title: Prognostic factors in pediatric pulmonary arterial hypertension: A systematic review and meta-analysis.
abstract: BACKGROUND
  Despite the introduction of targeted therapies in pediatric pulmonary arterial hypertension (PAH), prognosis remains poor. For the definition of treatment strategies and guidelines, there is a high need for an evidence-based recapitulation of prognostic factors. The aim of this study was to identify and evaluate prognostic factors in pediatric PAH by a systematic review of the literature and to summarize the prognostic value of currently reported prognostic factors using meta-analysis.
  
  
  RESULTS
  Medline, EMBASE and Cochrane Library were searched on April 1st 2014 to identify original studies that described predictors of mortality or lung-transplantation exclusively in children with PAH. 1053 citations were identified, of which 25 were included for further analysis. Hazard ratios (HR) and 95% confidence intervals were extracted from the papers. For variables studied in at least three non-overlapping cohorts, a combined HR was calculated using random-effects meta-analysis. WHO functional class (WHO-FC, HR 2.7), (N-terminal pro-) brain natriuretic peptide ([NT-pro]BNP, HR 3.2), mean right atrial pressure (mRAP, HR 1.1), cardiac index (HR 0.7), indexed pulmonary vascular resistance (PVRi, HR 1.3) and acute vasodilator response (HR 0.3) were identified as significant prognostic factors (p ≤ 0.001).
  
  
  CONCLUSIONS
  This systematic review combined with separate meta-analyses shows that WHO-FC, (NT-pro)BNP, mRAP, PVRi, cardiac index and acute vasodilator response are consistently reported prognostic factors for outcome in pediatric PAH. These variables are useful clinical tools to assess prognosis and should be incorporated in treatment strategies and guidelines for children with PAH.
authors.affiliation: Centre for Congenital Heart Diseases, Department of Paediatric Cardiology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands. Electronic address: m.ploegstra@umcg.nl.
authors.forename: Mark-Jan
authors.initials: MJ
authors.lastname: Ploegstra
authors.affiliation: Centre for Congenital Heart Diseases, Department of Paediatric Cardiology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
authors.forename: Willemijn M H
authors.initials: WMH
authors.lastname: Zijlstra
authors.affiliation: Centre for Congenital Heart Diseases, Department of Paediatric Cardiology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Douwes
authors.affiliation: Department of Epidemiology, University Medical Centre Groningen, University of Groningen, The Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.affiliation: Centre for Congenital Heart Diseases, Department of Paediatric Cardiology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
authors.forename: Rolf M F
authors.initials: RMF
authors.lastname: Berger
mesh_terms: D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Mortality; Pediatrics; Prognosis; Pulmonary hypertension