Vitamin B-12, folic acid, and growth in 6- to 30-month-old children: a randomized controlled trial

Pediatrics. 2015 Apr;135(4):e918-26. doi: 10.1542/peds.2014-1848.


Background: Folate and vitamin B-12 are important for growth. Many children in low- and middle-income countries have inadequate intakes of these nutrients.

Methods: We undertook a randomized, placebo controlled double-blind trial in 1000 North Indian children, 6 to 35 months of age, providing twice the recommended daily allowance of folic acid and/or vitamin B-12, or placebo, daily for 6 months. By using a factorial design, we allocated children in a 1:1:1:1 ratio in blocks of 16. We measured the effect of giving vitamin B-12, folic acid, or the combination of both on linear and ponderal growth. We also identified predictors for growth in multiple linear regression models and effect modifiers for the effect of folic acid or vitamin B-12 supplementation on growth.

Results: The overall effect of either of the vitamins was significant only for weight; children who received vitamin B-12 increased their mean weight-for-age z scores by 0.07 (95% confidence interval: 0.01 to 0.13). Weight-for-age z scores and height-for-age z scores increased significantly after vitamin B-12 supplementation in wasted, underweight, and stunted children. These subgrouping variables significantly modified the effect of vitamin B-12 on growth. Vitamin B-12 status at baseline predicted linear and ponderal growth in children not receiving vitamin B-12 supplements but not in those who did (P-interaction < .001).

Conclusions: We provide evidence that poor vitamin B-12 status contributes to poor growth. We recommend studies with larger doses and longer follow-up to confirm our findings.

Trial registration: NCT00717730.

Keywords: India; children; folate; growth; homocysteine; intervention; vitamin B-12.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height / drug effects*
  • Body Weight / drug effects*
  • Child, Preschool
  • Developing Countries*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • India
  • Infant
  • Linear Models
  • Male
  • Vitamin B 12 / administration & dosage*


  • Folic Acid
  • Vitamin B 12

Associated data

  • CTRI/CTRI/2010/091/001090