Maternal Vitamin B12 Deficiency And Perinatal And Child Neurodevelopmental Outcomes: A Systematic Review And Meta-Analysis

Background: Vitamin B12 is essential for one-carbon metabolism, deoxyribonucleic acid (DNA) synthesis, and myelination, and inadequate maternal status during pregnancy may influence fetal growth and child neurodevelopment. Objective: To evaluate the association between maternal vitamin B12 status and perinatal and child neurodevelopmental outcomes. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized clinical trials. The main outcomes were preterm birth, low birth weight, small for gestational age (SGA), and cognitive/global development. For binary outcomes, the natural logarithm of the relative risk (logRR) was the primary analytical effect measure; for neurodevelopment, Hedges g was used. Random-effects models were fitted, between-study variance was estimated by restricted maximum likelihood (REML), and inference used Knapp-Hartung (KH) adjustment. Results: For preterm birth, nine estimates yielded a pooled logRR of 0.190 (95% confidence interval [95% CI] KH: -0.046 to 0.427; p = 0.101; I2 = 19.2%). For low birth weight, nine estimates yielded a pooled logRR of 0.136 (95% CI KH: -0.013 to 0.286; p = 0.069; I2 = 4.8%). For SGA, six estimates yielded a pooled logRR of 0.047 (95% CI KH: -0.083 to 0.177; p = 0.397; I2 = 0%). Cognitive/global development, assessed in five independent studies, showed a pooled Hedges g of 0.266 (95% CI KH: 0.034 to 0.499; p = 0.034; I2 = 55.7%). Conclusions: logRR estimates for preterm birth and low birth weight were directionally compatible with higher risk among mothers with lower vitamin B12 availability, but their 95% CIs included the null. No consistent association was observed for SGA. Higher maternal vitamin B12 availability or supplementation was associated with a small favorable effect on cognitive/global development, with moderate heterogeneity.