Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data

Am J Epidemiol. 2017 Feb 1;185(3):212-223. doi: 10.1093/aje/kww212.


Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Keywords: low birth weight; pregnancy; preterm birth; systematic review; vitamin B12.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Birth Weight
  • Female
  • Humans
  • Infant, Low Birth Weight*
  • Infant, Newborn
  • Pregnancy / blood*
  • Pregnancy Complications*
  • Premature Birth / etiology*
  • Risk Factors
  • Vitamin B 12 / blood*
  • Vitamin B 12 Deficiency / complications*


  • Vitamin B 12