Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy

Jill M Mitchell; Clare L Rodrigues; Margo Dunworth; Julie Mc Ginley; Laura O'Byrne; Roisin Hall; Paul Corcoran; Indra San Lazaro Campillo; Peter Mc Kenna; John R Higgins; Joye McKernan; Ali S Khashan; Gillian M Maher; John Murphy; Brian H Walsh; Richard A Greene; Fergus P McCarthy

doi:10.1038/s41372-025-02547-z

Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy

Jill M Mitchell
, Clare L Rodrigues
, Margo Dunworth
, Julie Mc Ginley
, Laura O'Byrne
, Roisin Hall
, Paul Corcoran
, Indra San Lazaro Campillo
, Peter Mc Kenna
, John R Higgins
, Joye McKernan
, Ali S Khashan
, Gillian M Maher
, John Murphy
, Brian H Walsh
, Richard A Greene
, Fergus P McCarthy

Expert Advisory Group-National Maternity and Gynaecology Clinical Guideline Programme, National Women and Infants Health Programme, Health Service Executive-Institute of Obstetricians and Gynaecologists
National Perinatal Epidemiology Centre
Department of Obstetrics and Gynaecology
Cork Clinic

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: To develop and internally validate a model predicting neonatal mortality in infants with neonatal encephalopathy requiring therapeutic hypothermia (TH), using national data.

STUDY DESIGN: Data from 385 infants treated with TH across 19 hospitals (2016-2021) were analysed. Multivariable logistic regression with backward stepwise selection was applied. Discrimination was assessed using the C-statistic, with internal validation by bootstrapping. The THERM (Therapeutic Hypothermia Early Risk Model for Mortality) tool was developed to calculate individualised mortality risk.

RESULTS: Forty-six infants (11.9%) died within 28 days. Four predictors were retained: prelabour Caesarean section, adrenaline use, base excess ≤-22 mmol/L, and seizures during the first day of life. The model demonstrated excellent discrimination [optimism-adjusted C-statistic 0.885 (95% CI: 0.827-0.936)].

CONCLUSIONS: Four routinely collected variables predicted mortality in infants undergoing TH. The THERM tool provides a practical resource for clinicians, enabling personalised risk assessment and supporting parental counselling during the first day of life.

Original language	English
Journal	Journal of Perinatology
DOIs	https://doi.org/10.1038/s41372-025-02547-z
Publication status	E-pub ahead of print - 5 Jan 2026

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41372-025-02547-z

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Mitchell, J. M., Rodrigues, C. L., Dunworth, M., Mc Ginley, J., O'Byrne, L., Hall, R., Corcoran, P., Campillo, I. S. L., Mc Kenna, P., Higgins, J. R., McKernan, J., Khashan, A. S., Maher, G. M., Murphy, J., Walsh, B. H., Greene, R. A., & McCarthy, F. P. (2026). Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy. Journal of Perinatology. Advance online publication. https://doi.org/10.1038/s41372-025-02547-z

@article{b3b105c684b046eb8eff4b240e5574f7,

title = "Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy",

abstract = "OBJECTIVE: To develop and internally validate a model predicting neonatal mortality in infants with neonatal encephalopathy requiring therapeutic hypothermia (TH), using national data.STUDY DESIGN: Data from 385 infants treated with TH across 19 hospitals (2016-2021) were analysed. Multivariable logistic regression with backward stepwise selection was applied. Discrimination was assessed using the C-statistic, with internal validation by bootstrapping. The THERM (Therapeutic Hypothermia Early Risk Model for Mortality) tool was developed to calculate individualised mortality risk.RESULTS: Forty-six infants (11.9\%) died within 28 days. Four predictors were retained: prelabour Caesarean section, adrenaline use, base excess ≤-22 mmol/L, and seizures during the first day of life. The model demonstrated excellent discrimination [optimism-adjusted C-statistic 0.885 (95\% CI: 0.827-0.936)].CONCLUSIONS: Four routinely collected variables predicted mortality in infants undergoing TH. The THERM tool provides a practical resource for clinicians, enabling personalised risk assessment and supporting parental counselling during the first day of life.",

