Vitamin B-12, Folic Acid, and Growth in 6- to 30-Month-Old Children: A Randomized Controlled Trial

Randomized, placebo-controlled trial in North Indian children aged 6 to 30 months from urban communities in New Delhi. Active intervention groups included vitamin B-12 (n=252), folate (n=249), and vitamin B-12 plus folate (n=250), with 1:1:1:1 allocation across four arms and follow-up for 6 months.

Children were randomized to one of three daily oral paste supplements for 6 months: vitamin B-12 (1.8 µg per 10 g), folic acid (150 µg per 10 g), or vitamin B-12 plus folic acid (1.8 µg vitamin B-12 plus 150 µg folic acid per 10 g). Children aged 6-11 months received 5 g daily, and those older than 12 months received 10 g daily; the paste was administered at home by a field worker, with caregiver administration on Sundays and holidays.

Overall, supplementation produced modest growth benefits, with the clearest signal for vitamin B-12 and the combined vitamin B-12 plus folate regimen. Vitamin B-12 increased weight change slightly versus placebo (1.09 kg vs 1.03 kg; mean difference 0.06, 95% CI -0.01 to 0.13) and improved WAZ change (0.02 vs -0.05; mean difference 0.07, 95% CI 0.01 to 0.13). Folic acid showed a small, non-significant increase in length/height change versus placebo (5.46 cm vs 5.26 cm; mean difference 0.20, 95% CI -0.03 to 0.44), while the combination group had a weight increase of 120 g (95% CI 3 to 210 g) and a length increase of 0.35 cm (95% CI 0.0 to 0.66 cm). Authors concluded that poor vitamin B-12 and folate status contribute to poor growth, but that the effects were modest and likely require higher doses and longer follow-up for confirmation.

Effects were small and some primary comparisons were not statistically significant, limiting certainty about clinical importance. Follow-up was only 6 months, and adverse events were not reported. Generalizability is limited to young urban North Indian children with substantial baseline malnutrition and micronutrient deficiency risk, and subgroup benefits may not apply broadly.