Risk Factors for Clinical Seizures in Neonates with Hypoxic–ischemic Encephalopathy Treated with Therapeutic Hypothermia

Abstract

Background This study aimed to assess the risk factors for clinical seizures in newborns treated with whole body cooling (WBC) for hypoxic ischemic encephalopathy (HIE).

Methods Infants with gestational age≥36 weeks and birth weight≥2.000 g who were treated with WBC due to HIE were retrospectively enrolled in this study. Patients were assigned to two groups: infants without clinical seizures (Group 1) and infants with clinical seizures (Group 2). The two groups were compared to determine the risk factors for the occurrence of clinical seizures.

Results A total of 25 patients (Group 1=10 and Group 2=15) were included in the study. Prothrombin time (PT) was determined as independent risk factor for clinical seizures (p=0.046) and the odds ratio for the effect of PT was found as 1.475 (%95 CI:1.006–2.299). PT (area under the curve [AUC]=0.764; p=0.041), and increased cardiac troponin-I (cTnI) (AUC=0.935; p=0.002) were found to be significant risk factors for predicting the occurrence of clinical seizures. The optimal PT cut-off value was 22.7 sec, with a sensitivity and specificity of 45.4% and 90%, respectively; as well as positive and negative predictive value of 83.3% and 60.0%, respectively. The chest compression in the delivery room, severely abnormal amplitude integrated electroencephalography and high encephalopathy score were also found risk factors for occurrence of clinical seizures.

Conclusion Chest compression in the delivery room, high encephalopathy score, prolonged PT, and increased cTnI are significant factors for clinical seizures in newborns treated with WBC for HIE.

Zusammenfassung

Hintergrund Ziel dieser Studie war es, die Risikofaktoren für klinische Anfälle bei Neugeborenen zu bewerten, die mit Ganzkörperkühlung wegen hypoxischer ischämischer Enzephalopathie (HIE) behandelt wurden.

Methoden Säuglinge mit einem Gestationsalter von≥36 Wochen und einem Geburtsgewicht von≥2.000 g, die aufgrund von HIE mit Ganzkörperkühlung Ganzkörperkühlung behandelt wurden, wurden retrospektiv in diese Studie aufgenommen. Die Patienten wurden in zwei Gruppen eingeteilt: Säuglinge ohne klinische Anfälle (Gruppe 1) und Säuglinge mit klinischen Anfällen (Gruppe 2). Die beiden Gruppen wurden verglichen, um die Risikofaktoren für das Auftreten von klinischen Anfällen zu bestimmen.

Ergebnisse Insgesamt 25 Patienten (Gruppe 1=10 und Gruppe 2=15) wurden in die Studie eingeschlossen. Die Prothrombinzeit (PT) wurde als unabhängiger Risikofaktor für klinische Krampfanfälle (p=0,046) bestimmt und die Odds Ratio für die Wirkung der PT wurde mit 1,475 (%95 CI: 1,006–2,299) ermittelt. PT (Fläche unter der Kurve [AUC]=0,764; p=0,041) und erhöhte kardiale Troponin-I (cTnI) (AUC=0,935; p=0,002) erwiesen sich als signifikante Risikofaktoren für die Vorhersage des Auftretens klinischer Anfälle. Der optimale PT-Cut-off-Wert betrug 22,7 Sekunden mit einer Sensitivität und Spezifität von 45,4% bzw. 90%; sowie positiver und negativer Vorhersagewert von 83,3% bzw. 60,0%. Die Thoraxkompression im Kreißsaal, stark amplitudenintegrierte Elektroenzephalographie und ein hoher Enzephalopathie-Score wurden ebenfalls als Risikofaktoren für das Auftreten klinischer Anfälle festgestellt.

Key words

Neonate - seizure - hypoxic ischemic encephalopathy - therapeutic hypothermia - risk factors

Schlüsselwörter

Neugeborenes - Krampfanfall - hypoxische ischämische - Enzephalopathie - therapeutische Hypothermie - Risikofaktoren

