Maternal vitamin B12, vitamin D, and folic acid status during pregnancy and child neurodevelopment: a systematic review.

BACKGROUND

Adequate maternal micronutrient status during pregnancy may play an important role in fetal neurodevelopment. Emerging evidence suggests that deficiencies in vitamin B12, vitamin D, and folic acid, often exacerbated by modern dietary patterns characterized by high consumption of ultra-processed foods, may adversely affect cognitive, motor, and behavioral outcomes in offspring. Despite growing interest in this topic, the magnitude and consistency of these associations remain incompletely defined.

METHODS

We conducted a systematic review in accordance with PRISMA 2020 guidelines. Electronic databases (PubMed, Cochrane Library, LILACS, and ScienceDirect) were searched for studies published up to March 2025 that evaluated maternal vitamin B12, vitamin D, or folate status during pregnancy and subsequent neurodevelopmental outcomes in children. Eligible studies included observational studies and randomized controlled trials assessing cognitive, motor, and behavioral domains.

RESULTS

A total of 22 studies met the inclusion criteria, comprising 18 observational studies (81.8%) and 4 randomized controlled trials (18.2%). Vitamin D was the most frequently investigated micronutrient, followed by vitamin B12 and folate-related exposures. Adequate maternal vitamin B12 status was consistently associated with improved language, memory, and cognitive performance, while vitamin D deficiency during pregnancy was linked to poorer motor and neurocognitive outcomes. Folic acid supplementation, particularly when initiated in the periconceptional period, demonstrated the most consistent favorable associations extending beyond neural tube defect prevention, including improved cognitive and language development. However, substantial methodological heterogeneity limited quantitative synthesis.

CONCLUSION

Maternal vitamin B12, vitamin D, and folate status appear to play an important role in shaping early neurodevelopment. In the context of increasing consumption of ultra-processed foods and declining micronutrient density in modern diets, these findings underscore the need for strengthened nutritional surveillance, targeted supplementation strategies, and updated public health policies to support optimal neurodevelopmental outcomes.