**Background:** Folate and vitamin B12 are essential for DNA and protein synthesis, cell growth, and differentiation. Deficiencies of these nutrients are common in low- and middle-income countries, particularly among populations with limited intake of animal-source foods. The extent to which these deficiencies contribute to poor linear growth in children is not well established. The liver can store both vitamins, so supplementation effects may persist long after the intervention period.
**Methods:** This study is a 6-year follow-up of a factorial-designed, double-blind, randomized, placebo-controlled trial conducted in New Delhi, India. Originally, 1000 children aged 6–30 months were randomized in blocks of 16 (1:1:1:1 ratio) to receive daily for 6 months: placebo, approximately 2 RDA of vitamin B12 (1.8 mcg for children >12 months; 0.9 mcg for ≤12 months), approximately 2 RDA of folic acid (150 mcg for >12 months; 75 mcg for ≤12 months), or both vitamins. From September 2016, the research team contacted the original 1000 children; 791 consented and were included in the follow-up. Height was measured using Seca 213 stadiometers to the nearest 0.1 cm. Plasma cobalamin and folate were measured by microbiological assays, and total homocysteine (tHcy) was analyzed using commercial kits. Statistical analyses included multivariable regression models adjusted for wealth quintile, with subgroup analyses pre-specified based on the original trial results. Generalized additive models explored non-linear associations.
**Key Results:** Mean age at follow-up was 7.4 years (SD 0.7; range 6–9 years). Children randomized to vitamin B12 were somewhat taller than those not receiving vitamin B12 (mean difference 0.12 HAZ, 95% CI −0.01 to 0.25; corresponding to 0.7 cm, 95% CI −0.15 to 1.57), but this difference was not statistically significant. There was no effect of folic acid supplementation on linear growth. A significant subgroup effect was observed: among children with baseline plasma cobalamin <200 pmol/L, vitamin B12 supplementation improved HAZ by 0.34 (95% CI 0.11, 0.58; P for interaction = 0.01). In the observational analysis, baseline cobalamin concentration was positively associated with HAZ in children not given vitamin B12 (each doubling of cobalamin associated with 0.26 higher HAZ, 95% CI 0.15–0.38; P for interaction = 0.001), but not in supplemented children (−0.01, 95% CI −0.13 to 0.10). Similarly, each doubling of cobalamin was associated with a 30% reduction in stunting risk (RR 0.70, 95% CI 0.53–0.93) in the unsupplemented group, but not in the supplemented group (RR 1.25, 95% CI 0.90–1.74; P for interaction = 0.004). Baseline tHcy was negatively associated with HAZ (−0.15, 95% CI −0.27 to −0.01). Breastfeeding and higher wealth quintile were independent predictors of better growth outcomes.
**Clinical Implications:** This study provides evidence that vitamin B12 deficiency is a growth-limiting nutrient in North Indian children. The finding that supplementation benefits only those with low baseline status, and that baseline status predicts growth only in unsupplemented children, supports a causal role for vitamin B12 in linear growth. These results suggest that vitamin B12-fortified foods or oral supplements could improve growth outcomes in populations with limited access to animal-source foods. The lack of effect of folic acid indicates that folate is not a growth-limiting nutrient in this population. The study's strengths include the randomized design enabling causal inference, 80% follow-up after 6 years, and robust anthropometric measurements. Limitations include potential insufficient dose/duration of supplementation, possible interference from bacterial overgrowth, and 20% attrition. The findings support public health strategies to improve vitamin B12 status in young children in settings where animal-source foods are scarce.