{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T00:53:48Z","timestamp":1793926428155,"version":"4.8.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"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. Pharmacol."],"abstract":"<jats:p>Prenatal alcohol exposure (PAE) is a major early-life stressor associated with long-lasting neurodevelopmental and neurocognitive alterations. Increasing evidence from human studies indicates that PAE leaves persistent molecular signatures that can be detected in the placenta and in clinically accessible biological fluids. This Mini Review summarizes recent advances in the identification of epigenetic, immune, endocrine, and RNA-based biomarkers measured in placental tissue, umbilical cord blood, and peripheral fluids, and their associations with neurodevelopmental outcomes. We highlight convergent findings across heterogeneous study designs, discuss current methodological challenges and research gaps, and consider future directions toward integrative and longitudinal biomarker approaches. Together, the reviewed evidence supports the potential of placental and circulating biomarkers to improve early risk stratification and to advance understanding of neurodevelopmental alterations following PAE.<\/jats:p>","DOI":"10.3389\/fphar.2026.1816529","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:03Z","timestamp":1780378863000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Early biomarkers associated with prenatal alcohol exposure and neurodevelopmental outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"Isabel","family":"Ochando","sequence":"first","affiliation":[{"name":"Departamento de Histolog\u00eda y Anatom\u00eda, Facultad de Medicina, Universidad Miguel Hern\u00e1ndez","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sempere","sequence":"additional","affiliation":[{"name":"Departmento de Neuropediatria, Centre de Ter\u00e0pia Interfamiliar, HLA Vistahermosa Hospital","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Navarro","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC","place":["Alicante, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL)","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e70015","DOI":"10.1111\/jnc.70015","article-title":"Prenatal alcohol consumption alters protein fingerprint in umbilical cord blood serum and induces brain microvascular endothelial cell dysfunction","volume":"169","author":"Almeida","year":"2025","journal-title":"J. Neurochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1038\/s41598-018-38041-0","article-title":"Serum concentrations of IGF-I\/IGF-II as biomarkers of alcohol damage during foetal development and diagnostic markers of foetal alcohol syndrome","volume":"9","author":"Andreu-Fern\u00e1ndez","year":"2019","journal-title":"Sci. Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1186\/s12916-022-02699-1","article-title":"Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders","volume":"20","author":"Auvinen","year":"2022","journal-title":"BMC Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e70071","DOI":"10.1111\/jne.70071","article-title":"Predictive utility of placental hypothalamic\u2013pituitary\u2013adrenal axis biomarkers and infant neurodevelopment","volume":"37","author":"Bakhireva","year":"2025","journal-title":"J. Neuroendocrinol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12974-020-1717-8","article-title":"Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure","volume":"17","author":"Bodnar","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1503\/cmaj.141593","article-title":"Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan","volume":"188","author":"Cook","year":"2016","journal-title":"Can. Med. Assoc. J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5826","DOI":"10.3390\/ijms25115826","article-title":"Fetal brain-derived exosomal miRNAs from maternal blood: potential diagnostic biomarkers for fetal alcohol spectrum disorders (FASDs)","volume":"25","author":"Darbinian","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1038\/s41598-024-52737-6","article-title":"Prenatal alcohol exposure is associated with changes in placental gene co-expression networks","volume":"14","author":"Deyssenroth","year":"2024","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1111\/j.1530-0277.1988.tb00233.x","article-title":"Underreporting of alcohol use in pregnancy","volume":"12","author":"Ernhart","year":"1988","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1203\/01.PDR.0000135998.08025.FB","article-title":"Developmental origins of disease paradigm: a mechanistic and evolutionary perspective","volume":"56","author":"Gluckman","year":"2004","journal-title":"Pediatr. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1093\/alcalc\/agn105","article-title":"Foetal alcohol spectrum disorders and alterations in brain and behaviour","volume":"44","author":"Guerri","year":"2009","journal-title":"Alcohol Alcohol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1002\/bdr2.1488","article-title":"The association between prenatal alcohol exposure and protein expression in human placenta","volume":"111","author":"Holbrook","year":"2019","journal-title":"Birth Defects Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/S0140-6736(73)91092-1","article-title":"Recognition of the fetal alcohol syndrome in early infancy","volume":"302","author":"Jones","year":"1973","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/jcpp.12451","article-title":"Research review: executive function deficits in fetal alcohol spectrum disorders and attention\u2010deficit\/hyperactivity disorder \u2013 a meta\u2010analysis","volume":"57","author":"Kingdon","year":"2016","journal-title":"J. Child Psychol. Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"6601","DOI":"10.3390\/ijms24076601","article-title":"Expression quantitative trait methylation analysis identifies whole blood molecular footprint in fetal alcohol spectrum disorder (FASD)","volume":"24","author":"Krzyzewska","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1176\/appi.ajp.2020.20010086","article-title":"Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the adolescent brain cognitive development study","volume":"177","author":"Lees","year":"2020","journal-title":"Am. J. Psychiatry"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13148-018-0439-6","article-title":"DNA methylation as a predictor of fetal alcohol spectrum disorder","volume":"10","author":"Lussier","year":"2018","journal-title":"Clin. Epigenetics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1038\/s41598-020-80734-y","article-title":"Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders","volume":"11","author":"Mahnke","year":"2021","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s11065-011-9167-9","article-title":"Fetal alcohol spectrum disorders: neuropsychological and behavioral features","volume":"21","author":"Mattson","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.reprotox.2019.01.009","article-title":"Screening for prenatal alcohol exposure and corresponding short-term neonatal outcomes","volume":"85","author":"Maxwell","year":"2019","journal-title":"Reprod. Toxicol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"7019","DOI":"10.3390\/ijms25137019","article-title":"Moderate prenatal alcohol exposure increases toll-like receptor activity in umbilical cord blood at birth: a pilot study","volume":"25","author":"Maxwell","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1111\/acer.70013","article-title":"Abnormal neurobehavior profiles observed in the newborn period following low\u2010to\u2010moderate prenatal alcohol exposure","volume":"49","author":"Maxwell","year":"2025","journal-title":"Alcohol, Clin. Exp. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1001\/jama.2017.21896","article-title":"Prevalence of fetal alcohol spectrum disorders in 4 US communities","volume":"319","author":"May","year":"2018","journal-title":"JAMA"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1017\/S0954579412000764","article-title":"Linking prenatal maternal adversity to developmental outcomes in infants: the role of epigenetic pathways","volume":"24","author":"Monk","year":"2012","journal-title":"Dev. Psychopathol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s11065-011-9166-x","article-title":"Fetal alcohol spectrum disorders: an overview","volume":"21","author":"Riley","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/acer.12939","article-title":"Worldwide prevalence of fetal alcohol spectrum disorders: a systematic literature review including meta\u2010analysis","volume":"40","author":"Roozen","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"101586","DOI":"10.1016\/j.gim.2025.101586","article-title":"Discovery of a DNA methylation episignature as a molecular biomarker for fetal alcohol syndrome","volume":"27","author":"van der Laan","year":"2025","journal-title":"Genet. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"147951","DOI":"10.1016\/j.gene.2023.147951","article-title":"RNA-Seq analysis reveals prenatal alcohol exposure is associated with placental inflammatory cells and gene expression","volume":"894","author":"Williams","year":"2024","journal-title":"Gene"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1816529\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:04Z","timestamp":1780378864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1816529\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":28,"alternative-id":["10.3389\/fphar.2026.1816529"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1816529","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"article-number":"1816529"}}