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Neurodevelopmental Outcomes in Therapeutic Hypothermia: A Single Center Experience

Year 2021, Volume: 15 Issue: 2, 99 - 103, 30.03.2021
https://doi.org/10.12956/tchd.719789

Abstract

Objective: Hypoxic-ischemic encephalopathy (HIE) is an acute and progressive encephalopathy resulting from perinatal asphyxia. Approximately 15% infants with neonatal HIE die, whereas 25% exhibit subsequent neurological disabilities. In this study, it was intended to compare effects of total body cooling treatment administered for hypoxic-ischemic encephalopathy on neurological and developmental findings obtained at 18-36 months.

Material and Methods: Patients who have been hospitalized between 2013 and 2014 in Neonatal Intensive Care Unit with a diagnosis of hypoxic-ischemic encephalopathy and treated total body cooling were included. After discharge, neurological examinations of the patients were evaluated by developmental assessments with “Bayley Scales of Infant Development II” at 18-36 months.


Results:
Mean MDI score of 17 patients was 90.2±16.3, and mean PDI score was 93.8±17.3. MDI scores were < 70 in 11.8% (n = 2) of all cases, and PDI scores were < 70 in 5.9% (n=1) of all cases. In 5.9% (n=1) of all cases, deafness and cerebral palsy were detected. Developmental disorder were found in 17.6% (n=3) of all cases.

Conclusion: The therapeutic hypothermia in newborns decreased mortality in moderate and severe HIE and improved neurodevelopmental outcomes at 18th month. In our study, early neurological and developmental problem rates after therapeutic hypothermia were found similar with the literature. However, long period follow-up is necessary to determine minor disorders in these patients.

References

  • 1. Levene MI, Sands C, Grindulis H, Moore JR. Comparison of two methods of predicting outcome in perinatal asphyxia. Lancet 1986;1(8472):67‐9. 2. Türk Neonatoloji Derneği Hipoksik İskemik Ensefalopati Çalışma Grubu. Türkiye’de yenidoğan yoğun bakım ünitelerinde izlenen hipoksik iskemik ensefalopatili olgular, risk faktörleri, insidans ve kısa dönem prognozları. Çocuk Sağlığı ve Hastalıkları Dergisi 2008;51:123-129. 3. Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012;72(2):156–166. 4. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature.2000;407:802-9. 5. Northington FJ, Graham EM, Martin LJ. Apoptosis in perinatalhypoxic-ischemic brain injury: how important is it and should itbe inhibited? Brain Res. 2005;50:244---57. 6. Wassink G, Gunn ER, Drury PP, Bennet L, Gunn AJ. Themechanisms and treatment of asphyxial encephalopathy. FrontNeurosci. 2014;8:40. 7. Drury PP, Bennet L, Gunn AJ. Mechanisms of hypothermic neu-roprotection. Semin Fetal Neonatal Med. 2010;15:287-92 8. Zhou WH, Cheng GQ, Shao XM, Liu XZ, Shan RB, Zhuang DY, et al. China Study Group Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr. 2010;157(3):367–372. 372.e1–372.e3. 9. Simbruner G, Mittal RA, Rohlmann F, Muche R, neo.nEURO.network Trial Participants Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010;126(4):e771–e778. 10. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Infant Cooling Evaluation Collaboration Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165(8):692–700. 11. Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, et al. Eunice Kennedy Shriver NI Neonatal Research CHD Network Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med. 2012;366(22):2085–2092. 12. 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. 13. Kariholu U, Montaldo P, Markati T, Lally PJ, Pryce R, Teiserskas J, et al. Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2020 Mar;105(2):225-228. 14. Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, et al. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. 15. Bayley, N., Bayley scales of infant development: Manual. 1993: PsychologicalCorporation. 16.Gunn AJ, Wyatt JS, Whitelaw A, Barks J, Azzopardi D, Ballard R, et al; CoolCap Study Group. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr. 2008 Jan;152(1):55-8 17. Guillet R, Edwards AD, Thoresen M, Ferriero DM, Gluckman PD, Whitelaw A, et al; CoolCap Trial Group. Seven- to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res. 2012 Feb;71(2):205-9. 18. Finder M, Boylan GB, Twomey D, Ahearne C, Murray DM, Hallberg B. Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia. JAMA Pediatr. 2019 Nov 11. doi: 10.1001/jamapediatrics.2019.4011. 19. Drury PP, Gunn ER, Bennet L, Gunn AJ. Mechanisms of hypothermic neuroprotection. Clin Perinatol2014;41(1):161–75. 20. Akula VP, Joe P, Thusu K, Davis AS, Tamaresis JS, Kim S, et al. A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy. J Pediatr 2015;166(4):856–61.e1–2. 21. Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, et al. Neurological outcomes at 18 months of ageafter moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363. 22. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic en- cephalopathy. Cochrane Database Syst Rev 2013;(1):CD003311. 23. Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, Gallagher J, et al. Part 15: Neonatal Resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S909e19. 24. Galinsky R, Dean JM, Lear CA, Davidson JO, Dhillon S, Wassink G, et al. In the Era of Therapeutic Hypothermia, How Well Do Studies of Perinatal Neuroprotection Control Temperature? Dev Neurosci. 2017;39(1-4):7-22. 25. Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):57-67.

