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Neonates with mild hypoxic–ischaemic encephalopathy receiving supportive care versus therapeutic hypothermia in California
  1. Leah Yieh1,2,
  2. Henry Lee3,
  3. Tianyao Lu3,
  4. Ashley Song4,
  5. Cynthia L Gong1,2,
  6. Tai-Wei Wu1,
  7. Philippe Friedlich1,
  8. Ashwini Lakshmanan1,2,
  9. Dmitry Dukhovny5,
  10. Joel Hay2
  1. 1 Fetal and Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  2. 2 Leonard D. Schaeffer Center for Health Policy and Economics, School of Pharmacy, University of Southern California, Los Angeles, California, USA
  3. 3 California Perinatal Quality Care Collaborative, Stanford University School of Medicine and Lucile Packard Children’s Hospital, Stanford, California, USA
  4. 4 Department of Preventive Medicine, John Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
  5. 5 Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, USA
  1. Correspondence to Dr Leah Yieh, Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, CA 90027, USA; lyieh{at}


Objective The use of therapeutic hypothermia (TH) for mild hypoxic–ischaemic encephalopathy (HIE) remains controversial and inconsistent. We analysed trends in TH and maternal and infant characteristics associated with short-term outcomes of infants with mild HIE.

Design Retrospective cohort analysis of the California Perinatal Quality Care Collaborative database 2010–2018. E-value analysis was conducted to determine the potential impact of unmeasured confounding.

Setting California neonatal intensive care units.

Patients 1364 neonates with mild HIE.

Interventions Supportive care versus TH.

Main outcome measures Factors associated with TH and mortality.

Results The proportion of infants receiving TH increased from 46% in 2010 to 79% in 2018. TH was more likely in the setting of singleton birth (OR 2.69, 95% CI 1.21 to 5.39), no major birth defects (OR 2.18, 95% CI 1.42 to 3.30), operative vaginal delivery (OR 3.04, 95% CI 1.80 to 5.10) and 5-minute Apgar score ≤5 (OR 3.17, 95% CI 2.43 to 4.13). Mortality was associated with small for gestational age (OR 5.79, 95% CI 1.90 to 18.48), <38 weeks’ gestation (OR 7.31 95% CI 2.39 to 24.93), major birth defects (OR 11.62, 95% CI 3.97 to 38.00), inhaled nitric oxide (OR 12.73, 95% CI 4.00 to 44.53) and nosocomial infection (OR 7.98, 95% CI 1.15 to 47.03). E-value analyses suggest that unmeasured confounding may have contributed to some of the observed effects.

Conclusions Variation in management of mild HIE persists, but therapeutic drift has become more prevalent over time. Further studies are needed to assess long-term outcomes alongside resource utilisation to inform evidence-based practice.

  • neonatology
  • epidemiology
  • health services research

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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  • Contributors LY conceptualised and designed the study, analysed data, interpreted results and drafted the initial manuscript. Drs HL, CG, T-WW, PF, AL, DD and JH made contributions to analysing the data, interpreting the results and revising the manuscript. Dr AS and Mr TL contributed to data analysis and manuscript revisions. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

  • Funding LY’s work is supported by K12 Pediatrician-Scientist Research Career Development Award (00011187), Department of Pediatrics, Children’s Hospital Los Angeles and the Gerber Foundation (RGA012661).

  • Competing interests None declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.