TY - JOUR
T1 - Distinct cord blood C-peptide, adipokine, and lipidomic signatures by in utero HIV exposure
AU - Jao, Jennifer
AU - Balmert, Lauren C.
AU - Sun, Shan
AU - Qiu, Yunping
AU - Kraus, Thomas A.
AU - Kirmse, Brian
AU - Sperling, Rhoda S.
AU - Abrams, Elaine J.
AU - Myer, Landon
AU - Arpadi, Stephen
AU - Geffner, Mitchell E.
AU - LeRoith, Derek
AU - Kurland, Irwin J.
N1 - Funding Information:
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 Information:
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).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
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U2 - 10.1038/s41390-021-01705-1
DO - 10.1038/s41390-021-01705-1
M3 - Article
C2 - 34446848
AN - SCOPUS:85113546304
SN - 0031-3998
VL - 92
SP - 233
EP - 241
JO - Pediatric Research
JF - Pediatric Research
IS - 1
ER -
