title: Cardiovascular biomarkers pro-atrial natriuretic peptide and pro-endothelin-1 to monitor ductus arteriosus evolution in very preterm infants.
abstract: BACKGROUND
  The diagnostic and prognostic appraisal of patent ductus arteriosus (PDA) in preterm infants is still debatable.
  
  
  OBJECTIVE
  To compare plasma cardiovascular biomarkers with echocardiographic indices alongside ductus arteriosus (DA) evolution in very preterm infants within the first week of life.
  
  
  METHODS
  Mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET-1) levels were prospectively measured on the second and sixth days of life (DOL) in 52 preterm infants born before 32weeks of gestation. Echocardiographic indices to define DA patency and significance were simultaneously obtained. Logistic regression and receiver operating characteristics (ROC) analyses were used to assess and quantify the biomarkers' diagnostic capacities.
  
  
  RESULTS
  Thirty infants exhibited PDA on DOL 2; in 21 of these infants, DA was characterized as hemodynamically significant. Treatment failure after a first course of indomethacin was noted in 8 infants (DOL 6), whereas 7 participants underwent later surgical ligation. The diagnostic accuracy of cardiovascular biomarkers was moderate on DOL 2 but high on DOL 6. PDA was the only significant predictor of MR-proANP levels on DOL 6, independent of the effect of clinical confounders (regression coefficient 0.426, R(2) 0.60). Infants with MR-proANP ≥850pmol/l on DOL 2 had 3.9-fold higher risk (95% CI 1.01 to 14.5) of being diagnosed with significant DA, whereas infants with MR-proANP ≥700pmol/l on DOL 6 had 7.1-fold higher risk (1.9 to 27.2) for pharmaceutical treatment failure.
  
  
  CONCLUSIONS
  The cardiovascular plasma biomarker MR-proANP is a promising candidate for monitoring PDA evolution in very preterm infants.
authors.affiliation: Department of Neonatology, University Hospital Zurich, Switzerland; Department of Intensive Care Medicine and Neonatology, University Children's Hospital, Zurich, Switzerland.
authors.forename: Beate
authors.initials: B
authors.lastname: Grass
authors.affiliation: Department of Neonatology, University Hospital Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Baumann
authors.affiliation: Department of Neonatology, University Hospital Zurich, Switzerland.
authors.forename: Romaine
authors.initials: R
authors.lastname: Arlettaz
authors.affiliation: Neonatal Intensive Care Unit, University Hospital of Patras, Greece; University Children's Hospital Basel (UKBB), Switzerland.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Fouzas
authors.affiliation: Division of Neonatology, Children's Hospital Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Spanaus
authors.affiliation: Department of Neonatology, University Hospital Zurich, Switzerland; University Children's Hospital Basel (UKBB), Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. Electronic address: sven.wellmann@usz.ch.
authors.forename: Sven
authors.initials: S
authors.lastname: Wellmann
mesh_terms: D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004374:Ductus Arteriosus, Patent / Q000097:blood* / Q000000981:diagnostic imaging; D019332:Endothelin-1 / Q000097:blood*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D016015:Logistic Models; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D009320:Atrial Natriuretic Factor
keywords: Cardiovascular biomarker; Echocardiography; Endothelin-1; Heart; Natriuretic peptide; Newborn; Patent ductus arteriosus; Preterm infants