title: Antiretroviral exposure during pregnancy and adverse outcomes in HIV-exposed uninfected infants and children using a trigger-based design.
abstract: OBJECTIVE
  To evaluate the safety of in-utero antiretroviral exposure in children born to mothers with HIV, using a trigger-based design.
  
  
  METHODS
  The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in-utero antiretroviral drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting predefined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events.
  
  
  METHODS
  Adverse event "cases" were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various antiretroviral exposures during pregnancy.
  
  
  RESULTS
  Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any antiretroviral regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case [RR = 1.69, 95%confidence interval (CI) 1.08-2.64] and didanosine plus stavudine (<1% exposed) with increased risk of both neurodevelopmental (RR = 12.40, 95%CI 5.29-29.08) and language (RR = 4.84, 95%CI 1.14-20.51) cases.
  
  
  CONCLUSIONS
  Our findings support current recommendations for combination antiretroviral therapy during pregnancy, although higher risk of metabolic disorder with zidovudine exposure warrants further study.
authors.affiliation: aCenter for Biostatistics in AIDS ResearchbDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MassachusettscEunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MarylanddTulane University School of Medicine, New Orleans, LouisianaeUniversity of Alabama at Birmingham, Departments of Pediatrics and Microbiology, Birmingham, AlabamafDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MassachusettsgChildren's National Medical Center, Washington, DChFrontier Science Technology and Research Foundation (FSTRF), Amherst, New YorkiUniversity of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: Cenk
authors.initials: C
authors.lastname: Yildirim
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Crain
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Lucy
authors.initials: L
authors.lastname: Civitello
authors.forename: Angela
authors.initials: A
authors.lastname: Ellis
authors.forename: Laurie
authors.initials: L
authors.lastname: Butler
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rich
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; 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*; D011446:Prospective Studies; D014481:United States; D055815:Young Adult; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D044966:Anti-Retroviral Agents; D015215:Zidovudine