B-type Natriuretic Peptide: A Diagnostic Biomarker for a Hemodynamically Significant PDA

Hanan Zekri; Reem N. Said; Ranya A. Hegazy; Rania K. Darwish; Abdelkarim Kamel; Nahla Gamaleldin Abd El Hakim

doi:10.3889/oamjms.2022.7139

Authors

Hanan Zekri Department of Pediatrics, Cairo University, Giza, Egypt
Reem N. Said Department of Pediatrics, Cairo University, Giza, Egypt
Ranya A. Hegazy Department of Pediatrics, Cairo University, Giza, Egypt
Rania K. Darwish Department of Clinical Pathology, Cairo University, Giza, Egypt
Abdelkarim Kamel Department of Biochemistry, Cairo University, Giza, Egypt
Nahla Gamaleldin Abd El Hakim Department of Pediatrics, Cairo University, Giza, Egypt

DOI:

https://doi.org/10.3889/oamjms.2022.7139

Keywords:

Patent ductus arteriosus, Preterm infant, B-type natriuretic peptide, Echocardiogram

Abstract

Background: B-type natriuretic peptide (BNP) it has been reported to be a useful biomarker for the severity of hemodynamically significant patent ductus arteriosus (HsPDA) in premature infants. Objective: To assess serum levels of BNP in premature neonates with echocardiographically-confirmed hemodynamically significant and non-significant PDA (HnsPDA) and to explore the effect of PDA on left ventricular function. We also aimed to detect the level of BNP that differentiates between HsPDA and HnsPDA. Patients and methods: This was a cross-sectional observational study conducted on 73 randomly selected preterm neonates with HsPDA or hemodynamically nonsignificant PDA (HnsPDA), between May 2017 and May 2018. Echocardiography was done. BNP was measured using enzyme linked immunosorbent assay Results: There was no affection of left ventricular function in either group (LA/Ao ratio, FS, LVESD and LVEDD). PDA size, PFO size and PAP were significantly larger in HsPDA (p<0.001, p=0.001, p<0.001 respectively). Levels of BNP were significantly higher in HsPDA and correlated with the size of the PDA. At a cut-off value of 160.5 pg/ml, BNP had 80.49% sensitivity and 90.62% specificity with a positive predictive value of 91.7% and a negative predictive value of 78.04%, (AUC: 0.923, 95% C.I. 0.837 to 0.973). Conclusion: Levels of BNP in preterm babies with hemodynamically significant PDA rise early in neonatal life and correlate well with the size of the PDA. BNP can be used to screen for this condition. Ventricular dysfunction may not appear in the first 3 days of life.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

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(12):780-5. https://doi.org/10.1038/jp.2010.47 PMid:20376057 DOI: https://doi.org/10.1038/jp.2010.47

Hamrick SE, Hansmann G. Patent Ductus arteriosus of the preterm infant. Pediatrics. 2010;125:1020-30. https://doi.org/10.1542/peds.2009-3506 PMid:20421261 DOI: https://doi.org/10.1542/peds.2009-3506

Levy PT, Dioneda B, Holland MR, Sekarski TJ, Lee CK, Mathur A, et al. Right ventricular function in preterm and term neonates: reference values for right ventricle areas and fractional area of change. J Am Soc Echocardiogr. 2015;28(5):559-69. https://doi.org/10.1016/j.echo.2015.01.024 PMid:25753503 DOI: https://doi.org/10.1016/j.echo.2015.01.024

Kozik D, Ibrahim J, Wise-Faberowski L, Ricardo A, Victor O, Educardo M. Patent Ductus arteriosus. Crit Care Children Heart Dis 2010;14:145-57. https://doi.org/10.1007/978-1-84882-262-7_14 DOI: https://doi.org/10.1007/978-1-84882-262-7_14

Mertens L, Seri I, Marek J, Arlettaz R, Barker P, McNamamra P, et al. Targeted neonatal echocardiography in the neonatal intensive care unit: Practice guidelines and recommendations for training. J Am Soc Echocardiogr. 2011;24(10):1057-78. https://doi.org/10.1016/j.echo.2011.07.014 PMid:21933743 DOI: https://doi.org/10.1016/j.echo.2011.07.014

Kim J, Shim E. B-type natriuretic peptide assay for the diagnosis and prognosis of patent Ductus arteriosus in Preterm Infants. Korean Circ. 2012;42(3):192-6. https://doi.org/10.4070/kcj.2012.42.3.192 PMid:22493614 DOI: https://doi.org/10.4070/kcj.2012.42.3.192

De Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease. Lancet. 2003;362(9380):316-22. https://doi.org/10.1016/s0140-6736(03)13976-1 PMid:12892964 DOI: https://doi.org/10.1016/S0140-6736(03)13976-1

Ohashi A, Kaneko K. Serum brain natriuretic peptide for prediction of successful medical treatment of patent Ductus arteriosus in premature infants. J Thorac Cardiovasc Surg. 2009;138(1):261-2. https://doi.org/10.1016/j.jtcvs.2008.09.083 PMid:19577111 DOI: https://doi.org/10.1016/j.jtcvs.2008.09.083

Lee JH, Shin JH, Park KH, Rhie YJ, Park MS, Choi BM. Can early B-Type natriuretic peptide assays predict symptomatic patent Ductus arteriosus in extremely low birth weight infants? Neonatology. 2013;103:118-22. https://doi.org/10.1159/000343034 PMid:23182972 DOI: https://doi.org/10.1159/000343034

Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard score, expanded to include extremely premature infants. J Pediatr. 1991;119(3):417-23. https://doi.org/10.1016/s0022-3476(05)82056-6 PMid:1880657 DOI: https://doi.org/10.1016/S0022-3476(05)82056-6

Esan AJ. Hematological differences in newborn and aging: A review study. Hematol Transfus Int J. 2016;3(3):178-90. DOI: https://doi.org/10.15406/htij.2016.03.00067

Fu L, Zhang X. Correlation between changes in brain natriuretic peptide and echocardiographic features in persistent pulmonary hypertension of newborn. J Matern Fetal Neonatal Med. 2019;33:2176-80. https://doi.org/10.1080/14767058.2018.1543392 PMid:30995876 DOI: https://doi.org/10.1080/14767058.2018.1543392

Ko SM, Yoon YC, Cho KH, Lee Y, Han I, Park, K, et al. Primary surgical closure should be considered in premature neonates with large patent Ductus arteriosus. Korean J Thorac Cardiovasc Surg. 2013;46(3):178-84. https://doi.org/10.5090/kjtcs.2013.46.3.178 DOI: https://doi.org/10.5090/kjtcs.2013.46.3.178

Ramos FG, Rosenfeld CR, Roy L, Koch J, Ramaciotti C. Echocardiographic predictors of symptomatic patent Ductus arteriosus in extremely-low-birth-weight preterm neonates. J Perinatol. 2010;30(8):535-9. https://doi.org/10.1038/jp.2010.14 DOI: https://doi.org/10.1038/jp.2010.14

Gaspar HA, Morhy SS. The role of focused echocardiography in pediatric intensive care: A critical appraisal. Biomed Res Int. 2015;2015:596451. https://doi.org/10.1155/2015/596451 PMid:26605333 DOI: https://doi.org/10.1155/2015/596451

Yokoyama U, Minamisawa S, Ishikawa Y. Regulation of vascular tone and remodeling of the Ductus arteriosus. J Smooth Muscle Res. 2010;46(2):77-87. https://doi.org/10.1540/jsmr.46.77 PMid:20551589 DOI: https://doi.org/10.1540/jsmr.46.77

Drougia A, Giapros V, Krallis N, Theocharis P, Nikaki A, Tzoufi M, et al. Incidence and risk factors for cerebral palsy in infants with perinatal problems: A 15-year review. Early Hum Dev. 2007;83(8):541-7. https://doi.org/10.1016/j.earlhumdev.2006.10.004 PMid:17188824 DOI: https://doi.org/10.1016/j.earlhumdev.2006.10.004

Da Graca RL, Hassinger DC, Flynn PA, Sison CP, Nesin M, Auld PA. Longitudinal changes of brain-type natriuretic peptide in preterm neonates. Pediatrics. 2006;117(6):2183-9. https://doi.org/10.1542/peds.2005-1387 PMid:16740863 DOI: https://doi.org/10.1542/peds.2005-1387

El-Khuffash A, Molloy E. Are B-type natriuretic peptide (BNP) and N-terminal-pro-BNP useful in neonates? Arch Dis Child Fetal Neonatal Ed. 2007;92(4):F320-4. https://doi.org/10.1136/adc.2006.106039 PMid:17585100 DOI: https://doi.org/10.1136/adc.2006.106039

Van der Laan ME, Roofthooft MT, Fries MW, Berger RM, Schat TE, van Zoonen AG, et al. A hemodynamically significant patent Ductus arteriosus does not affect cerebral or renal tissue oxygenation in preterm infants. Neonatology. 2016;110(2):141-7. https://doi.org/10.1159/000445101 PMid:27088709 DOI: https://doi.org/10.1159/000445101

