Vitamin D supplementation among Bangladeshi children under-five years of age hospitalised for severe pneumonia: A randomised placebo controlled trial

Abstract

Introduction Vitamin D is important for its immunomodulatory role and there is an independent association between vitamin D deficiency and pneumonia. We assessed the effect of vitamin D supplementation on the outcome in children hospitalized for severe pneumonia. Methods This was a randomised, double blinded, placebo-controlled clinical trial in children aged >2–59 months with severe pneumonia attending Dhaka Hospital, icddr,b. Children received age-specific megadose of vitamin D3 (20,000IU: <6 months, 50,000 IU: 6–12 months, 100,000 IU:13–59 months) or placebo on first day and 10,000 IU as maintenance dose for next 4 days or until discharge (if discharged earlier) along with standard therapy. This trial is registered at ClinicalTrials.gov, number NCT02185196. Findings We enrolled 100 children in placebo group and 97 in vitamin D group. On admission, 50 (52%) and 49 (49%) of children in vitamin D and placebo groups, respectively were vitamin D deficient. Among children with a sufficient serum vitamin D level on admission, a lower trend for duration of resolution of severe pneumonia in hours [72(IQR:44–96)vs. 88(IQR:48–132);p = 0.07] and duration of hospital stay in days [4(IQR:3–5)vs.5(IQR:4–7);P = 0.09] was observed in vitamin D group compared to placebo. No beneficial effect was observed in vitamin D deficient group or irrespective of vitamin D status. Conclusion Age-specific mega dose of vitamin D followed by a maintenance dose shown to have no statistical difference between the two intervention groups, however there was a trend of reduction of time to recovery from pneumonia and overall duration of hospital stay in under-five children with a sufficient serum vitamin D level on hospital admission.

Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years

“…We used the Cochrane risk of bias tool (2019 version) 7 to evaluate the qualities of the RCTs. Our overall risk of bias assessment showed low risk in 14 studies, 9 , 10 , 11 , 12 , 18 , 23 , 24 , 28 , 30 , 31 , 33 , 37 , 38 , 39 some concerns in 4 studies, 19 , 20 , 22 , 29 and high risk in 14 studies. 8 , 13 , 14 , 15 , 16 , 17 , 21 , 25 , 26 , 27 , 32 , 34 , 35 , 36 This assessment is provided in detail in eTable 2 in the Supplement .…”

“…The main search resulted in 2063 studies potentially relevant for inclusion ( Figure 1 ); of these, 32 studies 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 (8400 unique participants) met our criteria and were included in this systematic review ( Table 1 ). A subgroup of 21 studies 8 , 9 , 10 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 (7358 unique participants) were eligible for meta-analysis because they included a control group receiving either low-dose vitamin D supplementation (≤400 IU/d) or placebo.…”

“…Daily oral high-dose vitamin D intervention ranged from 1200 to 10 000 IU/d, whereas bolus doses ranged from 30 000 IU/week to 600 000 IU as a single dose. Twenty-five of the 32 RCTs 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 , 28 , 32 , 33 , 34 , 35 , 36 , 37 had 2 intervention groups, whereas the remaining 7 studies 25 , 27 , 29 , 30 , 31 , 38 , 39 compared more than 2 groups. Only 1 study 11 used 6 years as the upper age limit in their eligibility criteria.…”

“…Intervention doses of less than 2000 IU/d as highest vitamin D supplementation given were only seen among infants, which corresponds to a high-dose intervention in this age group. Most studies had a clinical diagnosis or vitamin D deficiency as inclusion criteria, including rickets in 6 studies, 13 , 14 , 15 , 17 , 27 , 39 pneumonia in 6 studies, 8 , 18 , 23 , 24 , 29 , 38 vitamin D deficiency in 2 studies, 11 , 12 asthma in 2 studies, 10 , 22 and congenital hypothyroidism, 35 acute lower respiratory infection, 19 malnutrition, 9 atopic dermatitis, 37 vitamin D–deficient mothers, 20 prematurity, 26 and very low birth weight 32 each in 1 study. The remaining 9 studies 16 , 21 , 25 , 28 , 30 , 31 , 33 , 34 , 36 included healthy participants.…”

Vitamin D and Healthcare Service Utilization in Children: Insights from a Machine Learning Approach

“…It would be reasonably advantageous to supplement only patients who may benefit the most, namely the ones with severe deficiency, and therefore, interventional studies should be planned targeting this group rather than those with any deficiency in order to define vitamin D dosage, mode of delivery as well as duration of supplementation. Interestingly, it should be pointed out that even in children with a sufficient serum vitamin D level at hospital admission, a lower trend for the duration of resolution of severe pneumonia in hours (72 (IQR:44–96) vs. 88 (IQR:48–132); p = 0.07) and duration of hospital stay in days (4 (IQR:3–5) vs. 5 (IQR:4–7); p = 0.09) was observed in a vitamin D group compared with placebo [ 49 ]. Evidence from previous observational studies and RCTs suggested that there may be health economic benefits in raising the vitamin D level in adults in Western Europe [ 50 ].…”