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

27Maternal nutritional status influences fetal development and long-term risk for adult 28 non-communicable diseases. The underlying mechanisms of these long-term effects remain 29 poorly understood. We examined whether maternal biomarkers for metabolism and 30 inflammation during pregnancy were associated with child biomarkers in the 31 Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, 32 ISRCTN34151616) in Lombok, Indonesia wherein archived blood specimens and relevant 33 data were available from pregnant women and their children 9-12 years after birth. Forty-four 34 mother-child dyads comprising 132 specimens were analyzed by multiplex microbead 35 immunoassays to quantify vitamin D-binding protein (D), adiponectin (A), retinol-binding 36 protein 4 (R), C-reactive protein (C), and leptin (L). Principal component analysis (PCA) 37 revealed distinct variance patterns, i.e. principal components (PC), for baseline pregnancy 38 bp.pc1.DAR and bp.pc2.CL; combined follow-up and post-partum dp-39 pp.pc1.DARL and dp-pp.pc2.ACL; and children ch.pc1.DRC and 40 ch.pc2.DAL. Maternal multiple micronutrient (MMN) supplementation modified the 41 association between baseline maternal bp.pc2.CL and post-supplementation maternal dp-42 pp.pc2.ACL (p=0.022). Significant associations were found between maternal dp-43 pp.pc2.ACL and increased child's ch.pc1.DRC (p=0.036), and decreased child's 44 BMI z-score (BMIZ) (p=0.022); and between maternal dp-pp.pc1.DARL and 45 increased child's BMIZ (p=0.036). Child's ch.pc1.DRC was associated with decreased 46 birth weight (p=0.036), and increased child's BMIZ (p=0.002); and ch.pc2.DAL was 47 associated with increased child's BMIZ (p=0.005), decreased maternal height (p=0.030) and48 girls (p=0.002). Elevated adiponectin and leptin pattern in pregnancy was associated with 49 increased C-reactive protein and vitamin A and D binding proteins pattern in children, 3 50 suggesting biomarkers acting in concert may be more important than single biomarker 51 effects. Patterns in pregnancy proximal to birth were more associated with child status, and 52 child patterns were most frequently associated with child status, particularly child BMI. 53 Although MMN supplementation and certain maternal biomarker patterns have effects on 54 metabolism and inflammation in pregnancy and in the child, nevertheless, nutrition 55 conditions after birth may have a greater impact. 56 57 Keywords: biomarkers, PCA, pregnancy, BMI z-score, VDBP, adiponectin, RBP4, CRP, 58 leptin 59 60 61 62 63 64 65 66 67 68 69 4 70 INTRODUCTION 71 Emerging epidemiological evidence has shown that the risk for non-communicable 72 diseases (NCDs) during childhood or as an adult is mediated in part by maternal nutrition in 73 pregnancy and fetal growth [1-3]. Studies in animal models indicate that alterations in 74 nutritional, metabolic, immune and hormonal milieu in-utero profoundly affect long-term 75 health of the offspring, including increased risk for NCDs such as diab...