Post-Resuscitation Care

Rewarming of Newborns with Unintentional Hypothermia After Delivery

Last Full Review: ILCOR 2015
Last Update: 2024

Newborns are vulnerable to hypothermia immediately after birth due to their large surface area-to-body mass ratio, decreased subcutaneous fat, exposure to a low temperature delivery environment and other factors. Body temperature may fall by 2° C to 4° C in the first 10 to 20 minutes after birth (Dahm and James 1972, 504).

Hypothermia in newborns puts them at risk for several potentially life-threatening complications including hypoxia, metabolic acidosis, cardiovascular complications and hypoglycemia. Hypothermia is also an independent predictor (Trevisanuto et al.2018, 333) of neonatal mortality. 

Other reviews by the International Liaison Committee on Resuscitation (ILCOR) have examined methods for maintaining a normal body temperature immediately after birth (Wyckoff et al. 2022, e483; de Almeida et al. 2022). When unintentional hypothermia does occur in a newborn, rewarming is essential. How rewarming is accomplished—and how quickly—has been the focus of recent studies.

 

Evidence Summary

A 2024 ILCOR systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Rüdiger et al. 2024; Greif et al. 2024) sought evidence for rapid rewarming (0.5o C or greater per hour) compared with slow rewarming (less than 0.5o C per hour) of infants who are unintentionally hypothermic (less than 36.0o C) on admission. 

The review included one randomized controlled trial (RCT)  (Motil et al. 1974, 546) and two observational studies (Rech Morassutti et al. 2015, 557; Feldman et al. 2016, 295). The RCT (Motil et al. 1974, 546) included 40 term newborns of normal birthweight in a comparison of maximum temperature setpoints for the servo-controlled radiant warmers used for rewarming. Rates of rewarming depended on these setpoints, and an effect on mortality could not be determined. 

The observational studies enrolled a total of 280 neonates, with one including preterm infants born at 28 weeks’ or less and/or with a birth weight 1000 or less grams (Rech Morassutti et al. 2015, 557), while the second study (Feldman et al. 2016, 295) enrolled newborns with a birthweight less than 1500 grams. These two observational studies could not exclude benefit or harm from rapid rewarming compared with slow rewarming for the outcome of mortality (RR, 1.09, 95% CI, 0.7–1.71). Data was inconclusive or not available for all other critical and important outcomes.

The ILCOR treatment recommendations include (Rüdiger et al. 2024; Greif et al. 2024):

• For infants who are unintentionally hypothermic after birth, rewarming should be commenced, but there is insufficient evidence to recommend either rapid (0.5o C or greater per hour) or slow (less than 0.5o C per hour) rates of rewarming.
• A new good practice statement advises that regardless of the rewarming rate chosen, a protocol for rewarming should be used. Frequent or continuous monitoring of temperature should be undertaken, particularly if using a supraphysiological set temperature point to accelerate the rewarming rate, because of the risk of causing hyperthermia. In any hypothermic infant, monitor blood glucose due to the risk of hypoglycemia.

 

A review of rewarming rates in unintentionally hypothermic newborn infants was completed by the American Red Cross Scientific Advisory Council in 2024 (American Red Cross Scientific Advisory Council 2024). The systematic review and CoSTR by ILCOR (Rüdiger et al. 2023, 111113897; Greif et al. 2024) as well as one additional RCT (Jain et al. 2012) and three observational studies (Rossi et al. 2023, 1113897; Wilson et al. 2016, 61; Laptook et al. 2018, 53) confirmed the increased mortality risk in hypothermic preterm or low birth weight infants. 

The RCT studied the effect of rapid versus slow rewarming in the management of severely hypothermic low birth weight (less than 2.5 kilograms) preterm (less than 37 weeks’ gestation) neonates (Jain et al. 2021, 1). Primary outcomes were a stabilization score (TOPS: Temperature, Oxygenation, Perfusion and Saturation) and the Modified Sick Neonatal Score (MSNS) at baseline, 6 and 24 hours, and mortality until discharge. Mean TOPS and MSNS scores at baseline, 6 and 24 hours, were similar between the two warming groups, and mortality in rapid and slow rewarming groups was similar (OR, 1.46; 95% CI, 0.43–4.97, P=0.538). 

The American Red Cross Scientific Advisory Council review noted that two of three studies included in the ILCOR review used servo-controlled devices to monitor and control the rate of rewarming. If these devices are demonstrated to improve outcomes with rewarming in future studies, the cost of these devices (capable of operating in servo-mode) and disposable temperature probes may have implications in resource-limited settings. 

