{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:33:29Z","timestamp":1791581609384,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/00226"],"award-info":[{"award-number":["PI14\/00226"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["INT16\/00168"],"award-info":[{"award-number":["INT16\/00168"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/00130"],"award-info":[{"award-number":["PI15\/00130"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2019,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n To perform a comprehensive assessment of the placental aging process in small term fetuses classified as being small\u2010for\u2010gestational age (SGA) or having fetal growth restriction (FGR) through analysis of senescence and apoptosis markers.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This was a prospective nested case\u2013control study of singleton pregnancies delivered at term, including 21 control pregnancies with normally grown fetuses and 36 with a small fetus classified as SGA (birth weight between the 3\n rd<\/jats:sup>\n and 9\n th<\/jats:sup>\n percentiles and normal fetoplacental Doppler;\n n<\/jats:italic>\n \u2009=\u200918) or FGR (birth weight\u2009<\u20093\n rd<\/jats:sup>\n percentile and\/or abnormal cerebroplacental ratio and\/or uterine artery Doppler;\n n<\/jats:italic>\n \u2009=\u200918). Telomerase activity, telomere length (quantified by comparing the amount of amplification product for the telomere sequence (T) to that of a single copy of the gene 36B4 (S)) and RNA expression of senescence (Sirtuins 1, 3 and 6) and apoptosis (p53, p21, BAX and Caspases 3 and 9) markers (analyzed using the 2\n \u2013\u0394\u0394Ct<\/jats:sup>\n method) were determined in placental samples collected at birth and compared between the three groups.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared to pregnancies with a normally grown fetus, both SGA and FGR pregnancies presented signs of accelerated placental aging, including lower telomerase activity (mean\u2009\u00b1\u2009SD, 12.8\u2009\u00b1\u20096.6% in controls\n vs<\/jats:italic>\n 7.98\u2009\u00b1\u20094.2% in SGA\n vs<\/jats:italic>\n 7.79\u2009\u00b1\u20094.6% in FGR;\n P<\/jats:italic>\n \u2009=\u20090.008), shorter telomeres (mean\u2009\u00b1\u2009SD T\/S ratio, 1.20\u2009\u00b1\u20090.6 in controls\n vs<\/jats:italic>\n 1.08\u2009\u00b1\u20090.9 in SGA\n vs<\/jats:italic>\n 0.66\u2009\u00b1\u20090.5 in FGR;\n P<\/jats:italic>\n \u2009=\u20090.047) and reduced Sirtuin\u20101 RNA expression (mean\u2009\u00b1\u2009SD 2\n \u2013\u0394\u0394Ct<\/jats:sup>\n , 1.55\u2009\u00b1\u20090.8 in controls\n vs<\/jats:italic>\n 0.91\u2009\u00b1\u20090.8 in SGA\n vs<\/jats:italic>\n 0.63\u2009\u00b1\u20090.5 in FGR;\n P<\/jats:italic>\n \u2009=\u20090.001) together with increased p53 RNA expression (median (interquartile range) 2\n \u2013\u0394\u0394Ct<\/jats:sup>\n , 1.07 (0.3\u20133.3) in controls\n vs<\/jats:italic>\n 5.39 (0.6\u201315) in SGA\n vs<\/jats:italic>\n 3.75 (0.9\u20137.8) in FGR;\n P<\/jats:italic>\n \u2009=\u20090.040). FGR cases presented signs of apoptosis, with increased Caspase\u20103 RNA levels (median (interquartile range) 2\n \u2013\u0394\u0394Ct<\/jats:sup>\n , 0.94 (0.7\u20131.7) in controls\n vs<\/jats:italic>\n 3.98 (0.9\u201331) in FGR;\n P<\/jats:italic>\n \u2009=\u20090.031) and Caspase\u20109 RNA levels (median (interquartile range) 2\n \u2013\u0394\u0394Ct<\/jats:sup>\n , 1.21 (0.6\u20134.0) in controls\n vs<\/jats:italic>\n 3.87 (1.5\u20139.0) in FGR;\n P<\/jats:italic>\n \u2009=\u20090.037) compared with controls. In addition, Sirtuin\u20101 RNA expression, telomerase activity, telomere length and Caspase\u20103 activity showed significant linear trends across groups as severity of the condition increased.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Accelerated placental aging was observed in both clinical forms of late\u2010onset fetal smallness (SGA and FGR), supporting a common pathophysiology and challenging the concept of SGA fetuses being constitutionally small. Copyright \u00a9 2018 ISUOG. Published by John Wiley & Sons Ltd.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/uog.20103","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T03:46:40Z","timestamp":1534736800000},"page":"615-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Premature placental aging in term small\u2010for\u2010gestational\u2010age and growth\u2010restricted fetuses"],"prefix":"10.1002","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6795-0367","authenticated-orcid":false,"given":"C.","family":"Paules","sequence":"first","affiliation":[{"name":"Fetal Medicine Research Center, BCNatal \u2010 Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine, Hospital Cl\u00ednic and Hospital Sant Joan de Deu, ICGON, IDIBAPS, Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. P.","family":"Dantas","sequence":"additional","affiliation":[{"name":"Cardiovascular Institut, Hospital Clinic, IDIBAPS Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Fetal Medicine Research Center, BCNatal \u2010 Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine, Hospital Cl\u00ednic and Hospital Sant Joan de Deu, ICGON, IDIBAPS, Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Crovetto","sequence":"additional","affiliation":[{"name":"Fetal Medicine Research Center, BCNatal \u2010 Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine, Hospital Cl\u00ednic and Hospital Sant Joan de Deu, ICGON, IDIBAPS, Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Eixarch","sequence":"additional","affiliation":[{"name":"Fetal Medicine 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