The following is general information introducing research findings. Results reported in studies do not mean the same outcome for any individual, and most of these studies are small or early-stage.
Summary — Neonatal hypoxic-ischaemic encephalopathy (HIE) is brain injury caused by a shortage of oxygen and blood flow to the brain around birth, and is one cause of cerebral palsy. The current standard treatment is therapeutic hypothermia, cooling the baby soon after birth. In addition, studies giving the baby's own cord blood collected at birth were carried out by Duke University in the United States (2014) and a Japanese multicentre team (2020); both reported early-stage results confirming feasibility and safety.
What is neonatal hypoxic-ischaemic encephalopathy?
During delivery, events such as early separation of the placenta, compression of the umbilical cord or uterine rupture can sharply reduce oxygen and blood flow to the baby's brain. The resulting brain injury is called hypoxic-ischaemic encephalopathy. Soon after birth, babies may have weak breathing and muscle tone, reduced consciousness and seizures. It is graded as mild, moderate or severe, and moderate or severe cases can leave after-effects such as cerebral palsy, developmental delay, epilepsy and visual or hearing impairment.
Brain injury in HIE does not occur only at the moment of oxygen deprivation; it spreads over hours to days as a 'secondary injury' of inflammation and cell death. Reducing this secondary injury early after birth is therefore the central goal of treatment.
Current standard treatment: therapeutic hypothermia
Therapeutic hypothermia begins within six hours of birth and keeps the baby's body temperature at about 33–34°C for 72 hours. Lowering temperature is known to slow brain metabolism and the progression of secondary injury. A 2013 Cochrane systematic review pooling randomised trials concluded that hypothermia reduces death or major neurodevelopmental disability in newborns with moderate or severe HIE, and it has become standard care in neonatal intensive care units in many countries. Even with hypothermia, however, many babies are left with after-effects, so treatments to complement it are being studied.
Why cord blood is studied
Cord blood contains various cells, including haematopoietic stem cells and mesenchymal cells, and animal studies have reported that these cells reduce brain inflammation and protect nerves. The baby's own cord blood, collected at birth, carries no rejection concern and can be used straight away in the period just after birth when secondary injury is developing. For these reasons, giving it alongside hypothermia has been studied.
Duke University study (2014)
A Duke team gave 23 newborns with HIE receiving hypothermia several intravenous doses of their own cord blood cells, collected and processed at birth, within 72 hours of birth. The main aim was to confirm that this approach was feasible and safe in a neonatal intensive care unit. The team reported that infusions were carried out without major problems and also presented one-year outcomes compared with babies treated with hypothermia alone in the same period. It was not a randomised controlled study, however, and was not designed to judge efficacy.
Japanese multicentre study (2020)
In Japan, a team involving several university hospitals and perinatal medical centres carried out a pilot study, published in Scientific Reports, giving six newborns with moderate or severe HIE receiving hypothermia their own cord blood cells within 72 hours of birth. The aim was to confirm that collecting, processing and giving cord blood immediately after birth was feasible and safe in the Japanese medical setting, and the team reported feasibility and safety. The study is significant for carrying out such research using cord blood immediately after birth through a domestic multicentre network.
Relation to cerebral palsy research
HIE is one cause of cerebral palsy. Duke's randomised study of autologous cord blood in children aged 1–6 already diagnosed with cerebral palsy (2017) reported greater motor improvement at higher doses. Neonatal HIE research differs in attempting to intervene much earlier, just after the injury.
Open questions
Research on cord blood for HIE so far has confirmed feasibility and safety on a small scale; randomised studies comparing with hypothermia alone are needed to confirm efficacy. Building systems that can collect and process cord blood rapidly at birth is another important task.
Frequently asked questions
Q. Should cord blood be banked in advance?
In these studies, cord blood collected at the delivery hospital immediately after birth was processed straight away under the study protocol. There is no established evidence that private cord blood banking is effective as preparation for HIE, so whether to bank is a decision for families based on adequate information.
Q. Where is therapeutic hypothermia given?
Because it must start within six hours of birth, babies with suspected HIE are assessed quickly and treated in neonatal intensive care units, with rapid transfer to an equipped hospital if needed.
Q. When are after-effects known?
Neurodevelopment in babies with HIE is usually assessed with standardised developmental tests at around 18–24 months, and studies give weight to results at this age. Regular check-ups and early rehabilitation take place before then.
How to look up clinical trial information
Ongoing and completed clinical trials can be checked on public registries. ClinicalTrials.gov, run by the U.S. National Library of Medicine, and jRCT, run by Japan's Ministry of Health, Labour and Welfare, publish each study's purpose, eligibility criteria, intervention, outcomes, institutions and status. Results are later published as journal papers, and the reference links below this article lead to the original information. It is also worth knowing that interventions not publicly registered are difficult to verify from outside, in both design and results.
The above summarises results reported in published papers. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. Treatment of newborns is decided by the medical team.
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References
- Jacobs SE, Berg M, Hunt R, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;(1):CD003311. View on PubMed
- Cotten CM, Murtha AP, Goldberg RN, et al. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr. 2014;164(5):973-979. View on PubMed
- Tsuji M, Sawada M, Watabe S, et al. Autologous cord blood cell therapy for neonatal hypoxic-ischaemic encephalopathy: a pilot study for feasibility and safety. Sci Rep. 2020;10(1):4603. View on PubMed
- Sun JM, Song AW, Case LE, et al. Effect of autologous cord blood infusion on motor function and brain connectivity in young children with cerebral palsy: a randomized, placebo-controlled trial. Stem Cells Transl Med. 2017;6(12):2071-2078. View on PubMed
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