None of the included studies reported hyperthermia as an outcome. One observational study that did not meet the ILCOR review inclusion criteria found that 43 (12.5%) of 344 included infants developed hyperthermia (greater than 37.5 o C)  (Rossi et al. 2023, 1113897), with rapid, compared to a slow rewarming rate associated with hyperthermia (P=0.007). It is unclear whether the hyperthermia was related to specific settings of the devices used for rewarming in this study (radiant warmers and incubators in manual mode), or to other characteristics of the included infants, which further studies should consider.

Insights and Implications

The Red Cross guidelines are informed by this ILCOR review and essentially unchanged. There is insufficient evidence to recommend rapid versus slow rewarming in newborns who are unintentionally hypothermic following delivery or resuscitation. A new good practice statement suggests that hospitals and facilities where infants are delivered develop protocols for rewarming infants who are unintentionally hypothermic after birth. Because of the known risk of causing hyperthermia, frequent or continuous monitoring of temperature is advised, particularly if using a supraphysiological set temperature point to accelerate the rewarming rate. In addition, because hypoglycemia is a known risk in hypothermic infants, blood glucose should be monitored.

Therapeutic Hypothermia in Settings with Limited Resources

Last Full Review: ILCOR 2015
Last Update: 2024

Asphyxia is a leading cause of neonatal mortality and morbidity; other notable causes include cerebral palsy, blindness and deafness. In high-income countries, therapeutic hypothermia has become widely implemented in neonatal intensive care units as part of the standard protocol for managing term or near-term infants with hypoxic ischemic encephalopathy. However, there is limited evidence to support the use of therapeutic hypothermia in low-resource settings or in middle- and low-income countries. A 2015 Consensus on Science with Treatment Recommendations CoSTR (Perlman et al. 2015, S204) by the International Liaison Committee on Resuscitation (ILCOR) provided a weak recommendation suggesting that infants at term or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy in low-income countries and/or settings with limited resources may be treated with therapeutic hypothermia. Recent publications on this topic have led to a new systematic review by ILCOR.

 

Evidence Summary 

A 2024 ILCOR systematic review and CoSTR (Lee et al. 2024; Greif et al. 2024) sought evidence for the use of therapeutic hypothermia to a specified target temperature for a defined duration compared with standard care in late preterm and term infants (34+0 or more weeks’ gestation) with moderate-to-severe hypoxic ischemic encephalopathy managed in low-resource settings. 

The primary critical prespecified outcomes included death or neurodevelopmental impairment, defined as abnormal motor, sensory or cognitive function, using an appropriate standardized test at 18 months to 2 years. Secondary critical outcomes included death at hospital discharge, neurodevelopmental impairment at 19 months to 2 years, cerebral palsy, blindness and deafness. The review identified 21 randomized controlled trials involving 2145 infants with hypoxic ischemic encephalopathy, all conducted in low- and middle-income countries. Details of the included studies can be found in the online ILCOR CoSTR (Lee et al. 2024; Greif et al. 2024). Data was very limited for late preterm infants.

Definitions

Definitions in this review included:

• Moderate-to-severe hypoxic ischemic encephalopathy: Sarnat clinical staging system stages 2 or 3 or Thompson Score greater than 11, or as defined by the authors (Sarnat et al. 1976 696; Thompson et al. 1997 757).
• Low-resource setting (for study eligibility): 
  • Any study conducted in low- and middle-income countries as designated by the World Bank, by which economies are classified based on their Gross National Income per capita
  • Studies that were conducted in a low-resource setting in a high-income country
• Therapeutic hypothermia: Intended therapy to maintain core temperature of approximately 33.5° C, for a defined duration that is typically 72 hours
• Survival: Survival-to-hospital discharge, or as defined by the authors
• Neurodevelopmental impairment: Graded by standardized testing, as defined by the authors
• Late preterm: 34+0 to 36+6 weeks’ gestation.
• Term: 37+0 and higher weeks’ gestation.

