{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:21:01Z","timestamp":1788916861127,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic\u2013ischemic encephalopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study used a three\u2010case cohort approach. Three patients were administered 10\u2009mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil\u2010associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20\u2009mg\/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12\u2009h of administration and 2\u2009h after delivery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of seven patients were enrolled, and after excluding one patient who delivered before 37\u2009weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms\u2010like tyrosine kinase\u20101 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12\u2009h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jog.15871","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T14:42:00Z","timestamp":1704206520000},"page":"448-455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and dose\u2010finding trial of tadalafil administered for fetus in labor: A phase I clinical study"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7716-9101","authenticated-orcid":false,"given":"Yuya","family":"Tamaishi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-691X","authenticated-orcid":false,"given":"Hiroaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun\u2010ichi","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5761-8026","authenticated-orcid":false,"given":"Sho","family":"Takakura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-135X","authenticated-orcid":false,"given":"Shoichi","family":"Magawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8373-1567","authenticated-orcid":false,"given":"Kayo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mie University School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2005.01.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/reprod\/120.1.91"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(01)01332-1"},{"issue":"2","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/AOG.0b013e3181b48ef5","article-title":"ACOG practice bulletin no. 107: induction of labor","volume":"114","year":"2009","journal-title":"Obstet Gynecol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj1954.15.255"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-12-4-316"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031884"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055352"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.01.025"},{"issue":"7","key":"e_1_2_8_11_1","first-page":"632","article-title":"Sildenafil citrate and uteroplacental perfusion in fetal growth restriction","volume":"17","author":"Dastjerdi MV","year":"2012","journal-title":"J Res Med Sci"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13335"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-016-1098-x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13218"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13345"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1438401"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpx130"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1450863"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1461313"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1487946"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55100708"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2018.12.010"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2013.01.004"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12327"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-018-2859-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000480381"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14928"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-022-04562-w"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.05.030"}],"container-title":["Journal of Obstetrics and Gynaecology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jog.15871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T04:49:09Z","timestamp":1721796549000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/jog.15871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,2]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/jog.15871"],"URL":"https:\/\/doi.org\/10.1111\/jog.15871","archive":["Portico"],"relation":{},"ISSN":["1341-8076","1447-0756"],"issn-type":[{"value":"1341-8076","type":"print"},{"value":"1447-0756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,2]]},"assertion":[{"value":"2023-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}