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: there is a paucity of studies assessing cord blood and neonatal metabolic health in hiv-exposed uninfected (heu) newborns, an increasing population worldwide. 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. 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. research foundation, inc.>
