Journal of Women Health

ABSTRACT

Vitamin B12 (cobalamin) is an essential water-soluble micronutrient and a critical cofactor in one-carbon metabolism, acting synergistically with folate to support DNA synthesis, methylation, and nervous system integrity. Deficiency is highly prevalent worldwide, particularly among pregnant women and women of reproductive age in low- and middle-income countries. Growing evidence identifies inadequate maternal B12 status as a major risk factor for a spectrum of adverse reproductive and perinatal outcomes, including female infertility, recurrent pregnancy loss, preterm birth, low birth weight, neural tube defects, and impaired fetal neurodevelopment. Mechanistically, B12 deficiency disrupts the methionine cycle, leading to hyperhomocysteinemia, which compromises oocyte quality, implantation, placental development, and epigenetic programming of the fetus. Maternal B12 insufficiency may also predispose offspring to long-term metabolic and neurocognitive sequelae, consistent with the Developmental Origins of Health and Disease framework. This narrative review synthesizes evidence from observational studies, randomized controlled trials, and mechanistic research, linking maternal B12 status to preconception health, assisted reproductive technology (ART) outcomes, adverse pregnancy events, and long-term neurodevelopment in offspring. We highlight the urgent need for targeted preconception and early antenatal screening, particularly using functional biomarkers such as holotranscobalamin, alongside evidence-based supplementation strategies. Implementing these interventions in high-risk populations represents a cost-effective and high-impact approach to reduce preventable maternal, fetal, and neonatal morbidity associated with early-life B12 deficiency.

Keywords: Vitamin B12; Cobalamin; Pregnancy; Neural tube defects; Preterm birth; Reproduction; Infertility; Maternal nutrition.