Brain Natriuretic Propeptide as an Early Marker of Bronchopulmonary Dysplasia or Death in the Preterm Newborn

Abstract

Aim To investigate whether increased brain natriuretic propeptide (NT-proBNP) levels at 48 to 72 h of life are associated with the development of bronchopulmonary dysplasia (BPD) or death in premature neonates.

Methods A retrospective study was performed in neonates born before 32 weeks’ gestation or with birth weight below 1500 grams, in whom NT-proBNP determination and echocardiography were performed at 48 to 72 h of life. Associations between NT-proBNP levels and the combined outcome BPD or death were analyzed using multivariate logistic regression analysis.

Results 117 neonates with mean gestational age 27.8±2.1 weeks and birth weight 949.7±267.5 grams were included. Forty (34.2%) had an outcome of BPD or death. The risk of this combined outcome was found to be 3.95-fold higher (OR 3.95; 95% CI 1.1–14.6) in neonates with NT-proBNP levels above 17800 pg/mL.

Conclusion Increased NT-proBNP levels may be associated with a significant decrease in BPD-free survival in very immature newborns.

Zusammenfassung

Ziel Studie über die Verbindung zwischen erhöhter Konzentration von B-Typ Natriuretisches Peptid (NT-proBNP) in der 48. bis 72. Lebensstunde und der Entwicklung von bronchopulmonaler Dysplasie (BPD) oder Tod bei Frühgeborenen.

Methode Die Bestimmung von NT proBNP sowie die Durchführung einer Echokardiographie zwischen der 48. und 72. Lebensstunde bei Frühgeborenen mit einem Gestationsalter von weniger als 32 Schwangerschaftswochen oder einem Geburtsgewicht unter 1500 Gramm. Mittels multivariater logistischer Regression wurde analysiert ob es eine Verbindung zwischen den NT-proBNP-Konzentration und dem BPD-Ergebnis oder dem Tod gibt.

Ergebnisse 117 Frühgeborene mit mittlerem Gestationsalter von 27,8±2,1 Wochen und Geburtsgewicht von 949,7±267,5 gr. wurden einbezogen. Bei 40 Frühgeborenen (34,2%) kam es zu dem BPD oder dem Tod. Das Risiko erhöhte sich um das 3,95-Fache (OR 3,95; 95% CI 1,1–14,6) bei Frühgeborenen mit einer NT-proBNP-Konzentration über 17800 pg/mL.

Schlussfolgerung Eine erhöhte NT-proBNP-Konzentration könnte mit einer signifikanten Senkung der Wahrscheinlichkeit auf ein BPD-freies Überleben bei sehr unreifen Neugeborenen in Verbindung gebracht werden.

Key words

neonatal care - brain natriuretic propeptide - bronchopulmonary dysplasia - prematurity

Schlüsselwörter

Frühgeburt - B-typ natriuretisches Propeptid - Neonatale Pflege - Bronchopulmonale Dysplasie

