{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T03:29:23Z","timestamp":1769830163629,"version":"3.49.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Complicated pregnancies are nowadays a major public health concern, with possible lethality or sequelae both for the mother and the fetus. Blood coagulation disorders (including antiphospholipid syndrome, factor V Leiden mutation and antithrombin deficiency) and hypertensive gestational disorders are very well-known contributors of complicated pregnancies with poor fetal outcome, such as intrauterine growth retardation (IUGR) and fetal demise. Less commonly, vascular malformations of the placenta can also potentially lead to serious complications such as IUGR and fetal death. These malformations include hypercoiled umbilical cord, umbilical cord knot, umbilical cord varix, umbilical cord arterial or venous aneurysm, and velamentous insertion of the umbilical cord potentially leading to Benckiser's hemorrhage. Here, we report the case of a 29-year-old Gravida 2 Para 0 mother with previous history of stillbirth and smoking, admitted to the obstetrics department for the absence of fetal movement at 38 weeks of amenorrhea (WA). First-trimester and second-trimester routine ultrasounds were otherwise normal. Ultrasound performed at 38 WA revealed a 83 \u00d7 66 \u00d7 54 mm cystic heterogenous mass at the umbilical cord insertion. After delivery, fetal and placental pathology as well as maternal blood testing were performed. Fetal pathology was otherwise normal, except for diffuse congestion and meconial overload suggesting acute fetal distress. Fetal karyotype was normal (46 XX). Placental pathology revealed an umbilical artery aneurysm (UAA) at the base of the insertion of the umbilical cord, lined with a CD34<jats:sup>+<\/jats:sup> CD31<jats:sup>+<\/jats:sup> endothelium. After dissection, the aneurysm was filled with hemorrhagic debris, indicating aneurysm thrombosis. Histopathology revealed associated maternal vascular malperfusion (MVM) and increased peri-villous fibrin (IPF). Maternal blood tests revealed heterozygous factor V Leiden mutation, without other associated auto-immune conditions (such as antiphospholipid syndrome). Umbilical artery aneurysms remain extremely rare findings in the placenta, with &amp;lt;20 reported cases. Umbilical artery aneurysms have tendency to be located at the base of the insertion of the placenta, and lead to fetal demise in more than 60% of cases, mainly due to aneurysmal thrombosis, hematoma, possible vascular compression and\/or rupture. Umbilical vessel aneurysms can be associated with trisomy 18 or 13. In our case, the association of factor V Leiden mutation, a hypercoagulable state, with UAA could explain massive thrombosis of the aneurysmal lumen and sudden fetal demise. Further consideration of current guidelines for surveillance and management of UAA would allow appropriate planned delivery in maternal care settings.<\/jats:p>","DOI":"10.3389\/fmed.2022.1083806","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T14:27:47Z","timestamp":1672842467000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case report: Umbilical vessel aneurysm thrombosis and factor V Leiden mutation leading to fetal demise"],"prefix":"10.3389","volume":"9","author":[{"given":"Cam\u00e9lia","family":"Oualiken","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Martz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Idrissi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fara Tanjona","family":"Harizay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"De Maistre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lou","family":"Ricaud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges","family":"Tarris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1016\/S0140-6736(14)62032-8","article-title":"Stillbirth in France","volume":"384","author":"Serfaty","year":"2014","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.ogc.2020.04.008","article-title":"Stillbirth: evaluation and follow-up","volume":"47","author":"Page","year":"2020","journal-title":"Obstet Gynecol Clin North Am."},{"key":"B3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12884-016-0800-8","article-title":"From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth","volume":"16","author":"Burden","year":"2016","journal-title":"BMC Pregnancy Childbirth."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/S0140-6736(10)62233-7","article-title":"Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis","volume":"377","author":"Flenady","year":"2011","journal-title":"Lancet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1056\/NEJMoa1908753","article-title":"Causal genetic variants in stillbirth","volume":"383","author":"Stanley","year":"2020","journal-title":"N Engl J Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"115.e1","DOI":"10.1016\/j.ajog.2015.08.049","article-title":"Stillbirth evaluation: a stepwise assessment of placental pathology and autopsy","volume":"214","author":"Miller","year":"2016","journal-title":"Am J Obstet Gynecol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"6057","DOI":"10.1016\/j.vaccine.2016.03.044","article-title":"Stillbirth: case definition and guidelines for data collection, analysis, and presentation of maternal immunization safety data","volume":"34","author":"Da Silva","year":"2016","journal-title":"Vaccine."