{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:04:12Z","timestamp":1785423852194,"version":"3.56.0"},"reference-count":216,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"crossref","award":["P2022\/BMD-7321"],"award-info":[{"award-number":["P2022\/BMD-7321"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P2022\/BMD-7321"],"award-info":[{"award-number":["P2022\/BMD-7321"]}],"id":[{"id":"https:\/\/ror.org\/040scgh75","id-type":"ROR","asserted-by":"publisher"}]},{"name":"ProACapital"},{"name":"HALEKULANI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Maternal psychoactive substance use during pregnancy represents a major threat to placental integrity and fetal development. As the central interface for maternal\u2013fetal exchange, the placenta is highly susceptible to psychoactive substances, including alcohol, tobacco, cannabis, cocaine, opioids, and synthetic drugs, which can cross the placental barrier and induce structural and functional alterations. This review synthesizes current evidence on the biological mechanisms, diagnostic approaches, and forensic relevance of psychoactive substances-induced placental pathology. We summarize how different substances disrupt placental vascularization, oxidative balance, epigenetic regulation, and cellular viability, leading to impaired nutrient and oxygen transfer and increasing the risk of adverse outcomes such as intrauterine growth restriction, preterm birth, congenital anomalies, and long-term neurodevelopmental impairment. We further discuss the role of placental tissue in identifying prenatal drug exposure and reconstructing exposure timelines. Beyond its clinical relevance, placental examination provides objective evidence with potential forensic value in cases of suspected maternal substance use, while also informing non-punitive, evidence-based interventions. Overall, integrating placental pathology into reproductive health research and prenatal care offers a multidisciplinary framework to improve maternal\u2013fetal outcomes and guide public health strategies addressing substance use during pregnancy.<\/jats:p>","DOI":"10.3390\/cells15121128","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental Pathophysiology in Maternal Psychoactive Substance Use: Biological, Clinical, and Forensic Perspectives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-6397","authenticated-orcid":false,"given":"Oscar","family":"Fraile-Martinez","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Rubio-Bedoya","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cielo","family":"Garc\u00eda-Montero","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5909-788X","authenticated-orcid":false,"given":"Diego Liviu","family":"Boaru","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8591-6116","authenticated-orcid":false,"given":"Patricia","family":"de Castro-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-2476","authenticated-orcid":false,"given":"Julia","family":"Bujan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"L\u00f3pez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0412-939X","authenticated-orcid":false,"given":"Raul","family":"D\u00edaz-Pedrero","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-6198","authenticated-orcid":false,"given":"Natalio","family":"Garc\u00eda-Honduvilla","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melchor","family":"\u00c1lvarez-Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Prince of Asturias, Networking Research Center on for Liver and Digestive Diseases (CIBEREHD), 28806 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-258X","authenticated-orcid":false,"given":"Miguel A.","family":"Saez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Pathological Anatomy Service, University Hospital G\u00f3mez-Ulla, 28806 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-2668","authenticated-orcid":false,"given":"Juan A.","family":"De Le\u00f3n-Luis","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral","family":"Bravo","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense 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