Use of Proton-Pump Inhibitors in Early Pregnancy and the Risk of Birth Defects

Abstract

Proton-pump inhibitors (PPIs) are commonly prescribed for the treatment of gastroesophageal reflux in pregnant women, despite the relatively lack of data on their safety in early pregnancy. In a recent meta-analysis involving 7 studies, exposure of 1530 women to PPIs in the first trimester was not associated with a significant increase of birth defects. However, most of these women received only 1 PPI, omeprazole. Limited data is available on the safety of other PPIs in early pregnancy. This nationwide, registry-based cohort study investigated the association between the use of several PPIs in early pregnancy and the occurrence of major birth defects. Associations were assessed between exposure to any PPI or to omeprazole and major birth defects (selected according to the European surveillance of congenital anomalies [EUROCAT] statistics). Data from nationwide registries were linked and provided information on live births, prescriptions for PPIs, birth defects, and potential confounders. The study cohort was comprised of 840,968 live births occurring in Denmark from 1996 to 2008. Among these, major births defects were diagnosed during the first year of life in 21,985 infants (2.6%). Comparison of the prevalence of major birth defects among infants of mothers who were exposed to PPIs (exposed group) and those whose mothers were not exposed (unexposed group) was the primary study outcome. The use of PPIs was assessed during the primary analyses period (any time between 4 weeks before conception and the end of the first trimester). Of the 840,968 live births in the total cohort, 5082 occurred in the exposed group during the primary analysis period. There was no significant difference in the prevalence of diagnosed major birth defects between the groups: 174 infants in the exposed group (3.4%, 174/5082) versus 21,811 infants in the unexposed group (2.6%, 21,811/835,886); the adjusted prevalence odds ratio (OR) was 1.23, with a 95% confidence interval (CI) of 1.05 to 1.44. Analysis of PPI exposure limited to any time during the first trimester also showed no significant difference in major birth defects between the 2 groups: 3.2% (118/3651 infants) in the exposed group versus 2.6% (21,867/837,317) infants in the unexposed group (adjusted prevalence OR, 1.10; 95% CI, 0.91–1.34). No significant increase in risk of birth defects was found in the secondary analyses for exposure to individual PPIs during the first trimester or for limiting the analysis to infants whose mothers filled PPI prescriptions and had taken enough doses to have a theoretical chance of exposure in the first trimester. These findings show no significant association between the use of PPIs during the first trimester of pregnancy and the risk of major birth defects.