title: Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: a systematic review and meta-analysis.
abstract: BACKGROUND
  Vitamin B-12 and folate are micronutrients essential for normal embryogenesis. Vitamin B-12 insufficiency in pregnancy is high in certain parts of the world, such as India, and although this has been linked to low birth weight (LBW) in these populations, the relation between vitamin B-12 and birth weight (BW) elsewhere is unknown.
  
  
  OBJECTIVE
  We performed a systematic review to assess 1) the worldwide prevalence of vitamin B-12 insufficiency in pregnancy and 2) its association with BW.
  
  
  METHODS
  A search of 5 electronic databases was performed to identify eligible articles. Random-effects meta-analysis was conducted according to geographic regions and pregnancy trimesters for the prevalence subreview and by categorical measures of BW.
  
  
  RESULTS
  A total of 57 and 23 articles were included for the prevalence and BW subreviews, respectively. The pooled estimates of vitamin B-12 insufficiency were 21%, 19%, and 29% in the first, second, and third trimesters, respectively, with high rates for the Indian subcontinent and the Eastern Mediterranean. The large heterogeneity between studies was partially addressed by creating a standardized score for each study (mean vitamin B-12 insufficiency ÷ cutoff value), which internally corrected for geographic region, trimester, and assay type. Twelve of the 13 longitudinal studies included showed a decrease in mean or median vitamin B-12 across trimesters. Pooled analysis showed nonsignificantly lower maternal vitamin B-12 concentrations in LBW than in normal-BW infants and higher odds of LBW with lower vitamin B-12 values (adjusted OR: 1.70; 95% CI: 1.16, 2.50), but studies from India largely contributed to the latter.
  
  
  CONCLUSIONS
  Our review indicates that vitamin B-12 insufficiency during pregnancy is common even in nonvegetarian populations and that concentrations of vitamin B-12 decrease from the first to the third trimester. There is no consistent association between vitamin B-12 insufficiency and LBW. However, given the long-term risks of LBW, this observation warrants further cohort studies and randomized controlled trials.
authors.affiliation: Division of Health Sciences, Populations, Evidence, and Technologies Group, Warwick Medical School, The University of Warwick, Coventry, United Kingdom;
authors.forename: Nithya
authors.identifier: http://orcid.org/0000-0002-8549-2061
authors.initials: N
authors.lastname: Sukumar
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom; Edinburgh Migration, Ethnicity, and Health Research Group, Centre for Population Health Sciences, Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: Snorri B
authors.initials: SB
authors.lastname: Rafnsson
authors.affiliation: Department of Mathematics and Information Sciences, Faculty of Engineering and Environment, Northumbria University, Newcastle upon Tyne, United Kingdom; Health Economics and Evidence Synthesis Unit, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg;
authors.forename: Ngianga-Bakwin
authors.initials: NB
authors.lastname: Kandala
authors.affiliation: Edinburgh Migration, Ethnicity, and Health Research Group, Centre for Population Health Sciences, Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: Raj
authors.initials: R
authors.lastname: Bhopal
authors.affiliation: Diabetes Unit, King Edward Memorial Hospital and Research Centre, Rasta Peth, Pune, Maharashtra, India; and.
authors.forename: Chittaranjan S
authors.initials: CS
authors.lastname: Yajnik
authors.affiliation: Division of Health Sciences, Populations, Evidence, and Technologies Group, Warwick Medical School, The University of Warwick, Coventry, United Kingdom; Academic Department of Diabetes & Endocrinology, George Eliot Hospital, Nuneaton, United Kingdom p.saravanan@warwick.ac.uk.
authors.forename: Ponnusamy
authors.identifier: http://orcid.org/0000-0002-9566-2626
authors.initials: P
authors.lastname: Saravanan
mesh_terms: D001724:Birth Weight; D016208:Databases, Factual; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007230:Infant, Low Birth Weight; D039382:Maternal Nutritional Physiological Phenomena; D018977:Micronutrients / Q000008:administration & dosage / Q000097:blood; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D015995:Prevalence; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000453:epidemiology*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood
chemical_list: D018977:Micronutrients; D014803:Vitamin B Complex; D005492:Folic Acid; D014805:Vitamin B 12
keywords: geographic variation; low birth weight; meta-analysis; pregnancy; systematic review; vitamin B-12 insufficiency