title: Congenital diaphragmatic hernia: endothelin-1, pulmonary hypertension, and disease severity.
abstract: BACKGROUND
  Endothelin-1 (ET1) is dysregulated in pulmonary hypertension (PH). It may be important in the pathobiology of congenital diaphragmatic hernia (CDH).
  
  
  OBJECTIVE
  We hypothesized that ET1 levels in the first month would be higher in infants with CDH who subsequently expired or were discharged on oxygen (poor outcome). We further hypothesized that ET1 levels would be associated with concurrent severity of PH.
  
  
  METHODS
  We sampled plasma at 24 to 48 hours, and 1, 2, and 4 weeks of age in 40 prospectively enrolled newborns with CDH. We performed echocardiograms to estimate pulmonary artery pressure at less than 48 hours of age and weekly to 4 weeks. PH was classified in relationship to systemic blood pressure (SBP): less than 2/3 SBP, 2/3 SBP-systemic is related to pressure, or systemic-to-suprasystemic pressure.
  
  
  RESULTS
  ET1 levels at 1 and 2 weeks were higher in infants with poor outcome compared with infants discharged on room air (median and interquartile range: 27.2 [22.6, 33.7] vs. 19.1 [16.1, 29.5] pg/ml, P = 0.03; and 24.9 [17.6, 39.5] vs. 17.4 [13.7, 21.8] pg/ml, P = 0.01 at 1 and 2 weeks, respectively). Severity of PH was significantly associated with increasing ET1 levels at 2 weeks (16.1 [13.7, 21.8], 21.0 [17.4, 31.1], and 23.6 [21.9, 39.5] pg/ml for increasing PH class, P = 0.03). Increasing severity of PH was also associated with poor outcome at that time (P = 0.001).
  
  
  CONCLUSIONS
  Infants with CDH and poor outcome have higher plasma ET1 levels and severity of PH than infants discharged on room air. Severity of PH is associated with ET1 levels.
authors.affiliation: Department of Pediatrics, University of California San Francisco, 94143, USA. kellerr@peds.ucsf.edu
authors.forename: Roberta L
authors.initials: RL
authors.lastname: Keller
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Tacy
authors.forename: Karen
authors.initials: K
authors.lastname: Hendricks-Munoz
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Moon-Grady
authors.forename: John
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Phillip
authors.initials: P
authors.lastname: Moore
authors.forename: Kerilyn K
authors.initials: KK
authors.lastname: Nobuhara
authors.forename: Sam
authors.initials: S
authors.lastname: Hawgood
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Fineman
mesh_terms: D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004452:Echocardiography / Q000379:methods; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006548:Hernia, Diaphragmatic / Q000097:blood* / Q000150:complications; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000150:complications; D007231:Infant, Newborn; D011446:Prospective Studies; D012372:ROC Curve; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D019332:Endothelin-1