N-terminal pro brain natriuretic peptide as a marker of myocardial dysfunction in newborns with perinatal asphyxia


  • Mallesh Kariyappa Department of Pediatrics, Bengaluru Medical College and Research Institute, Bengaluru, Karnataka, India
  • Sandesh Shivarudrappa Department of Pediatrics, Bengaluru Medical College and Research Institute, Bengaluru, Karnataka, India




Hypoxic ischemic encephalopathy, Modified Sarnat stages, N-terminal pro BNP, Perinatal asphyxia


Background: Perinatal asphyxia refers to a condition during first and second stage of labour in which impaired gas exchange leads to foetal hypoxemia. Perinatal asphyxia causes cardiac dysfunction in 24 to 60 percent of the cases. The reduced cardiovascular reserve is associated with hypoxic brain damage and has high impact on neonatal mortality and adverse neurological outcomes. It has been challenging to diagnose myocardial dysfunction in resource constraint setting. Aim and objective of this study was to Determine N-Terminal Pro BNP concentrations in perinatal asphyxia and correlate with modified Sarnat stages of hypoxic ischemic encephalopathy.

Methods: Among 120 Neonates admitted in neonatal intensive care unit with diagnosis of perinatal asphyxia were considered for the study. 2mL of venous blood drawn within 48hours of life was analyzed for quantitative N-Terminal Pro BNP and was correlated with modified Sarnat stages of hypoxic ischemic encephalopathy.

Results: A Total of 120 cases of perinatal asphyxia were considered for the study, among which 44 cases had HIE stage 1, 48 had HIE stage 2 and rest 28 had HIE stage 3. The mean and standard deviation of N-Terminal Pro BNP concentrations in stage 1 was 1,502.86±3,581.170 pg/mL, stage 2 was 4,916.31±8,001.674 pg/mL and stage 3 was 8,912.41±13,927.152 pg/mL with significant p value of 0.003.

Conclusions: Early N-Terminal Pro BNP concentrations may provide a useful marker for the anticipated severity of myocardial dysfunction.


World Health Organization. Basic Newborn Resuscitation: A Practical Guide. Geneva, Switzerland: World Health Organization; 1997. Available at: www.who.int/reproductive health/publications/newborn_resus_citation/index.html.

Rowe RD, Hoffman T. Transient myocardial ischemia of the newborn infant: a form of severe cardiorespiratory distress in full-term infants. J Pediatr. 1972;81:243-50.

Flores-Nava G, Echevarría-Ybargüengoitia JL, Navarro-Barrón JL, García-Alonso A. Transient myocardial ischemia in newborn babies with perinatal asphyxia (hypoxic cardiomyopathy). Biol Med Hosp Infant Mex. 1990;47:809-14.

Aslam HM, Saleem S, Afzal R, Iqbal U, Saleem SM, Shaikh MW, et al. Risk factors of birth asphyxia. Italian J Pediatr. 2014 Dec 1;40(1):94.

Baqui AH, Darmstadt GL, Williams EK. Rates, timing and causes of neonatal deaths in rural India: implications for neonatal health programs. Bull World Health Organ. 2006;84:706-13.

Bang AT, Bang RA, Baitule S, Deshmukh M, Reddy MH. Burden of morbidities and the unmet need for health care in rural neonates: a prospective observational study in Gadchiroli, India. Indian Pediatr. 2001;38:952-65.

Antonucci R, Porcella A, Pilloni MD. Perinatal asphyxia in the term newborn. JPNIM. 2014;3(2):e030269.

Dilenge ME, Majnemer A, Shevell MI. Long-term developmental outcome of asphyxiated term neonates. J Child Neurol. 2001;16:781-92.

Manual of Neonatal Care, 7th edition, John P. Cloherty, Eric C. Eichenwald, Anne R. Hansen, Ann R. Stark, New Delhi, Wolters Kluwer; 2015:711.

National Neonatal and Perinatal Database Report 2002-2003.1-58. Available at: https://www.newbornwhocc.org/pdf/nnpd_report_2002-03.PDF.

Rajakumar PS, Bhat BV, Sridhar MG, Balachander J, Konar BC, Narayanan P, et al. Cardiac Enzyme Levels in Myocardial Dysfunction in Newborns with Perinatal Asphyxia. Indian J Pediatr. 2008;75(12):1223-5.

Vesely DL, Cliffs E. Atrial natriuretic hormones. New Jersey: Prentice Hall, 1992.

Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988;332(6159):78-81.

