This nationwide Danish registry-based cohort study assessed the safety of metoclopramide use in first-trimester pregnancy, comparing metoclopramide-exposed women (28, 486 live-born infants) with matched unexposed controls (113, 698 unexposed infants). Each exposed pregnancy was matched with up to 4 unexposed pregnancies according to age, calendar year, and propensity scores. The primary outcomes were major congenital malformations, spontaneous abortion, and stillbirth among live-born infants.
During the first year of life, 721 among the exposed infants (25.3 [95% CI, 24.5-27.1] per 1000 births) and 3024 among the unexposed infants (26.6 [25.7-27.5] per 1000 births) were diagnosed with any major malformation (adjusted prevalence OR, 0.93 [95% CI, 0.86-1.02]). In the analyses of individual malformation categories, there were no significant associations between metoclopramide use in the first trimester and any of the 20 malformations; the upper limits of the CIs in these analyses were below 2.0 in 17 of 20 analyses and below 2.6 in the remaining 3 analyses.
The cohort for the analysis of spontaneous abortion included 37,946 metoclopramide-exposed pregnancies, 151, 661 unexposed pregnancies, and a total of 10, 171 cases. Kaplan-Meier curves showed a lower cumulative incidence of spontaneous abortion among metoclopramide-exposed pregnancies compared with unexposed pregnancies (log-rank P < 0.001)
The analysis of stillbirth included 142 cases among 40, 306 metoclopramide-exposed pregnancies (3.5 [95% CI, 2.9-4.1] per 1000) and 634 cases among 161, 098 unexposed pregnancies (3.9 [95% CI, 3.6-4.2] per 1000). Metoclopramide was not associated with increased risk of stillbirth (adjusted HR, 0.90 [95% CI, 0.74-1.08].
A separate sensitivity analysis of malformations among pregnancies terminated antenatally found no evidence for increased risk of malformations overall or of those individual malformation categories for which the proportion of termination is high.
The authors note that their findings confirm those of previous studies (total 4,261 women exposed to metoclopramide in pregnancy), and expand substantially on the body of available safety data. Overall, they concluded that metoclopramide use in pregnancy was not associated with increased risk of major congenital malformations overall, any of the 20 individual malformation categories assessed, spontaneous abortion, or stillbirth. These safety data may help inform decision making when treatment with metoclopramide is considered in pregnancy.
The UKMI and CKS guidance recommend short-term treatment with promethazine or cyclizine as first line treatment for the treatment of nausea and vomiting in pregnancy. Metoclopramide is reserved as a second line treatment option as less data are available on use during pregnancy.
An EU review of the risks and benefits of metoclopramide in August 2013, concluded that the risks of neurological disorders outweighed the benefits, and therefore to help minimise this risk, the dose and duration of metoclopramide were restricted (for adults, the usual oral dose is 10mg three times daily up to 5 days). Unfortunately the review did not specifically address the use of metoclopramide in pregnancy.