study, analyzed the results, drafted the initial manuscript, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

References

    1. Eusebi LH, Ratnakumaran R, Yuan Y, et al. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut. 2018;67(3):430–40. https://doi.org/10.1136/gutjnl-2016-313589 . - DOI - PubMed
    1. Tuppin P, Rivière S, Deutsch D, et al. Burden of drug use for gastrointestinal symptoms and functional gastrointestinal disorders in France: a national study using reimbursement data for 57 million inhabitants. Therap Adv Gastroenterol. 2019;12(12):175628481985379. https://doi.org/10.1177/1756284819853790 . - DOI
    1. Katz PO, Dunbar K, Schnoll-Sussman FH, et al. ACG clinical guideline: guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2023;117(1):27–56. https://doi.org/10.14309/ajg.0000000000001538 . - DOI
    1. Zielinski R, Searing K, Deibel M. Gastrointestinal distress in pregnancy: prevalence, assessment, and treatment of 5 common minor discomforts. J Perinatal Neonatal Nurs. 2015;29:23–31. https://doi.org/10.1097/JPN.0000000000000078 . - DOI
    1. Engeland A, Bjørge T, Klungsøyr K, et al. Trends in prescription drug use during pregnancy and postpartum in Norway, 2005 to 2015. Pharmacoepidemiol Drug Saf. 2018;27:995–1004. https://doi.org/10.1002/pds.4577 . - DOI - PubMed

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