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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.

Rogne T, Tielemans MJ, Chong MF, Yajnik CS, Krishnaveni GV, Poston L, Jaddoe VW, Steegers EA, Joshi S, Chong YS, Godfrey KM, Yap F, Yahyaoui R, Thomas T, Hay G, Hogeveen M, Demir A, Saravanan P, Skovlund E, Martinussen MP, Jacobsen GW, Franco OH, Bracken MB, Risnes KR. (2017) Am J Epidemiol. Feb 1;185(3): 212-223. doi: 10.1093/aje/kww212. 

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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.