Hypothermia in the treatment of hypoxic-ischemic encephalopathy of the term newborn

Dr Juliana Patkaï.

Hypoxic-ischemic encephalopathy of the term newborn

The incidence of hypoxic-ischemic encephalopathy (HIE) is approximately 1.5 per 1000 live births at term. The moderate and severe forms are associated with a poor prognosis in terms of mortality and serious neurological sequelae, whether motor, cognitive, and/or sensory. The body temperature of the newborn drops spontaneously at birth after acute asphyxia, a physiological phenomenon that affords effective neuroprotection.

To date, six published large, randomized, controlled studies in patients who undergo therapeutic hypothermia have shown:

  • lower mortality;
  • reduction in the composite outcome of mortality and serious sequelae, with 9 as the number needed to treat to avoid an event;
  • improved survival without sequelae, with 8 as the number needed to treat;
  • reduced rate of serious sequelae in survivors.

Indications

Therapeutic hypothermia is of proven efficacy in moderate and severe forms of HIE, with greater benefit for moderate forms. Hypoxia affects brain cells in two phases of energy failure. First, there is energy deficiency concomitant with asphyxia, followed by a latency period of about 6 hours. Second, there is energy deficit. By reducing the energy consumption of brain cells, hypothermia prevents cells from entering a process of delayed cell death during the second phase. Currently, in the industrialized countries, moderate total-body hypothermia has become a common treatment of moderate or severe HIE in the term newborn. The French Society of Neonatology has defined three criteria that must be met for its use:

  • intensive care needed at birth because of acute asphyxia in the peripartum period documented by metabolic acidosis at birth;
  • clinical criteria of moderate or severe encephalopathy according to the classification of Sarnat and Sarnat;
  • alterations in the EEG trace reflecting cerebral hypoxia.

Modalities

To be effective, hypothermia must be initiated before 6 hours of life and maintained for 72 hours, with a target core temperature of 33.5 ± 0.5°C. Cooling mattresses linked to a controlled hypothermia device can be used to maintain a perfectly stable core temperature. Intensive care combines effective analgesia and sedation, assisted ventilation, and treatment of organ failure, which is often associated.

Conclusion

Despite the improvement afforded by hypothermia, the prognosis of HIE remains poor, with a 50% rate of death or sequelae in survivors. Other promising neuroprotective treatments are being studied, notably high-dose erythropoietin or xenon. The combination of several neuroprotective treatments, combined with tools for early prognosis such as MRI, biomarkers, or EEG, may in the near future improve survival without sequelae in these infants.

First published on the DHU Risks in Pregnancy website (June-July 2014)