},{"key":"B8","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2350\/06-02-0042.1","article-title":"Intrapartum stillbirths in hospital unrelated to uteroplacental vascular insufficiency","volume":"10","author":"Burke","year":"2007","journal-title":"Pediatr Dev Pathol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"698","DOI":"10.5858\/arpa.2015-0225-CC","article-title":"Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement","volume":"140","author":"Khong","year":"2016","journal-title":"Arch Pathol Lab Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1097\/01.grf.0000211957.68745.6b","article-title":"Thrombophilia and placental pathology","volume":"49","author":"Redline","year":"2006","journal-title":"Clin Obstet Gynecol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1080\/14767050802551795","article-title":"The effect of maternal thrombophilia on placental abruption: histologic correlates","volume":"22","author":"Kinzler","year":"2009","journal-title":"J Matern Fetal Neonatal Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.placenta.2009.09.005","article-title":"Gross abnormalities of the umbilical cord: related placental histology and clinical significance","volume":"30","author":"Tantbirojn","year":"2009","journal-title":"Placenta."},{"key":"B13","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1097\/GRF.0b013e3181eb68fe","article-title":"Placenta and umbilical cord abnormalities seen with stillbirth","volume":"53","author":"Pinar","year":"2010","journal-title":"Clin Obstet Gynecol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1097\/AOG.0000000000003676","article-title":"Umbilical cord abnormalities and stillbirth","volume":"135","author":"Hammad","year":"2020","journal-title":"Obstet Gynecol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0301-2115(99)00167-0","article-title":"Aneurysm of the umbilical vein: case report and review of literature","volume":"89","author":"Vandevijver","year":"2000","journal-title":"Eur J Obstet Gynecol Reprod Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"QD01","DOI":"10.7860\/JCDR\/2016\/14800.7030","article-title":"Prenatal diagnosis of umbilical artery aneurysm with good fetal outcome and review of literature","volume":"10","author":"Vyas","year":"2016","journal-title":"J Clin Diagn Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/OGX.0000000000000051","article-title":"Umbilical artery aneurysm: a case report, literature review, and management recommendations","volume":"69","author":"Doehrman","year":"2014","journal-title":"Obstet Gynecol Surv."},{"key":"B18","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ejogrb.2016.02.015","article-title":"Pregnancy loss: French clinical practice guidelines","volume":"201","author":"Huchon","year":"2016","journal-title":"Eur J Obstet Gynecol Reprod Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.annpat.2014.10.005","article-title":"[Standard protocol for fetal or perinatal autopsy Haute Autorit\u00e9 de sant\u00e9 ]","volume":"34","year":"2014","journal-title":"Ann Pathol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s10024-003-1004-6","article-title":"Standards for dysmorphological diagnosis in human fetuses","volume":"6","author":"Guihard-Costa","year":"2003","journal-title":"Pediatr Dev Pathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1159\/000264243","article-title":"Fetal biometry. Growth charts for practical use in fetopathology and antenatal ultrasonography. Introduction","volume":"10","author":"Guihard-Costa","year":"1995","journal-title":"Fetal Diagn Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s10024-002-0036-7","article-title":"Organ weights in human fetuses after formalin fixation: standards by gestational age and body weight","volume":"5","author":"Guihard-Costa","year":"2002","journal-title":"Pediatr Dev Pathol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.placenta.2010.10.008","article-title":"Placenta weight percentile curves for singleton and twins deliveries","volume":"32","author":"Almog","year":"2011","journal-title":"Placenta."},{"key":"B24","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1097\/00125480-200007040-00004","article-title":"Placental pathology for the surgical pathologist","volume":"7","author":"Vogler","year":"2000","journal-title":"Adv Anat Pathol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1080\/14767058.2016.1226796","article-title":"Management strategy of umbilical artery aneurysm complicated by cardiac anomaly: case study and literature review","volume":"30","author":"Matsuki","year":"2017","journal-title":"J Matern Fetal Neonatal Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"777","DOI":"10.5603\/GP.a2020.0128","article-title":"Umbilical artery aneurysm","volume":"91","author":"Szadok","year":"2020","journal-title":"Ginekol Pol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/0002-9378(78)90610-5","article-title":"Umbilical artery aneurysm","volume":"131","author":"Fortune","year":"1978","journal-title":"Am J Obstet Gynecol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1097\/AOG.0b013e3181e7d280","article-title":"Umbilical