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Original article

Vol. 151 No. 1314 (2021)

Centre-specific differences in short-term outcomes in neonates with hypoxic-ischaemic encephalopathy

Cite this as:
Swiss Med Wkly. 2021;151:w20489



To investigate and compare the centre-specific short-term outcome indicators seizures, arterial hypotension, infection and mortality during therapeutic hypothermia until discharge from the neonatal/paediatric intensive care unit in term and near-term neonates with hypoxic-ischaemic encephalopathy (HIE) registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2018.


Retrospective analysis of prospectively collected national register data between 1 January 2011 and 31 December 2018. Pregnancy, maternal, delivery and neonatal characteristics were compared between the centres. Four short-term outcomes were defined: seizures, arterial hypotension, infection and mortality. The outcome indicators were defined as stated in the protocol of the Swiss National Asphyxia and Cooling Register. Descriptive analyses of the de-identified centre to centre analysis were performed, and standardised observed-to-expected values (risk adjusted for male sex, small for gestational age, Sarnat score on admission, pregnancy/delivery complications) of each centre were compared using with the entire network indirectly standardised mortality/morbidity ratio charts.


570 cooled neonates with HIE receiving therapeutic hypothermia in 10 different centres were included. Clinical or subclinical seizures were reported in a median of 32% (range 17–49%). Arterial hypotension occurred in a median of 62% (range 30–90%). Median infection rate was 10% (range 0–31%). Median mortality rate until discharge was 14% (range 0–25%).


Short-term outcome indicators of seizures, arterial hypotension, infection and mortality showed significant differences in incidence between the centres. These data will help to establish benchmarks for the assessed outcome measures. Benchmarking is a continuous need with the ultimate goal of improving modifiable short-term outcomes in neonates with HIE.


  1. Hagmann CF, Brotschi B, Bernet V, Latal B, Berger TM, Robertson NJ. Hypothermia for perinatal asphyxial encephalopathy. Swiss Med Wkly. 2011;141:w13145.
  2. Brotschi B, Grass B, Ramos G, Beck I, Held U, Hagmann C, et al.; National Asphyxia Cooling Register Group. The impact of a register on the management of neonatal cooling in Switzerland. Early Hum Dev. 2015;91(4):277–84. doi:.
  3. Sarkar S, Barks J. Management of neonatal morbidities during hypothermia treatment. Semin Fetal Neonatal Med. 2015;20(2):97–102. doi:.
  4. Giesinger RE, Bailey LJ, Deshpande P, McNamara PJ. Hypoxic-Ischemic Encephalopathy and Therapeutic Hypothermia: The Hemodynamic Perspective. J Pediatr. 2017;180:22–30.e2. doi:.
  5. Fitzgerald MP, Massey SL, Fung FW, Kessler SK, Abend NS. High electroencephalographic seizure exposure is associated with unfavorable outcomes in neonates with hypoxic-ischemic encephalopathy. Seizure. 2018;61:221–6. doi:.
  6. Rao R, Lee KS, Zaniletti I, Yanowitz TD, DiGeronimo R, Dizon MLV, et al. Antimicrobial therapy utilization in neonates with hypoxic-ischemic encephalopathy (HIE): a report from the Children’s Hospital Neonatal Database (CHND). J Perinatol. 2020;40(1):70–8. doi:.
  7. 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. doi:.
  8. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al.; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361(14):1349–58. doi:.
  9. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, 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):1574–84. doi:.
  10. Azzopardi D, Strohm B, Linsell L, Hobson A, Juszczak E, Kurinczuk JJ, et al.; UK TOBY Cooling Register. Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK--analysis of national data. PLoS One. 2012;7(6):e38504. doi:.
  11. Diederen CMJ, van Bel F, Groenendaal F. Complications During Therapeutic Hypothermia After Perinatal Asphyxia: A Comparison with Trial Data. Ther Hypothermia Temp Manag. 2018;8(4):211–5. doi:.
  12. Mansky T, Völzke T, Nimptsch U. Improving outcomes using German Inpatient Quality Indicators in conjunction with peer review procedures. Z Evid Fortbild Qual Gesundhwes. 2015;109(9-10):662–70. doi:.
  13. Thompson CM, Puterman AS, Linley LL, Hann FM, van der Elst CW, Molteno CD, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86(7):757–61. doi:.
  14. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696–705. doi:.
  15. Thompson CM, Puterman AS, Linley LL, Hann FM, van der Elst CW, Molteno CD, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86(7):757–61. doi:.
  16. Donabedian A. The quality of care. How can it be assessed? JAMA. 1988;260(12):1743–8. doi:.
  17. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1–7. doi:.
  18. R: The R Project for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, Available from: [last accessed 2020 Feb 6].
  19. Weeke LC, Boylan GB, Pressler RM, Hallberg B, Blennow M, Toet MC, et al.; NEonatal seizure treatment with Medication Off -patent (NEMO)consortium. Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia. Eur J Paediatr Neurol. 2016;20(6):855–64. doi:.
  20. Grass B, Crosdale B, Keyzers M, Deshpande P, Hahn C, Ly LG, et al. Implementation of amplitude-integrated electroencephalography in tertiary Canadian Neonatal Intensive Care Units-a longitudinal study. Paediatr Child Health. 2020;25(8):511–7. doi:.
  21. Bashir RA, Espinoza L, Vayalthrikkovil S, Buchhalter J, Irvine L, Bello-Espinosa L, et al. Implementation of a Neurocritical Care Program: Improved Seizure Detection and Decreased Antiseizure Medication at Discharge in Neonates With Hypoxic-Ischemic Encephalopathy. Pediatr Neurol. 2016;64:38–43. doi:.
  22. Glass HC, Ferriero DM, Rowitch DH, Shimotake TK. The neurointensive nursery: concept, development, and insights gained. Curr Opin Pediatr. 2019;31(2):202–9. doi:.
  23. Novak CM, Eke AC, Ozen M, Burd I, Graham EM. Risk Factors for Neonatal Hypoxic-Ischemic Encephalopathy in the Absence of Sentinel Events. Am J Perinatol. 2019;36(1):27–33. doi:.
  24. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA. 2003;290(20):2677–84. doi:.
  25. Black C, Roos NP. Administrative data. Baby or bathwater? Med Care. 1998;36(1):3–5. doi:.
  26. Lilford R, Mohammed MA, Spiegelhalter D, Thomson R. Use and misuse of process and outcome data in managing performance of acute medical care: avoiding institutional stigma. Lancet. 2004;363(9415):1147–54. doi:.
  27. Bundesamt für Gesundheit (BAG). Qualitätsindikatoren der Schweizer Akutspitäler 2016. Bern: Bundesamt für Gesundheit; 2016.

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