{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:38:53Z","timestamp":1785901133982,"version":"3.56.0"},"reference-count":89,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014419","name":"EIT Health","doi-asserted-by":"publisher","award":["681045"],"award-info":[{"award-number":["681045"]}],"id":[{"id":"10.13039\/100014419","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medline\u00ae, Embase and Cochrane library (1967\u22122023) search for publications reporting IUSCT in humans. Two reviewers independently screened abstracts and full\u2010text papers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty six transplantation procedures in 52 fetuses were performed for haemoglobinopathies (<jats:italic>n<\/jats:italic>\u00a0=\u00a014), red cell\/bleeding disorders (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), immunodeficiencies (<jats:italic>n<\/jats:italic>\u00a0=\u00a015), storage disorders (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), osteogenesis imperfecta (<jats:italic>n<\/jats:italic>\u00a0=\u00a02) and healthy fetuses (<jats:italic>n<\/jats:italic>\u00a0=\u00a010). The average gestational age was 18.9\u00a0weeks; of procedures reporting the injection route, cells were delivered by intraperitoneal (<jats:italic>n<\/jats:italic>\u00a0=\u00a037), intravenous (<jats:italic>n<\/jats:italic>\u00a0=\u00a019), or intracardiac (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) injection or a combination (<jats:italic>n<\/jats:italic>\u00a0=\u00a03); most fetuses received one injection (<jats:italic>n<\/jats:italic>\u00a0=\u00a041). Haematopoietic (<jats:italic>n<\/jats:italic>\u00a0=\u00a040) or mesenchymal (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) stem cells were delivered. The cell dose was inconsistently reported (range 1.8\u22123.3\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup> cells total (<jats:italic>n<\/jats:italic>\u00a0=\u00a027); 2.7\u22125.0\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/kg estimated fetal weight (<jats:italic>n<\/jats:italic>\u00a0=\u00a017)). 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\u00a0\u2265\u00a0Grade 2 maternal adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Short\u2010, medium\u2010, and long\u2010term maternal and fetal adverse events should be reported in all IUSCT studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6459","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T03:51:22Z","timestamp":1700279482000},"page":"1622-1637","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Maternal and fetal safety outcomes after in utero stem cell injection: A systematic review"],"prefix":"10.1002","volume":"43","author":[{"given":"Rachel L.","family":"Sagar","sequence":"first","affiliation":[{"name":"Elizabeth Garrett Anderson Institute for Women's Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Walther\u2010Jallow","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention and Technology Division of Obstetrics and Gynecology, Karolinska Institutet ANA Futura  Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"G\u00f6therstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention and Technology Division of Obstetrics and Gynecology, Karolinska Institutet ANA Futura  Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Westgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention and Technology Division of Obstetrics and Gynecology, Karolinska Institutet ANA Futura  Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-6140","authenticated-orcid":false,"given":"Anna L.","family":"David","sequence":"additional","affiliation":[{"name":"Elizabeth Garrett Anderson Institute for Women's Health University College London  London UK"},{"name":"NIHR University College London Hospitals Biomedical Research Centre  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251\u2010004\u20100680\u20103"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v98.8.2396"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0265"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010019\u20100387\u20104"},{"key":"e_1_2_12_6_1","volume-title":"Clinicopathological Conference. A Case of Haemolytic Disease with Congenital Rubella Demonstrated at the","author":"Davis J","year":"1967"},{"key":"e_1_2_12_7_1","first-page":"441","article-title":"In utero transplantation of stem cells in humans","volume":"32","author":"Touraine J","year":"1990","journal-title":"Nouv Rev Fr Haematol"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2013-0210"},{"issue":"11","key":"e_1_2_12_9_1","article-title":"Mesenchymal stem cell engraftment in bone following in utero transplantation in a patient with severe osteogenesis imperfecta","volume":"104","author":"Le Blanc K","year":"2004","journal-title":"Blood"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.17319"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"issue":"1","key":"e_1_2_12_12_1","first-page":"35","article-title":"In utero hematopoietic stem cell transplants for inherited diseases","volume":"16","author":"Cowan MJ","year":"1994","journal-title":"Am J Pediatr Hematol Oncol"},{"key":"e_1_2_12_13_1","first-page":"515","article-title":"In utero stem cell therapy","volume":"37","author":"Diukman R","year":"1992","journal-title":"Journal of Reproductive Medicine for the Obstetrician and Gynecologist"},{"issue":"2","key":"e_1_2_12_14_1","first-page":"208","article-title":"RAC hears review of in utero stem cell transplant, gene therapy","volume":"15","author":"Golbus M","year":"1996","journal-title":"Biotechnol Law Rep"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5555.819"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199612123352404"},{"key":"e_1_2_12_17_1","first-page":"137","article-title":"In utero approach to hematopoietic stem cell transplantation","author":"Zanjani ED","year":"1997","journal-title":"Correction of Genetic Diseases by Transplantation Iv"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v94.7.2179.419k43_2179_2191"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2013\u20100090"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000159029.48678.93"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.10.575"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102006\u2010952156"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00223"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1530\/boneabs.1.pp1"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000020793"},{"key":"e_1_2_12_26_1","volume-title":"Stem Cell Therapy of Inherited Disorders","author":"Eddleman K","year":"1996"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.1999.v5.pm10232735"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1700665"},{"key":"e_1_2_12_29_1","article-title":"Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy","author":"Blakemore KJ","year":"1996","journal-title":"Am J Obstet Gynecol"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(86)92754\u20106"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018023176"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010142698"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.11.474"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702798"},{"key":"e_1_2_12_35_1","volume-title":"Proceedings of the International Fetal Medicine and Surgery Society UK","author":"Harrison","year":"1999"},{"issue":"3","key":"e_1_2_12_36_1","first-page":"637","article-title":"Evidence of induced non\u2010tolerance in HLA\u2010identical twins with hemoglobinopathy after in utero fetal transplantation","volume":"18","author":"Orlandi F","year":"1996","journal-title":"Bone Marrow Transpl"},{"issue":"4","key":"e_1_2_12_37_1","first-page":"450","article-title":"Reconstitution of T\u2010cell compartment after in utero stem cell transplantation: analysis of T\u2010cell repertoire and thymic output","volume":"89","author":"Pirovano S","year":"2004","journal-title":"Haematologica"},{"issue":"63","key":"e_1_2_12_38_1","article-title":"Bone marrow transplantation in utero: report of 5 cases affected by severe combined immunodeficiency","volume":"31","author":"Porta F","year":"2003","journal-title":"Bone Marrow Transplant"},{"key":"e_1_2_12_39_1","first-page":"s43","article-title":"Prenatal transplant in a fetus affected by Omenn syndrome","volume":"25","author":"Porta F","year":"2000","journal-title":"Bone Marrow Transpl"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1703410"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041\u20101345(99)00510\u20102"},{"key":"e_1_2_12_42_1","first-page":"S127","article-title":"In utero transplantation (IUT) of parental CD34\u00a0+\u00a0cells in patient affected by primary immunodeficiencies","volume":"21","author":"Lanfranchi A","year":"1998","journal-title":"Bone Marrow Transpl"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2009.08.005"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(96)09392\u20100"},{"key":"e_1_2_12_45_1","unstructured":"UgazioA LanfranchiA TettoniK PortaF.Intrauterine stem cell transplantantion for severe combined immunodeficiencies.1999;8:49\u201067."},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2009.031"},{"issue":"1","key":"e_1_2_12_47_1","first-page":"55","article-title":"In utero stem cells transplantation after a mild immunosuppression: evidence of paternal ABO cDNA in \u03b2\u2010thalassaemia affected fetus","volume":"3","author":"Renda MC","year":"2005","journal-title":"Blood Transfus"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v96.4.1608.h8001608a_1608_1609"},{"key":"e_1_2_12_49_1","first-page":"S109","article-title":"In utero stem cell transplantation for beta\u2010thalassemia: a case report","volume":"23","author":"Sanna M","year":"1999","journal-title":"Bone Marrow Transpl"},{"issue":"2","key":"e_1_2_12_50_1","first-page":"220","article-title":"In utero stem cell transplantation","volume":"39","author":"Monni G","year":"1998","journal-title":"Croat Med J"},{"key":"e_1_2_12_51_1","first-page":"189","article-title":"Clinical application of intrauterine bone marrow transplantation for treatment of genetic\u00a0diseases \u2010 feasibility studies","author":"Slavin S","year":"1992","journal-title":"Bone Marrow Transplant"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140\u20106736(93)92336\u2010r"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000077957"},{"issue":"1","key":"e_1_2_12_54_1","first-page":"98","article-title":"In utero transplantation of stem cells in humans: technical aspects and clinical experience during pregnancy","volume":"9","author":"Raudrant D","year":"1992","journal-title":"Bone