This study examines the effect of cord blood in the treatment of newborn infants with neonatal encephalopathy in combination with hypothermia, which is the standard treatment for this condition. The hypothesis is that the cord blood + hypothermia combination will produce better neuroprotection than the standard treatment of hypothermia alone.
The primary aim of this study is to determine the neuroprotective effect of intravenous administration of autologous cord blood in neonates with severe encephalopathy (hypoxic ischemic encephalopathy or cerebral infarction). It is hypothesized that the administration of autologous cord blood will be safe and well tolerated in neonates with severe encephalopathy. If a neonate is born with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the neonate will receive their own cord blood. The cord blood cells are divided into 3 doses and infused at 24, 48, and 72 hours after the birth. Infants will be randomised to treatment with autologous cord blood and hypothermia or hypothermia only and followed for safety and neurodevelopmental outcome up to 18 months. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants who allocated to hypothermia and xenon will also receive autologous cord blood in 24 hours from birth through a purpose designed delivery system. Additionally, postnatal neuro-developmental outcomes in neonates with encephalopathy after autologous cord blood therapy will be measured; HIE injury to the neonate/infant brain post autologous cord blood therapy by imaging will be characterized; MRI's will be obtained per clinical routine; serum levels of selected cytokine and neurotrophic factors in neonates with HIE before and after autologous cord blood therapy will be compared and immune cell phenotype and function in neonates with HIE before and after autologous cord blood therapy will be compared.
- Hypothermia Device
Intervention Desc: Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care. ARM 1: Kind: Experimental Label: Hypothermia Description: Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
- Autologous cord blood Drug
Intervention Desc: Autologous cord blood will be collected after birth and administered in divided aliquots during the first 3 days of life. At the same time, babies will referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care. ARM 1: Kind: Experimental Label: Cord blood with hypothermia Description: Autologous cord blood will be collected after birth and stored in Cord Blood Bank of hospital. All cord blood samples are routinely performed by dedicated, trained UCB collection staff and is restricted to deliveries of mothers who have given prior written informed consent for collection. If the mother delivered a baby with signs of HIE or cerebral infarction, Bank staff collected UCB utilizing standard procedures. Collected UCB was transported at roomtemperature in validated shippers to the NICU. Infusions were started when cells and study staff were available for administration and monitoring. Infants received up to 3 infusions, with the first dose as soon as possible after birth, and at, 48, and 72 postnatal hours. At the same time, babies will referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
- Allocation: Randomized
- Masking: Single Blind (Subject)
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Mortality||From birth to the age of 18 months||No|
|Primary||Disability Rate||From birth to the age of 18 months||No|
|Secondary||Neurodevelopment(Bayley Scores)||At the age of 12 months||No|
|Secondary||Brain Structural Alterations(MRI)||At the age of 7 days||No|
|Secondary||Brain Parenchyma Alterations(MRI)||At the age of 7 Days||No|
|Secondary||Intracranial Hemorrhage(MRI)||At the age of 7 days||No|
|Secondary||Number of Adverse Events||In 72 hours||No|
|Secondary||Number of Adverse Events(Blood Pressure)||In 72 hours||No|
|Secondary||Number of Adverse Events(Pulse)||In 72 hours||No|
|Secondary||Number of Adverse Events(Respiratory)||In 72 hours||No|
|Secondary||Incidence of Complication||From birth to the age of 28 days in each treatment period||No|
|Secondary||SDF-1 in Serum||At the age of 4 days||Yes|
|Secondary||TNF-alpha in Serum||At the age of 4 days||Yes|
|Secondary||IL-1 in Serum||At the age of 4 days||Yes|