Are Proton-Pump Inhibitors Safe During Early Pregnancy?

"In a large cohort study, use of PPIs during the first trimester did not increase risk for major birth defects"

Symptomatic gastroesophageal reflux disease (GERD) is a common condition associated with pregnancy. Although its prevalence increases with duration of pregnancy, symptoms often occur even in the first trimester. Proton-pump inhibitors (PPIs) are the most effective medical therapy for patients with moderate-to-severe GERD and are widely prescribed to pregnant women. However, safety data about the use of these agents during pregnancy or immediately prior to conception are limited (JW Gastroenterol Mar 29 2005). 

To evaluate the association between exposure to PPIs and the risk for birth defects, researchers conducted a retrospective cohort study of live births in Denmark using multiple national registries. The primary analysis assessed PPI exposure to women during the 4 weeks prior to conception through the first trimester of pregnancy (12 weeks). The primary outcome measure was all major birth defects.

Of 840,968 live births, 5082 involved exposure to PPIs during the study period. Exposure was associated with increased risk for birth defects (adjusted prevalence odds ratio, 1.23; 95% confidence interval, 1.05–1.44). However, when exposure was limited to the first trimester only, no significant risk for birth defects remained. In a secondary analysis, exposures to specific PPIs during the first trimester did not increase the risk for birth defects. Of note, omeprazole — the only category C drug (i.e., animal studies have shown risk to a fetus) — was associated with the lowest risk for birth defects, although this result was not statistically significant.

My Comment: Given the widespread use of both prescription and over-the-counter PPIs, these data showing an apparent lack of teratogenicity are reassuring. It is interesting that an editorialist suggests that omeprazole should perhaps be the PPI of choice in pregnancy, even though it is a category C drug. Nonetheless, my advice in treating pregnant patients is to make recommendations to the prescribing obstetrician rather than to be the primary prescriber of any agent.

Published in Journal Watch Gastroenterology January 21, 2011.

Original article:  Pasternak B and Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med 2010 Nov 25; 363:2114.

Mitchell AA. Proton-pump inhibitors and birth defects — Some reassurance, but more needed. N Engl J Med 2010 Nov 25; 363:2161.

by

Akshaya Srikanth

Pharm.D Internee

Hyderabad, India