PPI exposure during early pregnancy poses no excess risk of congenital malformations

The use of proton pump inhibitors (PPIs) during early pregnancy does not appear to put infants at increased risk of congenital malformations, as reported in a study. However, there seems to be a small risk increase for major congenital malformations and congenital heart defects.

The study used data from the National Health Insurance Service–National Health Information Database of South Korea (2010–2020) and identified 2,696,216 pregnancies in women (mean maternal age 32.1 years) and their live-born infants. Women who were exposed to known teratogens or who delivered infants with chromosomal abnormalities or genetic syndromes were excluded.

Researchers assessed the primary outcomes of major congenital malformations, congenital heart defects, cleft palate, hydrocephalus, and hypospadias in relation to PPI use during the first trimester. They also performed sibling-controlled analyses to account for familial factors.

A total of 40,540 (1.5 percent) had reported exposure to PPIs during the first trimester. The absolute risk of major congenital malformations in PPI-exposed and unexposed pregnancies was 396.7 and 323.4 per 10,000 infants, respectively.

The propensity score–adjusted relative risks associated with PPI exposure were 1.07 (95 percent confidence interval [CI], 1.02–1.13) for major congenital malformations, 1.09 (95 percent CI, 1.01–1.17) for congenital heart defects, 1.02 (95 percent CI, 0.72–1.43) for cleft palate, 0.94 (95 percent CI, 0.54–1.63) for hydrocephalus, and 0.77 (95 percent CI, 0.51–1.17) for hypospadias.

In the sibling-controlled analyses, PPI use showed no associations with the primary outcomes, including major congenital malformations (odds ratio [OR], 1.05, 95 percent CI, 0.91–1.22) and congenital heart defects (OR, 1.07, 95 percent CI, 0.88–1.30). Results of sensitivity analyses were consistent to the main findings.

The present data provide evidence that can guide clinicians and patients in decision-making about PPI use in the first trimester.