Maternal biomarker patterns for metabolism and inflammation in pregnancy are influenced by multiple micronutrient supplementation and associated with childrens’s biomarker patterns and nutritional status at 9-12 years of age in Lombok, Indonesia

Abstract

Maternal nutritional status influences fetal development and long-term risk for adult non-communicable diseases. The underlying mechanisms of these long-term effects remain poorly understood. We examined whether maternal biomarkers for metabolism and inflammation during pregnancy were associated with child biomarkers in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, ISRCTN34151616) in Lombok, Indonesia wherein archived blood specimens and relevant data were available from pregnant women and their children 9-12 years after birth. Forty-four mother-child dyads comprising 132 specimens were analyzed by multiplex microbead immunoassays to quantify vitamin D-binding protein (D), adiponectin (A), retinol-binding protein 4 (R), C-reactive protein (C), and leptin (L). Principal component analysis (PCA) revealed distinct variance patterns, i.e. principal components (PC), for baseline pregnancy bp.pc1.D{downarrow}A{downarrow}R{downarrow} and bp.pc2.C{downarrow}L{uparrow}; combined follow-up and post-partum dp-pp.pc1.D{uparrow}{downarrow}A{uparrow}R{uparrow}{downarrow}L{downarrow} and dp-pp.pc2.A{uparrow}C{uparrow}L{uparrow}; and children ch.pc1.D{uparrow}R{uparrow}C{uparrow} and ch.pc2.D{downarrow}A{uparrow}L{uparrow}. Maternal multiple micronutrient (MMN) supplementation modified the association between baseline maternal bp.pc2.C{downarrow}L{uparrow} and post-supplementation maternal dp-pp.pc2.A{downarrow}C{uparrow}L{uparrow} (p=0.022). Significant associations were found between maternal dp-pp.pc2.A{uparrow}C{uparrow}L{uparrow} and increased child s ch.pc1.D{uparrow}R{uparrow}C{uparrow} (p=0.036), and decreased child s BMI z-score (BMIZ) (p=0.022); and between maternal dp-pp.pc1.D{uparrow}{downarrow}A{uparrow}R{uparrow}{downarrow}L{uparrow} and increased child s BMIZ (p=0.036). Child s ch.pc1.D{uparrow}R{uparrow}C{uparrow} was associated with decreased birth weight (p=0.036), and increased childs BMIZ (p=0.002); and ch.pc2.D{downarrow}A{uparrow}L{uparrow} was associated with increased childs BMIZ (p=0.005), decreased maternal height (p=0.030) and girls (p=0.002). Elevated adiponectin and leptin pattern in pregnancy was associated with increased C-reactive protein and vitamin A and D binding proteins pattern in children, suggesting biomarkers acting in concert may be more important than single biomarker effects. Patterns in pregnancy proximal to birth were more associated with child status, and child patterns were most frequently associated with child status, particularly child BMI. Although MMN supplementation and certain maternal biomarker patterns have effects on metabolism and inflammation in pregnancy and in the child, nevertheless, nutrition conditions after birth may have a greater impact.