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.

中文翻译：

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子宫内 HIV 暴露的不同脐带血 C 肽、脂肪因子和脂质组学特征

背景

据报道，暴露于 HIV 的未感染 (HEU) 婴儿的早期代谢紊乱。

方法

2011 年至 2015 年，美国队列中招募了感染 HIV 的孕妇和未感染 HIV 的孕妇及其新生儿。我们使用 ELISA 和通过液相色谱/质谱法分析代谢物、脂质亚种和类花生酸。采用线性回归评估宫内 HIV/ART 与胰岛素和 C 肽的关联。图形套索回归用于识别与 C 肽相关的代谢物/脂质亚种网络之间的差异。

结果

在 118 名婴儿中，56 名暴露于 HEU、ART。在调整后的分析中，平均脐带胰岛素 ( β  = 0.295，p  = 0.03) 和 C 肽 ( β  = 0.522，p  < 0.01) 在 HEU 与 HUU 新生儿中显着更高。HEU 新生儿主要表现出复杂脂质和 C 肽之间的正相关，表明燃料储存，以及脐带类花生酸和细胞因子之间的增强关联。HUU 新生儿与脂质和 C 肽呈负相关，表明燃料利用率增加。

结论

HEU 与 HUU 新生儿的更高脐带胰岛素和 C 肽以及脐带代谢物、代谢相关细胞因子和类花生酸的差异可能反映燃料储存倾向和炎症环境，提示胎儿代谢变化与子宫内 HIV/艺术曝光。

影响

• 缺乏评估暴露于 HIV 的未感染 (HEU) 新生儿的脐带血和新生儿代谢健康的研究，全世界人口不断增加。

• 与未暴露于 HIV 的未感染 (HUU) 新生儿相比，HEU 新生儿表现出燃料稳态的改变以及与子宫内 HIV/抗逆转录病毒治疗 (ART) 暴露相关的炎症环境。

• 这些新生儿发现的长期影响尚不清楚，但随着这一重要且不断增长的人口进入成年期，值得继续评估。