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Brain injury following trial of hypothermia for neonatal hypoxic–ischaemic encephalopathy
  1. Seetha Shankaran1,
  2. Patrick D Barnes2,
  3. Susan R Hintz3,
  4. Abbott R Laptook4,
  5. Kristin M Zaterka-Baxter5,
  6. Scott A McDonald6,
  7. Richard A Ehrenkranz7,
  8. Michele C Walsh8,
  9. Jon E Tyson9,
  10. Edward F Donovan10,
  11. Ronald N Goldberg11,
  12. Rebecca Bara12,
  13. Abhik Das13,
  14. Neil N Finer14,
  15. Pablo J Sanchez15,
  16. Brenda B Poindexter16,
  17. Krisa P Van Meurs17,
  18. Waldemar A Carlo18,
  19. Barbara J Stoll19,
  20. Shahnaz Duara20,
  21. Ronnie Guillet21,
  22. Rosemary D Higgins22,
  23. for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
  1. 1Department of Pediatrics/Neonatology, Wayne State University Children's Hospital of Michigan, Detroit, Michigan, USA
  2. 2Department of Radiology and Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA
  3. 3Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA
  4. 4Department of Pediatrics, Women and Infants Hospital, Providence, Rhode Island, USA
  5. 5Department of Statistics and Epidemiology, RTI International, Research Park, North Carolina, USA
  6. 6RTI International, Statistics and Epidemiology, Research Park, North Carolina, USA
  7. 7Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA
  8. 8Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA
  9. 9Center for Clinical Research and Evidence Based Medicine, The University of Texas Medical School at Houston, Houston, Texas, USA
  10. 10Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA
  11. 11Department of Pediatrics, Duke University, Durham, North Carolina, USA
  12. 12Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USA
  13. 13RTI International, Statistics and Epidemiology Research Park, North Carolina, USA
  14. 14Department of Paediatrics/Neonatology, University of California San Diego Medical Center, La Jolla, California, USA
  15. 15Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  16. 16Department of Pediatrics, Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
  17. 17Division of Neonatology, Lucile Packard Children's Hospital, Palo Alto, California, USA
  18. 18Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA
  19. 19Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
  20. 20Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA
  21. 21University of Rochester School of Medicine and Dentistry, Rochester, NY
  22. 22Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Seetha Shankaran, Department of Pediatrics/Neonatology, Children's Hospital of Michigan, 3901 Beaubien Blvd, Detroit, MI 48201, USA; sshankar{at}


Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia.

Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age.

Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability.

Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy.

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  • Funding The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provided grant support for the Neonatal Research Network's whole-body hypothermia and follow-up studies.

  • Competing interests Dr Cotten reports having served on the data and safety monitoring board for the Inhibitex phase 3 study of Vernonate for the prevention of infections in preterm infants. Dr Donovan reports having received support from the Environmental Protection Agency (Lanphear) and the Gerber Foundation. Dr Carlo reports holding stock options at the Pediatrix Medical Group. Dr Stevenson reports having received research support from Pfizer.

  • Ethics approval The institutional review board at each of the participating centres approved this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Currently, unpublished data are unavailable pending further NICHD Neonatal Research Network analyses and publications.

    Data collected at participating sites of the NICHD Neonatal Research Network (NRN) were transmitted to RTI International, the data coordinating centre (DCC) for the network, which stored, managed and analysed the data for this study. On behalf of the NRN, Dr Abhik Das (DCC Principal Investigator) and Mr Scott A McDonald (DCC Statistician) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

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