Stem cell-based therapies following poor brain oxygenation at birth (hypoxic-ischaemic encephalopathy) in newborns

Review question

Do stem cell-based therapies save the lives, or improve the long-term development, of newborns who have poor brain oxygenation at birth ('hypoxic-ischaemic encephalopathy')?


Lack of oxygen at birth may damage the brain of the newborn. Babies with less severe brain damage may make a full recovery or only have mild problems. For other babies with more serious damage, this may lead to death or to problems later in life. For instance, some of these babies develop cerebral palsy, intellectual disabilities, or other problems. We currently have  only cooling as an approach to treat this condition. The aim of this review was to assess if stem cell-based therapies could reduce death and improve the long-term development of newborns with poor brain oxygenation at birth. During stem cell-based therapy, stem cells are given to the baby, for instance through injections. These stem cells may have come from humans or animals and may have been taken from cord blood, bone marrow or other parts of the body. These cells then repair the brain cells that the lack of oxygen has damaged.

Key results

We were not able to include any studies in our review. We identified three potential studies, but we excluded them due to the way they were designed which meant that their results could not answer our review question (phase 1 studies). Fifteen studies are ongoing.

How up to date is this review?

We searched for studies that were available up to June 2020.

Authors' conclusions: 

There is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.

Read the full abstract...

Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials.


To determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants.

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: 

Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs.

Data collection and analysis: 

For each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence.

Main results: 

Our search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded.