Therapeutic Hypothermia in Low- and Middle-Income Countries: New Evidence from the ILCOR Neonatal Life Support Task Force

herapeutic hypothermia (TH) has transformed the care of newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE) in high-income settings, where its benefits are well-established. But an important question has remained: Does TH offer the same benefits in low- and middle-income countries (LMICs), where health systems and neonatal intensive care resources may differ?

The International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force set out to answer this critical question in a systematic review and meta-analysis.

Study Objective

The goal was to evaluate the effectiveness and safety of TH for infants with moderate or severe HIE in LMICs.

Methods

Researchers searched Medline, Embase, and CENTRAL through September 2024.

• Inclusion: Randomized controlled trials (RCTs) of therapeutic hypothermia in LMICs.

• Assessment: Risk of bias using Cochrane RoB2 and certainty of evidence using GRADE.

• Outcomes:

  • Primary: Death or moderate-to-severe neurodevelopmental impairment (NDI) at 18–24 months.

  • Secondary: Death alone, NDI alone, and other key neonatal outcomes.

In total, 18 RCTs were included, involving primarily term infants (≥37 weeks). All studies applied TH protocols with access to intensive care, though the methods of cooling varied across sites.

Results

• Primary outcome (death or NDI at 18–24 months):Benefit or harm could not be excluded (RR 0.63; 95% CI 0.38–1.04; p = 0.07; I² = 80%; 4 studies, 717 infants; moderate certainty).

• Death by 18–24 months:Again, benefit or harm could not be excluded (RR 0.81; 95% CI 0.43–1.52; p = 0.51; I² = 67%; 4 studies, 722 infants; moderate certainty).

• Neurodevelopmental impairment (NDI) at 18–24 months:TH-treated infants possibly had lower NDI (RR 0.51; 95% CI 0.35–0.76; p < 0.0001; I² = 0%; 4 studies, 511 infants; low certainty).

Conclusions

For newborns in LMICs:

• Therapeutic hypothermia may reduce neurodevelopmental impairment at 18–24 months.

• The effect on survival remains uncertain.

• Where hospitals can follow defined TH protocols and provide adequate intensive care and follow-up, TH may offer meaningful benefit for term infants.

Why This Matters

These findings are especially important for LMICs where the burden of HIE is highest. The review highlights that infrastructure and consistent protocols are key—without these, the benefits of TH may not be realized.

The ILCOR Neonatal Life Support Task Force concludes that while TH shows promise, more high-quality, context-specific research is needed to fully understand its role in LMICs.

👉 Takeaway: Therapeutic hypothermia remains a potential tool for improving outcomes in LMICs—but its effectiveness depends heavily on local health system capacity, resources, and adherence to protocols.