title: Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis.
abstract: BACKGROUND
  The use of folic acid-fortified multivitamin supplements has long been associated with decreasing the risk of neural tube defects. Several studies have also proposed the effectiveness of these supplements in preventing other birth defects; however, such effects have never been systematically examined.
  
  
  OBJECTIVE
  We conducted a systematic review and meta-analysis to evaluate the protective effect of folic acid-fortified multivitamin supplements on other congenital anomalies.
  
  
  METHODS
  We searched Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases for studies describing the outcome of pregnancies in women using multivitamin supplements that were published in all languages from January 1966 to July 2005. The references from all collected articles were reviewed for additional articles. Two independent reviewers who were blinded to the source and identity of the articles extracted data based on predetermined inclusion and exclusion criteria. Using a random effects model, rates of congenital anomalies in babies born to women who were taking multivitamin supplements were compared with rates in the offspring of controls who were not.
  
  
  RESULTS
  From the initial search, 92 studies were identified; 41 of these met the inclusion criteria. Use of multivitamin supplements provided consistent protection against neural tube defects (random effects odds ratio[OR] 0.67, 95% confidence intervals [95% CI] 0.58-0.77 in case control studies; OR 0.52, 95% CI 0.39-0.69 in cohort and randomized controlled studies), cardiovascular defects (OR 0.78, 95% CI 0.67-0.92 in case control studies; OR 0.61, 95% CI 0.40-0.92 in cohort and randomized controlled studies), and limb defects (OR 0.48, 95% CI 0.30-0.76 in case control studies; OR 0.57, 95% CI 0.38-0.85 in cohort and randomized controlled studies). For cleft palate, case control studies showed OR 0.76 (95% CI 0.62-0.93), and cohort and randomized controlled studies showed OR 0.42 (95% CI 0.06-2.84); for oral cleft with or without cleft palate, case control studies showed OR 0.63 (95% CI 0.54-0.73), and cohort and randomized controlled studies showed OR 0.58 (95% CI 0.28-1.19); for urinary tract anomalies, case control studies showed OR 0.48 (95% CI 0.30-0.76), and cohort and randomized controlled studies showed OR 0.68 (95% CI 0.35-1.31); and for congenital hydrocephalus case control studies showed OR 0.37 (95% CI 0.24-0.56), and cohort and randomized controlled studies showed OR 1.54 (95% CI 0.53-4.50). No effects were shown in preventing Down syndrome, pyloric stenosis, undescended testis, or hypospadias.
  
  
  CONCLUSIONS
  Maternal consumption of folic acid-containing prenatal multivitamins is associated with decreased risk for several congenital anomalies, not only neural tube defects. These data have major public health implications, because until now fortification of only folic acid has been encouraged. This approach should be reconsidered.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto ON; The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto ON.
authors.forename: Y
authors.initials: Y
authors.lastname: Ingrid Goh
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto ON.
authors.forename: Enkelejd
authors.initials: E
authors.lastname: Bollano
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto ON; The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto ON.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Einarson
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto ON; The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto ON; Faculty of Medicine, University of Toronto, Toronto ON; lvey Chair in Molecular Toxicology, University of Western Ontario, London ON; Department of Medicine, University of Western Ontario, London ON.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000328:Adult; D002170:Canada / Q000453:epidemiology; D018376:Cardiovascular Abnormalities / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000517:prevention & control; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D006849:Hydrocephalus / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000453:epidemiology; D009056:Mouth Abnormalities / Q000453:epidemiology; D009436:Neural Tube Defects / Q000453:epidemiology; D011247:Pregnancy; D011295:Prenatal Care; D016032:Randomized Controlled Trials as Topic; D014564:Urogenital Abnormalities / Q000453:epidemiology; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D014815:Vitamins; D005492:Folic Acid