Distinct cord blood C-peptide, adipokine, and lipidomic signatures by in utero HIV exposure

Jennifer Jao, Lauren C. Balmert, Shan Sun, Yunping Qiu, Thomas A. Kraus, Brian Kirmse, Rhoda S. Sperling, Elaine J. Abrams, Landon Myer, Stephen Arpadi, Mitchell E. Geffner, Derek LeRoith, Irwin J. Kurland

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish
Pages (from-to)233-241
Number of pages9
JournalPediatric Research
Issue number1
StatePublished - Jul 2022


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