Terapotik Hipotermide Nörogelişimsel Sonuçlar: Tek merkez deneyimi

Year 2021, Volume: 15 Issue: 2, 99 - 103, 30.03.2021
https://doi.org/10.12956/tchd.719789

Abstract

Amaç: Hipoksik iskemik ensefalopati (HİE), perinatal asfiksi sonucunda gelişen akut ve ilerleyici bir ensefalopati tablosudur. Genellikle HİE tanılı hastaların %15’i kaybedilirken, yaklaşık %25’inde nörolojik bozukluk görülmektedir. Bu çalışmada HİE tanılı hastalarda total vücut soğutma tedavisinin 18-36. aylarındaki nörogelişimsel sonuçlar üzerine etkilerinin değerlendirilmesi amaçlanmıştır.
Gereç ve yöntemler: Çalışmaya 2013-2014 yıllarında, HİE tanısı ile yatırılarak total vücut soğutma uygulanan hastalar dahil edildi. Taburculuk sonrası izlemlerine devam edilen bu hastaların 18-36 ay arasında nörolojik muayeneleri ve “Bayley Bebekler için Gelişimsel Değerlendirme Ölçeği II” ile gelişimsel değerlendirmeleri yapıldı.
Bulgular: Çalışmaya alınan 17 hastanın ortalama mental gelişim endeksi (MDI) skoru 90.2±16.3, ortalama psikomotor gelişim endeksi (PDI) skoru 93.8±17.3, MDI skoru %11.8(n:2) olguda <70, PDI skoru %5.9 (n:1) olguda <70, sağırlık ve serebral palsi %5.9 (n:1) olguda saptanmış olup, körlük hiçbir hastada saptanmadı. Toplam nörogelişimsel sorun oranı ise %17.6(n:3) olarak saptandı.
Sonuç: HİE’li yenidoğanlarda hipotermi uygulamasıyla beraber orta ve ağır HİE’li olgularda mortalitenin azaldığı ve 18. ayda nörogelişimsel sonuçları olumlu etkilediği gösterilmiştir. Çalışmamızda da terapotik hipotermi sonrası erken dönem nörolojik ve gelişimsel sorun oranları literatür ile benzer bulunmuştur. Ancak bu hastalarda minör bozuklukların saptanması için izlemlerin devamı gerekmektedir.

