Cooling in Mild Encephalopathy
Whole-body Hypothermia Versus Normothermia in Mild Neonatal Encephalopathy: A Multicentre Randomised Controlled Trial
Imperial College London
426 participants
Mar 15, 2024
INTERVENTIONAL
Conditions
Summary
The goal of this randomised control trial is to establish the safety and efficacy of whole-body hypothermia for babies with mild hypoxic ischaemic encephalopathy, inform national and international guidelines, and establish uniform practice across the NHS. The main questions it aims to answer are: 1. Does whole-body cooling (33.5±0.5°C) initiated within six hours of birth and continued for 72 hours, improve cognitive development at 24 (±2) months of age after mild neonatal encephalopathy compared with normothermia (37±0.5°C)? 2. Does a prospective trial-based economic evaluation support the provision of cooling therapy for mild encephalopathy in the NHS on cost-effectiveness grounds? Participants will have the following interventions: * Randomisation into one of the following groups * Whole body hypothermia group * Targeted normothermia group * Bayley Scales of Infant and Toddler Development 4th Edition (Bayley-IV) examination at 24 (±2) months of age. Researchers will compare the mean Cognitive Composite Scale score from the Bayley IV examination between the two groups.
Eligibility
Inclusion Criteria5
- All babies born at or after 36 weeks of gestation with a birth weight of 1800g or more with birth acidosis or requiring resuscitation at birth will be screened for eligibility.
- Parents will be approached for consent if the baby meets all the three (A + B + C) criteria below:
- A. Evidence of intra-partum hypoxia-ischemia defined as any of - (i) Apgar score of \<6 at 10 minutes after birth; (ii) continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth; (iii) severe birth acidosis defined as any occurrence of pH =\<7.00 or a Base deficit \>=16mmol/l in any cord or baby gas sample within 60 minutes of birth.
- B. Evidence of mild hypoxic ischaemic encephalopathy defined as - two or more abnormal findings in any of the six categories of the modified Sarnat examination (level of consciousness, spontaneous activity, posture, tone, primitive reflexes, and autonomic nervous system) but not meeting the diagnosis of moderate or severe hypoxic ischaemic encephalopathy on a standardised examination performed by a certified examiner between 1 to 6 hours of age.
- C. Normal amplitude on aEEG performed for at least 30 minutes between 1 to 6 hours of age. Normal amplitude will be defined as upper margin of the aEEG activity more than 10 microvolts and the lower margin more than 5 microvolts on a single channel aEEG.
Exclusion Criteria5
- Infants who meet the BAPM criteria for whole-body hypothermia
- Infants without encephalopathy defined as less than two abnormalities on structured neurological examination.
- Infants with major congenital or chromosomal anomalies identified prior to randomisation.
- Infants with birthweight \<1800g.
- Infants who have already received sedation, muscle relaxation, or anti-convulsants prior to neurological assessment.
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Interventions
Whole-body hypothermia (33.5±0.5°C) initiated within 6 hours of birth and continued for 72 hours. The rectal temperature will be maintained at 33.5±0.5°C using a servo-controlled cooling machine.
The axillary temperature will be maintained at 37±0.5°C for the first 80 hours and any hyperthermia will be treated with a standardised protocol.
Neonatal intensive care monitoring and support including ventilatory and inotropic support as clinically indicated
The assessment will be carried out using the Bayley Scales of Infant and Toddler Development IV. In addition, all infants will have a detailed neurological examination, including Gross Motor Function Classification System (GMFCS) for cerebral palsy, vision, and hearing assessment. Babies who die or who cannot be assessed with the Bayley-IV due to severe disability will be allocated a Cognitive Scale Composite score one point below the basal test score. PARCA-R will be completed by the parents immediately.
Locations(39)
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NCT05889507