Anti-Nausea Drug in Early Pregnancy Not Linked to Birth Defects

Use of metoclopramide for nausea and vomiting during pregnancy was not associated with significantly increased risk of major congenital malformations overall, spontaneous abortion, and stillbirth, according to the findings of a new study conducted in Denmark.

More than half of all pregnant women experience nausea and vomiting in early pregnancy, and some women remain plagued by these symptoms in their second and third trimester. A small percentage of women who experience these symptoms of pregnancy, typically 10% to 15%, eventually will receive medication. Among the options for treatment is metoclopramide, one of the most commonly used prescription medications in pregnancy, according to background information in the study. However, its safety data in pregnancy is limited. Of the available studies, most involve metoclopramide use in the third trimester.

To determine whether use of metoclopramide in the first trimester was associated with major congenital malformations, researchers used a registry in Denmark to identify more than 1.2 million pregnancies that occurred between 1997 and 2011. Of those, they identified 28,486 pregnancies with metoclopramide exposure in the first trimester. The exposed group was than matched 1:4 with pregnancies unexposed to the drug on the basis of age, calendar year, and propensity score.

According to the study results, a major congenital malformation was diagnosed within the first year of life in 721 exposed infants (25.3 cases per 1000 births) and 3024 of 113,698 unexposed infants (26.6 cases per 1000 births), indicating no significant associations between metoclopramide use and overall malformations. In an analysis of 20 individual malformation categories, which included neural tube defects, transposition of great vessels, specific septal defects, cleft lip, cleft palate, and limb reduction, there was no association between malformations and metoclopramide use.

The researchers also reported that there was no increased risk of spontaneous abortion, stillbirth, preterm birth, low birth weight, and fetal growth restriction associated with metoclopramide use in early pregnancy.

These results help bolster the drug’s safety data and “may help inform decision making when treatment with metoclopramide is considered in pregnancy,” concluded the authors.

Pertinent Points:
- Use of metoclopramide in early pregnancy is not associated with an increased risk of major congenital malformations, spontaneous abortion, or stillbirth.
- These findings add to the limited body of evidence regarding metoclopramide use during pregnancy.

References:

Pasternak B, Svanström H, Mølgaard-Nielsen D, et al. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death.

JAMA.

2013;310;1601-1611.