Am J Perinatol 2022; 39(10): 1083-1088
DOI: 10.1055/s-0040-1721497
Original Article

Early Troponin I Levels in Newborns Undergoing Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy and Residual Encephalopathy at Discharge

Upender K. Munshi
1   Division of Neonatology, Department of Pediatrics, Bernard & Millie Duker Children's Hospital, Albany Medical Center, Albany, New York
,
1   Division of Neonatology, Department of Pediatrics, Bernard & Millie Duker Children's Hospital, Albany Medical Center, Albany, New York
,
Kate A. Tauber
1   Division of Neonatology, Department of Pediatrics, Bernard & Millie Duker Children's Hospital, Albany Medical Center, Albany, New York
,
Michael J. Horgan
1   Division of Neonatology, Department of Pediatrics, Bernard & Millie Duker Children's Hospital, Albany Medical Center, Albany, New York
› Institutsangaben

Abstract

Objective Elevation of serum troponin I has been reported in newborns with hypoxic ischemic encephalopathy (HIE), but it is diagnostic and prognostic utility for newborn under 6 hours is not clear. Study the predictive value of early serum troponin I levels in newborns with HIE undergoing therapeutic hypothermia (TH) for persistent residual encephalopathy (RE) at discharge.

Study Design Retrospective chart review of newborns admitted with diagnosis of HIE to neonatal intensive care unit (NICU) for TH over a period of 3 years. Troponin levels were drawn with the initial set of admission laboratories while initiating TH. Newborns were followed up during hospital course and stratified into three groups based on predischarge examination and their electrical encephalography and cranial MRI findings: Group 1: no RE, Group 2: mild-to-moderate RE, and Group 3: severe RE or needing assisted medical technology or death. Demographic and clinical characteristics including troponin I levels were compared in each group.

Results Out of 104 newborns who underwent TH, 65 infants were in Group 1, 26 infants in Group 2, and 13 newborns in Group 3. All groups were comparable in demographic characteristics. There was a significant elevation of serum troponin in group 2 (mild-to-moderate RE) and group 3 (severe RE) as compared with group 1 (no RE). Receiver operator curve analysis for any RE (groups 2 and 3) compared with group 1 (no RE as control) had 0.88 (0.81–0.95) area under curve, p < 0.001. A cut-off level of troponin I ≥0.12 µg/L had a sensitivity of 77% and specificity of 78% for diagnosis of any RE, positive predictive value of 68%, and a negative predictive value of 84%.

Conclusion In newborns undergoing TH for HIE, the elevation of troponin within 6 hours of age predicts high risk of having RE at discharge.

Key Points

  • Troponin I elevation is a biomarker of myocardial ischemia in adults and children.

  • Myocardial ischemia may be part of multi-organ injury in neonatal HIE.

  • Early elevation of troponin I level may correlate with the severity of neonatal HIE and predict residual encephalopathy in newborn at discharge from initial hospitalization.



