{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:55:39Z","timestamp":1784213739437,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>EXTrauterine Environment for Neonatal Development (EXTEND) is a\u2009system to support ongoing fetal growth and organ development in an extrauterine environment, utilizing a pumpless low\u2010resistance oxygenator circuit. The aim of this study was to evaluate hemodynamics and cardiac function in fetal sheep sustained on the EXTEND system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a prospective study of fetal sheep supported for a minimum of 3\u2009weeks on EXTEND. Hemodynamic parameters were assessed weekly and included heart rate, mean arterial pressure (MAP), Doppler\u2010echocardiography\u2010derived cardiac output (CO), pulsatility indices (PIs) of the fetal middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus and cardiac function, as assessed by speckle\u2010tracking\u2010derived global longitudinal strain and strain rate in the right (RV) and left (LV) ventricles. Parameters were compared at 0\u2009days and 1, 2 and 3\u2009weeks following placement on EXTEND.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 10 fetal sheep enrolled, seven survived for 3\u2009weeks and were included in the analysis. Median gestational age at cannulation was 107 (range, 95\u2013109) days. Heart rate decreased and MAP increased significantly, but within acceptable ranges, during the study period. The quantities and relative ratios of right and left CO remained stable within the anticipated physiological range throughout the study period. Vascular tracings and PIs appeared to be similar to those seen normally in the natural <jats:italic>in\u2010utero<\/jats:italic> state, with MCA\u2010PI being higher than UA\u2010PI. UA tracings demonstrated maintained abundant diastolic flow despite the absence of placental circulation. In both the RV and LV, strain decreased significantly at 1 and 2\u2009weeks relative to baseline but returned to baseline values by week 3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The EXTEND mechanical support system replicates natural physiology and creates a stable and sustainable cardiovascular construct that supports growth over a 3\u2010week period. However, there is a period of depressed contractility within the first week with subsequent improvement by week\u20093. This may reflect a period of physiological accommodation that warrants further investigation. This study lays the foundation for further exploration as the EXTEND system moves towards human application. \u00a9 2019 The Authors. <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.20295","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T06:40:29Z","timestamp":1555396829000},"page":"516-522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Fetal echocardiographic assessment of cardiovascular impact of prolonged support on EXTrauterine Environment for Neonatal Development (EXTEND) system"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-5576","authenticated-orcid":false,"given":"K.","family":"Ozawa","sequence":"first","affiliation":[{"name":"Center for Fetal Research, Department of Surgery The Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Fetal Heart Program Cardiac Center at The Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Center of Maternal\u2013Fetal Neonatal and Reproductive Medicine, National Center for Child Health and Development (NCCHD)  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Davey","sequence":"additional","affiliation":[{"name":"Center for Fetal Research, Department of Surgery The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Tian","sequence":"additional","affiliation":[{"name":"Fetal Heart Program Cardiac Center at The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Hornick","sequence":"additional","affiliation":[{"name":"Center for Fetal Research, Department of Surgery The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Y.","family":"Mejaddam","sequence":"additional","affiliation":[{"name":"Center for Fetal Research, Department of Surgery The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. E.","family":"McGovern","sequence":"additional","affiliation":[{"name":"Center for Fetal Research, Department of Surgery The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. W.","family":"Flake","sequence":"additional","affiliation":[{"name":"Center for Fetal Research, Department of Surgery The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8625-6565","authenticated-orcid":false,"given":"J.","family":"Rychik","sequence":"additional","affiliation":[{"name":"Fetal Heart Program Cardiac Center at The Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15112"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000330762"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.12.015"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.554006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP275367"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(83)90684-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.7863\/ultra.15.08060"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/echo.13542"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2005.852050"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2006.04.011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2017.04.006"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.21.2.163"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00523.2003"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.4.826"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199312000-00020"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.7863\/jum.2002.21.8.857"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00864.2009"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335403"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2009.12.024"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334413"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2011.09.016"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2012.09.011"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341717"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2017.11.007"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2012.10.007"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.06.012"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2017.01.010"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2007.09.007"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124338"}],"container-title":["Ultrasound in Obstetrics &amp; 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