The Safety of Metoclopramide Use in the First Trimester of Pregnancy

Metoclopramide has been the drug of choice in many countries to manage nausea and vomiting in pregnant women despite lack of substantial evidence of its safety in this population when used as recommended. The few studies that have investigated the safety to the fetus of maternal exposure to metoclopramide during the first trimester are small studies with a total enrollment of only 800 pregnant women. This retrospective cohort study investigated the safety for the fetus of exposure to metoclopramide during the first trimester of pregnancy. Between 1998 and 2007, computerized data on medications dispensed for pregnant Israeli women were linked to databases containing maternal and infant hospital records. The metoclopramide group (n = 3458) was comprised of infants of singleton girls and women who had taken the drug during the first trimester. The no exposure group (n = 78,245) was comprised of infants of mothers not treated with the drug. The data was adjusted for potential confounders including maternal age, parity, self-reported smoking status during pregnancy, presence or absence of maternal diabetes mellitus, and presence or absence of peripartum fever. There were no significant differences in the risk of adverse outcomes between the 2 groups. The risks of major congenital malformations during the first trimester was 5.3% (182/3458) in the metoclopramide group and 4.9% (3834/78,245) in the unexposed group; the adjusted odds ratio (aOR) was 1.04, with a 95% confidence interval (CI) of 0.89 to 1.21. In the metoclopramide and unexposed groups, the risk of low birth weight was 8.5% and 8.3% (aOR, 1.01; 95% CI, 0.89-1.14), the risk of preterm delivery was 6.3% and 5.9% (aOR, 1.15; 95% CI, 0.99-1.34), and risk of perinatal death was 1.5% and 2.2% (aOR, 0.87; 95% CI, 0.55-1.38). No significant difference in the outcome data for major congenital malformations was found when therapeutic abortions were included in the analysis (6.1 %, metoclopramide group vs 5.9%, unexposed group). These findings are consistent with previous studies showing no significant association between exposure to metoclopramide during the first trimester and adverse perinatal outcomes.