To assess a) the impact of daily preventive zinc tablets (7 mg; PZ), multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP) or placebo on Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein 3 (IGFBP3) and IGF1 bioavailability (indexed by molar IGF1:IGFBP3 ratio), among Laotian children aged 6-23 mo; b) potential effect modification by baseline physical growth status.
Methods : Plasma samples from 419 children participating in the parent trial (n=3407) were collected at baseline and after ~9 mo (endline). Determination of IGF1 and IGFBP3 were done via an automated chemiluminescent assay. Linear regression models were used to assess main and modifying effects of PZ and MNP on IGF1 and IGFBP3, controlling for age, sex, district and baseline values of each biomarker.
The parent trial found no overall treatment effects on physical growth. In this subgroup, mean age at baseline was 14.2 ± 5.1 mo and ~38% were stunted. IGF1 and IGFBP3 at baseline were 45.9 ng/ml and 2143.0 ng/ml, respectively. At endline, geometric mean IGF1 (~39.0 – 39.2 ng/ml; p=0.99), IGFBP3 (2038-2076 ng/ml; p=0.83) and molar IGF1:IGFBP3 ratio (0.071-0.073; p=0.74) did not differ by group. Baseline weight-for-age z-score (WAZ) modified the treatment effect on IGFBP3 (p for interaction=0.05) and molar IGF1:IGFBP3 (p for interaction=0.04). In non-underweight children (WAZ ≥ -2), mean IGFBP3 in the PZ group (2000 ng/ml) was significantly lower than in the placebo (2148 ng/ml; p=0.03) and MNP (2157 ng/ml; p=0.03) groups. In underweight children, however, the IGFBP3 in the PZ group (2039 ng/ml) was higher than the placebo (1774 ng/ml; p=0.05) but not the MNP (1881 ng/ml; p=0.15) group. PZ (relative to placebo and MNP) appeared to reduce the bioavailability of IGF1 in underweight children, while increasing IGF1 bioavailability in non-underweight children (p interaction = 0.04).
IGF1 in this population did not respond to PZ or MNP. PZ (relative to placebo and MNP) was associated with higher endline IGFBP3 concentrations in underweight children but lower values in non-underweight children. These results suggest that PZ affected activity in the GH-IGF axis in these children, but additional evidence is needed to understand long term implications for growth in this population.
Funding Sources :
By The Thrasher Research Fund, with support from the Mathile Institute for the Advancement of Human Nutrition, Nutrition International and the Bill & Melinda Gates Foundation.