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Am J Perinatol
DOI: 10.1055/a-2752-8853
Original Article

Servo-Controlled versus Manual Cooling for Therapeutic Hypothermia in Neonatal Hypoxic–Ischemic Encephalopathy: A Retrospective Comparative Study

Authors

  • Maurício Magalhães

    1   Division of Neonatology, Department of Pediatrics, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil
    2   Protecting Brains & Saving Futures, Clinical Research Department, São Paulo, Brazil
    3   Santa Casa de São Paulo School of Medicine, São Paulo, Brazil

  • Danieli M. K. Leandro

    1   Division of Neonatology, Department of Pediatrics, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil
    2   Protecting Brains & Saving Futures, Clinical Research Department, São Paulo, Brazil

  • Silvia S. de Azevedo

    2   Protecting Brains & Saving Futures, Clinical Research Department, São Paulo, Brazil

  • Juliana Q. Teixeira

    2   Protecting Brains & Saving Futures, Clinical Research Department, São Paulo, Brazil

  • Hannah A. Hiratzuka

    1   Division of Neonatology, Department of Pediatrics, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil

  • Marcelo J. Mimica

    2   Protecting Brains & Saving Futures, Clinical Research Department, São Paulo, Brazil
    3   Santa Casa de São Paulo School of Medicine, São Paulo, Brazil

  • Gabriel F. T. Variane

    1   Division of Neonatology, Department of Pediatrics, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil
    2   Protecting Brains & Saving Futures, Clinical Research Department, São Paulo, Brazil

Funding Information This study was an investigator-initiated study funded by Becton, Dickinson and Company, New Jersey, United States.
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Abstract

Objective

This study aimed to compare temperature control during therapeutic hypothermia (TH) in neonates with moderate or severe hypoxic–ischemic encephalopathy (HIE) using manual cooling (MC) or a servo-controlled (SC) system.

Study Design

Retrospective cohort study including neonates with ≥ 35 weeks' gestation with moderate or severe HIE who were treated with TH between 2018 and 2020, using MC with ice packs or a SC system. Temperature curves and clinical outcomes were compared between the two methods of cooling. Data were summarized using descriptive statistics. Groups were compared with appropriate parametric or nonparametric tests. Temperature stability and rewarming variability were evaluated, and secondary outcomes were analyzed using risk ratios with 95% confidence intervals and logistic regression adjusted for encephalopathy severity.

Result

During the study period, 56 neonates with moderate or severe HIE were cooled, 31 (55.4%) with MC and 25 (44.6%) with a SC system. Baseline characteristics and time to target temperature were similar. SC achieved more stable hypothermia, with less variability (p = 0.014) and reduced time outside the therapeutic range (2.7 vs. 8.1%, p = 0.005). Extreme temperature deviations occurred only in the MC group. Rewarming rates were comparable, although variability was greater with MC. Clinical outcomes showed lower risk of hypotension (RR: 0.647, 95% CI: 0.409–1.02; p = 0.044), inotrope use (RR: 0.647, 95% CI: 0.409–1.02; p = 0.044), and abnormal magnetic resonance imaging (MRI) findings (12.0 vs. 46.2%; RR: 0.26, 95% CI: 0.08–0.81; p = 0.013) in the SC group. After adjusting for clinical encephalopathy severity, SC remained independently protective against abnormal MRI (aOR: 0.19; 95% CI: 0.04–0.865; p = 0.03) and hypotension (aOR: 0.27; 95% CI: 0.08–0.95; p = 0.04). Mortality occurred only in the MC group.

Conclusion

While both methods were effective, the SC system offered more stable temperature control and may reduce complications during and after TH.

Key Points

  • Temperature stability is critical for the effectiveness of TH.

  • SC cooling provided more stable temperature control than MC.

  • SC cooling and MC were feasible in a neonatal intensive care unit setting.

  • SC cooling may reduce neurological complications during and after TH.

Keywords

therapeutic hypothermia - neonatal intensive care unit - hypoxic–ischemic encephalopathy - manual cooling - servo-controlled cooling

Supplementary Material



Publication History

Received: 05 September 2025

Accepted: 20 November 2025

Article published online:
05 December 2025

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