Metabolomic profiling of preterm birth in pregnant women living with HIV.

Autor: Tobin NH; Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Murphy A; Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Li F; Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Brummel SS; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Fowler MG; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Mcintyre JA; Anova Health Institute, Johannesburg, South Africa.; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa., Currier JS; Division of Infectious Diseases, Department of Internal Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Chipato T; University of Zimbabwe College of Health Sciences, Harare, Zimbabwe., Flynn PM; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA., Gadama LA; Department of Obstetrics and Gynecology, Johns Hopkins Research Project, Kamuzu University of Health Sciences, Blantyre, Malawi., Saidi F; University of North Carolina Project Malawi, Lilongwe, Malawi., Nakabiito C; MU-JHU Research Collaboration (MUJHU CARE LTD) CRS, Kampala, Uganda., Koos BJ; Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Aldrovandi GM; Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. galdrovandi@mednet.ucla.edu.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2023 Oct 25; Vol. 19 (11), pp. 91. Date of Electronic Publication: 2023 Oct 25.
DOI: 10.1007/s11306-023-02055-1
Abstrakt: Background: Preterm birth is a leading cause of death in children under the age of five. The risk of preterm birth is increased by maternal HIV infection as well as by certain antiretroviral regimens, leading to a disproportionate burden on low- and medium-income settings where HIV is most prevalent. Despite decades of research, the mechanisms underlying spontaneous preterm birth, particularly in resource limited areas with high HIV infection rates, are still poorly understood and accurate prediction and therapeutic intervention remain elusive.
Objectives: Metabolomics was utilized to identify profiles of preterm birth among pregnant women living with HIV on two different antiretroviral therapy (ART) regimens.
Methods: This pilot study comprised 100 mother-infant dyads prior to antiretroviral initiation, on zidovudine monotherapy or on protease inhibitor-based antiretroviral therapy. Pregnancies that resulted in preterm births were matched 1:1 with controls by gestational age at time of sample collection. Maternal plasma and blood spots at 23-35 weeks gestation and infant dried blood spots at birth, were assayed using an untargeted metabolomics method. Linear regression and random forests classification models were used to identify shared and treatment-specific markers of preterm birth.
Results: Classification models for preterm birth achieved accuracies of 95.5%, 95.7%, and 80.7% in the untreated, zidovudine monotherapy, and protease inhibitor-based treatment groups, respectively. Urate, methionine sulfone, cortisone, and 17α-hydroxypregnanolone glucuronide were identified as shared markers of preterm birth. Other compounds including hippurate and N-acetyl-1-methylhistidine were found to be significantly altered in a treatment-specific context.
Conclusion: This study identified previously known as well as novel metabolomic features of preterm birth in pregnant women living with HIV. Validation of these models in a larger, independent cohort is necessary to ascertain whether they can be utilized to predict preterm birth during a stage of gestation that allows for therapeutic intervention or more effective resource allocation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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