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

Abstract

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.

The Impact of Third Trimester Maternal Serum Vitamin B12 and Folate Status on Fetal Birth Weight. Is Maternal Serum Homocysteine a Predictor of Low Birth Weight Infants?

“…The effects of maternal B12 level on birth weight is still controversial, our results showed that the mean maternal vitamin B12 level in mothers with LBW [38] reviewed 29 articles and they concluded that although there is an association between low maternal vitamin B12 and intrauterine growth retardation, but no studies have definitively determined the cut off value for serum vitamin B12 level during pregnancy. Recently, a meta-analysis was done included eighteen studies observed no linear association between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of LBW in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31) [39]. However, several studies did not detect any association between maternal vitamin B12 levels and fetal growth restriction [3] [42].…”

Epidemiology of late preterm and early term births – An international perspective

“…Associations between sociodemographic characteristics and early delivery may be explained by lifestyle and environmental determinants [49], including maternal body mass index [50], diet and micronutrient intake [51,52], physical activity [53], stress [54], employment conditions [55], active and passive smoking [49], and exposure to environmental pollutants [56]. Most of the research on the social and behavioral determinants of early delivery has focused on preterm birth; however, some studies find similar associations for early term births.…”

Low serum folate status in the second trimester increase the risk of low birthweight in Chinese women

“…Similar to the other studies, the relationship between B12 and LBW was not found in our current work. However, a recent meta‐analysis observed B12 deficiency (<148 pmol/L) to be associated with increased risk of LBW infants with an adjusted risk ratio 1.15 …”