Nizarali Z, Marques T, Costa C, Barroso R, Cunha M. Patent Ductus arteriosus: Perinatal risk factors. J Neonatal Biol. 2012;1:3. https://doi.org/10.4172/2167-0897.1000109 DOI: https://doi.org/10.4172/2167-0897.1000109

Flynn PA, da Graca RL, Auld PA. 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. Pediatrics. 2005;147(1):738-42. https://doi.org/10.1016/j.jpeds.2005.03.040 PMid:16027692 DOI: https://doi.org/10.1016/j.jpeds.2005.03.040

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

Kalra V, De Bari V, Zauk A, Kataria P, Mydriakis D, Kiblawi F. Point-of-care testing for B-type natriuretic peptide in premature neonates with patent Ductus arteriosus. Ann Clin Lab Sci. 2011;41(2):131-7.

Choi BM, Lee KH, Eun BL, Yoo KH, Hong YS, Son CS. Utility of rapid B-type natriuretic peptide assay for diagnosis of symptomatic patent Ductus arteriosus in preterm infants. Pediatrics. 2005;115(3):e255-61. https://doi.org/10.1542/peds.2004-1837 PMid:15687418

Tauber K, Granina E, Doyle R, Munshi UK. Gestational and postnatal age influence B-type natriuretic peptide level used in diagnosis of a hemodynamically significant patent Ductus arteriosus in preterm infants. J Clin Neonatol. 2016;5(3):143-9. https://doi.org/10.4103/2249-4847.191241 DOI: https://doi.org/10.4103/2249-4847.191241

Cuna A, Kandasamy J, Fineberg N, Sims B. B-type natriuretic peptide is a biomarker for pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Res Rep Neonatol. 2013;3:33-6. https://doi.org/10.2147/rrn.s42236 DOI: https://doi.org/10.2147/RRN.S42236

Gong H, Wang X, Shi Y, Shang WJ, Ling YI, Pan LJ, et al. Correlation between brain natriuretic peptide levels and the prognosis of patients with left ventricular diastolic dysfunction. Exp Ther Med. 2016;11(6):2583-9. https://doi.org/10.3892/etm.2016.3203 PMid:27313677 DOI: https://doi.org/10.3892/etm.2016.3203

Ognean M, Boanta O, Kovacs S, Zgarcea C, Dumitra R, Olariu E, et al. Persistent Ductus arteriosus in critically Ill preterm infants. J Crit Care Med (Targu Mures). 2016;2(4):175-84. https://doi.org/10.1515/jccm-2016-0026 PMid:29967857 DOI: https://doi.org/10.1515/jccm-2016-0026

Steinhorn R. Neonatal pulmonary hypertension. Pediatr Crit Care Med. 2010;11(2):79-84. PMid:20216169 DOI: https://doi.org/10.1097/PCC.0b013e3181c76cdc

Lu D, Liu Y, Tong X. Clinical characteristics and cardiac hemodynamic changes of patent Ductus ateriosus in preterm infants. Zhonghua Er Ke Za Zhi. 2015;53(3):187-93. PMid:26165015

Choi BM, Lee KH, Eun BL, Yoo KH, Hong YS, Son CS, et al. Utility of rapid B-Type natriuretic peptide assay for diagnosis of symptomatic patent Ductus arteriosus in preterm infants. Pediatrics. 2005;115(3):255-61. https://doi.org/10.1542/peds.2004-1837 PMid:15687418 DOI: https://doi.org/10.1542/peds.2004-1837

Cuna A, Kandasamy J, Sims B. B-type natriuretic peptide and mortality in extremely low birth weight infants with pulmonary hypertension: A retrospective cohort analysis. BMC Pediatric. 2014;14:68. https://doi.org/10.1186/1471-2431-14-68 DOI: https://doi.org/10.1186/1471-2431-14-68

El-Khuffash A, Molloy E. The use of N-terminal-pro-BNP in preterm infants. Int J Pediatr. 2009;2009:175216. https://doi.org/10.1155/2009/175216 PMid:20069108 DOI: https://doi.org/10.1155/2009/175216

Kulkarni M, Gokulakrishman G, Price J, Fernandes CJ, Leeflang M, Pammi M. Diagnosing signiﬁcant PDA using natriuretic peptides in preterm. Pediatrics. 2015;135(2):e510-25. https://doi.org/10.1542/peds.2014-1995 PMid:25601976 DOI: https://doi.org/10.1542/peds.2014-1995