Neuroprotective Effect of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonatal Encephalopathy

A Multi-Centre Safety and Efficacy Study of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonates Encephalopathy in China

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.

Inclusion Criteria:

1. Gestational age ≥ 34 weeks
2. Birth weight ≥ 1800 grams
3. 10-minute Apgar score ≤5 or continued need for ventilation or severe acidosis, defined as pH <7.0
4. Moderate to severe encephalopathy (Sarnat II to III)
5. A moderately or severely abnormal background aEEG voltage, or seizures identified by aEEG, if monitored
6. Up to 24 hours of age
7. Autologous umbilical cord blood available to infuse 3 doses within 72 hours after birth
8. Parental informed consent

Exclusion Criteria:

1. Known major congenital anomalies, such as chromosomal anomalies, heart diseases
2. Major intracranial hemorrhage identified by brain ultrasonography or computed tomography
3. Severe intrauterine growth restriction (weight <1800g)
4. Severe infectious disease, such as sepsis
5. Inability to enroll by 24 hours of age
6. Volume of collected cord blood <40 ml
7. Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist
8. Parents refuse consent