 

Key Findings

Key findings from the systematic review and meta-analyses include (Lee et al. 2024; Greif et al. 2024):

• For the outcome of combined death or neurodevelopmental impairment at 18 to 24 months, there was a probable clinical benefit with the use of therapeutic hypothermia compared with no hypothermia in term- or late-preterm infants with moderate-to-severe hypoxic ischemic encephalopathy in middle- or low-income countries (RR 0.67; 95% CI, 0.45–0.99;P=0.04; ARD 151 fewer infants died or had neurodevelopmental impairment per 1000 [95% CI from 252 fewer to 5 fewer]), moderate-certainty evidence downgraded for risk of bias from five randomized controlled trials (RCTs) enrolling 813 participants (Aker et al. 2022, 32; Li et al. 2009, 147; Thayyil et al. 2021, e1273; Zhou et al. 2010, 367; Zou et al. 2019, 2332).
• For the outcome of death at hospital discharge, there was possible clinical benefit from the use of therapeutic hypothermia versus no therapeutic hypothermia in infants with moderate-to-severe hypoxic ischemic encephalopathy in middle- or low-income countries (RR, 0.70; 95% CI, 0.47–1.02; P=0.06; ARD 64 fewer infants died per 1000 [95% CI from 114 fewer to 4 more]), moderate-certainty evidence from 15 RCTs enrolling 1488 participants (Aker et al. 2022, 32; Akisu et al. 2003, 45; Bharadwaj et al. 2012, 382; Wyckoff et al. 2021, 229; Chen et al. 2018, 1046; Joy et al. 2013, 17; Liao et al. 2018, 64; Lin et al. 2006, 180; Rakesh et al. 2018, 2418; Robertson et al. 2008, 801; Sun et al. 2012, e316; Tanigasalam et al. 2016, 2545; Thayyil et al. 2021, e1273; Yang et al. 2020, 300060520943770; Zou et al. 2019, 2332).
• For the outcome of cerebral palsy, a clinical benefit was shown with the use of therapeutic hypothermia compared with no hypothermia in term- or late-preterm infants with moderate-to-severe-hypoxic ischemic encephalopathy in middle- or low-income countries (RR, 0.52; 95% CI, 0.37–0.72; P<0.0001; ARD 89 fewer infants per 1000 had cerebral palsy [95% CI from 52 fewer to 117 fewer]), high-certainty evidence from six RCTs, enrolling 919 participants (Aker et al. 2022, 32; Jose et al. 2017, 86; Li et al. 2009, 147; Sun et al. 2012, e316; Thayyil et al. 2021, e1273; Zhou et al. 2010, 367).
• For the outcome of blindness at follow-up, there was a probable clinical benefit with the use of therapeutic hypothermia compared with no hypothermia in term- or late-preterm infants with moderate-to-severe hypoxic ischemic encephalopathy in middle- or low-income countries (RR, 0.48; 95% CI, 0.22–1.03; P=0.06; ARD 28 fewer infants were blind per 1000 [95% CI from 41 fewer to 2 more]), moderate-certainty evidence, downgraded for risk of bias, from four RCTs enrolling 718 participants (Das et al. 2017, 157; Gane et al. 2014, 134; Jose et al. 2017, 86; Thayyil et al. 2021, e1273).
• For the outcome of deafness at follow-up, there was probable clinical benefit with the use of therapeutic hypothermia compared with no hypothermia in term or late preterm infants with moderate- or severe-hypoxic ischemic encephalopathy in middle- or low-income countries (RR, 0.42; 95% CI, 0.21–0.82; P=0.01; ARD 42 fewer infants were deaf per 1000 [95% CI from 57 fewer to 13 fewer]), moderate-certainty evidence, downgraded for risk of bias, from four RCTs enrolling 718 participants (Das et al. 2017, 157; Gane et al. 2014, 134; Jose et al. 2017, 86; Thayyil et al. 2021, e1273).
• No difference in the risk of developing persistent pulmonary hypertension of the newborn was found with use of therapeutic hypothermia versus no hypothermia encephalopathy, based on evidence from three RCTs (Aker et al. 2020, 405; Tanigasalam 2016, 2545; Thayyil et al. 2021, e1273).

 

Subgroup analysis was completed for servo-controlled versus non–servo-controlled methods to induce hypothermia. The non–servo-controlled methods were found to be more efficacious than servo-controlled methods for critical outcomes of death or neurodevelopmental impairment at follow-up, death at follow-up and death at hospital discharge. 

An updated ILCOR treatment recommendation (Lee et al. 2024; Greif et al. 2024) suggests the use of therapeutic hypothermia in comparison with standard care alone for term (37+0 or more weeks’ gestational age) infants with evolving moderate-to-severe hypoxic ischemic encephalopathy in low- and middle-income counties in settings where a suitable level of supportive neonatal care is available.

For late-preterm infants 34+0 to 36+6 weeks’ gestation, a recommendation for the use of therapeutic hypothermia cannot be made due to insufficient evidence (Lee et al. 2024; Greif et al. 2024).

A new good practice statement from ILCOR (Lee et al. 2024; Greif et al. 2024) advises that therapeutic hypothermia should only be considered, initiated and conducted under clearly defined protocols with treatment in neonatal facilities capable of multidisciplinary care with adequate resources available to offer:

• Intravenous therapy
• Respiratory support
• Pulse oximetry 
• Antibiotics
• Anti-seizure medication
• Transfusion services
• Radiology (including ultrasound) 
• Pathology testing, as required

 

Treatment should be consistent with the protocols used in randomized clinical trials. Most protocols included commencement of cooling within 6 hours after birth, strict temperature control to a specified range (typically 33° C to 34° C) and most commonly for a duration of 72 hours with rewarming over at least 4 hours. Adoption of hypothermia techniques without close monitoring, protocols or availability of comprehensive neonatal intensive care may lead to harm.

An American Red Cross Scientific Advisory Council review (American Red Cross Scientific Advisory Council 2024b) on the topic of therapeutic hypothermia in late preterm and term infants with hypoxic ischemic encephalopathy included the ILCOR CoSTR, but also included a 2014 clinical report (Papile et al. 2014, 1146) from the American Academy of Pediatrics (AAP), Committee on Fetus and Newborn. The committee reviewed the evidence for the safety and efficacy of hypothermia as a neuroprotective therapy for neonatal hypoxic ischemic encephalopathy, and formulated a therapeutic recommendation for initiating therapeutic hypothermia. The framework for implementation should meet the inclusion criteria outlined in published clinical trials, based on a review of six large clinical trials with 1200 infants enrolled with entry criteria for infants of more than 36 weeks’ gestational age for therapeutic hypothermia. The American Red Cross Scientific Advisory Council review notes that a gestational age 36 or more weeks’ has become a standard entry criterion in United States institutional protocols for therapeutic hypothermia, and is therefore included in the Red Cross Guidelines good practice statement. 

The AAP report (Papile et al. 2014, 1146) states that therapeutic hypothermia for newborns less than 35 weeks’ gestation should only be performed in a research setting. For newborn infants in low- and middle-income countries with a gestational age of 34+0 to 36+6 weeks’ and evolving moderate-to-severe hypoxic ischemic encephalopathy, the ILCOR CoSTR (Lee et al. 2024; Greif et al. 2024) reaffirms that there continues to be insufficient evidence to make a recommendation regarding therapeutic hypothermia.

Insights and Implications 

The ILCOR systematic review and CoSTR (Lee et al. 2024; Greif et al. 2024) were intended to assess the use of therapeutic hypothermia in late preterm and term infants (34+0 or more weeks’ gestation) with moderate to severe hypoxic ischemic encephalopathy managed in low-resource settings. A low-resource setting for study eligibility was defined as any study conducted in low- and middle-income countries as designated by the World Bank, and studies that were conducted in a low-resource setting in a high-income country. However, none of the included studies were conducted in a low-resource setting in a high-income country. In addition, descriptions of care provided in the included studies suggest that many of the neonatal units provided high-resourced services despite originating in low- or middle-include countries. The ILCOR CoSTR discussion acknowledges that the recommendation for therapeutic hypothermia is made in relation to low- and middle-income countries rather than to the low-resource settings intended by the Population, Intervention, Control, Outcomes, Study design and Timeframe (PICOST) question (Lee et al. 2024; Greif et al. 2024).

While the Red Cross guidelines are informed by ILCOR, we recognize that the United States is classified as a high-income country. Therapeutic hypothermia for hypoxic ischemic encephalopathy has become standard treatment, and the necessary resources are—in most cases—accessible at neonatal intensive care facilities onsite or in nearby specialty care centers. 

Cooling is initiated in some cases by dedicated neonatal transport teams during transfer to a specialty care center for infants born at hospitals where hypothermia is not available. Protocols commonly include criteria for a gestational age of 36 weeks’ or more. The good practice statement that therapeutic hypothermia may be considered in late preterm infants who are 36+0 to 36+6 weeks’ gestation, is made in relation to care provided in U.S. healthcare centers with experience in providing therapeutic hypothermia and with pre-existing protocols.

