title: Meconium Atazanavir Concentrations and Early Language Outcomes in HIV-Exposed Uninfected Infants With Prenatal Atazanavir Exposure.
abstract: OBJECTIVE
  To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral (ARV) quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in 1-year olds.
  
  
  METHODS
  Pregnant women with HIV and their uninfected infants enrolled in the Surveillance Monitoring of Antiretroviral Therapy Toxicities study. Meconium ARV concentrations were quantified by liquid chromatography-tandem mass spectrometry. Language development at 1 year was assessed with MacArthur-Bates Communicative Development Inventory (CDI) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Late language emergence was defined as ≥ 1 of 4 CDI scores ≤ 10th percentile for age. Associations between fetal ATV exposure timing and duration, meconium ATV concentration, and language outcomes were evaluated, adjusting for potential confounders.
  
  
  RESULTS
  Through 2013, meconium samples were available from 175 of 432 infants with prenatal ATV exposure. Valid Bayley-III (n = 93) and CDI (n = 106) assessments also were available. After adjustment for potential confounders, higher ATV meconium concentrations were associated with lower late language emergence risk (P = 0.04) and cumulative ATV exposure duration also was associated with higher Bayley-III Language scores (P = 0.03). Maternal ATV duration and initiation week correlated with ATV meconium concentrations (positively and negatively, respectively).
  
  
  CONCLUSIONS
  Higher meconium ATV concentrations were protective against developmental language delays at 1 year, suggesting the importance of fetal ATV detoxification into meconium. This information supports ATV exposure safety for infant language development. ATV is a preferred ARV for pregnant women with HIV, suggesting the importance of ATV safety investigations. Additionally, further pursuit of the influences on language development in HIV-exposed uninfected infants is required.
authors.affiliation: *Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; §Speech, Language, Hearing Department, University of Kansas, Lawrence, KS; ‖Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA; and ¶Department of Research Pediatrics, Maternal, Child, and Adolescent Program for Infectious Diseases and Virology, Keck School of Medicine of USC, Los Angeles, CA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Himes
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huo
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Mabel L
authors.initials: ML
authors.lastname: Rice
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Sirois
authors.forename: Toni
authors.initials: T
authors.lastname: Frederick
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000032:analysis*; D000069446:Atazanavir Sulfate; D002853:Chromatography, Liquid; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007804:Language Development; D008297:Male; D008431:Maternal-Fetal Exchange; D008470:Meconium / Q000737:chemistry*; D009842:Oligopeptides / Q000032:analysis*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D011725:Pyridines / Q000032:analysis*; D053719:Tandem Mass Spectrometry
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate