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Medline ® Abstracts for References 64,65

of 'Treatment and outcome of nausea and vomiting of pregnancy'

The safety of metoclopramide use in the first trimester of pregnancy.
Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A
N Engl J Med. 2009;360(24):2528.
BACKGROUND: In various countries, metoclopramide is the antiemetic drug of choice in pregnant women, but insufficient information exists regarding its safety in pregnancy.
METHODS: We investigated the safety of metoclopramide use during the first trimester of pregnancy by linking a computerized database of medications dispensed between January 1, 1998, and March 31, 2007, to all women registered in the Clalit Health Services, southern district of Israel, with computerized databases containing maternal and infant hospital records from the district hospital during the same period. We assessed associations between the use of metoclopramide in pregnancy and adverse outcomes for the fetus, adjusting for parity, maternal age, ethnic group, presence or absence of maternal diabetes, smoking status, and presence or absence of peripartum fever.
RESULTS: There were 113,612 singleton births during the study period. A total of 81,703 of the infants (71.9%) were born to women registered in Clalit Health Services; 3458 of them (4.2%) were exposed to metoclopramide during the first trimester of pregnancy. Exposure to metoclopramide, as compared with no exposure to the drug, was not associated with significantly increased risks of major congenital malformations (5.3% and 4.9%, respectively; odds ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.21), low birth weight (8.5% and 8.3%; odds ratio, 1.01; 95% CI, 0.89 to 1.14), preterm delivery (6.3% and 5.9%; odds ratio, 1.15; 95% CI, 0.99 to 1.34), or perinatal death (1.5% and 2.2%; odds ratio, 0.87; 95% CI, 0.55 to 1.38). The results were materially unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis.
CONCLUSIONS: In this large cohort of infants, exposure to metoclopramide in the first trimester was not associated with significantly increased risks of any of several adverse outcomes. These findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy.
Department of Epidemiology and Health Services Evaluation, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Metoclopramide in pregnancy and risk of major congenital malformations and fetal death.
Pasternak B, Svanström H, Mølgaard-Nielsen D, Melbye M, Hviid A
JAMA. 2013 Oct;310(15):1601-11.
IMPORTANCE: Metoclopramide, a drug frequently used for nausea and vomiting in pregnancy, is thought to be safe, but information on the risk of specific malformations and fetal death is lacking.
OBJECTIVE: To investigate the safety of metoclopramide use in pregnancy.
DESIGN, SETTING, AND PARTICIPANTS: Register-based cohort study in Denmark, 1997-2011. From a cohort of 1,222,503 pregnancies, metoclopramide-exposed and unexposed women were matched (1:4 ratio) on the basis of age, calendar year, and propensity scores.
MAIN OUTCOMES AND MEASURES: Primary outcomes were major congenital malformations overall, 20 individual malformation categories (selected according to power criteria), spontaneous abortion, and stillbirth. In matched analyses, logistic regression was used to estimate prevalence odds ratios of malformations and Cox regression to estimate hazard ratios (HRs) of spontaneous abortion.
RESULTS: Among 28,486 women exposed to metoclopramide in the first trimester, 721 had an infant with a major congenital malformation (25.3 [95% CI, 23.5-27.1]cases per 1000 births), compared with 3024 among 113,698 unexposed women (26.6 [95% CI, 25.7-27.5]per 1000 births). There were no significant associations between metoclopramide use and malformations overall (prevalence odds ratio, 0.93 [95% CI, 0.86-1.02]) or any of the 20 individual malformation categories, eg, neural tube defects, transposition of great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip, cleft palate, anorectal atresia/stenosis, and limb reduction (upper limit of 95% CI below 2.0 for 17 of 20 categories). Metoclopramide was not associated with increased risk of spontaneous abortion (757 cases [20.0 {95% CI, 18.5-21.4} per 1000]among 37,946 metoclopramide-exposed women and 9414 cases [62.1 {95% CI, 60.9-63.3} per 1000]among 151,661 unexposed women; HR, 0.35 [95% CI, 0.33-0.38]) and stillbirth (142 cases [3.5 {95% CI, 2.9-4.1} per 1000]among 40,306 metoclopramide-exposed women and 634 cases [3.9 {95% CI, 3.6-4.2} per 1000]among 161,098 unexposed women; HR, 0.90 [95% CI, 0.74-1.08]).
CONCLUSIONS AND RELEVANCE: 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.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. bjp@ssi.dk