Top

Published in:

01-04-2018 | Original Article

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus

Authors: Sarah Louise Harris, Kiran More, Bronwyn Dixon, Richard Troughton, Chris Pemberton, John Horwood, Nicola Ellis, Nicola Austin

Published in: European Journal of Pediatrics | Issue 4/2018

Abstract

This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated.

Conclusion: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design.

What is Known:

• NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA).

What is new:

• NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage

• Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.

Bagnoli F, Rossetti A, Casucci M, Mori A (2010) Aminoterminal B-type natriuretic peptide (NT-proBNP) in the therapy of patent ductus arteriosus. Minerva Pediatr 62(3 Suppl 1):67–70PubMed

Bahlmann F, Krummenauer F, Spahn S, Gallinat R, Kampmann C (2011) Natriuretic peptide levels in intrauterine growth-restricted fetuses with absent and reversed end-diastolic flow of the umbilical artery in relation to ductus venosus flow velocities. J Perinat Med 39(5):529–537CrossRefPubMed

Bakker J, Gies I, Slavenburg B, Bekers O, Delhaas T, van Dieijen-Visser M (2004) Reference values for N-terminal pro-B-type natriuretic peptide in umbilical cord blood. Clin Chem 50(12):2465. https://doi.org/10.1373/clinchem.2004.040253 CrossRefPubMed

Baptista MJ, Rocha G, Clemente F, Azevedo LF, Tibboel D, Leite-Moreira AF, Guimaraes H, Areias JC, Correia-Pinto J (2008) N-terminal-pro-B type natriuretic peptide as a useful tool to evaluate pulmonary hypertension and cardiac function in CDH infants. Neonatology 94(1):22–30CrossRefPubMed

Barnes SC, Collinson PO, Galasko G, Lahiri A, Senior R (2004) Evaluation of N-terminal pro-B type natriuretic peptide analysis on the Elecsys 1010 and 2010 analysers. Ann Clin Biochem 41(Pt 6):459–463. https://doi.org/10.1258/0004563042466848 CrossRefPubMed

Bar-Oz B, Lev-Sagie A, Arad I, Salpeter L, Nir A (2005) N-terminal pro-B-type natriuretic peptide concentrations in mothers just before delivery, in cord blood, and in newborns. Clin Chem 51(5):926–927. https://doi.org/10.1373/clinchem.2005.048892 CrossRefPubMed

Benitz WE, Committee On Fetus And Newborn (2016) Patent ductus arteriosus in preterm infants. Pediatrics 137(1):e20153730. https://doi.org/10.1542/peds.2015-3730 CrossRef

Bettencourt PM (2005) Clinical usefulness of B-type natriuretic peptide measurement: present and future perspectives. Heart 91(11):1489–1494. https://doi.org/10.1136/hrt.2005.063784 CrossRefPubMedPubMedCentral

Casals G, Ros J, Sionis A, Davidson MM, Morales-Ruiz M, Jimenez W (2009) Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes. Am J Physiol Heart Circ Physiol 297(2):H550–H555. https://doi.org/10.1152/ajpheart.00250.2009 CrossRefPubMed

10.

Chen S, Tacy T, Clyman R (2010) How useful are B-type natriuretic peptide measurements for monitoring changes in patent ductus arteriosus shunt magnitude? J Perinatol 30(12):780–785CrossRefPubMed

11.

Clyman RI, Chorne N (2007) Patent ductus arteriosus: evidence for and against treatment. J Pediatr 150(3):216–219. https://doi.org/10.1016/j.jpeds.2006.12.048 CrossRefPubMedPubMedCentral

12.

Clyman RI, Couto J, Murphy GM (2012) Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all? Semin Perinatol 36(2):123–129. https://doi.org/10.1053/j.semperi.2011.09.022 CrossRefPubMedPubMedCentral

13.

Condo M, Evans N, Bellu R, Kluckow M (2012) Echocardiographic assessment of ductal significance: retrospective comparison of two methods. Arch Dis Child Fetal Neonatal Ed 97(1):F35–F38. https://doi.org/10.1136/adc.2010.207233 CrossRefPubMed

14.

