Download PDF
Am J Perinatol 2016; 33(02): 195-202
DOI: 10.1055/s-0035-1563712
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Newborns Referred for Therapeutic Hypothermia: Association between Initial Degree of Encephalopathy and Severity of Brain Injury (What About the Newborns with Mild Encephalopathy on Admission?)

Maude Gagne-Loranger
1   Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada
,
Megan Sheppard
1   Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada
,
Nabeel Ali
2   Division of Newborn Medicine, Department of Pediatrics, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Canada
,
Christine Saint-Martin
3   Department of Radiology, Montreal Children's Hospital, McGill University, Montreal, Canada
,
Pia Wintermark
1   Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada
› Author Affiliations
Further Information

Publication History

10 May 2015

28 July 2015

Publication Date:
09 September 2015 (online)

    Permissions and Reprints

Abstract

Objective The aim of this article was to describe the severity of brain injury and/or mortality in a cohort of newborns referred for therapeutic hypothermia, in relation to the degree of encephalopathy on admission, and to especially look at the ones with initial mild encephalopathy.

Study Design Term newborns with perinatal depression referred to our neonatal intensive care unit for possible hypothermia treatment from 2008 to 2012 were enrolled prospectively. The modified Sarnat score on admission was correlated with severity of brain injury on brain imaging and/or autopsy.

Results A total of 215 newborns were referred for possible cooling. Sixty percent (128/215) were cooled. Most of the not-cooled newborns with an available brain magnetic resonance imaging (85% = 50/59) had an initial mild encephalopathy, and 40% (20/50) developed brain injury. Some cooled newborns had an initial mild encephalopathy (12% = 13/108); only 31% (4/13) developed brain injury.

Conclusion Our results demonstrated that several newborns with an initial mild encephalopathy developed subsequent brain injury, especially when they were not cooled.

Keywords

asphyxiated newborns - neonatal encephalopathy - magnetic resonance imaging - brain injury

Note

M. G.-L. and M. S. contributed equally.


 

  • References

  • 1 Azzopardi DV, Strohm B, Edwards AD , et al; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361 (14) 1349-1358
    CrossrefPubMedGoogle Scholar
  • 2 Azzopardi D, Strohm B, Marlow N , et al; TOBY Study Group. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med 2014; 371 (2) 140-149
    CrossrefPubMedGoogle Scholar
  • 3 Eicher DJ, Wagner CL, Katikaneni LP , et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005; 32 (1) 11-17
    CrossrefPubMedGoogle Scholar
  • 4 Gluckman PD, Wyatt JS, Azzopardi D , et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460) 663-670
    CrossrefPubMedGoogle Scholar
  • 5 Jacobs SE, Morley CJ, Inder TE , 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
    CrossrefPubMedGoogle Scholar
  • 6 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
    PubMedGoogle Scholar
  • 7 Shankaran S, Laptook AR, Ehrenkranz RA , 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) 1574-1584
    CrossrefPubMedGoogle Scholar
  • 8 Shankaran S, Laptook AR, Tyson JE , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr 2012; 160 (4) 567-572.e3
    CrossrefPubMedGoogle Scholar
  • 9 Shankaran S, Pappas A, McDonald SA , et al; Eunice Kennedy Shriver NICHD Neonatal Research Network. Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 2012; 366 (22) 2085-2092
    CrossrefPubMedGoogle Scholar
  • 10 Zhou WH, Cheng GQ, Shao XM , 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
    CrossrefPubMedGoogle Scholar
  • 11 Finer NN, Robertson CM, Peters KL, Coward JH. Factors affecting outcome in hypoxic-ischemic encephalopathy in term infants. Am J Dis Child 1983; 137 (1) 21-25
    PubMedGoogle Scholar
  • 12 Robertson C, Finer N. Term infants with hypoxic-ischemic encephalopathy: outcome at 3.5 years. Dev Med Child Neurol 1985; 27 (4) 473-484
    PubMedGoogle Scholar
  • 13 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 (6) 558-566
    PubMedGoogle Scholar
  • 14 Shah PS. Hypothermia: a systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med 2010; 15 (5) 238-246
    CrossrefPubMedGoogle Scholar
  • 15 Inder TE, Hunt RW, Morley CJ , et al. Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy. J Pediatr 2004; 145 (6) 835-837
    CrossrefPubMedGoogle Scholar
  • 16 Rutherford M, Ramenghi LA, Edwards AD , et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol 2010; 9 (1) 39-45
    CrossrefPubMedGoogle Scholar
  • 17 Rutherford MA, Azzopardi D, Whitelaw A , et al. Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy. Pediatrics 2005; 116 (4) 1001-1006
    CrossrefPubMedGoogle Scholar
  • 18 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
    CrossrefPubMedGoogle Scholar
  • 19 al Naqeeb N, Edwards AD, Cowan FM, Azzopardi D. Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography. Pediatrics 1999; 103 (6, Pt 1) 1263-1271
    CrossrefPubMedGoogle Scholar
  • 20 Barkovich AJ, Hajnal BL, Vigneron D , et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998; 19 (1) 143-149
    PubMedGoogle Scholar
  • 21 DuPont TL, Chalak LF, Morriss MC, Burchfield PJ, Christie L, Sánchez PJ. Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy. J Pediatr 2013; 162 (1) 35-41
    CrossrefPubMedGoogle Scholar
  • 22 Odd DE, Lewis G, Whitelaw A, Gunnell D. Resuscitation at birth and cognition at 8 years of age: a cohort study. Lancet 2009; 373 (9675) 1615-1622
    CrossrefPubMedGoogle Scholar
  • 23 van Handel M, Swaab H, de Vries LS, Jongmans MJ. Behavioral outcome in children with a history of neonatal encephalopathy following perinatal asphyxia. J Pediatr Psychol 2010; 35 (3) 286-295
    CrossrefPubMedGoogle Scholar
  • 24 Shalak LF, Laptook AR, Velaphi SC, Perlman JM. Amplitude-integrated electroencephalography coupled with an early neurologic examination enhances prediction of term infants at risk for persistent encephalopathy. Pediatrics 2003; 111 (2) 351-357
    Google Scholar
  • 25 Massaro AN, Murthy K, Zaniletti I , et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group. J Perinatol 2015; 35 (4) 290-296
    CrossrefPubMedGoogle Scholar
  • 26 Chaudhary R, Farrer K, Broster S, McRitchie L, Austin T. Active versus passive cooling during neonatal transport. Pediatrics 2013; 132 (5) 841-846
    Google Scholar
  • 27 Kendall GS, Kapetanakis A, Ratnavel N, Azzopardi D, Robertson NJ ; Cooling on Retrieval Study Group. Passive cooling for initiation of therapeutic hypothermia in neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 2010; 95 (6) F408-F412
    CrossrefPubMedGoogle Scholar
  • 28 Khurshid F, Lee KS, McNamara PJ, Whyte H, Mak W. Lessons learned during implementation of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy in a regional transport program in Ontario. Paediatr Child Health (Oxford) 2011; 16 (3) 153-156
    CrossrefPubMedGoogle Scholar
  • 29 Wilkinson DJ, Thayyil S, Robertson NJ. Ethical and practical issues relating to the global use of therapeutic hypothermia for perinatal asphyxial encephalopathy. Arch Dis Child Fetal Neonatal Ed 2011; 96 (1) F75-F78
    CrossrefPubMedGoogle Scholar