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Metabolic risks at birth of neonates exposed in utero to HIV-antiretroviral therapy relative to unexposed neonates: an NMR metabolomics study of cord blood
Authors:Gontse P Moutloatse  Madeleine J Bunders  Mari van Reenen  Shayne Mason  Taco W Kuijpers  Udo F H Engelke  Ron A Wevers  Carools J Reinecke
Institution:1.Centre for Human Metabolomics, Faculty of Natural Sciences,North-West University (Potchefstroom Campus),Potchefstroom,South Africa;2.Department of Experimental Medicine, Academic Medical Centre (AMC),University of Amsterdam (UvA),Amsterdam,The Netherlands;3.Emma Children’s Hospital, AMC,University of Amsterdam,Amsterdam,The Netherlands;4.Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children’s Hospital, AMC,University of Amsterdam,Amsterdam,The Netherlands;5.Translational Metabolic Laboratory - 830 TML, Department Laboratory Medicine,Radboud University Medical Centre,Nijmegen,The Netherlands
Abstract:

Introduction

Antiretroviral therapy (ART) for HIV-infected pregnant women is highly effective in preventing mother-to-child transmission (PMTCT) of the virus, but deleterious metabolic and mitochondrial observations in infants born to HIV-infected women treated with ART during pregnancy are periodically reported.

Objectives

This study addresses the concern of HIV-ART-induced metabolic perturbations through a metabolomics study of cord blood collected during transitional neonatal hypoglycaemia following birth from newborns either exposed or unexposed to fetal HIV-ART.

Methods

Proton magnetic resonance spectra from cord blood of 11 in utero HIV-ART-exposed and 14 unexposed newborns, as well as serum from 8 control infants, generated 114 spectral bins which were used to identify significant metabolites by means of univariate and multivariate statistical analyses.

Results

The metabolite profiles differed significantly between that from the unexposed newborns and that from infants—interpreted to characterize the state of transitional neonatal hypoglycaemia (low glucose and high lactic acid and ketone bodies). Quantitative analysis of potential ATP generation showed no meaningful difference in the global metabolite profiles of HIV-ART-exposed and unexposed neonates, but Volcano plot analysis, affirmed by odds ratios, indicated that exposure to HIV-ART affected the plasma 3-hydroxybutyric acid and hypoxanthine concentrations.

Conclusions

The metabolite profile for transitional neonatal hypoglycaemia indicated that HIV-ART did not compromise the exposed neonates to the energy stress of allostasis experienced at birth. Increased hypoxanthine and 3-hydroxybutyric acid indicates metabolic stress at birth in some of the newborns exposed to HIV-ART and raises a concern about unrecognized prolonged allostasis with potential neurological consequences for these infants.
Keywords:
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