Cytokines Associated With Cord Blood Cell Therapy for Neonatal Encephalopathy

The effects and mechanisms of umbilical cord blood cell therapy for perinatal brain injury are not well understood. This is a multicenter study to measure serum levels of inflammatory cytokines and trophic factors associated with perinatal brain injury and repair in term gestation newborns with neonatal encephalopathy (hypoxic-ischemic encephalopathy). This study proceeds along with the study "Autologous cord blood cell therapy for neonatal encephalopathy (ClinicalTrials.gov identifier: NCT02256618)". Blood samples are obtained before the first cell infusion, and subsequently 2h, 24h, 48h, and 7 days after the first cell infusion. Blood samples are obtained in the same manner from newborns with neonatal encephalopathy who are not receiving the cell therapy.

• Autologous cord blood cell therapy (Biological): The neonates receive their own non-cryopreserved volume- and red blood cell-reduced cord blood cells. The cord blood cells are divided into 3 doses and intravenously infused at 12-24, 36-48, and 60-72 hours after the birth.

Primary outcomes

• Changes in serum levels of cytokines and trophic factors [From birth up to 10 days of age]

Secondary outcomes

• Association with neuroimaging and neurodevelopmental functional outcome [18 months]: Neuroimaging at 12 months of age and neurodevelopmental function at 18 months of age will be assessed whether they are associated with serum levels of cytokines and trophic factors during the early neonatal period.

Sex: All, ages: any to 24 Hours

Inclusion Criteria:

Infants are eligible if they meet all the following inclusion criteria except 4.

1. ≥36 weeks gestation
2. Either a 10-minute Apgar score ≤5, continued need for resuscitation for at least 10 minutes, or severe acidosis, defined as pH <7.0 or base deficit ≥16 mmol/L in a sample of umbilical cord blood or any blood during the first hour after birth
3. Moderate to severe encephalopathy (Sarnat II to III)
4. A moderately or severely abnormal background amplitude-integrated EEG (aEEG) voltage, or seizures identified by aEEG, if monitored
5. Up to 24 hours of age
6. A person with parental authority must have consented for the study.

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 growth restriction, with birth-weight less than 1800 g
4. Severe infectious disease, such as sepsis
5. Infants judged critically ill and unlikely to benefit from neonatal intensive care including hypothermia by the attending neonatologist

• Haruo Shintaku, MD, PhD, Study director, Osaka City University Graduate School of Medicine