High-dose vitamin D3 in the treatment of severe acute malnutrition: a multicenter double-blind randomized controlled trial

Abstract

Vitamin D deficiency is common in children with severe acute malnutrition, in whom it is associated with severe wasting. Ready-to-use therapeutic food (the standard treatment) contains modest amounts of vitamin D that do not reliably correct deficiency. The aim of this study was to determine whether high-dose oral vitamin D3 enhances weight gain and development in children with uncomplicated severe acute malnutrition. We conducted a randomized placebo-controlled trial of high-dose vitamin D3 supplementation in children aged 6-58 mo with uncomplicated severe acute malnutrition in Pakistan. Participants were randomly assigned to receive 2 oral doses of 200,000 IU vitamin D3 or placebo at 2 and 4 wk after starting ready-to-use therapeutic food. The primary outcome was the proportion of participants gaining >15% of baseline weight at 8 wk after starting ready-to-use therapeutic food (the end of the study). Secondary outcomes were mean weight-for-height or -length z score and the proportion of participants with delayed development at the end of the study (assessed with the Denver Development Screening Tool II), adjusted for baseline values. Of the 194 randomly assigned children who started the study, 185 completed the follow-up and were included in the analysis (93 assigned to intervention, 92 to control). High-dose vitamin D3 did not influence the proportion of children gaining >15% of baseline weight at the end of the study (RR: 1.04; 95% CI: 0.94,1.15, P=0.47), but it did increase the weight-for-height or -length z score (adjusted mean difference: 1.07; 95% CI: 0.49,1.65, P<0.001) and reduce the proportion of participants with delayed global development [adjusted RR (aRR): 0.49; 95% CI: 0.31, 0.77, P=0.002], delayed gross motor development (aRR: 0.29; 95% CI: 0.13, 0.64, P=0.002), delayed fine motor development (aRR: 0.59; 95% CI: 0.38, 0.91, P=0.018), and delayed language development (aRR: 0.57; 95% CI: 0.34, 0.96, P=0.036). High-dose vitamin D3 improved the mean weight-for-height or -length z score and developmental indexes in children receiving standard therapy for uncomplicated severe acute malnutrition in Pakistan. This trial was registered at clinicaltrials.gov as NCT03170479.