Severe malnutrition, growth and zinc supplementation
Aims: To describe early linear and ponderal growth, collagen turnover, bone osteoblastic activity and growth, and insulin like growth factor (IGF) axis activity during rehabilitation of severely malnourished children and compare the effect of 3 regimens of zinc supplementation. Methods: 141 children were randomised in a double blind trial to either regimen 1: 1.5 mg/kg/day (mg of elemental zinc per kg body weight of zinc sulphate) for 15 days followed by placebo for 15 days, or regimen 2: 6.0mg/kg/day for 15 days followed by placebo for 15 days, or regimen 3: 6.0mg/kg/day for 30 days. Markers of collagen formation (serum pro-collagen type 1 c terminal propeptide (PICP), and type 3 n terminal propeptide (P3NP)) and degradation (plasma cross-linked telopeptide of type 1 collagen (ICTP)), osteoblastic activity (bone alkaline phosphatase (BAP)), IGFl and insulin like growth factor binding proteins 2 and 3 (IGFBP2 and IGFBP3) were assessed. Results: There were no significant differences between zinc regimens in anthropometric or biochemical marker change. Mortality was significantly increased in children who received high dose zinc (6.0mg/kg) initially (Yates corrected chi-square p value of 0.033). Linear growth was significantly associated with initial weight-for-height Z score (WHZ). Plasma IGF-I, IGFBP-3, PICP, P3NP and BAP were low and increased whilst IGFBP-2 and ICTP were increased and fell during refeeding (P 0.001). IGFBP2 correlated positively with ICTP and negatively with PICP, BAP, IGFl and IGFBP3 (p 0.01). Ponderal growth correlated with increases in IGF-I, IGFBP-3, PICP, P3NP and BAP over 30 days (P 0.01). Linear growth over 90 days correlated with increases of IGFBP-3 (P 0.05), PICP (P 0.01) and P3NP (P 0.01). Conclusions: Alterations in the Growth Hormone /IGF axis in response to diet may control the coupling of bone resorption to formation and collagen deposition. There is no benefit in using higher dose zinc regimens and they might contribute to increased mortality.