Publikationsverlauf

Eingereicht: 23. Juli 2020

Angenommen: 30. Oktober 2020

Artikel online veröffentlicht:
07. Dezember 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Black RE, Cousens S, Johnson HL. et al; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010; 375 (9730): 1969-1987
  • 2 Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2004; 89 (02) F152-F155
  • 3 Kanik E, Ozer EA, Bakiler AR. et al. Assessment of myocardial dysfunction in neonates with hypoxic-ischemic encephalopathy: is it a significant predictor of mortality?. J Matern Fetal Neonatal Med 2009; 22 (03) 239-242
  • 4 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
  • 5 Sweetman D, Armstrong K, Murphy JF, Molloy EJ. Cardiac biomarkers in neonatal hypoxic ischaemia. Acta Paediatr 2012; 101 (04) 338-343
  • 6 Karaarslan S, Alp H, Baysal T, Çimen D, Örs R, Oran B. Is myocardial performance index useful in differential diagnosis of moderate and severe hypoxic-ischaemic encephalopathy? A serial Doppler echocardiographic evaluation. Cardiol Young 2012; 22 (03) 335-340
  • 7 Fathil MF, Md Arshad MK, Gopinath SC. et al. Diagnostics on acute myocardial infarction: cardiac troponin biomarkers. Biosens Bioelectron 2015; 70: 209-220
  • 8 Katrukha IA. Human cardiac troponin complex. Structure and functions. Biochemistry (Mosc) 2013; 78 (13) 1447-1465
  • 9 Mueller C. Use of high-sensitivity troponin for the diagnosis of acute myocardial infarction. Coron Artery Dis 2013; 24 (08) 710-712
  • 10 Thygesen K, Alpert JS, Jaffe AS. et al. Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction, Authors/Task Force Members Chairpersons, Biomarker Subcommittee, ECG Subcommittee, Imaging Subcommittee, Classification Subcommittee, Intervention Subcommittee, Trials & Registries Subcommittee, Trials & Registries Subcommittee, Trials & Registries Subcommittee, Trials & Registries Subcommittee, ESC Committee for Practice Guidelines (CPG), Document Reviewers. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012; 60 (16) 1581-1598
  • 11 Shastri AT, Samarasekara S, Muniraman H, Clarke P. Cardiac troponin I concentrations in neonates with hypoxic-ischaemic encephalopathy. Acta Paediatr 2012; 101 (01) 26-29
  • 12 Trevisanuto D, Picco G, Golin R. et al. Cardiac troponin I in asphyxiated neonates. Biol Neonate 2006; 89 (03) 190-193
  • 13 El-Khuffash AF, Molloy EJ. Serum troponin in neonatal intensive care. Neonatology 2008; 94 (01) 1-7
  • 14 Montaldo P, Rosso R, Chello G, Giliberti P. Cardiac troponin I concentrations as a marker of neurodevelopmental outcome at 18 months in newborns with perinatal asphyxia. J Perinatol 2014; 34 (04) 292-295
  • 15 Abiramalatha T, Kumar M, Chandran S, Sudhakar Y, Thenmozhi M, Thomas N. Troponin-T as a biomarker in neonates with perinatal asphyxia. J Neonatal Perinatal Med 2017; 10 (03) 275-280
  • 16 Inserra E, Caredda E, Santantonio A. et al. The predictive accuracy of high sensitivity cardiac troponin I in neonatal encephalopathy. Clin Lab 2020;66(01):
  • 17 Shankaran S, Laptook AR, Ehrenkranz RA. et al. National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
  • 18 Azzopardi D, Brocklehurst P, Edwards D. et al. TOBY Study Group. The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr 2008; 8: 17
  • 19 Gluckman PD, Wyatt JS, Azzopardi D. et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460): 663-670
  • 20 Shalak LF, Laptook AR, Velaphi SC, Perlman JM. Amplitude-integrated electroencephalography coupled with an early neurologic examination enhances prediction of term infants at risk for persistent encephalopathy. Pediatrics 2003; 111 (02) 351-357
  • 21 Grass B, Scheidegger S, Latal B, Hagmann C, Held U, Brotschi B. National Asphyxia and Cooling Register Group, Follow-up Group. Short-term neurological improvement in neonates with hypoxic-ischemic encephalopathy predicts neurodevelopmental outcome at 18-24 months. J Perinat Med 2020; 48 (03) 296-303
  • 22 Weeke LC, Groenendaal F, Mudigonda K. et al. A novel magnetic resonance imaging score predicts neurodevelopmental outcome after perinatal asphyxia and therapeutic hypothermia. J Pediatr 2018; 192: 33-40.e2
  • 23 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
  • 24 Gunn AJ, Wyatt JS, Whitelaw A. et al. CoolCap Study Group. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr 2008; 152 (01) 55-58 , 58.e1
  • 25 Sweetman DU, Kelly L, Hurley T. et al. Troponin T correlates with MRI results in neonatal encephalopathy. Acta paediatrica 2020;
  • 26 Prempunpong C, Chalak LF, Garfinkle J. et al. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol 2018; 38 (01) 80-85
  • 27 Kracer B, Hintz SR, Van Meurs KP, Lee HC. Hypothermia therapy for neonatal hypoxic ischemic encephalopathy in the state of California. J Pediatr 2014; 165 (02) 267-273
  • 28 Massaro AN, Murthy K, Zaniletti I. et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group. J Perinatol 2015; 35 (04) 290-296
  • 29 Murray DM, O'Connor CM, Ryan CA, Korotchikova I, Boylan GB. Early EEG grade and outcome at 5 years after mild neonatal hypoxic ischemic encephalopathy. Pediatrics 2016; 138 (04) e20160659
  • 30 Montaldo P, Lally PJ, Oliveira V. et al. Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study. Arch Dis Child Fetal Neonatal Ed 2019; 104 (05) F515-F520
  • 31 Conway JM, Walsh BH, Boylan GB, Murray DM. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome: a systematic review. Early Hum Dev 2018; 120: 80-87
  • 32 Reiss J, Sinha M, Gold J, Bykowski J, Lawrence SM. Outcomes of infants with mild hypoxic ischemic encephalopathy who did not receive therapeutic hypothermia. Biomed Hub 2019; 4 (03) 1-9
  • 33 Thoresen M. Cooling after perinatal asphyxia. Semin Fetal Neonatal Med 2015; 20 (02) 65
  • 34 Chalak L, Latremouille S, Mir I, Sánchez PJ, Sant'Anna G. A review of the conundrum of mild hypoxic-ischemic encephalopathy: current challenges and moving forward. Early Hum Dev 2018; 120: 88-94