author = "Mitchell, \{Jill M\} and Rodrigues, \{Clare L\} and Margo Dunworth and \{Mc Ginley\}, Julie and Laura O'Byrne and Roisin Hall and Paul Corcoran and Campillo, \{Indra San Lazaro\} and \{Mc Kenna\}, Peter and Higgins, \{John R\} and Joye McKernan and Khashan, \{Ali S\} and Maher, \{Gillian M\} and John Murphy and Walsh, \{Brian H\} and Greene, \{Richard A\} and McCarthy, \{Fergus P\}",

note = "{\textcopyright} 2026. The Author(s).",

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doi = "10.1038/s41372-025-02547-z",

language = "English",

journal = "Journal of Perinatology",

issn = "0743-8346",

publisher = "Springer Nature",

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Mitchell, JM, Rodrigues, CL, Dunworth, M, Mc Ginley, J, O'Byrne, L, Hall, R, Corcoran, P, Campillo, ISL, Mc Kenna, P, Higgins, JR , McKernan, J , Khashan, AS , Maher, GM, Murphy, J, Walsh, BH, Greene, RA & McCarthy, FP 2026, 'Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy', Journal of Perinatology. https://doi.org/10.1038/s41372-025-02547-z

TY - JOUR

T1 - Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy

AU - Mitchell, Jill M

AU - Rodrigues, Clare L

AU - Dunworth, Margo

AU - Mc Ginley, Julie

AU - O'Byrne, Laura

AU - Hall, Roisin

AU - Corcoran, Paul

AU - Campillo, Indra San Lazaro

AU - Mc Kenna, Peter

AU - Higgins, John R

AU - McKernan, Joye

AU - Khashan, Ali S

AU - Maher, Gillian M

AU - Murphy, John

AU - Walsh, Brian H

AU - Greene, Richard A

AU - McCarthy, Fergus P

PY - 2026/1/5

Y1 - 2026/1/5

N2 - OBJECTIVE: To develop and internally validate a model predicting neonatal mortality in infants with neonatal encephalopathy requiring therapeutic hypothermia (TH), using national data.STUDY DESIGN: Data from 385 infants treated with TH across 19 hospitals (2016-2021) were analysed. Multivariable logistic regression with backward stepwise selection was applied. Discrimination was assessed using the C-statistic, with internal validation by bootstrapping. The THERM (Therapeutic Hypothermia Early Risk Model for Mortality) tool was developed to calculate individualised mortality risk.RESULTS: Forty-six infants (11.9%) died within 28 days. Four predictors were retained: prelabour Caesarean section, adrenaline use, base excess ≤-22 mmol/L, and seizures during the first day of life. The model demonstrated excellent discrimination [optimism-adjusted C-statistic 0.885 (95% CI: 0.827-0.936)].CONCLUSIONS: Four routinely collected variables predicted mortality in infants undergoing TH. The THERM tool provides a practical resource for clinicians, enabling personalised risk assessment and supporting parental counselling during the first day of life.

AB - OBJECTIVE: To develop and internally validate a model predicting neonatal mortality in infants with neonatal encephalopathy requiring therapeutic hypothermia (TH), using national data.STUDY DESIGN: Data from 385 infants treated with TH across 19 hospitals (2016-2021) were analysed. Multivariable logistic regression with backward stepwise selection was applied. Discrimination was assessed using the C-statistic, with internal validation by bootstrapping. The THERM (Therapeutic Hypothermia Early Risk Model for Mortality) tool was developed to calculate individualised mortality risk.RESULTS: Forty-six infants (11.9%) died within 28 days. Four predictors were retained: prelabour Caesarean section, adrenaline use, base excess ≤-22 mmol/L, and seizures during the first day of life. The model demonstrated excellent discrimination [optimism-adjusted C-statistic 0.885 (95% CI: 0.827-0.936)].CONCLUSIONS: Four routinely collected variables predicted mortality in infants undergoing TH. The THERM tool provides a practical resource for clinicians, enabling personalised risk assessment and supporting parental counselling during the first day of life.

U2 - 10.1038/s41372-025-02547-z

DO - 10.1038/s41372-025-02547-z

M3 - Article

C2 - 41490924

SN - 0743-8346

JO - Journal of Perinatology

JF - Journal of Perinatology

ER -

Development of a prediction model for mortality in infants undergoing therapeutic hypothermia for neonatal encephalopathy

Abstract

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