Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Closed

Effects of zinc alone versus multiple micronutrients on IGFBP3, IGF1 and growth in Laotian children

Maxwell Barffour, PhD

Summary

BACKGROUND: Although supplementation with zinc alone improves growth, multiple micronutrient supplementation is a more desirable strategy for targeting multiple micronutrient deficiency in low income settings. Because supplementation with a standard MNP (containing 4.1-5 mg Zn, 12. 5 mg iron and 13 other micronutrient) does not improve growth, likely because of interactions involving zinc and iron, there is a need to show whether increasing the zinc content of MNP (relative to the iron dose) will improve growth outcomes in children. Furthermore, in light of growing concerns that the conventional anthropometric measures are not sensitive indicators of growth rate, there is a need to explore the use of growth biomarkers, such as growth hormones in defining growth status, growth potential and response to micronutrient supplements. GAP: This study was designed to evaluate the comparative benefits of preventive zinc supplementation alone versus a high-zinc MNP on plasma concentration of IGFBP3 and IGF1, and to determine whether IGFBP3 and IGF1 mediates the growth response to zinc and MNP. HYPOTHESES: • Compared to the placebo control group, IGFBP3 and IGF1 concentrations after 36 weeks of supplementation will be higher in both PZ and MNP groups, controlling for baseline values. • A positive response in IGFBP3 or IGF1 will be associated with a higher linear growth rate and reduced stunting prevalence in the MNP and PZ groups relative to the placebo group. METHODS: A double-blind, placebo controlled, randomized trial investigating the comparative growth benefits of daily supplementation for 36 weeks with zinc supplementation (7 mg/d) versus daily MNP (containing 10 mg zinc) among rural Laotian children. Analyses of baseline and endline plasma IGF1 and IGFBP3 concentration in the placebo (n=155), PZ (n=112) and MNP (n=141) groups. Determination of plasma IGF1 and IGFBP3 were done via an automated chemiluminescent assay. Anthropometry was assessed at baseline, 18 weeks and 36 weeks. ANCOVA was used to assess main effects and statistical interactions. RESULTS: At 36 weeks, geometric mean IGF1 (~39.0 – 39.2 ng/ml; p=0.99) and IGFBP3 (2038-2076 ng/ml; p=0.83) did not differ by group. At 18 weeks, LAZ in the PZ group (-1.45) was higher than the MNP (-1.70) and control (-1.55) groups (p=0.01) among children in highest baseline IGF1 tertile (p for interaction =0.006). At 36 weeks, WAZ in the PZ group (-1.55) was significantly higher than the MNP (-1.75) and control (-1.65) groups (p=0.03), among children in the lowest baseline IGFBP3 tertile (p for interactions=0.06). No other interactions were observed. IMPACT: Although IGF1 and IGFBP3 did not respond to PZ and MNP, baseline IGF1 and IGFBP3 significantly modified the impact of PZ and MNP on linear and ponderal growth. Our data suggest that IGF1 bioavailability drives catch-up growth in zinc-supplemented children. The assessment of growth biomarkers, as part of physical growth monitoring or growth promoting programs, may enhance the interpretation of program results

Supervising Institution:
University of California, Davis

Mentors
Robin Bernstein

Project Location:
Laos, United States

Award Amount:
$26,749