• References

• 1 Bancalari E, Claure N, Sosenko IRS. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol 2003; 8: 63-71
• 2 Bhatt A, Pryhuber G, Huyck H. et al. Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 164: 1971-1980
• 3 Brown E. Increased risk of bronchopulmonary dysplasia in infants with patent ductus arteriosus. J Pediatr 1979; 95: 865-866
• 4 Chen H-L, Yang R-C, Lee W-T. et al. Lung function in very preterm infants with patent ductus arteriosus under conservative management: an observational study. BMC Pediatr 2015; 15: 167
• 5 Chen S, Tacy T, Clyman R. How useful are B-type natriuretic peptide measurements for monitoring changes in patent ductus arteriosus shunt magnitude?. J Perinatol 2010; 30: 780-785
• 6 Clyman RI. The role of patent ductus arteriosus and its treatments in the development of bronchopulmonary dysplasia. Semin Perinatol 2013; 37: 102-107
• 7 Coalson J, Winter V, Siler-Khodr T. et al. Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 1999; 160: 1333-1346
• 8 Czernik C, Metze B, Müller C. et al. Urinary N-terminal B-type natriuretic peptide predicts severe retinopathy of prematurity. Pediatrics 2011; 128: e454-e459
• 9 Doyle L, Anderson P. Long-term outcomes of bronchopulmonary dysplasia. Semin Fetal Neonatal Med 2009; 14: 391-395
• 10 Hammerman C, Shchors I, Schimmel MS. et al N-terminal-pro-B-type natriuretic peptide in premature patent ductus arteriosus: a physiologic biomarker, but is it a clinical tool?. Pediatr Cardiol 2010; 31: 62-65
• 11 Heuchan AM, Clyman RI. Managing the patent ductus arteriosus: current treatment options. Arch Dis Child Fetal Neonatal Ed 2014; 99: F431-F436
• 12 Ichiki T, Lee C, Burnett J. Biology of the Natriuretic Peptides. In: Januzzi J. (Ed.) Cardiac Biomarkers in Clinical Practice. 1st ed Burlington, Massachusetts: Jones & Bartlett Learning; 2011
• 13 Jain A, Shah P. Diagnosis, Evaluation, and Management of Patent Ductus Arteriosus in Preterm Neonates. JAMA Pediatr 2015; 169: 863-872
• 14 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723-1729
• 15 Joseph L, Nir A, Hammerman C. et al. N-terminal pro-B-type natriuretic peptide as a marker of bronchopulmonary dysplasia in premature infants. Am J Perinatol 2010; 27: 381-386
• 16 Martinovici D, Vanden Eijnden S, Unger P. et al. Early NT-proBNP is able to predict spontaneous closure of patent ductus arteriosus in preterm neonates, but not the need of its treatment. Pediatr Cardiol 2011; 32: 953-957
• 17 McCurnin D, Seidner S, Chang L. et al. Ibuprofen-induced patent ductus arteriosus closure: physiologic, histologic, and biochemical effects on the premature lung. Pediatrics 2008; 121: 945-956
• 18 Mine K, Ohashi A, Tsuji S. et al. B-type natriuretic peptide for assessment of haemodynamically significant patent ductus arteriosus in premature infants. Acta Paediatr 2013; 102: e347-e352
• 19 Montaner Ramón A, Galve Pradel A, Fernández Espuelas C et al. Utilidad del propéptido natriurético cerebral en el diagnóstico y manejo del ductus arterioso permeable. An Pediatría 2016 [Epub ahead of print]
• 20 Nakamura T, Takasaki J, Ogawa Y. Inflammatory changes in the lungs of premature infants with symptomaticpatent ductus arteriosus. Pediatr Int 2002; 44: 363-367
• 21 Nuntnarumit P, Chongkongkiat P, Khositseth A. N-terminal-pro-brain natriuretic peptide: a guide for early targeted indomethacin therapy for patent ductus arteriosus in preterm Infants. Acta Paediatr 2011; 100: 1217-1221
• 22 Sallmon H, Koehne P, Hansmann G. Recent Advances in the Treatment of Preterm Newborn Infants with Patent Ductus Arteriosus. Clin Perinatol 2016; 43: 113-129
• 23 Schmidt B, Davis P, Moddemann D. et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344: 1966-1972
• 24 Sellmer A, Bjerre JV, Schmidt MR. et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed 2013; 98: F505-F510
• 25 Sellmer A, Hjortdal VE, Bjerre JV. et al. N-Terminal Pro-B Type Natriuretic Peptide as a Marker of Bronchopulmonary Dysplasia or Death in Very Preterm Neonates: A Cohort Study. PLoS One 2015; 10: e0140079
• 26 Speer C. Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med 2006; 11: 354-362
• 27 Stoll BJ, Hansen NI, Bell EF. et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993–2012. JAMA 2015; 314: 1039-1051
• 28 Varsila E, Hallman M, Venge P. et al. Closure of patent ductus arteriosus decreases pulmonary myeloperoxidase in premature infants with respiratory distress syndrome. Biol Neonate 1995; 67: 167-171