Proton pump inhibitors and birth defects: are concerns laid to rest?

▶ Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects N Engl J Med 2010;363:2114–23.

Heartburn is common during pregnancy, but data on the safety of proton pump inhibitors (PPIs) to treat gastro-oesophageal symptoms in this situation are lacking. The authors performed a cohort study to assess the relationship between PPI use in early pregnancy and the risk of major birth defects.

Using nationwide registries in Denmark, a cohort of more than 840 000 live born infants during a 12-year period was assembled, and major birth defects were identified. Mothers of these children who filed a prescription during or just prior to pregnancy were also identified, and the proportion of children with a major birth defect were compared between mothers with and those without PPI exposure, controlling for numerous potential confounders including birth year, prior history of birth defects, mother's age and parity, smoking status and use of other drugs.

Overall, the prevalence of PPI use during pregnancy increased during the 12 years. Prevalence of major birth defects in infants whose mothers had been exposed to PPIs between 4 weeks before conception and the end of the first trimester of pregnancy was 3.4%, as compared to 2.6% in the group whose mothers had not been exposed. The odds of a major birth defect in mothers exposed to PPI from 4 weeks before conception to the end of the 1st trimester were 1.23 (95% CI 1.05 to 1.44). However, there was no significant association detected between PPI exposure during the 1st trimester only and odds of major birth defect (1.10; 95% CI 0.91 to 1.34), or during the 2nd or …