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Evolution of the Sarnat exam and association with 2-year outcomes in infants with moderate or severe hypoxic-ischaemic encephalopathy: a secondary analysis of the HEAL Trial
  1. Ulrike Mietzsch1,2,
  2. Sarah E Kolnik1,2,
  3. Thomas Ragnar Wood1,
  4. Niranjana Natarajan3,4,
  5. Fernando F Gonzalez5,6,
  6. Hannah Glass6,7,8,
  7. Dennis E Mayock1,
  8. Sonia L Bonifacio9,10,
  9. Krisa Van Meurs9,10,
  10. Bryan A Comstock11,
  11. Patrick J Heagerty11,
  12. Tai-Wei Wu12,13,
  13. Yvonne W Wu5,7,
  14. Sandra E Juul1
  15. on behalf of the HEAL Trial Study Group
    1. 1 Pediatrics, Division of Neonatology, University of Washington School of Medicine, Seattle, Washington, USA
    2. 2 Pediatrics, Division of Neonatology, Seattle Children's Hospital, Seattle, Washington, USA
    3. 3 Child Neurology, University of Washington School of Medicine, Seattle, Washington, USA
    4. 4 Neurology, Division of Child Neurology, Seattle Children's Hospital, Seattle, Washington, USA
    5. 5 Pediatrics, University of California San Francisco School of Medicine, San Francisco, California, USA
    6. 6 Pediatrics, University of California San Francisco Benioff Children's Hospital, San Francisco, California, USA
    7. 7 Neurology, University of California San Francisco School of Medicine, San Francisco, California, USA
    8. 8 Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USA
    9. 9 Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, California, USA
    10. 10 Pediatrics, Division of Neonatal and Developmental Medicine, Lucile Packard Children's Hospital School, Palo Alto, California, USA
    11. 11 Biostatistics, University of Washington School of Public Health, Seattle, Washington, USA
    12. 12 Pediatrics, Division of Neonatology, University of Southern California Keck School of Medicine, Los Angeles, California, USA
    13. 13 Pediatrics, Children's Hospital Los Angeles Division of Neonatology, Los Angeles, California, USA
    1. Correspondence to Dr Ulrike Mietzsch, Pediatrics, Division of Neonatology, University of Washington School of Medicine, Seattle, WA, 98105, USA; mietzu{at}uw.edu

    Abstract

    Objective To study the association between the Sarnat exam (SE) performed before and after therapeutic hypothermia (TH) and outcomes at 2 years in infants with moderate or severe hypoxic-ischaemic encephalopathy (HIE).

    Design Secondary analysis of the High-dose Erythropoietin for Asphyxia and EncephaLopathy Trial. Adjusted ORs (aORs) for death or neurodevelopmental impairment (NDI) based on SE severity category and change in category were constructed, adjusting for sedation at time of exam. Absolute SE Score and its change were compared for association with risk for death or NDI using locally estimated scatterplot smoothing curves.

    Setting Randomised, double-blinded, placebo-controlled multicentre trial including 17 centres across the USA.

    Patients 479/500 enrolled neonates who had both a qualifying SE (qSE) before TH and a SE after rewarming (rSE).

    Interventions Standardised SE was used across sites before and after TH. All providers underwent standardised SE training.

    Main outcome measures Primary outcome was defined as the composite outcome of death or any NDI at 22–36 months.

    Results Both qSE and rSE were associated with the primary outcome. Notably, an aOR for primary outcome of 6.2 (95% CI 3.1 to 12.6) and 50.3 (95% CI 13.3 to 190) was seen in those with moderate and severe encephalopathy on rSE, respectively. Persistent or worsened severity on rSE was associated with higher odds for primary outcome compared with those who improved, even when qSE was severe.

    Conclusion Both rSE and change between qSE and rSE were strongly associated with the odds of death/NDI at 22–36 months in infants with moderate or severe HIE.

