快樂小藥師 Im pharmacist nichts glücklich

Question

What is the risk to the unborn baby of proton pump inhibitor therapy during pregnancy? Should these drugs be avoided altogether in pregnant women?

Response from Sunanda V. Kane, MD, MSPH 
Associate Professor of Medicine, Mayo Clinic, Rochester, Minnesota

The first proton-pump inhibitor (PPI) on the market was omeprazole, which carries a C rating because of the lack of controlled data on its use in pregnancy. Since then, 3 other PPIs have been introduced with prospective controlled data to substantiate their pregnancy category ratings of B. In an early study of first trimester exposure to PPI, 295 women exposed to PPI were compared with 800 women who were not exposed.^[1] No significant difference in birth outcomes was found in this study.

Obstetricians recommend over-the-counter antacids and H2 receptor antagonists as first-line therapy for heartburn symptoms in pregnant women, but PPI therapy is warranted for women who have persistent uncontrolled symptoms. A study published in The New England Journal of Medicine ^[2] in 2010 described a Danish cohort of more than 5000 pregnant women who had first trimester exposure to PPI therapy. Although statistically significant, the difference in rates of congenital abnormalities in the newborns of exposed (3.2%) and nonexposed (2.6%) women was hardly convincing for a clinically relevant risk.

The risk for birth defects associated with drugs comes from exposure in the first trimester. Heartburn significant enough to warrant daily therapy does not occur in most women until the later months of pregnancy, when the critical period for birth defects is over. Recently, an abstract presented at Digestive Disease Week^[3] suggested that prolonged PPI use during pregnancy was associated with an increased risk for cardiac malformations in the newborn (odds ratio, 2.14; 95% confidence interval, 1.3-3.3). That study has not been published in full and the timing of PPI exposure during pregnancy in study participants is unclear.

A meta-analysis published in 2009^[4]did not suggest any increased risk with PPI use during any stage of pregnancy. Therefore, on the basis of available data, it appears that women in whom PPI therapy is indicated to control heartburn symptoms are not at increased risk for fetal malformations.

References

1. Diav-Citrin O, Arnon J, Shechtman S, et al. The safety of proton pump inhibitors in pregnancy: a multicenter prospective controlled study. Aliment Pharmacol Ther. 2005;21:269-275. Abstract
2. Rhim AD, Hardy JR, Haynes K, Testani JM, Yang YX. Maternal use of proton pump inhibitors during pregnancy is associated with an increased risk for cardiac birth defects. Program and abstracts of Digestive Disease Week 2010; May 1-6, 2010; New Orleans, Louisiana. Abstract 475b.
3. Pasternak B, Hviid A. Use of proton pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med. 2010;363:2114-2123. Abstract
4. Gill SK, O'Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol. 2009;104:1541-1545. Abstract