Is use of proton pump inhibitors safe during early pregnancy?

Findings from sibling-controlled analyses showed that PPIs were unlikely to be significant teratogens. Given the increasing PPI use during pregnancy, the results, published in JAMA Network Open, may be helpful for patients and clinicians to make decisions on PPI use in the first trimester.

GERD (Gastroesophageal reflux disease) is a common occurrence in pregnancy, affecting up to 80% of pregnant women. The symptoms, if mild, can be alleviated by lifestyle modifications, but many patients often require acid-suppressive medications to manage their inadequately controlled symptoms. Worldwide, proton pump inhibitors have increased during pregnancy, possibly due to their acid-suppressing effect. However, many observational studies have raised concerns about an increased risk of specific congenital malformations.

Against the above background, Ahhyung Choi from Sungkyunkwan University in Suwon, South Korea, and colleagues aimed to investigate the association between PPI exposure during early pregnancy and the congenital malformations risk in a population-based cohort study.

For this purpose, the researchers used data from South Korea's National Health Insurance Service–National Health Information Database. To account for familial factors, sibling-controlled analyses were also conducted. They identified 2 696 216 pregnancies in women aged 19 to 44 from 2011 to 2019 and their live-born infants. Women exposed to known teratogens or who delivered infants with genetic syndromes or chromosomal abnormalities were excluded.

The study's primary outcomes were congenital heart defects, major congenital malformations, hydrocephalus, congenital heart defects, hypospadias, and cleft palate. The subtypes of congenital heart defects and major congenital malformations were evaluated as exploratory outcomes.

The study led to the following findings:

• Of 2 696 216 pregnancies (mean maternal age, 32.1 years), 40 540 (1.5%; mean age, 32.4 years) had PPIs exposure during the first trimester.
• The absolute significant congenital malformations risk was 396.7 per 10 000 infants in PPI-exposed pregnancies and 323.4 per 10 000 infants in unexposed pregnancies.
• The propensity score–adjusted relative risks were 1.07 for major congenital malformations, 1.09 for congenital heart defects, 1.02 for cleft palate, 0.94 for hydrocephalus, and 0.77 for hypospadias.
• In the sibling-controlled analyses, no associations were observed between PPI use and primary outcomes, including major congenital malformations (odds ratio, 1.05) and congenital heart defects (odds ratio, 1.07).
• A range of sensitivity analyses revealed results similar to the main findings.

"Our study found that PPI use during the pregnancy's first trimester was not linked with a substantial increase in the risk of congenital heart defects, major congenital malformations, hypospadias, hydrocephalus, and cleft palate, although we observed small increases in the risk of congenital heart defects and major congenital malformations," the team stated in their study.

A wide range of sensitivity and sibling-controlled analyses indicated that PPIs are unlikely to be a major teratogen.

Reference:

Choi A, Noh Y, Jeong HE, et al. Association Between Proton Pump Inhibitor Use During Early Pregnancy and Risk of Congenital Malformations. JAMA Netw Open. 2023;6(1):e2250366. doi:10.1001/jamanetworkopen.2022.50366