title: Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a systematic review and meta-analysis.
abstract: Although lifelong combination antiretroviral therapy (ART) is recommended for all individuals with HIV, few data exist for pregnancy outcomes associated with ART initiation before conception. We assessed adverse pregnancy outcomes associated with ART initiated before conception compared with that of ART started after conception.
  
  
  
  We did a systematic review of studies from low-income, middle-income, and high-income countries by searching the Cochrane Central Register of Controlled Trials, Embase, LILACS, MEDLINE, Toxline, Web of Knowledge, and WHO Global Index Medicus and trials in progress (International Clinical Trials Registry Platform) for randomised trials, quasi-randomised trials, and prospective cohort studies done between Jan 1, 1980, and June 1, 2016, in which timing of ART initiation in pregnant women living with HIV was reported. We used the risk ratio (RR) and corresponding 95% CIs as the primary measure to assess the association between the selected outcomes and ART initiation before conception versus after conception. We used a random-effects model to pool risk ratios.
  
  
  
  We included 11 studies with 19 189 mother-infant pairs. Women who started ART before conception were significantly more likely to deliver preterm (pooled RR 1·20, 95% CI 1·01-1·44) or very preterm (1·53, 1·22-1·92), or to have low-birthweight infants (1·30, 1·04-1·62) than were those who began ART after conception. Few data exist for neonatal mortality. The risk of very low birthweight, small for gestational age, severe small for gestational age, stillbirth, and congenital anomalies did not differ significantly between women who were taking ART before conception and those who began ART after conception.
  
  
  
  The benefits of ART for maternal health and prevention of perinatal transmission outweigh risks, but data for the extent and severity of these risks are scarce and of low quality. As use of ART before conception rapidly increases globally, monitoring for potential adverse pregnancy outcomes will be crucial.
  
  
  
  WHO.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK; Department of Public Health (IHCAR), Karolinska Institute, Stockholm, Sweden; Centre for Evidence-based Health Care, Stellenbosch University, South Africa.
authors.forename: Olalekan A
authors.initials: OA
authors.lastname: Uthman
authors.affiliation: Department of Medicine and Centre for Infectious Diseases, Stellenbosch University, South Africa; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA; Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: jbn16@pitt.edu.
authors.forename: Jean B
authors.initials: JB
authors.lastname: Nachega
authors.affiliation: Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Anderson
authors.affiliation: University of British Columbia, Vancouver, BC, Canada; Precision Global Health, Vancouver, BC, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Kanters
authors.affiliation: Precision Global Health, Vancouver, BC, Canada.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Françoise
authors.initials: F
authors.lastname: Renaud
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Shaffiq
authors.initials: S
authors.lastname: Essajee
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; World Health Organization, Geneva, Switzerland.
authors.forename: Meg C
authors.initials: MC
authors.lastname: Doherty
authors.affiliation: Elizabeth Glazer Pediatric AIDS Foundation, Washington, DC, USA.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001724:Birth Weight / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007391:International Cooperation; D009035:Mothers; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011446:Prospective Studies; D012959:Socioeconomic Factors
chemical_list: D019380:Anti-HIV Agents