Predictive value of serum NT-proBNP concentrations for assessment hemodynamically significant patent ductus arteriosus in very preterm infants

Authors

DOI:

https://doi.org/10.15574/SP.2021.113.28

Keywords:

hemodynamically significant patent ductus arteriosus, PDA, NT-proBNP, prognostic value, very preterm infants

Abstract

Hemodynamically significant patent ductus arteriosus (PDA) is a common complication in very preterm infants born at less than 32 weeks of gestation. At the same time, currently, there are no uniform criteria to identify the actual hemodynamic significance of PDA and generally accepted management approaches to such infants.

Purpose — to assess the predictive value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels for hemodynamically significant PDA in very preterm infants.

Materials and methods. Fifty-two preterm infants with gestational age <32 weeks, chronological age <72 h, and PDA diameter >1.5 mm were involved in a randomized study. Twenty-seven (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent daily echocardiographic and two serum NT-proBNP measurements within the first 10 days after birth. According to the results of echocardiographic and clinical monitoring, 2 groups of patients were formed retrospectively. In 22 (42%) of them hemodynamically significant PDA (hsPDA) was diagnosed, and 30 (58%) had hemodynamically insignificant ductus arteriosus.

Results. The percentage of infants who received pharmacological PDA treatment was not significantly different between the groups (p>0.05). Serum NT-proBNP concentrations at the median age of 2 and 8 days were significantly higher in infants with hsPDA (p<0.01). By the eighth day of life, the NT-proBNP level in both groups significantly decreased but remained considerably higher in newborns with hsPDA. Serum NT-proBNP concentrations on the second-third day of life could reliably predict hsPDA (AUC=0.93; 95% confidence interval: 0.86–1.0; p<0.05).

Conclusions. Serum NT-proBNP concentrations on the second day of life >12000 pg/ml could reliably predict hsPDA.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies.

No conflict of interest was declared by the authors.

 

References

Arlettaz R. Echocardiographic Evaluation of Patent Ductus Arteriosus in Preterm Infants. (2017). Front Pediatr. 5: 147. https://doi.org/10.3389/fped.2017.00147; PMid:28680875 PMCid:PMC5478876

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; PMid:15855678

Benitz WE, Committee on Fetus and Newborn Patent Ductus Arteriosus in Preterm Infants. (2016). Pediatrics. 137 (1): e20153730. https://doi.org/10.1542/peds.2015-3730; PMid:26672023

Benitz WE. (2010). Treatment of persistent patent ductus arteriosus in pre-term infants: time to accept the null hypothesis? J Perinatol. 30 (4): 241-252. https://doi.org/10.1038/jp.2010.3; PMid:20182439

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): 780-785. https://doi.org/10.1038/jp.2010.47; PMid:20376057

El Khuffash A, Davis PG, Walsh K, Molloy EJ. (2008). Cardiac troponin T and N-terminal-pro-B natriuretic peptide reflect myocardial function in preterm infants. J Perinatol. 28 (7): 482-486. https://doi.org/10.1038/jp.2008.21; PMid:18322550

El Khuffash A, Molloy E. (2009). The use of N-terminal-pro-BNP in preterm infants. Int J Pediatr: 175216. https://doi.org/10.1155/2009/175216; PMid:20069108 PMCid:PMC2804037

El Khuffash AF, Amoruso M, Culliton M, Molloy EJ. (2007). N-terminal pro-B-type natriuretic peptide as a marker of ductal haemodynamic significance in preterm infants: a prospective observational study. Arch Dis Child Fetal Neonatal Ed. 92 (5): F421-422. https://doi.org/10.1136/adc.2007.119701; PMid:17712194 PMCid:PMC2675377

Farooquia MA, Elsayeda Y, Jeyaraman MM, Dingwalld O, Tagina M et al. (2019). Pre-symptomatic targeted treatment of patent ductus arteriosus in preterm newborns: A systematic review and meta-analysis. J Neonatal Perinatal Med. 12 (1): 1-7. https://doi.org/10.3233/NPM-17130; PMid:30040749

Fried I, Bar Oz B, Algur N, Fried E, Gavri S 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): e1165-1168. https://doi.org/10.1542/peds.2006-0569; PMid:16966393

Harkin P, Marttila R, Pokka T, Saarela T, Hallman M. (2018). Morbidities associated with patent ductus arteriosus in preterm infants. Nationwide cohort study. J Matern Fetal Neonatal Med. 31 (19): 2576-2583. https://doi.org/10.1080/14767058.2017.1347921; PMid:28651469

