Do stem cell-based therapies save the lives or improve the long-term development of preterm newborns who have or may develop bleeding to the brain ("germinal matrix-intraventricular haemorrhage")?
Newborns born too early ("preterm"), especially babies born before 28 weeks of pregnancy, sometimes develop bleeding to the brain. Babies with less severe bleeding may make a full recovery or may have only mild problems. For other babies with more serious bleeding, 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. Currently no approaches are available to prevent or treat this condition.
The aim of this review was to assess whether stem cell-based therapies could reduce death and improve the long-term development of newborns born too early. During cell stem-based therapy, stem cells are given to the baby, for instance, through injection. 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 have been damaged by bleeding.
We were not able to include any studies in our review. We did identify five studies, but we excluded them because of the way they were designed, which meant that their results could not answer our review question (all were "phase 1" studies).
We searched for studies that were available up to 7 January 2019.
Currently no evidence is available to show the benefits or harms of stem cell-based interventions for treatment or prevention of GM-IVH in preterm infants.
Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a substantial issue in neonatal intensive care units worldwide. Current therapies to prevent or treat GMH-IVH are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, and/or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies.
To determine the benefits and harms of stem cell-based interventions for prevention or treatment of germinal matrix-intraventricular haemorrhage (GM-IVH) in preterm infants.
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1), in the Cochrane Library; MEDLINE via PubMed (1966 to 7 January 2019); Embase (1980 to 7 January 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 7 January 2019). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
We attempted to identify randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing (1) stem cell-based interventions versus control; (2) mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; (3) stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or (4) MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH.
For each of the included trials, two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs, other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). Primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, GM-IVH, and extension of pre-existing non-severe GM-IVH. We planned to use the GRADE approach to assess the quality of evidence.
Our search strategy yielded 769 references. We did not find any completed studies for inclusion. One randomised controlled trial is currently registered and ongoing. Five phase 1 trials are described in the excluded studies.