Saito Y, Nakao K, Itoh H, Yamada T, Mukoyama M, Arai H, et al. Brain natriuretic peptide is a novel cardiac hormone. Bioch Biophysi Res Communica. 1989;158(2):360-8.

Vesely DL, Douglass MA, Dietz JR, Gower Jr WR, McCormick MT, Rodriguez-Paz G, et al. Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans. Circulation. 1994;90(3):1129-40.

Singh G, Kuc RE, Maguire JJ, Fidock M, Davenport AP. Novel snake venom ligand dendroaspis natriuretic peptide is selective for natriuretic peptide receptor-A in human heart: down regulation of natriuretic peptide receptor-A in heart failure. Circ Res 2006;99:183-90.

Hunt PJ, Yandle TG, Nicholls MG, Richards AM, Espiner EA. The amino-terminal portion of probrain natriuretic peptide (proBNP) circulates in human plasma. Biochem Biophys Res Commun 1995;214:1175-83.

Witthaut R. Science review: natriuretic peptides in critical illness. Crit Care. 2004;8:342-9.

Reynolds EW, Ellington JG, Vranicar M, Bada HS. Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatrics. 2004;114:1297-304.

O’Mara PW, Poole SD, Brown N, Ding T, Paria B, Reese J. Regulation of the fetal and newborn ductus arteriosus (da) by natriuretic peptides. E-PAS. 2006;59:2875.314.

Maack T. Receptors of atrial natriuretic factor. Annu Rev Physiol. 1992;54:11-27.

Committee on Fetus and Newborn, American Academy of Pediatrics and Committee on Obstetric Practice, American College of Obstetricians and Gynecologists. Use and Abuse of the Apgar Score. Pediatr. 1996;98;141-2.

Cantinotti M, Storti S, Parri MS, Murzi M, Clerico A. Reference values for plasma B-type natriuretic peptide in the first days of life. Clin Chem. 2009;55(7):1438-40

Agrawal J, Shah GS, Poudel P, Baral N, Agrawal A, Mishra OP. Electrocardiographic and enzymatic correlations with outcome in neonates with hypoxic-ischemic encephalopathy. Ital J Pediatr. 2012;38:33.

Jain D, Pandey AK, Das BK, Prasad R. Cardiac Function in Perinatal Asphyxia. Sch J App Med Sci. 2016;4(7):2718-28.

Lakshmanan R, Verma YS. Cardiac changes in asphyxiated neonates-need for early detection to improve long-term outcome. Int J Contemp Pediatr. 2017;4(5):1844-50.

Shadique AM, Sailavasan M. A prospective study on cardiac changes (electrocardiographic, enzymatic and echocardiographic) in birth asphyxiated neonates admitted in tertiary care centre. Int J Contemp Pediatr. 2019;6:269-74.

Koch A, Singer H. Normal values of B type natriuretic peptide in infants, children, and adolescents. Heart 2003;89:875-8.

Kunii Y, Kamada M, Ohtsuki S, Araki T, Kataoka K, Kageyama M, et al. Plasma brain natriuretic peptide and the evaluation of volume overload in infants and children with congenital heart disease. Acta Med Okayama. 2003;57:191-7.

Bar-Oz B, Lev-Sagie A, Arad I, Salpeter L, Nir A. N-terminal pro-B-type natriuretic peptide concentrations in mothers just before delivery, in cord blood, and in newborns. ClinChem 2005;51:926-7.

Mir TS, Marohn S, Läer S, Eiselt M, Grollmus O, Weil J. Plasma concentrations of N-terminal pro-brain natriuretic peptide in control children from the neonatal to adolescent period and in children with congestive heart failure. Pediatrics. 2002;110:e76.

Mir TS, Laux R, Hellwege HH, Liedke B, Heinze C, von Buelow H, et al. Plasma concentrations of aminoterminal pro atrial natriuretic peptide and aminoterminal pro brain natriuretic peptide in healthy neonates: marked and rapid increase after birth. Pediatrics. 2003;112:896-9.

Jain DD, Pandey DA, Das DB, Prasad DR. Cardiac function in perinatal asphyxia. J Appl Med Sci. 2016;4:2718-28.

Simović AM, Košutić JL, Prijić SM, Knežević JB, Vujić AJ, Stojanović ND. The role of biochemical markers as early indicators of cardiac damage and prognostic parameters of perinatal asphyxia. Vojnosanitetski pregled. 2014;71(2):149-55.






Original Research Articles