Abstract
Background
Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported.
Methods
Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide.
Results
Of 118 infants, 56 were HEU, ART exposed. In adjusted analyses, mean cord insulin (β = 0.295, p = 0.03) and C-peptide (β = 0.522, p < 0.01) were significantly higher in HEU vs. HUU newborns. HEU neonates exhibited primarily positive associations between complex lipids and C-peptide, indicative of fuel storage, and augmented associations between cord eicosanoids and cytokines. HUU neonates exhibited negative associations with lipids and C-peptide indicative of increased fuel utilization.
Conclusion
Higher cord insulin and C-peptide in HEU vs. HUU newborns as well as differences in cord metabolites, metabolic-related cytokines, and eicosanoids may reflect a propensity for fuel storage and an inflammatory milieu suggestive of fetal metabolic changes associated with in utero HIV/ART exposure.
Impact
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There is a paucity of studies assessing cord blood and neonatal metabolic health in HIV-exposed uninfected (HEU) newborns, an increasing population worldwide.
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Compared to HIV-unexposed uninfected (HUU) newborns, HEU newborns exhibit alterations in fuel homeostasis and an inflammatory milieu associated with in utero HIV/antiretroviral therapy (ART) exposure.
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The long-term implications of these neonatal findings are as yet unknown, but merit continued evaluation as this important and growing population ages into adulthood.
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Acknowledgements
We would like to thank all the study participants and staff at the Mount Sinai Medical Center Obstetrical Clinic. This work was supported by K23HD070760 and by the Icahn School of Medicine at Mount Sinai Dean’s Office and ConduITS—the Institutes for Translational Sciences (CTSA) (UL1TR001433). Y.Q. was supported by NIDDK P60DK020541. I.J.K. was supported by grants NIDDK P60DK020541 (Einstein DRTC) and NIAID 1U19AI091175 (Einstein CMCR), and had support of a S10 SIG Award for the Sciex 6500+ QTRAP (1S10OD021798-01) which was used to perform the mass spectrometric assay evaluations in this study.
Funding
This work was supported in part by NICHD K23HD070760 and by the Icahn School of Medicine at Mount Sinai Dean’s Office and ConduITS—the Institutes for Translational Sciences (CTSA) (UL1TR001433). Y.Q. is supported by NIDDK P60DK020541. I.J.K. was supported by grants NIDDK P60DK020541 (Einstein DRTC) and NIAID 1U19AI091175 (Einstein CMCR), and the mass spectrometric work at Einstein DRTC-SIMC was supported by a S10 SIG Award for the Sciex 6500+ QTRAP (1S10OD021798-01).
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J.J., R.S.S., E.J.A. and D.L. conceptualized this study. J.J. wrote the first draft of the manuscript, and I.J.K. assisted with important edits. J.J. conducted data analyses involving clinical data, while L.C.B. conducted the data analyses involving omics data, and S.S. assisted with all data analyses. L.C.B. contributed to the “Methods” section. I.J.K. contributed to the “Results” and “Discussion” section. J.J., I.J.K., M.E.G. and D.L. made significant edits before completing the final manuscript. Y.Q., T.A.K., B.K., S.A., L.M., E.J.A. and R.S.S. all reviewed and edited the manuscript. J.J. finalized the manuscript. All authors approved the final manuscript.
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All participants provided written informed consent. This study was approved by the Institutional Review Board of the Icahn School of Medicine at Mount Sinai.
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Jao, J., Balmert, L.C., Sun, S. et al. Distinct cord blood C-peptide, adipokine, and lipidomic signatures by in utero HIV exposure. Pediatr Res 92, 233–241 (2022). https://doi.org/10.1038/s41390-021-01705-1
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DOI: https://doi.org/10.1038/s41390-021-01705-1
