title: Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States.
abstract: We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PI-containing as opposed to NNRTI-containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children.
authors.affiliation: 1 Children's National Health System , Division of Genetics & Metabolism, Washington, DC.
authors.forename: Brian
authors.initials: B
authors.lastname: Kirmse
authors.affiliation: 2 Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research , Boston, Massachusetts.
authors.forename: Tzy-Jyun
authors.initials: TJ
authors.lastname: Yao
authors.affiliation: 1 Children's National Health System , Division of Genetics & Metabolism, Washington, DC.
authors.forename: Sean
authors.initials: S
authors.lastname: Hofherr
authors.affiliation: 2 Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research , Boston, Massachusetts.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kacanek
authors.affiliation: 2 Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research , Boston, Massachusetts.
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.affiliation: 3 New York University/Langone School of Medicine , Division of Pediatric Infectious Disease and Immunology, New York, New York.
authors.forename: Charlotte V
authors.initials: CV
authors.lastname: Hobbs
authors.affiliation: 4 National Institutes of Health (NICHD) , Maternal and Pediatric Infectious Disease Branch, Bethesda, Maryland.
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.affiliation: 3 New York University/Langone School of Medicine , Division of Pediatric Infectious Disease and Immunology, New York, New York.
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.affiliation: 5 Tulane University School of Medicine , New Orleans, Louisiana.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.affiliation: 1 Children's National Health System , Division of Genetics & Metabolism, Washington, DC.
authors.forename: Marshall
authors.initials: M
authors.lastname: Summar
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D014481:United States; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C116917:acylcarnitine; D002331:Carnitine