PPI use in the first trimester was not associated with increased risk for birth defects; PPI use 1 to 4 weeks before conception was

Windrim R. — Tue, 21 Jun 2011 00:00:00 GMT

Question

Is exposure to proton-pump inhibitors (PPIs) in early pregnancy associated with risk for major birth defects?

Methods

Design

Cohort study with linkage of national birth, prescription, and patient registers.

Setting

Denmark.

Participants

840 968 infants born alive between 1996 and 30 September 2008 who were followed for ≤ 1 year.

Risk factor

Use of PPIs, defined as prescriptions for PPIs filled by mothers from 4 weeks before conception to delivery. (PPIs were available only by prescription for the first 10 years of the study period.) PPIs used were omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole.

Outcomes

Major birth defects, defined according to the European surveillance of congenital anomalies classification, with some modifications.

Main results

5082 mothers used PPIs from 4 weeks before conception to the end of the first trimester. Overall, 3.4% of infants born to mothers exposed to PPIs during this period had major birth defects compared with 2.6% of infants born to mothers not exposed to PPIs (prevalence odds ratio 1.23, 95% CI 1.05 to 1.44, adjusted for propensity score). Results by period of exposure showed that infants born to women who used PPIs 1 to 4 weeks before conception had an increased risk for major birth defects; infants born to women who used PPIs during the first trimester or second and third trimesters did not have an increased risk for major birth defects (Table). Analysis by type of PPI showed no association with risk for major birth defects except for an increased risk with use of lansoprazole 1 to 4 weeks before conception (adjusted prevalence odds ratio 1.91, CI 1.30 to 2.80).

Conclusion

Use of proton-pump inhibitors (PPIs) during the first trimester of pregnancy was not associated with an increased risk for major birth defects; however, use of PPIs 1 to 4 weeks before conception was associated with an increased risk for major birth defects.Association between maternal use of proton-pump inhibitors (PPIs) before or during pregnancy and major birth defectsTime of exposure to PPIsBirth defects in mothers exposed to PPIs, %Birth defects in mothers not exposed to PPIs, %Adjusted prevalence odds ratios (95% CI)*1 to 4 wk before conception3.9%2.6%1.39 (1.10 to 1.76)First trimester3.2%2.6%1.10 (0.91 to 1.34)Second and third trimesters3.1%2.6%1.09 (0.92 to 1.29)*CI defined in Glossary. Adjusted for propensity score and effects of exposure to PPIs in either of the other 2 exposure times. Propensity scores were based on the following confounders: birth year; history of birth defects in siblings; maternal age at conception, level of education, socioeconomic class, place of birth, residence at conception, parity, smoking during pregnancy, diabetes, and epilepsy; first-trimester hospitalization for infectious disease; first-trimester hospital contact for genitourinary infection; and first-trimester use of antiepileptic, β-blocker, benzodiazepine, selective serotonin reuptake inhibitor, analgesic, or corticosteroid.

Annals of Internal Medicine: Seizure Disorders Topic Collection

PPI use in the first trimester was not associated with increased risk for birth defects; PPI use 1 to 4 weeks before conception was