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. AIMS: 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. CONCLUSION: The cardiovascular plasma biomarker MR-proANP is a promising candidate for monitoring PDA evolution in very preterm infants