Hundscheid T, Onland W, van Overmeire B, Dijk P, van Kaam AHLC et al. (2018). Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus Trial). BMC Pediatr. 18 (1): 262. https://doi.org/10.1186/s12887-018-1215-7; PMid:30077184 PMCid:PMC6090763

Kulkarni M, Gokulakrishnan G, Price J, Fernandes CJ, Leeflang M, Pammi M. (2015). Diagnosing significant PDA using natriuretic peptides in pre-term neonates: a systematic review. Pediatrics. 135 (2): e510-525. https://doi.org/10.1542/peds.2014-1995; PMid:25601976

Lechner E, Wiesinger Eidenberger G, Wagner O, Weissensteiner M, Schreier Lechner E et al. (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; PMid:19581836

Letshwiti JB, Sirc J, O'Kelly R, Miletin J. (2011). Serial N-Terminal Pro-Brain Natriuretic Peptide Measurement as a Predictor of Clinically Significant Ductus Arteriosus in Preterm Infants beyond the First Week of Life. E-PAS2011.3832.313. https://doi.org/10.1038/pr.2011.892

Letzner J, Berger F, Schwabe S, Benzing J, Morgenthaler NG et al. (2012). Plasma C-Terminal Pro-Endothelin-1 and the Natriuretic Pro-Peptides NT-proBNP and MR-proANP in Very Preterm Infants with Patent Ductus Arteriosus. Neonatology. 101 (2): 116-124. https://doi.org/10.1159/000330411; PMid:21952518

Levin ER, Gardner DG, Samson WK. (1998). Natriuretic peptides. N Engl J Med. 339 (5): 321-328. https://doi.org/10.1056/NEJM199807303390507; PMid:9682046

Mannarino S, Garofoli F, Mongini E, Cerbo RM, Codazzi AC et al. (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; PMid:20488634

Mir TS, Laux R, Hellwege HH, Liedke B, Heinze C et al. (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): 869-896. https://doi.org/10.1542/peds.112.4.896; PMid:14523183

Nuntnarumit P, Khositseth A, Thanomsingh P. (2009). N-terminal probrain natriuretic peptide and patent ductus arteriosus in preterm infants. J Perinatol. 29 (2): 137-142. https://doi.org/10.1038/jp.2008.185; PMid:19020527

Ramakrishnan S, Heung YM, Round J, Morris TP, Collinson P, Williams AF. (2009). Early N-terminal pro-brain natriuretic peptide measurements predict clinically significant ductus arteriosus in preterm infants. Acta Paediatr. 98 (8): 1254-1259. https://doi.org/10.1111/j.1651-2227.2009.01315.x; PMid:19432837

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; PMid:12928255

Richardson DK, Corcoran JD, Escobar GJ, Lee SK. (2001). SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risks cores. J Pediatr. 138 (1): 92-100. https://doi.org/10.1067/mpd.2001.109608; PMid:11148519

Sasi A, Deorari A. (2011). Patent ductus arteriosus in preterm infants. Indian Pediatr. 48 (4): 301-308. https://doi.org/10.1007/s13312-011-0062-5; PMid:21532100

Shah PS. (2019). Pharmacologic management of patent ductus arteriosus in the very preterm neonate. In: Hemodynamics and cardiology: neonatology questions and controversies. Third edition. Philadelphia, PA: Elsevier, Inc: 411-425. https://doi.org/10.1016/B978-0-323-53366-9.00023-5

Shepherd JL, Noori S. (2019). What is a hemodynamically significant PDA in preterm infants? Congenit Heart Dis. 14 (1): 21-26. https://doi.org/10.1111/chd.12727; PMid:30548469

Smith A, El Khuffash A. (2020). Defining «Haemodynamic Significance» of the Patent Ductus Arteriosus: Do We Have All the Answers? Neonatology: 1-8. https://doi.org/10.1159/000506988; PMid:32450558

Stoupakis G, Klapholz M. (2003). Natriuretic peptides: biochemistry, physiology, and therapeutic role in heart failure. Heart Dis. 5 (3): 215-223. https://doi.org/10.1097/01.HDX.0000074517.30102.64; PMid:12783635

Vanderheyden M, Bartunek J, Goethals M. (2004). Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail. 6 (3): 261-268. https://doi.org/10.1016/j.ejheart.2004.01.004; PMid:14987574

Zonnenberg I, de Waal K. (2012). The definition of a haemodynamic significant duct in randomized controlled trials: a systematic literature review. Acta Paediatr. 101 (3): 247-251. https://doi.org/10.1111/j.1651-2227.2011.02468.x; PMid:21913976

Published

2021-02-19

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Original articles