Prenatal and Early Childhood Exposure to Proton Pump Inhibitors and Antibiotics and the Risk of Childhood Cancer: A Nationwide Population-Based Cohort Study

Unnur Gudnadottir (), Emma Fransson, Gustaf Ljungman, Anna Wikman, Erika Vlieghe, Lars Engstrand and Nele Brusselaers
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Unnur Gudnadottir: Centre for Translational Microbiome Research, Karolinska Institutet
Emma Fransson: Centre for Translational Microbiome Research, Karolinska Institutet
Gustaf Ljungman: Uppsala University
Anna Wikman: Uppsala University
Erika Vlieghe: Global Health Institute, University of Antwerp
Lars Engstrand: Centre for Translational Microbiome Research, Karolinska Institutet
Nele Brusselaers: Centre for Translational Microbiome Research, Karolinska Institutet

Drug Safety, 2025, vol. 48, issue 4, No 5, 375-388

Abstract: Abstract Background Our microbiome is established during infancy, a time important for later health and long-term effects. Proton pump inhibitors and antibiotics are regularly prescribed during pregnancy. Both drugs cause microbiome disturbance and have been associated with increased cancer risk in adults, but effects of these drugs on the growing foetus and infant remain understudied. Aim The aim of this study is to study the association between prenatal and early life proton pump inhibitor and antibiotics exposure and the risk of childhood cancer. Methods This study is a retrospective population-based cohort design, using registry data on all births (n = 722,372) in Sweden between 2006 and 2016, according to the STROBE checklist. For women who had multiple children in the timeframe of the study, only the first child during the time period was included in the cohort. Exposure was defined as either ≥ 1 proton pump inhibitor or antibiotics prescription during pregnancy, or during the first 2 years of life. Outcome was defined as cancer at any time during the follow-up or cancer after the age of 2 years for early life exposure. Multivariable Cox proportional hazard models were used to calculate hazard ratios. Results In total, 1091 (0.2%) children were diagnosed with malignant cancer during the follow-up. Prenatal exposure to proton pump inhibitors and antibiotics were not associated with an increased risk of cancer. Regarding early life exposure, proton pump inhibitors were associated with an increased risk of cancer at age two or older (adjusted hazard ratio [aHR] 3.68, 95% confidence interval [CI] 2.24–6.06). Conclusions We did not find evidence that prenatal proton pump inhibitors and antibiotics were associated with overall childhood cancer. However, proton pump inhibitors during early life were associated with an increased risk of childhood cancer, but indication on drug use was not available and confounding by indication may be present. Graphical Abstract

Date: 2025
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DOI: 10.1007/s40264-024-01500-x

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