Perinatal asphyxia-induced brain injury is one of the most common causes of morbidity and mortality in term and preterm neonates. Birth asphyxia accounts for 23% of neonatal deaths globally and survivors suffer from long term neurological disability and impairment. Although many neuroprotective strategies appeared promising in animal models, most of them were not feasible and effective in human newborns. However, hypothermia was reported not to be effective if introduced beyond and thus should be introduced within 6 hrs after birth.Applying this selection criterion naturally would deprive many patients of the opportunity of hypothermia treatment.

Hypoxic-ischemic encephalopathy of the newborn infant remains a significant socio-economic health problem worldwide. Moderate to severe HIE of newborn infants is associated with a high rate of death or long-term disabilities. Historically, treatment has been purely supportive including stabilizing cardio-respiratory functions and treating convulsions. Recent multi-center trials assessing the effects of hypothermia demonstrated improved outcome in term neonates with moderate hypoxic-ischemic encephalopathy (HIE). However, hypothermia was not effective beyond 6 hrs after brain injury. The aim of this study was to investigate whether systemic hypothermia induced up to 10 hrs after birth would improve the neurodevelopmental outcome at 18 months in infants with moderate or severe HIE.

Inclusion Criteria:

1. Gestation age ≥37 weeks and body weight >2500g.

2. with one of the following factors:

   1. Apgar score<5 at 5min;
   2. Assisted respiration >3min due to respiratory distress;
   3. pH≤7.1 of cord or arterial blood within 60min after birth;
   4. clinical manifestation of encephalopathy during the first 10 hrs of life.

Exclusion Criteria:

1. Major congenital abnormalities;
2. Head trauma or skull fracture causing major intracranial hemorrhage;
3. Mild HIE;
4. Financial problems of the parents;
5. Lack of permanent address;
6. Postnatal age > 10 hrs