{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:44:52Z","timestamp":1781826292083,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","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":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We have developed novel methods for isolating fetal central nervous system (CNS)\u2010derived extracellular vesicles (FCEs) from maternal plasma as a non\u2010invasive platform for testing aspects of fetal neurodevelopment in early pregnancy. We investigate the hypothesis that levels of defined sets of functional proteins in FCEs can be used to detect abnormalities in fetal neuronal and glial proliferation, differentiation, and survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Maternal plasma was obtained between 10 and 19\u00a0weeks from women with current heavy EtOH exposure and matched controls. FCE levels of synaptophysin, synaptotagmin, synaptopodin, and neurogranin were quantified normalized to the exosome marker CD81. Quantitative RT\u2010PCR was performed with specific primers for miR\u20109.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FCE cargo protein levels of synaptophysin, synaptotagmin, synaptopodin, and neurogranin were all significantly reduced in pregnancies exposed to current heavy EtOH use (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001 for all). Both synaptophysin and neurogranin appeared to be particularly discriminatory with no overlap between exposed and control subjects. Up to tenfold inhibition (90%) in MicroRNA\u20109 was observed in FCEs from EtOH exposed fetuses compared with controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that FCEs purified from maternal plasma may be a powerful tool to assess abnormal proliferation and differentiation of CNS stem cells as early as the late first trimester.<\/jats:p><jats:p><jats:boxed-text content-type=\"box\" position=\"float\"><jats:sec><jats:title>What's already known about this topic?<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Exosomes\/extracellular vesicles (ECVs) are emerging as exciting novel biomarkers in neurologic disease (Alzheimers)<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>What does this study add?<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Evidence that Fetal CNS ECVs can be isolated from maternal blood<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The origin of the ECVs appears to be the fetal brain and not the placenta<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Findings with ECVs correlates with fetal exposure to alcohol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Potential for first trimester prenatal diagnosis of fetal neurologic disease<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.5474","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T02:32:50Z","timestamp":1557369170000},"page":"609-615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Noninvasive assessment of fetal central nervous system insult: Potential application to prenatal diagnosis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-2809","authenticated-orcid":false,"given":"Laura","family":"Goetzl","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Texas Houston Health Sciences  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-4940","authenticated-orcid":false,"given":"Nune","family":"Darbinian","sequence":"additional","affiliation":[{"name":"Shriners Pediatric Research Center, Center for Neural Repair and Rehabilitation Temple University  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-1551","authenticated-orcid":false,"given":"Nana","family":"Merabova","sequence":"additional","affiliation":[{"name":"Shriners Pediatric Research Center, Center for Neural Repair and Rehabilitation Temple University  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.21896"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02156.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1988.tb00223.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970601)48:5<439::AID-JNR5>3.0.CO;2-F"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","unstructured":"GilmoreEC WalshCA.2013.Genetic causes of microcephaly and lessons for neuronal development. 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