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One hundred sixty seven survivors among very low birthweight infants with a gestational age of less than 35 weeks have been studied prospectively. The purpose of this study was to clarify the relationship of severe prenatal and perinatal complications and hypocarbic alkalosis, defined as a carbon dioxide tension (Paco2)

Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12-24, 36-48, and 60-72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. the physiological parameters and peripheral blood parameters did not change much between preand postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe. Acute brain dysfunction may occur unexpectedly during and immediately after birth. Brain dysfunction noted immediately after birth, from any cause, is collectively termed neonatal encephalopathy 1. The signs and symptoms of neonatal encephalopathy include altered levels of consciousness, weak muscle tone, impaired feeding, respiratory distress, and seizures. In many infants with neonatal encephalopathy, the pivotal pathophysiology is an insufficient supply of blood flow and oxygen to the brain in the ante-, intra-, or very immediate postpartum period. In these cases, neonatal encephalopathy is named hypoxic-ischaemic encephalopathy (HIE) 2. Mild hypothermia is the only therapy proven effective for term newborns with HIE 3,4. Even if infants with HIE receive therapeutic hypothermia, 40-44% die or survive with severe neurological impairments, including cerebral palsy and intellectual disability 3,4. The therapeutic time window is within 6 hours after birth for hypothermia to be effective 3,5,6. Hence, it is an urgent task to develop a novel therapy for HIE, especially a therapy with a long therapeutic time window 7. Cell-based therapy has attracted much attention because of not only its regenerative property but also its long therapeutic time window 8. Preclinical studies with animal models with neonatal encephalopathy show that cell therapies initiated hours or days after the injury are beneficial. Although a variety of cell therapies have been