Multiple Micronutrient Supplementation Improves Vitamin B₁₂ and Folate Concentrations of HIV Infected Children in Uganda: a Randomized Controlled Trial

Background: The effect of multiple micronutrient supplementation on vitamin B₁₂ and folate has hither to not been reported in African HIV infected children. This paper describes vitamin B₁₂ and folate status of Ugandan HIV infected children aged 1-5 years and reports the effect of multiple micronutrient supplementation on serum vitamin B12 and folate concentrations.

Methods: Of 847 children who participated in a multiple micronutrient supplementation trial, 214 were assessed for vitamin B₁₂ and folate concentrations pre and post supplementation. One hundred and four children were randomised to two times the recommended dietary allowance (RDA) of a 14 multiple micronutrient supplement (MMS) and 114 to a 'standard of care' supplement of 6 multivitamins (MV). Serum vitamin B12 was measured by an electrochemiluminescence immunoassay and folate by a competitive protein-binding assay using Modular E (Roche) automatic analyzer. Vitamin B₁₂ concentrations were considered low if less than 221 picomoles per litre (pmol/L) and folate if < 13.4 nanomoles per litre (nmol/L). The Wilcoxon Signed Ranks test was used to measure the difference between pre and post supplementation concentrations.

Results: Vitamin B₁₂ was low in 60/214 (28%) and folate in 62/214 (29.0%) children. In the MMS group, the median concentration (IQR) of vitamin B₁₂ at 6 months was 401.5 (264.3 - 518.8) pmol/L compared to the baseline of 285.5 (216.5 - 371.8) pmol/L, p < 0.001. The median (IQR) folate concentrations increased from 17.3 (13.5-26.6) nmol/L to 27.7 (21.1-33.4) nmol/L, p < 0.001. In the 'standard of care' MV supplemented group, the median concentration (IQR) of vitamin B₁₂ at 6 months was 288.5 (198.8-391.0) pmol/L compared to the baseline of 280.0 (211.5-386.3) pmol/L while the median (IQR) folate concentrations at 6 months were 16.5 (11.7-22.1) nmol/L compared to 15.7 (11.9-22.1) nmol/L at baseline. There was a significant difference in the MMS group in both vitamin B₁₂ and folate concentrations but no difference in the MV group.

Conclusions: Almost a third of the HIV infected Ugandan children aged 1-5 years had low serum concentrations of vitamin B₁₂ and folate. Multiple micronutrient supplementation compared to the 'standard of care' supplement of 6 multivitamins improved the vitamin B12 and folate status of HIV infected children in Uganda.

Trial Registration: http://ClinicalTrials.govNCT00122941).