Short-term neurological improvement in neonates with hypoxic-ischemic encephalopathy predicts neurodevelopmental outcome at 18–24 months

Beate GrassORCID iD: https://orcid.org/0000-0002-4965-2814, Simone Scheidegger
  • Department of Pediatric and Neonatal Intensive Care, University Children’s Hospital Zurich, Zurich, Switzerland
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, Beatrice Latal
  • Child Development Center, University Children’s Hospital Zurich, Zurich, Switzerland
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, Cornelia Hagmann
  • Department of Pediatric and Neonatal Intensive Care, University Children’s Hospital Zurich, Zurich, Switzerland
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, Ulrike Held
  • Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
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, Barbara Brotschi
  • Department of Pediatric and Neonatal Intensive Care, University Children’s Hospital Zurich, Zurich, Switzerland
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Abstract

Objectives

To evaluate the association of short-term neurological improvement until day of life 4 in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with neurodevelopmental outcome at 18–24 months.

Methods

This is a retrospective analysis of prospectively collected data of 174 neonates with HIE registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2013. TH was initiated according to national guidelines, and Sarnat staging was performed daily. Short-term neurological improvement was defined if Sarnat stage improved from admission until day 4 of life. Standardized neurodevelopmental assessments were performed at 18–24 months. Unfavorable outcome was defined as death before 2 years of age or severe or moderate disability at follow-up.

Results

One hundred and sixty-four of 174 neonates (94%) received TH, of those 30 (18%) died in the neonatal period (no late mortality). Eighty-one percent of the survivors (109/134) were seen at 18–24 months. Of the 164 cooled neonates, 62% had a short-term neurological improvement, and the Sarnat score remained unchanged in 33%. Short-term neurological improvement was associated with an odds ratio (OR) of 0.118 [95% confidence interval (CI) 0.051–0.271] for an unfavorable outcome at 18–24 months.

Conclusion

Short-term neurological improvement predicts neurodevelopmental outcome at 18–24 months in the era of TH. Clinical examination must be part of a comprehensive evaluation for prognostication in HIE.

  • 1.

    Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009;361:1349–58.

  • 2.

    Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574–84.

  • 3.

    Bonifacio SL, deVries LS, Groenendaal F. Impact of hypothermia on predictors of poor outcome: how do we decide to redirect care? Semin Fetal Neonatal Med 2015;20:122–7.

  • 4.

    Shankaran S, Natarajan G, Chalak L, Pappas A, McDonald SA, Laptook AR. Hypothermia for neonatal hypoxic-ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field. Semin Perinatol 2016;40:385–90.

  • 5.

    Gunn AJ, Wyatt JS, Whitelaw A, Barks J, Azzopardi D, Ballard R, et al. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr 2008;152:55–8, 8.e1.

  • 6.

    Shankaran S, Laptook AR, Tyson JE, Ehrenkranz RA, Bann CM, Das A, et al. Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr 2012;160:567–72.e3.

  • 7.

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

  • 8.

    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.

  • 9.

    Hagmann CF, Brotschi B, Bernet V, Latal B, Berger TM, Robertson NJ. Hypothermia for perinatal asphyxial encephalopathy. Swiss Med Wkly 2011;141:w13145.

  • 10.

    Brotschi B, Grass B, Ramos G, Beck I, Held U, Hagmann C, et al. The impact of a register on the management of neonatal cooling in Switzerland. Early Hum Dev 2015;91:277–84.

  • 11.

    Scheidegger S, Held U, Grass B, Latal B, Hagmann C, Brotschi B, et al. Association of perinatal risk factors with neurological outcome in neonates with hypoxic ischemic encephalopathy. J Matern Fetal Neonatal Med 2019;1–8 [Epub ahead of print].

  • 12.

    Bayley N. Bayley scales of infant development, 2nd ed. San Antonio, TX: Psychological Corporation, 1993.

  • 13.

    Bayley N. Manual for the Bayley scales of infant and toddler development, 3rd ed. San Antonio, TX: Harcourt Assessment, 2006.

  • 14.

    Griffith R. The abilities of young children. High Wycombe, UK: The TestAgency Ltd, 1984.

  • 15.

    Jary S, Whitelaw A, Walløe L, Thoresen M. Comparison of Bayley-2 and Bayley-3 scores at 18 months in term infants following neonatal encephalopathy and therapeutic hypothermia. Dev Med Child Neurol 2013;55:1053–9.

  • 16.

    Cirelli I, Bickle Graz M, Tolsa JF. Comparison of Griffiths-II and Bayley-II tests for the developmental assessment of high-risk infants. Infant Behav Dev 2015;41:17–25.

  • 17.

    Armstrong RW. Definition and classification of cerebral palsy. Dev Med Child Neurol 2007;49:166.

  • 18.

    Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 1997;39:214–23.

  • 19.

    Laptook AR, Shankaran S, Tyson JE, Munoz B, Bell EF, Goldberg RN, et al. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial. J Am Med Assoc 2017;318:1550–60.

  • 20.

    von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370:1453–7.

  • 21.

    R Core Team. R: a language and environment for statistical computing. R Foundation of Statistical Computing, Vienna, Austria, 2018. URL https://www.R-project.org/.

  • 22.

    Largo RH, Pfister D, Molinari L, Kundu S, Lipp A, Duc G. Significance of prenatal, perinatal and postnatal factors in the development of AGA preterm infants at five to seven years. Dev Med Child Neurol 1989;31:440–56.

  • 23.

    Kirkwood and Sterne, Essential medical statistics, 2nd ed. p 430 ff.

  • 24.

    Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365:663–70.

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