Perinatal asphyxial encephalopathy, child development, cerebral palsy Pregnancy and Childbirth Other birth injuries to central nervous system
Conditions
Interventions
Full term infants will be randomised within six hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2 degrees celsius or to whole body cooling with the rectal tempera
Sponsors
Imperial College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Infants will be assessed sequentially by criteria 1, 2 and 3 listed below: 1. Infants greater than or equal to 36 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) with ONE of the following: 1.1. Apgar score of less than five at ten minutes after birth 1.2. Continued need for resuscitation, including endotracheal or mask ventilation, at ten minutes after birth 1.3. Acidosis defined as either umbilical cord pH or any arterial pH within 60 minutes of birth less than pH 7.00 1.4. Base deficit greater than or equal to 16 mmol/l in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood) If the infant meets criteria 1 then assess for neurological abnormality (by trained study personnel): 2. Moderate to severe encephalopathy consisting of altered state of consciousness (lethargy, stupor or coma) and at least one or more of hypotonia, abnormal reflexes including oculomotor or pupillary abnormalities, an absent or weak suck or clinical seizures, as recorded by study personnel. If the infant meets criteria 1 & 2 then assess by amplitude-integrated electroencephalography (aEEG) (read by trained study personnel): 3. 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: 3.1. Normal background with some seizure activity 3.2. Moderately abnormal activity 3.3. Suppressed activity 3.4. Continuous seizure activity TCS study: 1. Previously specified that they do not want to be contacted again 2. Previously recruited in the TOBY study within 6 hours of birth 3. Confirmed moderate or severe neonatal encephalopathy
Exclusion criteria
Exclusion criteria: 1. Infants expected to be greater than 5.5 hours of age at the time of randomization 2. Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis TCS study: Non-participation will only occur if consent is not obtained or contact with the family cannot be achieved. Children who did not take part in the TOBY study are not eligible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome for this trial is a combined endpoint: death in the first 18 months of life OR Severe neurodevelopmental disability. TCS study: Frequency of survival with an IQ greater than 84; timepoint: 6 years to 7 years and 4 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measures added as of 16/10/2007: Short term (before discharge from hospital): 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: 3.1. Neuromotor disability (Level 3-5 on General Motor Function (GMF) Assessment Scale classification), mental delay (the Bayley Scales of Infant Development - Mental Development Indices (MDI) score less than 70), epilepsy, cortical visual impairment, sensorineural hearing loss 4. The Bayley Scales of Infant Development - Psychomotor Development Indices (PDI) score 5. Sensorineural hearing loss: greater than or equal to 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) TCS study: 1. Overall IQ from Wechsler Preschool and Primary Scale of Intelligence tests (WPPSI III) 2. Overall Working Memory Test Battery for Children (WMTB-C) Scale 3. Overall Strengths and Difficulties Quotient score (SDQ) for behavioural problems 4. Overall ADHD Score (Du Paul RS IV) 5. Prevalence of Cerebral Palsy 6. Gross Motor Function Classification System level GMFCS) 7. Unimpaired outcome and overall grade of disability 8. Teachers academic achievement score 9. Health Utility Index (HUI-III) 10. Overall number of deaths in each group to age 7 years and 4 months | — |
Countries
Finland, Hungary, Ireland, Israel, Sweden, United Kingdom
Outcome results
None listed