Oral vitamin B12 reduces deficiency risk in children but shows little impact on growth or cognition

Rationale Vitamin B12 deficiency is an important public health problem in children, and has been associated with anaemia and impaired growth, cognition, and development. Vitamin B12 deficiency may develop in children due to lower content in breast milk, low dietary intake, and as requirements increase with age. Vitamin B12 supplementation may confer benefits to child growth and development, due to its role in DNA synthesis and methylation, red blood cell formation, and folate metabolism. However, no systematic reviews have been conducted to examine the effects of vitamin B12 supplementation in children. Objectives To determine the effects of vitamin B12 supplementation on growth, development, and cognition in children less than 12 years of age. Search methods We searched CENTRAL, MEDLINE, Embase, 12 other databases, and two trial registries on 23 September 2025. We screened reference lists of studies. Eligibility criteria We included randomised controlled trials evaluating the effects of oral vitamin B12 supplementation, alone or in combination with other micronutrients, in children < 12 years of age. We excluded cross‐over trials, trials targeting pregnant or breastfeeding women, or participants with critical illnesses, and interventions delivered by intravenous/intramuscular injections. Outcomes Critical outcomes were vitamin B12 status, anaemia, haemoglobin, growth, cognitive function, developmental outcomes, and any adverse effects. Important outcomes included megaloblastic anaemia, body composition, health‐related quality of life, morbidity, and all‐cause mortality. Risk of bias We used Cochrane RoB 2 to evaluate bias. Synthesis methods We conducted meta‐analyses using fixed‐effect models. If there was substantial heterogeneity, we used random‐effect models. When meta‐analyses were not conducted, we described findings from individual trials, and considered synthesis and presentation of findings using other methods. We used GRADE to evaluate the certainty of evidence for critical outcomes. Included studies We included 16 trials (4083 children; 2 days to 11 years) in 10 countries, including India, Japan, Thailand, Nepal, United Kingdom, Italy, Spain, the United States, El Salvador, and Guatemala. Follow‐up periods for outcomes in most studies ranged from five weeks to 31 months, with one study extending follow‐up to nine years. Duration of vitamin B12 supplementation varied, ranging from 28 days to 31 months, with doses from 0.9 µg/day to 150 µg/day. Nine trials, including 2391 children, contributed data to meta‐analyses. Synthesis of results Supplementation with vitamin B12 alone versus placebo There may be little to no difference between groups in height/length (mean difference (MD) ‐0.19 cm, 95% confidence interval (CI) ‐2.44 to 2.06; 2 trials, 143 children; low‐certainty evidence). There may be little to no difference between groups in cognitive function (e.g. attention) (standardised mean difference (SMD) 0.09, 95% CI ‐0.10 to 0.28; 2 trials, 438 children, low‐certainty evidence). There may be little to no difference between groups in motor skill development (6 to 9 years, NEuroPSYchological assessment, Second Edition (NEPSY‐II); 1 trial, 403 children, low‐certainty evidence). Vitamin B12 supplementation in children reduces vitamin B12 deficiency (absolute risk difference (ARD) 56 fewer per 1000, 95% CI 68 fewer to 24 fewer; 1.8% versus 7.6%; risk ratio (RR) 0.27, 95% CI 0.11 to 0.69; 3 trials, 642 children; high‐certainty evidence), and probably increases total vitamin B12 concentrations (MD 68.53 pmol/L, 95% CI 41.83 to 95.23; 7 trials, 705 children; moderate‐certainty evidence), compared to placebo, with an average increase of 68.5 pmol/L. There may be little to no difference between groups in anaemia (ARD 21 more per 1000, 95% CI 26 fewer to 191 more; 9.1% versus 4.5%; RR 1.48, 95% CI 0.41 to 5.27; 2 trials, 144 children; low‐certainty evidence). No trials reported the occurrence of any adverse effects. Supplementation with vitamin B12 alone versus no intervention The evidence is very uncertain about the effects of vitamin B12 on height/length (2 trials, 70 children; very low‐certainty evidence), compared to no intervention. No trials reported data for the other critical outcomes. Supplementation with vitamin B12 and other micronutrients, compared to the same formulation without vitamin B12 There may be little to no difference between groups in height/length (MD ‐0.22 cm, 95% CI ‐0.65 to 0.20; 2 trials, 608 children; low‐certainty evidence). There may be little to no difference between groups in cognitive function (e.g. attention) (SMD 0.00, 95% CI ‐0.13 to 0.13; 3 trials, 956 children; low‐certainty evidence). There may be little to no difference between groups in development outcomes (e.g. motor skill development) (SMD ‐0.05, 95% CI ‐0.18 to 0.08; 2 trials, 960 children; low‐certainty evidence). Children who received vitamin B12 supplementation and other micronutrients may have little to no difference in vitamin B12 deficiency (ARD 2 fewer per 1000, 95% CI 7 fewer to 32 more; 0.7% versus 0.8%; RR 0.77, 95% CI 0.12 to 5.16; 2 trials, 534 children; low‐certainty evidence), or total vitamin B12 concentrations (MD 34.32 pmol/L, 95% CI ‐31.13 to 99.77; 3 trials, 731 children; low‐certainty evidence), compared to supplements without vitamin B12. There may be little to no difference between groups in anaemia (21.7% versus 25.0%; 1 trial, 35 children; low‐certainty evidence). There may be little to no difference between groups in any adverse effects (9.2% versus 5.9%; 1 trial, 574 children; low‐certainty evidence). The certainty of evidence for critical outcomes ranged from high to very low; we downgraded for imprecision due to small sample sizes or few events, risk of bias in outcome measurement, randomisation methods, selective reporting bias, or inconsistency due to substantial statistical heterogeneity. Few studies reported growth, cognition, development, anaemia, or any adverse effects. Authors' conclusions Vitamin B12 supplementation (alone or when supplemented with other micronutrients) in children may have little to no effect on growth (i.e. height/length), cognitive function (e.g. attention), development outcomes (e.g. motor skill development), or anaemia, compared to placebo, no intervention, or the same supplements without vitamin B12. Vitamin B12 supplementation in children reduces vitamin B12 deficiency and probably improves total vitamin B12 concentrations, compared to placebo. However, vitamin B12 supplementation with other micronutrients may result in little to no difference in vitamin B12 deficiency and total vitamin B12 concentrations, compared to the same formulation without vitamin B12. Funding This review had no dedicated funding. Registration Protocol available via DOI 10.1002/14651858.CD015264. PICOs PICOs Population Intervention Comparison Outcome