• Intracranial haemorrhage [ Time Frame: Before discharge from hospital ]
• Persistent hypotension [ Time Frame: Before discharge from hospital ]
• Pulmonary haemorrhage [ Time Frame: Before discharge from hospital ]
• Pulmonary hypertension [ Time Frame: Before discharge from hospital ]
• Prolonged blood coagulation time [ Time Frame: Before discharge from hospital ]
• Culture proven sepsis [ Time Frame: Before discharge from hospital ]
• Necrotising enterocolitis [ Time Frame: Before discharge from hospital ]
• Cardiac arrhythmia [ Time Frame: Before discharge from hospital ]
• Thrombocytopenia [ Time Frame: Before discharge from hospital ]
• Major venous thrombosis [ Time Frame: Before discharge from hospital ]
• Renal failure treated with dialysis [ Time Frame: Before discharge from hospital ]
• Pneumonia [ Time Frame: Before discharge from hospital ]
• Pulmonary airleak [ Time Frame: Before discharge from hospital ]
• Duration of hospitalisation [ Time Frame: Before discharge from hospital ]
• Mortality [ Time Frame: 18 months ]
• Severe neurodevelopmental disability [ Time Frame: 18 months ]
• Multiple handicap (defined as the presence of any two of the following in an infant; neuromotor disability (Level 3-5 on GMF classification), mental delay (Bayley MDI score < 70), epilepsy, cortical visual impairment, sensorineural hearing loss) [ Time Frame: 18 months ]
• Bayley PDI score [ Time Frame: 18 months ]
• Sensorineural hearing loss: 40 dB [ Time Frame: 18 months ]
• Epilepsy (defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment) [ Time Frame: 18 months ]
• Microcephaly (head circumference more than 2 standard deviations below the mean). [ Time Frame: 18 months ]

• 1. Intracranial haemorrhage
• 2. Persistent hypotension
• 3. Pulmonary haemorrhage
• 4. Pulmonary hypertension
• 5. Prolonged blood coagulation time
• 6. Culture proven sepsis
• 7. Necrotising enterocolitis
• 8. Cardiac arrhythmia
• 9. Thrombocytopenia
• 10. Major venous thrombosis
• 11. Renal failure treated with dialysis
• 12. Pneumonia
• 13. Pulmonary airleak
• 14. Duration of hospitalisation
• Long term (at 18 months):
• 1. Mortality
• 2. Severe neurodevelopmental disability
• 3. Multiple handicap (defined as the presence of any two of the following in an infant; neuromotor disability (Level 3-5 on GMF classification), mental delay (Bayley MDI score < 70), epilepsy, cortical visual impairment, sensorineural hearing loss)
• 4. Bayley PDI score
• 5. Sensorineural hearing loss: 40 dB
• 6. Epilepsy (defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment)
• 7. Microcephaly (head circumference more than 2 standard deviations below the mean).

Hypothesis: Prolonged whole body cooling in term infants with perinatal asphyxial encephalopathy reduces death and severe neurodevelopmental disability.

This study aims to determine whether whole body cooling to 33-34°C is a safe treatment that improves survival, without severe neurological or neurodevelopmental impairments at 18 months, of term infants suffering perinatal asphyxial encephalopathy.

This is a multicentre prospective randomised controlled trial to determine whether a reduction of body temperature by 3-4°C following perinatal asphyxia improves survival without neurodevelopmental disability.

Full term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 ± 0.2°C or to whole body cooling with the rectal temperature kept at 33.5 ± 0.5°C for 72 hours followed by slow rewarming.

The outcome will be assessed at 18 months of age by survival and neurological and neurodevelopmental testing.

Eligibility criteria:

Term infants less than 6 hours after birth with moderate or severe perinatal asphyxia (a combination of clinical and EEG criteria).

Exclusion criteria:

Infants expected to be 6 hours of age at the time of randomisation or infants with major congenital abnormalities.

Intervention:

Intensive care with whole body cooling versus intensive care without whole body cooling (babies are cooled to 33.5°C for 72 hours)

Main Outcomes:

Death and severe neurodevelopmental impairment at 18 months of age

Secondary Outcomes:

Cerebral thrombosis or haemorrhage, persistent hypotension, pulmonary hypertension, abnormal coagulation, arrhythmia and sepsis in the neonatal period. Neurological impairments at 18 months

Number of patients required: 236.

On 30th November 2006, when recruitment closed, 325 babies had been recruited.

• Asphyxia Neonatorum
• Hypoxia
• Encephalopathy
• Seizures

Inclusion criteria

The infant will be assessed sequentially by criteria A, B and C listed below:

A. Infants =>36 completed weeks gestation admitted to the NICU with at least one of the following:

• Apgar score of =<5 at 10 minutes after birth
• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
• Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary pH <7.00)
• Base Deficit =>16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth

Infants that meet criteria A will be assessed for whether they meet the neurological abnormality entry criteria (B) by trained personnel:

B. Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:

• hypotonia
• abnormal reflexes including oculomotor or pupillary abnormalities
• absent or weak suck
• clinical seizures

Infants that meet criteria A & B will be assessed by aEEG (read by trained personnel):

C. At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following:

• normal background with some seizure activity
• moderately abnormal activity
• suppressed activity
• continuous seizure activity

Exclusion criteria

• Infants expected to be > 6 hours of age at the time of randomisation
• Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis