title: Metoclopramide in pregnancy and risk of major congenital malformations and fetal death.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. bjp@ssi.dk
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.forename: Ditte
authors.initials: D
authors.lastname: Mølgaard-Nielsen
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000022:Abortion, Spontaneous / Q000139:chemically induced; D000328:Adult; D000932:Antiemetics / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D006801:Humans; D008787:Metoclopramide / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D012042:Registries / Q000706:statistics & numerical data; D012306:Risk; D050497:Stillbirth / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000932:Antiemetics; D008787:Metoclopramide