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Original research
Predictive performance of multiple organ dysfunction in asphyxiated newborns treated with therapeutic hypothermia on 24-month outcome: a cohort study
  1. Juliette Langeslag1,2,
  2. Wes Onland1,2,
  3. Douwe Visser1,2,
  4. Floris Groenendaal3,
  5. Linda de Vries3,
  6. Anton H van Kaam1,2,
  7. T R de Haan1,2
  8. The PharmaCool Study Group
    1. 1Department of Neonatology, Amsterdam UMC Locatie University of Amsterdam, Emma Children's Hospital, Meibergdreef 9, Amsterdam, The Netherlands
    2. 2Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
    3. 3Department of Neonatology, Whilhelmina Children's Hospital, University Medical Center Utrecht, and Brain Center, Utrecht, The Netherlands
    4. 1Department of Neonatology, Amsterdam UMC Location University of Amsterdam, Emma Children's Hospital, Meibergdreef 9, Amsterdam, the Netherlands
    5. 2Department of Neonatology, Radboud University Medical Center- Amalia Childrens Hospital, Nijmegen, the Netherlands
    6. 3Department of Neonatology, University Medical Center Brussel, Brussel, Belgium
    7. 4Department of Neonatology, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, the Netherlands
    8. 5Department of Neonatology, Maxima Medical Center, Veldhoven, the Netherlands
    9. 6Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Brain Center, Utrecht, the Netherlands
    10. 7Department of Neonatology, Amsterdam UMC Location University of Amsterdam, Emma Children's Hospital, Meibergdreef 9, Amsterdam, The Netherlands
    11. 8Department of Neonatology, Sophia Children's Hospital, Erasmus MC, Rotterdam, the Netherlands
    12. 9Department of Neonatology, Leiden University Medical Center, Leiden, the Netherlands
    13. 10Department of Neonatology, ISALA Medical Center, Zwolle, the Netherlands
    14. 11Department of Neonatology, University Medical Center Gent, Gent, Belgium
    1. Correspondence to Dr T R de Haan, Department of Neonatology, Emma Childrens' Hospital UMC, Amsterdam, Noord-Holland, Netherlands; t.r.dehaan{at}amsterdamumc.nl

    Abstract

    Background Perinatal asphyxia may be followed by multiple organ dysfunction (MOD) and is often included in prognostication of the individual patient, but evidence of discriminating accuracy is lacking. The aim of this study was to assess whether MOD in asphyxiated neonates during therapeutic hypothermia (TH) predicts mortality or neurodevelopmental impairment (NDI) at 24 months of age and which peripartum variables are associated with the onset of MOD.

    Methods A retrospective analysis of a prospective cohort study of asphyxiated newborns undergoing TH was performed. MOD was defined as dysfunction of the brain (encephalopathy) combined with two or more organ systems. Outcome was routinely assessed by standardised developmental testing at the age of 24 months. The predictive accuracy of MOD on the combined outcome and its components (death and NDI) was expressed as areas under the receiver operating characteristic curves (AUROCs). The associations of peripartum variables and development of MOD were expressed as ORs and their CIs.

    Results 189 infants (median gestation 40 (range 36–42 weeks) with moderate to severe hypoxic ischaemic encephalopathy were included. 47% developed MOD. The prediction of the combined 24-month outcome or its components showed AUROCs <0.70. Associated with MOD were pH at birth (OR 0.97, CI 0.95 to 0.99), lactate at birth (OR 1.09, CI 1.04 to 1.15), Base Excess (BE) at birth (OR 0.94, CI 0.90 to 0.99) and epinephrine administration during resuscitation (OR 2.09, CI 1.02 to 4.40).

    Conclusion MOD has a low discriminating accuracy in predicting mortality or NDI at 24 months age and might not be useful for prognostication. Signs of acid–base disturbance and adrenalin use at birth are associated with the development of MOD.

    • neonatology
    • neurology

    Data availability statement

    Data are available upon reasonable request. Data generated or analysed during the study are available from the corresponding author by request.

    http://dx.doi.org/10.1136/archdischild-2023-325585

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      Data availability statement

      Data are available upon reasonable request. Data generated or analysed during the study are available from the corresponding author by request.

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      Footnotes

      • Twitter @fgroenendaal

      • Collaborators Chris van den Akker, Willem P de Boode, Filip Cools, Peter H Dijk, Koen P Dijkman, Floris Groenendaal, Timo R de Haan, Sinno H P Simons, Sylke J Steggerda, Henrica L M van Straaten and Alexandra Zecic

      • Contributors JL prepared the database, performed the statistical analyses, prepared the data tables, drafted the initial manuscript and revised the manuscript. LdV and FG made substantial contributions to the interpretation of data, and reviewed and revised the manuscript for important intellectual content. TRdH, WO, DV and AHvK are local investigators, made substantial contributions to the concept and design of the study, had full access to all of the data in the study, take responsibility for the integrity of the data and the accuracy of the data analysis, and critically reviewed the manuscript for important intellectual content. TRdH acts as guarantor.

        All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

      • Funding This study was funded by a project grant from The Netherlands Organization for Health Research and Development ZonMW Priority Medicines for Children (grant number 40-41500-98-9002).

      • Competing interests TRdH reports grants from The Netherlands Organization for Health Research and Development ZonMW during the conduct of the study.

      • 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.