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Metabolic risks of neonates at birth following in utero exposure to HIV-ART: the amino acid profile of cord blood

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Abstract

Introduction

Untargeted metabolomics of cord blood indicated that antiretroviral therapy to HIV-infected mothers (HIV-ART) did not compromise the exposed neonates with regard to the stress of neonatal hypoglycaemia at birth. However, identified biomarkers reflected stress in their energy metabolism, raising concern over developmental risks in some newborns exposed to ART.

Objectives

This study addresses the concern over HIV-ART-induced metabolic perturbations by expanding the metabolomics study to the amino acid profiles in cord blood collected at birth from newborns either exposed or unexposed to HIV-ART in utero.

Methods

Amino acid profiles derived from liquid chromatographic triple quadruple spectra of cord blood from neonates exposed and unexposed to HIV-ART (cohort 1) were investigated using a metabolomics approach. Amino acid data, generated by ultra performance liquid chromatography–tandem mass spectrometry from similar cases (cohort 2), were included for comparison.

Results

Multivariate and supporting statistics indicated differentiation between the exposed and unexposed neonates in both cohorts, caused by a general decrease or downregulation of amino acid concentrations in the cord blood samples from the exposed cases. Specifically, significant upregulation of aspartic acid in both cohorts and downregulation of arginine, and of threonine, tryptophan and lysine in cohorts 1 and 2, respectively, were observed.

Conclusions

The benefits of ART for HIV-infected pregnant women are well established. However, the amino acid profile of cord blood, obtained from the two independent cohorts, adds to observed metabolic risks of in utero HIV-ART-exposed newborns. These risks could potentially have adverse consequences for the future health of some exposed infants.

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Acknowledgements

We thank Dr. K. Boer, Prof. T. W. Kuijpers, Dr. M. Godfried, Dr. J. Nellen, Dr. E. van Leeuwen and Dr. H. J. Scherpbier for caring for the pregnant women and their infants and collection of cord blood samples. This work was supported by the Netherlands Organisation for Scientific Research through an Agiko stipendium (92003417) and the Dutch AIDS Foundation (2006015). Further support for this research was provided by the Technological Innovation Agency (TIA) of the Department of Science and Technology of South Africa. We also acknowledge the National Research Foundation (NRF) of South Africa for awarding GM a postgraduate busary. The views and findings of this investigation are those of the authors and do not reflect or represent any policies of the funders.

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Authors and Affiliations

  1. Centre for Human Metabolomics, Faculty of Natural Sciences, North-West University (Potchefstroom Campus), Potchefstroom, South Africa

    Gontse P. Moutloatse, Zander Lindeque, Mari van Reenen & Carolus J. Reinecke

  2. Department of Analytical Biosciences, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands

    Johannes C. Schoeman & Thomas Hankemeier

  3. Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 AZ, Amsterdam, The Netherlands

    Madeleine J. Bunders

  4. Emma Childrens Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 AZ, Amsterdam, The Netherlands

    Madeleine J. Bunders

Authors
  1. Gontse P. Moutloatse
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  2. Johannes C. Schoeman
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  3. Zander Lindeque
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  4. Mari van Reenen
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  5. Thomas Hankemeier
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  6. Madeleine J. Bunders
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  7. Carolus J. Reinecke
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Corresponding author

Correspondence to Carolus J. Reinecke.

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The authors declare that there is no conflict of interest.

Ethical approval

Neonates: Ethical approval for the study and for the use of the samples from the two neonatal groups was obtained from the Ethics Committee of the Academic Medical Centre at the University of Amsterdam. Infants: Ethical approval for the samples from the infant group was obtained from the Ethics Committees of North-West University (Reference No. 02M02), including informed consent from the parents for serum analyses and eventual publication of results from anonymous cases in accordance with the ethical requirements of the diagnostic laboratory (Potchefstroom Laboratory for Inborn Errors of Metabolism).

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Moutloatse, G.P., Schoeman, J.C., Lindeque, Z. et al. Metabolic risks of neonates at birth following in utero exposure to HIV-ART: the amino acid profile of cord blood. Metabolomics 13, 89 (2017). https://doi.org/10.1007/s11306-017-1222-y

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  • DOI: https://doi.org/10.1007/s11306-017-1222-y

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