Effect of Antenatal Micronutrient Supplementation on the Plasma Proteome in School Aged Children in Nepal.
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Date
2015
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Abstract
Objectives: Antenatal micronutrient interventions may influence maternal and offspring health in
chronically undernourished settings; however, molecular mechanisms remain largely
unexplored. We examined effects of multiple combinations of antenatal micronutrients as
supplements on the plasma proteome of offspring at 6-8 years of age.
Methods: We applied quantitative mass spectrometry to measure plasma protein abundance in
500 children whose mothers had been randomized to receive daily supplements of folic acid (FA),
iron-folic acid (IFA), iron-folic acid-zinc (IFAZn), multiple micronutrient (MM), or placebo (control)
from 1st trimester to 3 months postpartum (all tablets contained vitamin A). We identified
differentially abundant proteins and sets of proteins sharing a common biological function by
enrichment analysis using the Gene Ontology (GO) database. Results: With a relaxed discovery threshold (false discovery rate <0.25), maternal FA
supplementation increased the abundance of insulin-like growth factor-1 (IGF1) by 33.7 (95% CI:
14.7-55.8)%; maternal IFA supplementation increased tissue inhibitor of metalloproteinase 1 by
12.5 (5.9-19.6)%. All supplements containing iron-folic acid increased IGF1, IGF2, and IGFbinding
protein 5 by 23.9 (9.1-40.7)%, 28.6 (10.7-49.4)%, and 23.7 (10.5-38.5)%, respectively, and
decreased stromal interaction molecule 1 by 63.3 (36.7-78.8)%. With a discovery threshold of 0.05,
maternal IFA supplementation negatively enriched proteins localized in microtubules (GO:5874)
with an enrichment score (ES) of -0.62 and maternal IFA and MM supplementation positively
enriched proteins with growth factor activity (GO:8083) with ES of 0.70 and 0.75, respectively (all
p-values <0.0001).
Conclusions: Antenatal micronutrient supplementation exerts subtle metabolic effects on proteins
involved in regulating growth/development and intracellular structure in school-aged children.
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Lee Sun Eun, West Keith P, Cole Robert N, Ruczinski Ingo, Schulze Kerry, Wu Lee, Yager James D, Groopman John, Christian Parul. Effect of Antenatal Micronutrient Supplementation on the Plasma Proteome in School Aged Children in Nepal. European Journal of Nutrition & Food Safety. 2015 Special issue; 5(5): 1074-1075.