Marrow Transpl"},{"issue":"2","key":"e_1_2_12_55_1","first-page":"49","article-title":"Stem cell transplantation in primary immunodeficiency, with special reference to the first prenatal, in utero, transplants","volume":"19","author":"Touraine JL","year":"1991","journal-title":"Allergol Immunopathol"},{"issue":"3","key":"e_1_2_12_56_1","first-page":"92","article-title":"New developments in stem cell transplantation with special reference to the first in utero transplants in humans","volume":"7","author":"Touraine JL","year":"1991","journal-title":"Bone Marrow Transpl"},{"issue":"1","key":"e_1_2_12_57_1","first-page":"1706","article-title":"In utero transplantation of hemopoietic stem cells in humans","volume":"23","author":"Touraine JL","year":"1991","journal-title":"Transpl Proc"},{"issue":"2","key":"e_1_2_12_58_1","first-page":"379","article-title":"In utero transplantation of fetal liver stem cells in humans","volume":"17","author":"Touraine J","year":"1991","journal-title":"Blood Cell"},{"key":"e_1_2_12_59_1","first-page":"187","article-title":"The fetal liver as a source of stem cells for transplantation into fetuses in utero","volume":"177","author":"Touraine JL","year":"1992","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a137554"},{"issue":"1","key":"e_1_2_12_61_1","first-page":"121","article-title":"In utero transplantation of stem cells in humans: immunological aspects and clinical follow\u2010up of patients","volume":"9","author":"Touraine J","year":"1992","journal-title":"Bone Marrow Transpl"},{"issue":"1","key":"e_1_2_12_62_1","first-page":"121","article-title":"Rationale and results of in utero transplants of stem cells in humans","volume":"10","author":"Touraine JL","year":"1992","journal-title":"Bone Marrow Transpl"},{"issue":"1","key":"e_1_2_12_63_1","first-page":"1012","article-title":"Transplantation of fetal liver stem cells into patients and into human fetuses, with induction of immunologic tolerance","volume":"25","author":"Touraine JL","year":"1993","journal-title":"Transpl Proc"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0955\u20103886(93)90013\u2010k"},{"key":"e_1_2_12_65_1","first-page":"169","volume-title":"Gluckman E Colombel eds Ontogeny of Haematopoiesis","author":"Touraine J","year":"1995"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1159\/000203741"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.1.1996.5.195"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041\u20101345(99)00545\u2010x"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041\u20101345(98)01606\u20106"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041\u20101345(00)02665\u20108"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(89)92819\u20105"},{"key":"e_1_2_12_72_1","first-page":"265","volume-title":"Tolerance to alloantigen\u2019s and recognition for allo\u00a0+\u00a0x induced in humans by fetal stem cell\u00a0transplantation","author":"Touraine JL","year":"1994"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041\u20101345(97)00455\u20107"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041\u20101345(96)00432\u20100"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.123602"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890\u2010199604270\u201000010"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109378(97)80010\u20105"},{"key":"e_1_2_12_78_1","unstructured":"Mapping.MedDRA[Internet];2023.https:\/\/www.meddra.org\/mapping"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6047"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1159\/000362812"},{"issue":"1","key":"e_1_2_12_81_1","first-page":"35","article-title":"In utero hematopoietic stem cell transplants for inherited diseases","volume":"16","author":"Cowan MJ","year":"1994","journal-title":"Am J Pediatr Hematol Oncol"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(86)92754\u20106"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.12590"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2016.03.037"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2016.1151870"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2007.07.007"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5421"},{"key":"e_1_2_12_88_1","first-page":"1","article-title":"On safety and efficacy follow\u2010up \u2010 risk management of Advanced Therapy","volume":"44","author":"Guideline EMA","year":"2008","journal-title":"Medicinal Products"},{"key":"e_1_2_12_89_1","first-page":"1","article-title":"Development of a neonatal adverse event severity scale through a Delphi consensus approach on behalf of the International Neonatal Consortium","volume":"0","author":"Salaets T","year":"2019","journal-title":"Arch Dis Child"},{"key":"e_1_2_12_90_1","unstructured":"International Neonatal Consortium (INC).Terminology Files[Internet];2023.https:\/\/evs.nci.nih.gov\/ftp1\/Pediatric_Terminologies\/INC\/About.html"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T17:01:10Z","timestamp":1708621270000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,17]]},"references-count":89,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/pd.6459"],"URL":"https:\/\/doi.org\/10.1002\/pd.6459","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,17]]},"assertion":[{"value":"2023-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}