artery aneurysm","volume":"116","author":"Hill","year":"2010","journal-title":"Obstet Gynecol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/uog.69","article-title":"Umbilical artery aneurysm: prenatal identification in three fetuses with trisomy 18","volume":"21","author":"Sepulveda","year":"2003","journal-title":"Ultrasound Obstet Gynecol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2350\/06-07-0136.1","article-title":"Third trimester intrauterine fetal death caused by arterial aneurysm of the umbilical cord","volume":"10","author":"Weber","year":"2007","journal-title":"Pediatr Dev Pathol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1159\/000322960","article-title":"Large umbilical artery aneurysm with a live healthy baby delivered at 31 weeks","volume":"29","author":"Olog","year":"2011","journal-title":"Fetal Diagn Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"251","DOI":"10.7863\/jum.2007.26.2.251","article-title":"Prenatal diagnosis of umbilical artery aneurysm: a potentially lethal anomaly","volume":"26","author":"Shen","year":"2007","journal-title":"J Ultrasound Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/uog.7576","article-title":"Umbilical cord cysts in the second and third trimesters: significance and prenatal approach","volume":"36","author":"Zangen","year":"2010","journal-title":"Ultrasound Obstet Gynecol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.jpeds.2016.06.060","article-title":"Umbilical cord pseudocyst in a newborn","volume":"177","author":"Whipple","year":"2016","journal-title":"J Pediatr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"101772","DOI":"10.1016\/j.eucr.2021.101772","article-title":"Patent urachus or bladder exstrophy occulta? A case of prenatally disappeared umbilical cord cyst","volume":"39","author":"Chien","year":"2021","journal-title":"Urol Case Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"736","DOI":"10.7326\/0003-4819-130-9-199905040-00013","article-title":"Increased risk for fetal loss in carriers of the factor V Leiden mutation","volume":"130","author":"Meinardi","year":"1999","journal-title":"Ann Intern Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ejogrb.2010.07.031","article-title":"Thrombophilic risk factors for placental stillbirth","volume":"153","author":"Simchen","year":"2010","journal-title":"Eur J Obstet Gynecol Reprod Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/S0140-6736(03)12771-7","article-title":"Thrombophilic disorders and fetal loss: a meta-analysis","volume":"361","author":"Rey","year":"2003","journal-title":"Lancet."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1097\/00006250-200112000-00010","article-title":"Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia","volume":"98","author":"Many","year":"2001","journal-title":"Obstet Gynecol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"341","DOI":"10.2350\/09-05-0657-OA.1","article-title":"Avascular villi, increased syncytial knots, and hypervascular villi are associated with pregnancies complicated by factor V Leiden mutation","volume":"13","author":"Rogers","year":"2010","journal-title":"Pediatr Dev Pathol."},{"key":"B41","first-page":"530","article-title":"Umbilical artery aneurysm: prenatal diagnosis and management","volume":"80","author":"Siddiqi","year":"1992","journal-title":"Obstet Gynecol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1186\/s12884-021-04264-9","article-title":"Umbilical artery thrombosis diagnosed at different gestational ages and fetal outcomes: a case series","volume":"21","author":"Wei","year":"2021","journal-title":"BMC Pregnancy Childbirth."},{"key":"B43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3109\/15513818809022278","article-title":"Thrombosis of the umbilical cord: analysis of 52 cases and literature review","volume":"8","author":"Heifetz","year":"1988","journal-title":"Pediatr Pathol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2721","DOI":"10.1161\/01.CIR.91.11.2721","article-title":"Angiotensin-converting enzyme I\/D polymorphism and arterial wall thickness in a general population. The Vobarno Study","volume":"91","author":"Castellano","year":"1995","journal-title":"Circulation."},{"key":"B45","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1055\/s-0037-1613472","article-title":"The deletion polymorphism in the angiotensin-converting enzyme gene is a moderate risk factor for venous thromboembolism","volume":"89","author":"von Depka","year":"2003","journal-title":"Thromb Haemost."},{"key":"B46","doi-asserted-by":"publisher","first-page":"R833","DOI":"10.1152\/ajpregu.00211.2021","article-title":"ACE2: a key modulator of the renin-angiotensin system and pregnancy","volume":"321","author":"Tamanna","year":"2021","journal-title":"Am J Physiol Regul Integr Comp Physiol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1083806\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T14:27:50Z","timestamp":1672842470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1083806\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":46,"alternative-id":["10.3389\/fmed.2022.1083806"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.1083806","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]},"article-number":"1083806"}}