Crispi F, Hernandez-Andrade E, Pelsers MM, Plasencia W, Benavides-Serralde JA, Eixarch E, Le Noble F, Ahmed A, Glatz JF, Nicolaides KH et al (2008) Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses. Am J Obstet Gynecol 199(3):254 e1–254 e8CrossRef

15.

Cuna A, Kandasamy J, Fineberg N, Sims B (2013) B-type natriuretic peptide is a biomarker for pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Res Rep Neonatology. 2013(3):33–36

16.

da Graca RL, Hassinger DC, Flynn PA, Sison CP, Nesin M, Auld PA (2006) Longitudinal changes of brain-type natriuretic peptide in preterm neonates. Pediatrics 117(6):2183–2189. https://doi.org/10.1542/peds.2005-1387 CrossRefPubMed

17.

Davlouros PA, Karatza AA, Xanthopoulou I, Dimitriou G, Georgiopoulou A, Mantagos S, Alexopoulos D (2011) Diagnostic role of plasma BNP levels in neonates with signs of congenital heart disease. Int J Cardiol 147(1):42–46. https://doi.org/10.1016/j.ijcard.2009.07.029 CrossRefPubMed

18.

de Lemos JA, McGuire DK, Drazner MH (2003) B-type natriuretic peptide in cardiovascular disease. The Lancet 362(9380):316–322. https://doi.org/10.1016/S0140-6736(03)13976-1 CrossRef

19.

Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K (2005) National Institutes of Child Health and Human Development Neonatal Research Network. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics 116(6):1353–1360. https://doi.org/10.1542/peds.2005-0249 CrossRefPubMed

20.

El-Khuffash AF, Slevin M, McNamara PJ, Molloy EJ, Troponin T (2011) N-terminal pro natriuretic peptide and a patent ductus arteriosus scoring system predict death before discharge or neurodevelopmental outcome at 2 years in preterm infants. Arch Dis Child Fetal Neonatal Ed 96(2):F133–F137. https://doi.org/10.1136/adc.2010.185967 CrossRefPubMed

21.

Evans N (2012) Diagnosis of the preterm patent ductus arteriosus: clinical signs, biomarkers, or ultrasound? Semin Perinatol 36(2):114–122. https://doi.org/10.1053/j.semperi.2011.09.021 CrossRefPubMed

22.

Flynn PA, da Graca RL, Auld PA, Nesin M, Kleinman CS (2005) The use of a bedside assay for plasma B-type natriuretic peptide as a biomarker in the management of patent ductus arteriosus in premature neonates. J Pediatr 147(1):38–42. https://doi.org/10.1016/j.jpeds.2005.03.040 CrossRefPubMed

23.

Foo JY, Wan Y, Schulz BL, Kostner K, Atherton J, Cooper-White J, Dimeski G, Punyadeera C (2013) Circulating fragments of N-terminal pro-B-type natriuretic peptides in plasma of heart failure patients. Clin Chem 59(10):1523–1531. https://doi.org/10.1373/clinchem.2012.200204 CrossRefPubMed

24.

Fowlie PW, Davis PG, McGuire W (2010) Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 7:CD000174

25.

Fried I, Bar-Oz B, Algur N, Fried E, Gavri S, Yatsiv I, Perles Z, Rein AJ, Zonis Z, Bass R et al (2006) Comparison of N-terminal pro-B-type natriuretic peptide levels in critically ill children with sepsis versus acute left ventricular dysfunction. Pediatrics 118(4):e1165–e1168. https://doi.org/10.1542/peds.2006-0569 CrossRefPubMed

26.

Girsen A, Ala-Kopsala M, Makikallio K, Vuolteenaho O, Rasanen J (2007) Cardiovascular hemodynamics and umbilical artery N-terminal peptide of proB-type natriuretic peptide in human fetuses with growth restriction. Ultrasound Obstet Gynecol 29(3):296–303. https://doi.org/10.1002/uog.3934 CrossRefPubMed

27.