    • Neonatology
    • Neurology

    Data availability statement

    Data are available upon reasonable request. Data are available upon request and will be publicly available soon.

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    Data availability statement

    Data are available upon reasonable request. Data are available upon request and will be publicly available soon.

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    Footnotes

    • UM and SEK are joint first authors.

    • YWW and SEJ are joint senior authors.

    • Collaborators HEAL consortium: Kaashif A Ahmad, Pediatrix Medical Group of San Antonio, San Antonio, Texas; Marianna Baserga, University of Utah, Salt Lake City, Utah; Ellen Bendel-Stenzel, Mayo Clinic, Rochester, Minnesota; Kristen L Benninger, Nationwide Children’s Hospital, Columbus, Ohio; Lina Chalak, University of Texas Southwestern Medical Center, Dallas, Texas; Taeun Chang, Children’s National Hospital, Washington DC; John Flibotte, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Andrea L Lampland, Children’s Minnesota, Minneapolis/St Paul, Minnesota; Nathalie L Maitre, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia; Amit M Mathur, Saint Louis University School of Medicine, St. Louis, Missouri; Stephanie Merhar, Cincinnati Children’s Hospital, Cincinnati, Ohio; Brenda B Poindexter, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia; Rakesh Rao, Washington University, St. Louis, Missouri; David Riley, Cook Children’s Medical Center, Fort Worth, Texas; Christopher D Smyser, Washington University, St. Louis, Missouri; Gregory M Sokol, Indiana School of Medicine, Indianapolis, Indiana; Joern-Hendrik Weitkamp, Vanderbildt University Medical Center, Nashville, Tennessee; Toby Yanowitz, University of Pittsburgh School of Medicine & Children’s Hospital of Pittsburgh of UPMC and Magee, Pittsburgh, Pennsylvania.

    • Contributors UM conceptualised and designed the study, collected data, drafted the initial manuscript, and critically reviewed and revised the manuscript. SEK conceptualised and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript. TRW conceptualised and designed the study, carried out the statistical analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript. NN collected data and critically reviewed and revised the manuscript. HG critically reviewed and revised the manuscript. FFG collected data and critically reviewed and revised the manuscript. DEM collected data and critically reviewed and revised the manuscript. SLB collected data and critically reviewed and revised the manuscript. KVM collected data and critically reviewed and revised the manuscript. BAC coordinated and supervised data collection, carried out the initial analyses, and critically reviewed and revised the manuscript. PJH designed the study, coordinated and supervised data collection, guided the initial analyses, and critically reviewed and revised the manuscript. T-WW collected data and critically reviewed and revised the manuscript. YWW conceptualised and designed the study, collected data, and critically reviewed and revised the manuscript. SEJ conceptualised and designed the study, collected data, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. PJH, SEJ and YWW act as overall guarantors of the study.

    • Funding The study was funded by the National Institute of Neurological Disease and Stroke (NINDS), 1U01NS092764, U01NS092553.

    • Competing interests YW, SJ, BC, PH receive support to their institution from the NIH/NINDS for the presented study. FG, HG, KVM, BC, PH receive grants paid to the institution from the NIH and NIH/NINDS, KVM receives grant support from PCORI, and NN receives support from Biogen and UCB Pharma paid to the institution. SEJ receives royalties for editing Avery’s Disease of the Newborn. UM, HG and KVM receive payments for expert testimony. FFG receives grant support for travel/meeting attendance from the NIH. HG and SEJ disclose participation on data safety monitoring board or advisory boards for NIH IACQUIRE (HG) and ALBINO (SEJ). FFG discloses membership of the Societies for Pediatric Research executive council, HG discloses a leadership/fiduciary role within the Pediatric Academic Societies, and NN discloses an unpaid position as board member of Wonderland Child and Family Services. HG discloses stocks/stock options with ELEMENO Health. SEK, TRW, DEM, SLB have nothing to disclose.

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