Glucose Management: During or Immediately After Resuscitation 

Last Full Review: ILCOR 2025
Last Update: 2020

Infants requiring resuscitation at birth are at risk of developing hypoglycemia as well as iatrogenic hyperglycemia from glucose therapy. A 2010 International Liaison Committee on Resuscitation (ILCOR) systematic review (Perlman, 2010, S516) focused on treatment of newborns who have received drugs for resuscitation using a glucose infusion. A 2020 evidence update (Wyckoff et al. 2020, S185) identified additional studies that were reported to suggest the need to maintain vigilance for neonatal hypoglycemia and hyperglycemia following resuscitation, and that protocols for glucose management may help avoid large swings in blood glucose as well as hypoglycemia and hyperglycemia. In order to reframe the original question on neonatal hypoglycemia and hyperglycemia for a new systematic review, ILCOR used a scoping review approach in 2025.

 

Evidence Summary 

A 2025 (ILCOR) scoping review and synthesis (McKinlay et al. 2024; Liley et al. 2025, S165) used a Participants, Concepts and Context framework (Pollock et al. 2021, 2102) to identify studies providing evidence to answer three questions:

1. When and how should blood glucose be monitored in newborn infants receiving resuscitation?
2. When and how should glucose therapies be used during and after neonatal resuscitation?
3. What is the optimal blood glucose concentration range for newborn infants during and after resuscitation?

 

For the first question of when and how should blood glucose be monitored during resuscitation, observational studies were identified that described serial monitoring of blood glucose to assess the frequency of neonatal dysglycemia (hyperglycemia, hypoglycemia, or both). All but one study included infants born at 34+0 weeks’ gestation or greater, and all but two studies used intermittent blood glucose sampling. Definitions of hyperglycemia and hypoglycemia varied between studies. Some studies described resuscitative interventions that might be associated with increased or decreased risk of dysglycemia, such as the administration of epinephrine and performing chest compressions. The proportion of infants with hypoglycemia and hyperglycemia in the first 6 hours after birth and on neonatal intensive care unit (NICU) admission was reported in several studies and varied widely (McKinlay et al. 2024; Liley et al. 2025, S165).

For the question on when and how should glucose or other treatments to control blood glucose be used during and after neonatal resuscitation, no human studies were identified and evidence from animal studies was described as inconsistent, with some studies suggesting neuroprotection when glucose was infused during asphyxia or recovery from hypoxia-ischemia, and others suggesting harm or no benefit. Studies described routine commencement of intravenous dextrose in infants admitted to the NICU after resuscitation, but an optimal strategy to achieve euglycemia was not identified (McKinlay et al. 2024; Liley et al. 2025, S165).

For the question regarding the optimal blood glucose concentration range for newborns during and after resuscitation, no studies were identified that directly investigated an optimal glucose range.

A previous 2010 recommendation by ILCOR stated that intravenous glucose infusion should be considered as soon as practical after resuscitation, with the goal of avoiding hypoglycemia (Perlman, 2010, S516). This recommendation was created prior to the use of the current ILCOR methodology of performing systematic reviews with the use of the Grading of Recommendations Assess, Development and Evaluation (GRADE) framework, and it has been superseded by two new good practice statements (McKinlay et al. 2024; Liley et al. 2025, S165):

• Among newborn infants receiving resuscitation, blood glucose concentration should be measured early in the post-resuscitation period and monitored with serial measurements until maintained within a normal range. Infants at greatest risk of hypoglycemia and hyperglycemia during the post-resuscitation period include preterm infants, infants receiving chest compressions or epinephrine, and those with hypoxic ischemic encephalopathy.
• Treatment with intravenous glucose infusions should be guided by the infant’s blood glucose concentration with the goal of avoiding both hypoglycemia and hyperglycemia.

 

Insights and Implications 

The available evidence for this review suggests that both hypoglycemia and hyperglycemia are common in the first hours after resuscitation of newborns, and both may be associated with harm. However, the studies primarily addressed term and late preterm newborns at high risk for or already with hypoxic ischemic encephalopathy and other conditions associated with dysglycemia (e.g., preterm infants during the post-resuscitation period, infants receiving chest compressions or epinephrine). The scoping review unfortunately did not identify sufficient evidence for a future ILCOR systematic review of specific interventions in glucose management during and after neonatal resuscitation. The optimal target range for blood glucose post-resuscitation remains uncertain, and research is needed to identify best practices for monitoring and managing dysglycemia.