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Predictors of Neurodevelopmental Outcomes in Newborns Undergoing Hypothermia Therapy

  • Chun, Min-Kyo (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Sung, Hyun-Jung (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Park, Joo-Hyung (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lim, Gye-Yeon (Department of Radiology, College of Medicine, The Catholic University of Korea) ;
  • Kim, So-Young (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 투고 : 2018.08.08
  • 심사 : 2018.11.13
  • 발행 : 2019.02.28

초록

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.

키워드

참고문헌

  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. https://doi.org/10.1542/peds.2014-0899
  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. https://doi.org/10.1056/NEJMoa1315788
  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. https://doi.org/10.1056/NEJMoa1112066
  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. https://doi.org/10.1001/archpediatrics.2011.1772
  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. https://doi.org/10.1136/archdischild-2015-309639
  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. https://doi.org/10.1136/bmj.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. https://doi.org/10.1038/pr.2011.30
  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. https://doi.org/10.1111/dmcn.12726
  10. Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol 2012;72:156-66. https://doi.org/10.1002/ana.23647
  11. Dammann O, Ferriero D, Gressens P. Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters. Pediatr Res 2011;70:1-2. https://doi.org/10.1203/PDR.0b013e318223f38d
  12. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976;33:696-705. https://doi.org/10.1001/archneur.1976.00500100030012
  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. https://doi.org/10.1136/adc.2003.047985
  14. Simon NP. Long-term neurodevelopmental outcome of asphyxiated newborns. Clin Perinatol 1999;26:767-78. https://doi.org/10.1016/S0095-5108(18)30050-2
  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. https://doi.org/10.1542/peds.2012-1297
  16. Massaro AN. MRI for neurodevelopmental prognostication in the high-risk term infant. Semin Perinatol 2015;39:159-67. https://doi.org/10.1053/j.semperi.2015.01.009
  17. Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol 2014;41:149-59. https://doi.org/10.1016/j.clp.2013.10.008
  18. Shankaran S. Therapeutic hypothermia for neonatal encephalopathy. Curr Opin Pediatr 2015;27:152-7. https://doi.org/10.1097/MOP.0000000000000199
  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. https://doi.org/10.1371/journal.pone.0038504
  20. Sarkar S, Barks J. Management of neonatal morbidities during hypothermia treatment. Semin Fetal Neonatal Med 2015;20:97-102. https://doi.org/10.1016/j.siny.2015.01.007
  21. Armstrong K, Franklin O, Sweetman D, Molloy EJ. Cardiovascular dysfunction in infants with neonatal encephalopathy. Arch Dis Child 2012;97:372-5. https://doi.org/10.1136/adc.2011.214205
  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. https://doi.org/10.1001/archpediatrics.2011.43
  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 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;26:322-8. https://doi.org/10.1177/0883073810380915
  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. https://doi.org/10.1159/000468976
  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. https://doi.org/10.1038/jp.2017.14
  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. https://doi.org/10.1007/s00011-012-0554-3
  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. https://doi.org/10.1016/j.jpeds.2012.02.047
  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. https://doi.org/10.1038/jcbfm.2012.83
  30. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003;111:1805-12. https://doi.org/10.1172/JCI18921
  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. https://doi.org/10.1136/archdischild-2013-305763
  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. https://doi.org/10.1148/radiol.11110213
  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. https://doi.org/10.1038/pr.2011.8
  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. https://doi.org/10.1001/archpediatrics.2012.284
  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. https://doi.org/10.1136/bcr-2013-203080