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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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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.


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.


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.


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.


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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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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Correspondence to Carolus J. Reinecke.

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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).

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