Publication History

Article published online:
01 March 2022

• References

• 1 Akisu M, Kumral A, Canpolat FE. Turkish Neonatal Society Guideline on neonatal encephalopathy. Turk Pediatri Ars 2018; 53: S32-S44
• 2 Amare HT, Amare AT. Etiology, clinical features, and short-term outcome of seizures in newborns admitted to the University Of Gondar Hospital, Ethiopia. Pediatric Health Med Ther 2019; 10: 107-113
• 3 Askenazi DJ, Ambalavanan N, Goldstein SL. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn?. Pediatr Nephrol 2009; 24: 265-274
• 4 Bednarek N, Mathur A, Inder T. et al. Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy. Neurology 2012; 78: 1420-1427
• 5 Boylan GB, Kharoshankaya L, Wusthoff CJ. Seizures and hypothermia: Importance of electroencephalographic monitoring and considerations for treatment. Semin Fetal Neonatal Med 2015; 20: 103-108
• 6 Cornet MC, Pasupuleti A, Fang A. et al. Predictive value of early EEG for seizures in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia. Pediatr Res 2018; 84: 399-402
• 7 de Jager CP, van Wijk PT, Mathoera RB. et al. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010; 14: R192
• 8 Gitto E, Karbownik M, Reiter RJ. et al. Effects of melatonin treatment in septic newborns. Pediatr Res 2001; 50: 756-760
• 9 Glass HC, Glidden D, Jeremy RJ. et al. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury. J Pediatr 2009; 155: 318-323
• 10 Glass HC, Pham TN, Danielsen B. et al. Antenatal and intrapartum risk factors for seizures in term newborns: A population-based study, California 1998-2002. J Pediatr 2009; 154: 24-8.e.1
• 11 Glass HC, Wusthoff CJ, Shellhaas RA. et al. Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology 2014; 82: 1239-1244
• 12 Gouda MH, Hammad BS, Amen MA. Short-term prognostic value of serum cardiac troponin I levels in neonates with perinatal asphyxia. Alex J Pediatr 2017; 30: 108-119
• 13 Gunn A, Thoresen M. Neonatal encephalopathy and hypoxic-ischemic encephalopathy. In De Vries L, Glass H (Eds.), Neonatal Neurology (Vol. 162 (3rd series). Elseiver; 2019: 217-237
• 14 Hellström-Westas L, de Vries LS, Rosén I. Atlas of AMPLITUDE-INTEGRATED EEGs in the NEWBORN. 2nd ed. CRC Press; 2008
• 15 Jacobs SE, Berg M, Hunt R. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013; CD003311
• 16 Jain SV, Mathur A, Srinivasakumar P. et al. Prediction of neonatal seizures in hypoxic-ischemic encephalopathy using electroencephalograph power analyses. Pediatr Neurol 2017; 67: 64-70.e2
• 17 Joseph CH, Lian WB, Yeo CL. Nosocomial infections (late onset sepsis) in the neonatal intensive care unit (NICU). Proceedings of Singapore Healthcare 2012; 4: 238-244
• 18 Kwon JM, Guillet R, Shankaran S. et al. Clinical seizures in neonatal hypoxic-ischemic encephalopathy have no independent impact on neurodevelopmental outcome: secondary analyses of data from the neonatal research network hypothermia trial. J Child Neurol 2011; 26: 322-328
• 19 Liu J, Li J, Gu M. The correlation between myocardial function and cerebral hemodynamics in term infants with hypoxic-ischemic encephalopathy. J Trop Pediatr 2007; 53: 44-48
• 20 Martinello K, Hart AR, Yap S. et al. Management and investigation of neonatal encephalopathy: 2017 update. Arch Dis Child Fetal Neonatal Ed 2017; 102: F346-F358
• 21 Mastrangelo M, Fiocchi I, Fontana P. et al. Acute neonatal encephalopathy and seizures recurrence: a combined aEEG/EEG study. Seizure 2013; 22: 703-707
• 22 Michniewicz B, Szpecht D, Sowińska A. et al. Biomarkers in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia. Childs Nerv Syst 2020; 36: 2981-2988
• 23 Montaldo P, Rosso R, Chello G. et al. Cardiac troponin I concentrations as a marker of neurodevelopmental outcome at 18 months in newborns with perinatal asphyxia. J Perinatol 2014; 34: 292-295
• 24 Murray DM, Boylan GB, Fitzgerald AP. et al. Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden. Arch Dis Child Fetal Neonatal Ed 2008; 93: F183-F186
• 25 Murray DM, Ryan CA, Boylan GB. et al. Prediction of seizures in asphyxiated neonates: correlation with continuous video-electroencephalographic monitoring. Pediatrics 2006; 118: 41-46
• 26 Neonatal encephalopathy and neurologic outcome, second edition Report of the American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy. Obstet Gynecol 2014; 123: 896-901
• 27 Perlman JM, Risser R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers?. Pediatrics 1996; 97: 456-462
• 28 Prithviraj D, Reddy B Deepthi. et al. Laboratory findings and clinical correlation in assessing the severity of perinatal asphyxia. Int J Sci Stud 2016; 4: 220-227
• 29 Rakshasbhuvankar A, Paul S, Nagarajan L. et al. Amplitude-integrated EEG for detection of neonatal seizures: a systematic review. Seizure 2015; 33: 90-98
• 30 Report of ILAE task Force on Neonatal Seziures. Available from: https://www.ilae.org/guidelines/definition-and-classification/neonatal-seizure-classificationAccessed December 10, 2018
• 31 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch. Neurol. 1976; 33: 696-705
• 32 Shah DK, Wusthoff CJ, Clarke P. et al. Electrographic seizures are associated with brain injury in newborns undergoing therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed 2014; 99: F219-F224
• 33 Shastri AT, Samarasekara S, Muniraman H. et al. Cardiac troponin I concentrations in neonates with hypoxic-ischaemic encephalopathy. Acta Paediatr 2012; 101: 26-29
• 34 Srinivasakumar P, Zempel J, Wallendorf M. et al. Therapeutic hypothermia in neonatal hypoxic ischemic encephalopathy: electrographic seizures and magnetic resonance imaging evidence of injury. J Pediatr 2013; 163: 465-470
• 35 Sweetman D, Kelly LA, Zareen Z. et al. Coagulation profiles are associated with early clinical outcomes in neonatal encephalopathy. Front Pediatr 2019; 7: 399
• 36 Tripathi GK, Katara AA, Awasthi SW. et al. Correlation of coagulation profile in liver disease patients in a tertiary care hospital. Int J Cur Res Rev 2016; 8: 1-3
• 37 Yuan X, Kang W, Song J. et al. Prognostic value of amplitude-integrated EEG in neonates with high risk of neurological sequelae. Ann Clin Transl Neurol 2020; 7: 210-218