Comparison of Efficacy and Safety of Parenteral vs Oral Route of Vitamin B12 Supplementation for the Treatment of Vitamin B12 Deficiency Anemia in Children: A Systematic Review

Abstract Context Vitamin B12 deficiency in children is treated with either parenteral or oral supplementation. Although the efficacy of supplementation is reportedly comparable for the 2 routes in adults, there is limited data for children. Objective The objective of this review was to compare the efficacy and safety of parenteral vs oral B12 supplementation in children with vitamin B12 deficiency anemia. Data Sources A comprehensive literature search was conducted in PubMed, EMBASE, the Cochrane Library, Scopus, Web of Science, four Clinical Trials Registries, and 2 gray literature databases, for randomized controlled trials (RCTs) comparing the parenteral vs oral routes of administering B12 in children with vitamin B12 deficiency anemia. Data Extraction Among 6467 citations screened, there was only 1 eligible RCT, in which children with vitamin B12 deficiency anemia received 1 dose of 1000 µg parenterally before being randomized to either parenteral or oral therapy. Data Analysis After 3 months, the parenteral route resulted in higher B12 levels compared with the oral route (median [IQR]: 653 [459, 835] vs 506 [399, 726] pg/mL). The changes from baseline in vitamin B12 levels (median [IQR]: 600 [389, 775] vs 399 [313, 606] pg/mL, P = .016) and hemoglobin (2.7 [0.4, 4.6] vs 0.5 [−0.1, 1.2] g/dL, P = .001) were also significantly greater with the parenteral route. There was no data on safety. In terms of quality, the RCT was judged to be at “high risk of bias.” Conclusion Limited evidence from a single, methodologically weak RCT suggested that the parenteral route is more efficacious than the oral route. However, considering the limitations in quality and quantity of the available evidence, this should be interpreted with caution. Systematic Review Registration PROSPERO registration No. CRD42024526597.