Maternal biomarker patterns for metabolism and inflammation in pregnancy are influenced by multiple micronutrient supplementation and associated with child biomarker patterns and nutritional status at 9-12 years of age.

Lidwina Priliani,Safarina G Malik,Sukma Oktavianthi,Anuraj H Shankar,Elizabeth L Prado,Nancy Beam

doi:10.1371/journal.pone.0216848

Abstract

Maternal nutritional status influences fetal development and long-term risk for adult non-communicable diseases. However, the underlying mechanisms remain poorly understood. We examined whether biomarkers for metabolism and inflammation during pregnancy were associated with maternal health and with child biomarkers and health at 9–12 years of age in 44 maternal-child dyads from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, ISRCTN34151616) in Lombok, Indonesia. Archived blood for each dyad from maternal enrollment, later in pregnancy, postpartum, and from children at 9–12 years comprised 132 specimens. Multiplex microbead immunoassays were used 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↓A↓R↓ and bp.pc2.C↓L↑; combined follow-up during pregnancy and postpartum, dp-pp.pc1.D↑↓A↑R↑↓L↓ and dp-pp.pc2.A↑C↑L↑; and children, ch.pc1.D↑R↑C↑ and ch.pc2.D↓A↑L↑. Maternal multiple micronutrient (MMN) supplementation led to an association of baseline maternal bp.pc2.C↓L↑ with decreased post-supplementation maternal dp-pp.pc2.A↑C↑L↑ (p = 0.022), which was in turn associated with both increased child ch.pc1.D↑R↑C↑ (p = 0.036) and decreased child BMI z-score (BMIZ) (p = 0.022). Further analyses revealed an association between maternal dp-pp.pc1.D↑↓A↑R↑↓L↓ and increased child BMIZ (p = 0.036). Child ch.pc1.D↑R↑C↑ was associated with decreased birth weight (p = 0.036) and increased child BMIZ (p = 0.002). Child ch.pc2.D↓A↑L↑ was associated with increased child BMIZ (p = 0.005), decreased maternal height (p = 0.030) and girls (p = 0.002). A pattern of elevated maternal adiponectin and leptin in pregnancy was associated with increased C-reactive protein, vitamin A, and D binding proteins pattern in children, suggesting biomarkers acting in concert may have qualitative as well as quantitative influence beyond single biomarker effects. Patterns in pregnancy proximal to birth were more associated with child status. In addition, child patterns were more associated with child status, particularly child BMI. MMN supplementation affects maternal biomarker patterns of metabolism and inflammation in pregnancy, and potentially in the child. However, child nutrition conditions after birth may have a greater impact on metabolism and inflammation.

Highlights

Emerging epidemiological evidence has shown that the risk for non-communicable diseases (NCDs) during childhood or as an adult is mediated in part by maternal nutrition in pregnancy and fetal growth [1,2,3]
Increased concentrations of both leptin and retinol binding protein 4 (RBP4) have been associated with increased body mass index (BMI) [16,17], while adiponectin concentration was negatively associated with BMI [18]
Child status at age 9–12 years was characterized by height and weight which were converted to BMI-for-age z-score (BMIZ) following World Health Organization norms [41], and by systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Summary

Introduction

Emerging epidemiological evidence has shown that the risk for non-communicable diseases (NCDs) during childhood or as an adult is mediated in part by maternal nutrition in pregnancy and fetal growth [1,2,3]. Adipocytokines, including leptin, adiponectin, and retinol binding protein 4 (RBP4), play an important role in regulating metabolism, energy homeostasis and inflammatory responses [8,9,10,11]. RBP4, previously thought to act as a specific transport protein for retinol, has been added to the family of adipocytokines given its role in obesity-induced insulin resistance [15]. Increased concentrations of both leptin and RBP4 have been associated with increased body mass index (BMI) [16,17], while adiponectin concentration was negatively associated with BMI [18]. A previous study reported that maternal leptin and adiponectin concentrations were correlated with fetal leptin and adiponectin concentrations [23]

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Conclusion