title: Fetal production of growth factors and inflammatory mediators predicts pulmonary hypertension in congenital diaphragmatic hernia.
abstract: BACKGROUND
  Congenital diaphragmatic hernia (CDH) represents a spectrum of lung hypoplasia, and consequent pulmonary hypertension (PH) is an important cause of postnatal morbidity and mortality. We studied biomarkers at the maternal-fetal interface to understand factors associated with the persistence of PH.
  
  
  METHODS
  Maternal and cord blood samples from fetuses with CDH and unaffected controls were analyzed using a human 39plex immunoassay kit. Cellular trafficking between the mother and the fetus was quantified using quantitative real-time PCR for nonshared alleles. Biomarker profiles were then correlated with CDH severity on the basis of the degree of PH.
  
  
  RESULTS
  Cord blood levels of epidermal growth factor, platelet-derived growth factor, and several inflammatory mediators increased significantly as the severity of CDH increased, whereas maternal levels of growth factors and mediators decreased significantly with CDH severity. Maternal cells were increased in fetuses with severe CDH as compared with controls, with elevated levels of the CXC chemokine ligand-10 in patients with the highest trafficking.
  
  
  CONCLUSIONS
  Patients with CDH demonstrate proinflammatory and chemotactic signals in fetal blood at the time of birth. Because some of these molecules have been implicated in the development of PH, prenatal strategies targeting specific molecular pathways may be useful adjuncts to current fetal therapies.
authors.affiliation: Department of Pediatrics, University of California, San Francisco (UCSF), San Francisco, CA, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Fleck
authors.forename: Geoanna
authors.initials: G
authors.lastname: Bautista
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Roberta L
authors.initials: RL
authors.lastname: Keller
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Moon-Grady
authors.forename: Kelly
authors.initials: K
authors.lastname: Gonzales
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: C J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Hanmin
authors.initials: H
authors.lastname: Lee
authors.forename: Doug
authors.initials: D
authors.lastname: Miniati
authors.forename: Tippi C
authors.initials: TC
authors.lastname: MacKenzie
mesh_terms: D015415:Biomarkers / Q000097:blood*; D018925:Chemokines / Q000097:blood; D004815:Epidermal Growth Factor / Q000097:blood; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000002:abnormalities*; D006548:Hernia, Diaphragmatic / Q000150:complications; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D007118:Immunoassay; D018836:Inflammation Mediators / Q000097:blood; D016015:Logistic Models; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D018925:Chemokines; D018836:Inflammation Mediators; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor