title: Multivitamin use and adverse birth outcomes in high-income countries: a systematic review and meta-analysis.
abstract: In high-income countries, a healthy diet is widely accessible. However, a change toward a poor-quality diet with a low nutritional value in high-income countries has led to an inadequate vitamin intake during pregnancy.
  
  
  
  We conducted a systematic review and meta-analysis to evaluate the association between multivitamin use among women in high-income countries and the risk of adverse birth outcomes (preterm birth [primary outcome], low birthweight, small for gestational age, stillbirth, neonatal death, perinatal mortality, and congenital anomalies without further specification).
  
  
  
  We searched electronic databases (MEDLINE, Embase, Cochrane, Scopus, and CINAHL) from inception to June 17, 2016, using synonyms of pregnancy, study/trial type, and multivitamins. Eligible studies were all studies in high-income countries investigating the association between multivitamin use (3 or more vitamins or minerals in tablets or capsules) and adverse birth outcomes. We evaluated randomized, controlled trials using the Cochrane Collaboration tool. Observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were applied on raw data for outcomes with data for at least 2 studies and were conducted using RevMan (version 5.3). Outcomes were pooled using the random-effect model. The quality of evidence was assessed using the Grades of Research, Assessment, Development and Evaluation approach.
  
  
  
  We identified 35 eligible studies including 98,926 women. None of the studies compared the use of folic acid and iron vs the use of multivitamins. The use of multivitamin did not change the risk of the primary outcome, preterm birth (relative risk, 0.84 [95% confidence interval, 0.69-1.03]). However, the risk of small for gestational age (relative risk, 0.77 [95% confidence interval, 0.63-0.93]), neural tube defects (relative risk, 0.67 [95% confidence interval, 0.52-0.87]), cardiovascular defects (relative risk, 0.83 [95% confidence interval, 0.70-0.98]), urine tract defects (relative risk, 0.60 [95% confidence interval, 0.46-0.78]), and limb deficiencies (relative risk, 0.68 [95% confidence interval, 0.52-0.89]) was decreased. Of the 35 identified studies, only 4 were randomized, controlled trials. The degree of clinical evidence according to the Grades of Research, Assessment, Development, and Evaluation system was low or very low for all outcomes except for recurrence of neural tube defects in which a moderate degree of clinical evidence was found.
  
  
  
  Routine multivitamin use in high-income countries can be recommended but with caution because of the low quality of evidence. Randomized, controlled trials or well-performed, large prospective cohort studies are needed.
authors.affiliation: Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Copenhagen, Denmark. Electronic address: trapwolf@gmail.com.
authors.forename: Hanne T
authors.initials: HT
authors.lastname: Wolf
authors.affiliation: Research Unit, Department of Women's and Children's Health, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne K
authors.initials: HK
authors.lastname: Hegaard
authors.affiliation: Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Copenhagen, Denmark.
authors.forename: Lene D
authors.initials: LD
authors.lastname: Huusom
authors.affiliation: Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Copenhagen, Denmark.
authors.forename: Anja B
authors.initials: AB
authors.lastname: Pinborg
mesh_terms: D000013:Congenital Abnormalities; D019049:Developed Countries; D004032:Diet; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins
keywords: adverse birth outcome; congenital birth defects; meta-analysis; multivitamin; pregnancy; systematic review