Neonatal Med.  2019 Feb;26(1):17-23. 10.5385/nm.2019.26.1.17.

Predictors of Neurodevelopmental Outcomes in Newborns Undergoing Hypothermia Therapy

• Chun MK
• Sung HJ
• Park JH
• Lim GY
• Kim SY

• KMID: 2440696
• DOI: http://doi.org/10.5385/nm.2019.26.1.17

Abstract

PURPOSE
This study aimed to identify the early predictors of neurodevelopmental outcomes in infants undergoing therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy.
METHODS
The medical records of 24 neonates who underwent hypothermia therapy for hypoxic ischemic encephalopathy at the neonatal intensive care unit of Yeouido St. Mary's Hospital of the Catholic University of Korea between August 2013 and May 2016 were reviewed. Patients were divided into two groups according to their neurological outcome at the age of 18 to 24 months: a normal group (n=14), which included patients with normal neurological function, and an abnormal group (n=10), which included patients with neurological deficits. The clinical characteristics, clinical outcomes, and laboratory findings before and after hypothermia treatment were compared between the groups.
RESULTS
There were no significant differences in the demographic characteristics between the two groups. With regard to clinical outcomes, only brain magnetic resonance imaging (MRI) findings showed significant differences between the normal and abnormal groups (21.4% vs. 100.0%, P < 0.001). With regard to laboratory findings, there were significant differences in the white blood cell (WBC) count after hypothermia treatment between the normal and abnormal groups (9.78±3.52 vs. 14.90±3.48, P=0.003). However, logistic regression analysis showed that the WBC count was not an independent risk factor for abnormal neurodevelopment (P>0.05).
CONCLUSION
The presence of abnormal lesions on MRI was the most useful predictor of poor neurodevelopmental outcome in infants treated with therapeutic hypothermia after perinatal asphyxia.

Keyword

Newborn; Hypoxia-ischemia, brain; Hypothermia treatment; Magnetic resonance imaging; Treatment outcome; Risk factors

MeSH Terms

Asphyxia
Brain
Humans
Hypothermia*
Hypothermia, Induced
Hypoxia-Ischemia, Brain
Infant
Infant, Newborn*
Intensive Care, Neonatal
Korea
Leukocytes
Logistic Models
Magnetic Resonance Imaging
Medical Records
Risk Factors
Treatment Outcome

Reference

1. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013; 1:CD003311.

2. Committee on Fetus and Newborn, Papile LA, Baley JE, Benitz W, Cummings J, Carlo WA, et al. Hypothermia and neonatal encephalopathy. Pediatrics. 2014; 133:1146–50.

3. Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014; 371:140–9.

4. Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, et al. Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med. 2012; 366:2085–92.

5. Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012; 166:558–66.

6. Martinello K, Hart AR, Yap S, Mitra S, Robertson NJ. Management and investigation of neonatal encephalopathy: 2017 update. Arch Dis Child Fetal Neonatal Ed. 2017; 102:F346–58.

7. Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010; 340:c363.

8. Guillet R, Edwards AD, Thoresen M, Ferriero DM, Gluckman PD, Whitelaw A, et al. Seven- to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res. 2012; 71:205–9.

9. Merchant N, Azzopardi D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischaemic encephalopathy. Dev Med Child Neurol. 2015; 57 Suppl 3:8–16.

10. Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012; 72:156–66.

11. Dammann O, Ferriero D, Gressens P. Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters. Pediatr Res. 2011; 70:1–2.

12. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976; 33:696–705.

13. Pierrat V, Haouari N, Liska A, Thomas D, Subtil D, Truffert P, et al. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population based study. Arch Dis Child Fetal Neonatal Ed. 2005; 90:F257–61.

14. Simon NP. Long-term neurodevelopmental outcome of asphyxiated newborns. Clin Perinatol. 1999; 26:767–78.

15. van Laerhoven H, de Haan TR, Offringa M, Post B, van der Lee JH. Prognostic tests in term neonates with hypoxic-ischemic encephalopathy: a systematic review. Pediatrics. 2013; 131:88–98.

16. Massaro AN. MRI for neurodevelopmental prognostication in the high-risk term infant. Semin Perinatol. 2015; 39:159–67.

17. Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014; 41:149–59.

18. Shankaran S. Therapeutic hypothermia for neonatal encephalopathy. Curr Opin Pediatr. 2015; 27:152–7.

19. Azzopardi D, Strohm B, Linsell L, Hobson A, Juszczak E, Kurinczuk JJ, et al. Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK: analysis of national data. PLoS One. 2012; 7:e38504.

20. Sarkar S, Barks J. Management of neonatal morbidities during hypothermia treatment. Semin Fetal Neonatal Med. 2015; 20:97–102.

21. Armstrong K, Franklin O, Sweetman D, Molloy EJ. Cardiovascular dysfunction in infants with neonatal encephalopathy. Arch Dis Child. 2012; 97:372–5.

22. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011; 165:692–700.

23. Glass HC, Hong KJ, Rogers EE, Jeremy RJ, Bonifacio SL, Sullivan JE, et al. Risk factors for epilepsy in children with neonatal encephalopathy. Pediatr Res. 2011; 70:535–40.

24. Kwon JM, Guillet R, Shankaran S, Laptook AR, McDonald SA, Ehrenkranz RA, et al. Clinical seizures in neonatal hypoxicischemic encephalopathy have no independent impact on neurodevelopmental outcome: secondary analyses of data from the neonatal research network hypothermia trial. J Child Neurol. 2011; 26:322–8.

25. Goeral K, Urlesberger B, Giordano V, Kasprian G, Wagner M, Schmidt L, et al. Prediction of outcome in neonates with hypoxic-ischemic encephalopathy II: role of amplitude-integrated electroencephalography and cerebral oxygen saturation measured by near-infrared spectroscopy. Neonatology. 2017; 112:193–202.

26. Chandrasekaran M, Chaban B, Montaldo P, Thayyil S. Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: a meta-analysis. J Perinatol. 2017; 37:684–9.

27. Roka A, Beko G, Halasz J, Toldi G, Lakatos P, Azzopardi D, et al. Changes in serum cytokine and cortisol levels in normothermic and hypothermic term neonates after perinatal asphyxia. Inflamm Res. 2013; 62:81–7.

28. Massaro AN, Chang T, Kadom N, Tsuchida T, Scafidi J, Glass P, et al. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia. J Pediatr. 2012; 161:434–40.

29. Jenkins DD, Rollins LG, Perkel JK, Wagner CL, Katikaneni LP, Bass WT, et al. Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Cereb Blood Flow Metab. 2012; 32:1888–96.

30. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003; 111:1805–12.

31. Chakkarapani E, Davis J, Thoresen M. Therapeutic hypothermia delays the C-reactive protein response and suppresses white blood cell and platelet count in infants with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2014; 99:F458–63.

32. Alderliesten T, de Vries LS, Benders MJ, Koopman C, Groenendaal F. MR imaging and outcome of term neonates with perinatal asphyxia: value of diffusion-weighted MR imaging and (1) H MR spectroscopy. Radiology. 2011; 261:235–42.

33. Shankaran S, Barnes PD, Hintz SR, Laptook AR, Zaterka-Baxter KM, McDonald SA, et al. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2012; 97:F398–404.

34. Corbo ET, Bartnik-Olson BL, Machado S, Merritt TA, Peverini R, Wycliffe N, et al. The effect of whole-body cooling on brain metabolism following perinatal hypoxic-ischemic injury. Pediatr Res. 2012; 71:85–92.

35. Cheong JL, Coleman L, Hunt RW, Lee KJ, Doyle LW, Inder TE, et al. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: substudy of a randomized trial. Arch Pediatr Adolesc Med. 2012; 166:634–40.

36. Chiang MC, Lin KL, Lin JJ, Lien R. Cranial hemorrhage and outcome of neonates treated with therapeutic hypothermia for hypoxic ischemic encephalopathy. J Paediatr Child Health. 2018; 54(Suppl 1):67.

37. Wang D, McMillan H, Bariciak E. Subdural haemorrhage and severe coagulopathy resulting in transtentorial uncal herniation in a neonate undergoing therapeutic hypothermia. BMJ Case Rep. 2014; 2014:bcr2013203080.