Higher-dose vitamin B12 modestly improves infant cognition
In predominantly vegetarian pregnant women, 250 micrograms daily vitamin B12 improved infants’ mental development scores compared with 50 micrograms.
*Multicentre double-blind randomized controlled trial; Level 1b (OCEBM).
Citation
Nagpal J, Mathur M, Rawat S, et al. Maternal supplementation of vitamin B12 in predominantly vegetarian pregnant women improves their vitamin B12 status and the neurodevelopment of their infants: the MATCOBIND multicentric double-blind randomised control trial. BMJ Paediatrics Open. 2026;10:e004112. doi:10.1136/bmjpo-2025-004112.
Background
Vitamin B12 deficiency is common in pregnancy when diets contain little animal-source food, and has been linked to poorer early brain development. Prior trials have shown mixed neurodevelopment results, possibly due to low doses or short supplementation periods.
Patients
Pregnant women in the first trimester at two tertiary maternity centres (India and Nepal), predominantly vegetarian. Exclusions included current vitamin B12 supplement use, multiple pregnancy, chronic medical disease, and serious maternal infection.
Intervention
Oral methylcobalamin 250 micrograms daily from enrollment until 6 months after birth.
Control
Oral methylcobalamin 50 micrograms daily for the same period.
Outcome
Primary: infant neurodevelopment at 9–12 months using the Development Assessment Scale of Indian Infants (developmental quotient scores). Maternal and infant blood vitamin B12 status during pregnancy and at follow-up.
Follow-up Period
Infants assessed at 9–12 months; mothers supplemented through 6 months after birth.
Results
531 mother–infant pairs completed follow-up (250 micrograms: 255; 50 micrograms: 276).
| Outcome |
250 micrograms/day |
50 micrograms/day |
Effect |
| Infant mental developmental quotient (primary) |
103.7 |
101.7 |
Mean difference 1.94 points (95% CI 0.51 to 3.36) |
| Maternal blood vitamin B12 in third trimester |
293 pg/mL |
264 pg/mL |
Higher with 250 micrograms/day |
| Maternal vitamin B12 deficiency in third trimester |
15.7% |
23.0% |
Absolute risk reduction 7.3%; number needed to treat ≈14 |
Developmental quotient is a standardized score where higher is better.
Analysis was intention-to-treat. Motor development and infant growth measures were not meaningfully different between groups.
Limitations
No true placebo group (ethical reasons), so benefits are relative to a lower dose. Follow-up was limited to the first year, and the ~2-point mental score increase may be modest for families. About 25% were lost to follow-up; results may not generalize beyond predominantly vegetarian populations or to all settings (country subgroup differences were seen).
Funding
Newton Fund (India biotechnology department and UK research councils); no funder role.
Clinical Application
For predominantly vegetarian pregnant patients, consider higher-dose daily vitamin B12 (250 micrograms) through early postpartum to improve maternal status and modestly improve infant mental development.