Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.

James G Scott,Alison D Gernand,Keith P West,Abu Ahmed Shamim,Lee Wu,Margia Arguello,Kerry J Schulze,Hasmot Ali,Parul Christian,Ashika Nanayakkara-Bind

doi:10.1371/journal.pone.0137269

James G Scott, Alison D Gernand + Show 8 more

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https://doi.org/10.1371/journal.pone.0137269

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Journal: PloS one	Publication Date: Oct 2, 2015
Citations: 12	License type: CC BY 4.0

Affiliation: Johns Hopkins University, Pennsylvania State University

Abstract

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.Trial RegistrationClinicalTrials.gov NCT00860470

Highlights

Intrauterine growth restriction remains a widespread public health issue across the globe [1]
In a rural area with low socioeconomic status and high rates of maternal and child malnutrition, we examined the impact of maternal multiple micronutrient (MM) supplementation compared to IFA on select fetal growth factors
There were no overall differences in maternal plasma levels of human placental lactogen (hPL) or placental growth hormone (PGH) or cord plasma levels of insulin, insulin-like growth factor-1 (IGF-1), or insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) between supplementation groups

Summary

Introduction

Intrauterine growth restriction remains a widespread public health issue across the globe [1]. Insulin and proteins in the insulin-like growth factor (IGF) family are some of the dominant regulators of fetal growth [6, 7]. PGH is somatotrophic [8] and concentrations are decreased in maternal plasma of infants with IUGR [9]. Both hPL and PGH are believed to create peripheral insulin resistance in the mother that allows for preferential glucose supply to the fetus [10]. Insulin and IGF-1 are structurally homologous and are likely the most prominent endocrine regulators of fetal growth [10], while IGF binding protein-1 (IGFBP-1) binds to IGF-1 to limit its activity. Cord concentrations of IGFBP-1 are inversely associated with birth weight [11]

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