Diagnosing significant PDA using natriuretic peptides in preterm neonates: a systematic review

Pediatrics. 2015 Feb;135(2):e510-25. doi: 10.1542/peds.2014-1995. Epub 2015 Jan 19.


Background and objectives: Echocardiogram is the gold standard for the diagnosis of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates. A simple blood assay for brain natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in the diagnosis and management of hsPDA. Our objectives were to determine the diagnostic accuracy of BNP and NT-proBNP for hsPDA in preterm neonates and to explore heterogeneity by analyzing subgroups.

Methods: The systematic review was performed as recommended by the Cochrane Diagnostic Test Accuracy Working Group. Electronic databases, conference abstracts, and cross-references were searched. We included studies that evaluated BNP or NT-proBNP (index test) in preterm neonates with suspected hsPDA (participants) in comparison with echocardiogram (reference standard). A bivariate random effects model was used for meta-analysis, and summary receiver operating characteristic curves were generated.

Results: Ten BNP and 11 NT-proBNP studies were included. Studies varied by methodological quality, type of commercial assay, thresholds, age at testing, gestational age, and whether the assay was used to initiate medical or surgical therapy. Sensitivity and specificity for BNP at summary point were 88% and 92%, respectively, and for NT-proBNP they were 90% and 84%, respectively.

Conclusions: The studies evaluating the diagnostic accuracy of BNP and NT-proBNP for hsPDA varied widely by assay characteristics (assay kit and threshold) and patient characteristics (gestational and chronological age); therefore, generalizability between centers is not possible. We recommend that BNP or NT-proBNP assays be locally validated for specific patient population and outcomes, to initiate therapy or follow response to therapy.

Keywords: BNP; NT-pro BNP; PDA; meta-analyses; neonate; preterm infants; systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Ductus Arteriosus, Patent / blood*
  • Ductus Arteriosus, Patent / diagnosis*
  • Echocardiography
  • Female
  • Gestational Age
  • Hemodynamics / physiology
  • Humans
  • Infant, Newborn
  • Infant, Premature, Diseases / blood*
  • Infant, Premature, Diseases / diagnosis*
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests


  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain