Use of metoclopramide in the first trimester and risk of major congenital malformations: A systematic review and meta-analysis

PLoS One. 2021 Sep 20;16(9):e0257584. doi: 10.1371/journal.pone.0257584. eCollection 2021.


Background: Nausea and vomiting of pregnancy affects up to 80% of pregnant women, it typically occurs during the first trimester which is the most sensitive time for environmental exposures given organogenesis. Metoclopramide is an antiemetic drug used widely during NVP, but the findings of studies evaluating its safety of use in pregnancy is inconsistent. Therefore, we conducted a systematic review and meta-analysis to assess whether metoclopramide use during first trimester of pregnancy is associated with the risk of major congenital malformations.

Methods: The systematic search using database included Pubmed, Embase, Web of science, and Cochrane library. Studies written in English, comprising with an exposed group and a control group, reporting major congenital malformation as an outcome were included.

Results: Six studies assessing a total number of 33374 metoclopramide-exposed and 373498 controls infants were included in this meta-analysis. No significant increase in the rate of major congenital malformation was detected following metoclopramide use during first trimester (OR, 1.14; 95% CI, 0.93-1.38).

Conclusions: Metoclopramide use during first trimester of pregnancy was not associated with the risk of major congenital malformations.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antiemetics / adverse effects*
  • Antiemetics / therapeutic use
  • Congenital Abnormalities / etiology*
  • Female
  • Humans
  • Metoclopramide / adverse effects*
  • Metoclopramide / therapeutic use
  • Nausea / drug therapy
  • Odds Ratio
  • Pregnancy
  • Pregnancy Trimester, First
  • Vomiting / drug therapy


  • Antiemetics
  • Metoclopramide

Grant support

This work was supported by the Major Scientific and Technological Projects for collaborative prevention and control of birth defects in Hunan Province (2019SK1010), the Health Commission of Hunan Province (20200786), and the Hunan Provincial Science and Technology Department (2018JJ6008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.