Maternal and fetal safety outcomes after in utero stem cell injection: A systematic review

ObjectiveTo investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT).MethodsMedline (R), Embase and Cochrane library (1967-2023) search for publications reporting IUSCT in humans. Two reviewers independently screened abstracts and full-text papers.ResultsSixty six transplantation procedures in 52 fetuses were performed for haemoglobinopathies (n = 14), red cell/bleeding disorders (n = 4), immunodeficiencies (n = 15), storage disorders (n = 7), osteogenesis imperfecta (n = 2) and healthy fetuses (n = 10). The average gestational age was 18.9 weeks; of procedures reporting the injection route, cells were delivered by intraperitoneal (n = 37), intravenous (n = 19), or intracardiac (n = 4) injection or a combination (n = 3); most fetuses received one injection (n = 41). Haematopoietic (n = 40) or mesenchymal (n = 12) stem cells were delivered. The cell dose was inconsistently reported (range 1.8-3.3 x 109 cells total (n = 27); 2.7-5.0 x 109/kg estimated fetal weight (n = 17)). The acute fetal procedural complication rate was 4.5% (3/66); the acute fetal mortality rate was 3.0% (2/66). Neonatal survival was 69.2% (36/52). Immediate maternal and pregnancy outcomes were reported in only 30.8% (16/52) and 44.2% (23/52) of cases respectively. Four fetal/pregnancy outcomes would also classify as >= Grade 2 maternal adverse events.ConclusionsShort-, medium-, and long-term maternal and fetal adverse events should be reported in all IUSCT studies. What is already known about this topic?Fetal therapy, such as fetal blood transfusion, is commonly used to treat fetal anemia with a good fetal safety profile. Certain genetic disorders such as Osteogenesis Imperfecta (OI) and alpha thalassaemia major are commonly diagnosed prenatally. These diseases may be amenable to treatment by In utero stem cell transplantation (IUSCT). Clinical trials will require an understanding of the safety of IUSCT for both mother and fetus.What does this study add? (67 words)This systematic review found that the acute fetal complication rate of IUSCT was 4.5% per procedure. Fetal outcomes were commonly the focus of publications. Maternal adverse events and pregnancy outcomes have been poorly reported. As fetal therapeutic procedures must balance maternal and fetal risk/benefit, we recommend that studies of in utero cell transplantation report not only on efficacy but also maternal and fetal adverse events.