Hammerer-Lercher A, Mair J, Tews G, Puschendorf B, Sommer R (2005) N-terminal pro-B-type natriuretic peptide concentrations are markedly higher in the umbilical cord blood of newborns than in their mothers. Clin Chem 51(5):913–915. https://doi.org/10.1373/clinchem.2004.046557 CrossRefPubMed

28.

Hamrick SE, Hansmann G (2010) Patent ductus arteriosus of the preterm infant. Pediatrics 125(5):1020–1030. https://doi.org/10.1542/peds.2009-3506 CrossRefPubMed

29.

Januzzi JL, Troughton R (2013) Are serial BNP measurements useful in heart failure management? Serial natriuretic peptide measurements are useful in heart failure management. Circulation 127(4):500–508. https://doi.org/10.1161/CIRCULATIONAHA.112.120485 CrossRefPubMed

30.

Joseph L, Nir A, Hammerman C, Goldberg S, Ben Shalom E, Picard E (2010) N-terminal pro-B-type natriuretic peptide as a marker of bronchopulmonary dysplasia in premature infants. Am J Perinatol 27(5):381–386. https://doi.org/10.1055/s-0029-1243312 CrossRefPubMed

31.

Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR (2006) Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 117(4):1113–1214. https://doi.org/10.1542/peds.2005-1528 CrossRefPubMed

32.

Konig K, Guy KJ, Walsh G, Drew SM, Watkins A, Barfield CP (2014) The relationship between BNP, NTproBNP and echocardiographic measurements of systemic blood flow in very preterm infants. J Perinatol 34(4):296–300. https://doi.org/10.1038/jp.2014.2 CrossRefPubMed

33.

Kort E (2016) Patent ductus arteriosus in the preterm infant: an update on morbidity and mortality. Curr Pediatr Rev 12(2):98–105. https://doi.org/10.2174/157339631202160506001621 CrossRefPubMed

34.

Kulkarni M, Gokulakrishnan G, Price J, Fernandes CJ, Leeflang M, Pammi M (2015) Diagnosing significant PDA using natriuretic peptides in preterm neonates: a systematic review. Pediatrics 135(2):e510–e525. https://doi.org/10.1542/peds.2014-1995 CrossRefPubMed

35.

Lechner E, Wiesinger-Eidenberger G, Wagner O, Weissensteiner M, Schreier-Lechner E, Leibetseder D, Arzt W, Tulzer G (2009) Amino terminal pro B-type natriuretic peptide levels are elevated in the cord blood of neonates with congenital heart defect. Pediatr Res 66(4):466–469. https://doi.org/10.1203/PDR.0b013e3181b3aee4 CrossRefPubMed

36.

Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA (2002) Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347(3):161–167. https://doi.org/10.1056/NEJMoa020233 CrossRefPubMed

37.

Malviya MN, Ohlsson A, Shah SS (2013) Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev 3:CD003951

38.

Mannarino S, Garofoli F, Mongini E, Cerbo RM, Codazzi AC, Tzialla C, Mazzucchelli I, Perotti G, Tinelli C, De Silvestri A, Manzoni P, Stronati M (2010) BNP concentrations and cardiovascular adaptation in preterm and fullterm newborn infants. Early Hum Dev 86(5):295–298. https://doi.org/10.1016/j.earlhumdev.2010.04.003 CrossRefPubMed

39.

McNamara PJ, Sehgal A (2007) Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Ed 92(6):F424–F427. https://doi.org/10.1136/adc.2007.118117 CrossRefPubMedPubMedCentral

40.

Merz W, Gembruch U (2014) Old tool – new application: NT-proBNP in fetal medicine. Ultrasound Obstet Gynecol 44(4):377–385. https://doi.org/10.1002/uog.13443 CrossRefPubMed

41.

Mir TS, Laux R, Hellwege HH, Liedke B, Heinze C, von Buelow H, Laer S, Weil J (2003) Plasma concentrations of aminoterminal pro atrial natriuretic peptide and aminoterminal pro brain natriuretic peptide in healthy neonates: marked and rapid increase after birth. Pediatrics 112(4):896–899. https://doi.org/10.1542/peds.112.4.896 CrossRefPubMed

42.

Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwachtgen L, Koch A, Falkenberg J, Mir TS (2009) NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol 30(1):3–8. https://doi.org/10.1007/s00246-008-9258-4 CrossRefPubMed

43.

Occhipinti F, De Carolis M, De Rosa G, Bersani I, Lacerenza S, Cota F, Rubortone SA, Romagnoli C (2014) Correlation analysis between echocardiographic flow pattern and N-terminal-pro-brain natriuretic peptide for early targeted treatment of patent ductus arteriosus. J Matern Fetal Neonatal Med 27(17):1800–1804. https://doi.org/10.3109/14767058.2014.880879 CrossRefPubMed

44.

Rauh M, Koch A (2003) Plasma N-terminal pro-B-type natriuretic peptide concentrations in a control population of infants and children. Clin Chem 49(9):1563–1564. https://doi.org/10.1373/49.9.1563 CrossRefPubMed

45.

Reynolds EW, Ellington JG, Vranicar M, Bada HS (2004) Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatrics 114(5):1297–1304. https://doi.org/10.1542/peds.2004-0525 CrossRefPubMed

46.

Sehgal A, Menahem S (2013) Interparametric ccorrelation between echocardiographic markers in preterm infants with patent ductus arteriosus. Pediatr Cardiol 34(5):1217–1217CrossRef

47.

Sehgal A, Paul E, Menahem S (2013) Functional echocardiography in staging for ductal disease severity: role in predicting outcomes. Eur J Pediatr 172(2):179–184. https://doi.org/10.1007/s00431-012-1851-0 CrossRefPubMed

48.

Sellmer A, Bjerre JV, Schmidt MR, McNamara PJ, Hjortdal VE, Host B, Bech BH, Henriksen TB (2013) Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed 98(6):F505–F510. https://doi.org/10.1136/archdischild-2013-303816 CrossRefPubMed

49.

Sellmer A, Hjortdal VE, Bjerre JV, Schmidt MR, McNamara PJ, Bech BH, Henriksen TB et al (2015) N-terminal pro-B type natriuretic peptide as a marker of bronchopulmonary dysplasia or death in very preterm neonates: a cohort study. PLoS One 10(10):e0140079. https://doi.org/10.1371/journal.pone.0140079 CrossRefPubMedPubMedCentral

50.

Smith J, Goetze JP, Andersen CB, Vejlstrup N (2010) Practical application of natriuretic peptides in paediatric cardiology. Cardiol Young 20(4):353–363. https://doi.org/10.1017/S1047951110000211 CrossRefPubMed

51.

Steinhelper ME (1993) Structure, expression, and genomic mapping of the mouse natriuretic peptide type-B gene. Circ Res 72(5):984–992. https://doi.org/10.1161/01.RES.72.5.984 CrossRefPubMed

52.

Weber M, Hamm C (2006) Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart 92(6):843–849CrossRefPubMedPubMedCentral

53.

Yajamanyam P, Kanani A, Rasiah S (2015) Management of patent ductus arteriosus in preterm infants-where do we stand? A UK national perspective. Congenit Heart Dis 10(1):86–87. https://doi.org/10.1111/chd.12170 CrossRefPubMed

Title: Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus
Authors: Sarah Louise Harris
Kiran More
Bronwyn Dixon
Richard Troughton
Chris Pemberton
John Horwood
Nicola Ellis
Nicola Austin
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 4/2018
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-018-3089-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2018

Clinical spectrum of paediatric coeliac disease: a 10-year single-centre experience

Characteristics of revisits of children at risk for serious infections in pediatric emergency care

Deltoid muscle morphometry as an index of impaired skeletal muscularity in neonatal intensive care

Knowledge of allergies and performance in epinephrine auto-injector use: a controlled intervention in preschool teachers

Blistering eruptions in Henoch-Schönlein syndrome: more common than assumed

Paediatric departments need to improve residents’ training in adolescent medicine and health: a position paper of the European Academy of Paediatrics