Maternal Vitamin B12 Deficiency and perinatal and Child Neurodevelopmental Outcomes: A Systematic Review and Meta-Analysis
Year: 2026
Type: preprint
Study designs: Systematic Review, Meta-Analysis
Abstract: ABSTRACT 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.
Source: medRxiv
Authors: Eduarda Rodrigues Belfort de Carvalho, Hércules Kanaan Pereira Sousa, Thiago de Sousa Siqueira, Ricardo Rezende de Queiroz, Juliana Borges Tavares da Silva, Ana Júlia Hortegal Cavalcante, Paloma Layonara Vieira Viana, Maria Eduarda Araújo Magalhães, Gabriel Segrini Fidencio, Ana Raquel Batista de Carvalho
Institution: Centro Universitário UNINOVAFAPI
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221079047