References

  • 1. Levene MI, Sands C, Grindulis H, Moore JR. Comparison of two methods of predicting outcome in perinatal asphyxia. Lancet 1986;1(8472):67‐9. 2. Türk Neonatoloji Derneği Hipoksik İskemik Ensefalopati Çalışma Grubu. Türkiye’de yenidoğan yoğun bakım ünitelerinde izlenen hipoksik iskemik ensefalopatili olgular, risk faktörleri, insidans ve kısa dönem prognozları. Çocuk Sağlığı ve Hastalıkları Dergisi 2008;51:123-129. 3. Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012;72(2):156–166. 4. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature.2000;407:802-9. 5. Northington FJ, Graham EM, Martin LJ. Apoptosis in perinatalhypoxic-ischemic brain injury: how important is it and should itbe inhibited? Brain Res. 2005;50:244---57. 6. Wassink G, Gunn ER, Drury PP, Bennet L, Gunn AJ. Themechanisms and treatment of asphyxial encephalopathy. FrontNeurosci. 2014;8:40. 7. Drury PP, Bennet L, Gunn AJ. Mechanisms of hypothermic neu-roprotection. Semin Fetal Neonatal Med. 2010;15:287-92 8. Zhou WH, Cheng GQ, Shao XM, Liu XZ, Shan RB, Zhuang DY, et al. China Study Group Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr. 2010;157(3):367–372. 372.e1–372.e3. 9. Simbruner G, Mittal RA, Rohlmann F, Muche R, neo.nEURO.network Trial Participants Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010;126(4):e771–e778. 10. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Infant Cooling Evaluation Collaboration Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165(8):692–700. 11. Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, et al. Eunice Kennedy Shriver NI Neonatal Research CHD Network Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med. 2012;366(22):2085–2092. 12. 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. 13. Kariholu U, Montaldo P, Markati T, Lally PJ, Pryce R, Teiserskas J, et al. Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2020 Mar;105(2):225-228. 14. Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, et al. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. 15. Bayley, N., Bayley scales of infant development: Manual. 1993: PsychologicalCorporation. 16.Gunn AJ, Wyatt JS, Whitelaw A, Barks J, Azzopardi D, Ballard R, et al; CoolCap Study Group. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr. 2008 Jan;152(1):55-8 17. Guillet R, Edwards AD, Thoresen M, Ferriero DM, Gluckman PD, Whitelaw A, et al; CoolCap Trial Group. Seven- to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res. 2012 Feb;71(2):205-9. 18. Finder M, Boylan GB, Twomey D, Ahearne C, Murray DM, Hallberg B. Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia. JAMA Pediatr. 2019 Nov 11. doi: 10.1001/jamapediatrics.2019.4011. 19. Drury PP, Gunn ER, Bennet L, Gunn AJ. Mechanisms of hypothermic neuroprotection. Clin Perinatol2014;41(1):161–75. 20. Akula VP, Joe P, Thusu K, Davis AS, Tamaresis JS, Kim S, et al. A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy. J Pediatr 2015;166(4):856–61.e1–2. 21. Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, et al. Neurological outcomes at 18 months of ageafter moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363. 22. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic en- cephalopathy. Cochrane Database Syst Rev 2013;(1):CD003311. 23. Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, Gallagher J, et al. Part 15: Neonatal Resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S909e19. 24. Galinsky R, Dean JM, Lear CA, Davidson JO, Dhillon S, Wassink G, et al. In the Era of Therapeutic Hypothermia, How Well Do Studies of Perinatal Neuroprotection Control Temperature? Dev Neurosci. 2017;39(1-4):7-22. 25. Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):57-67.
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Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section ORIGINAL ARTICLES
Authors

Kıymet Çelik 0000-0002-4522-6885

Zeynep Üstünyurt 0000-0001-8297-2097

Ezgi Yangın This is me 0000-0003-0836-7379

Rüya Çolak 0000-0002-8732-7932

Senem Alkan Özdemir 0000-0003-0474-7120

Özgür Olukman 0000-0003-4006-0465

Şebnem Çalkavur This is me 0000-0002-3820-2690

Publication Date March 30, 2021
Submission Date April 13, 2020
Published in Issue Year 2021 Volume: 15 Issue: 2

Cite

Vancouver Çelik K, Üstünyurt Z, Yangın E, Çolak R, Alkan Özdemir S, Olukman Ö, Çalkavur Ş. Terapotik Hipotermide Nörogelişimsel Sonuçlar: Tek merkez deneyimi. Türkiye Çocuk Hast Derg. 2021;15(2):99-103.


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