{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:27:19Z","timestamp":1789072039942,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI18\/01700"],"award-info":[{"award-number":["PI18\/01700"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PI18\/01700"],"award-info":[{"award-number":["PI18\/01700"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["RTC-2017-6471-1"],"award-info":[{"award-number":["RTC-2017-6471-1"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["AEI\/FEDER"],"award-info":[{"award-number":["AEI\/FEDER"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RTC-2017-6471-1"],"award-info":[{"award-number":["RTC-2017-6471-1"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AEI\/FEDER"],"award-info":[{"award-number":["AEI\/FEDER"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"European Regional Development Funds"},{"DOI":"10.13039\/100017487","name":"Instituto Tecnol\u00f3gico y de Energ\u00edas Renovables","doi-asserted-by":"crossref","award":["OA23\/043"],"award-info":[{"award-number":["OA23\/043"]}],"id":[{"id":"10.13039\/100017487","id-type":"DOI","asserted-by":"crossref"}]},{"award":["OA23\/043"],"award-info":[{"award-number":["OA23\/043"]}],"id":[{"id":"https:\/\/ror.org\/015g99884","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Cabildo Insular de Tenerife. Spain","award":["CGIEU0000219140"],"award-info":[{"award-number":["CGIEU0000219140"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The link between neurodevelopment in infants exposed to maternal gestational diabetes mellitus (GDM) and fetal DNA methylation remains unexplored. We conducted this hypothesis-generating study to investigate the association between fetal DNA methylation and neurodevelopmental outcomes in children of mothers with GDM. We carried out a prospective, observational pilot cohort study comparing infants exposed to maternal GDM with an unexposed control group. Umbilical cord blood DNA methylation was assessed using targeted methylome sequencing covering 3.34 million CpG sites. Infant neurodevelopment was evaluated at age two years using the Bayley-III Scales. Bioinformatics processing identified differentially methylated regions (DMRs), followed by multiple enrichment analyses of DMR-associated genes and partial correlation analyses. Multi-dimensional enrichment analysis of the 1053 identified DMR-associated genes revealed a significant convergence of pathways related to neurogenesis, synaptic components, and axonal guidance. Infants born to mothers with GDM exhibited lower scores in cognitive, language, and motor domains, which were associated with identifiable DNA methylation signatures at birth. Significant correlations were observed in genes essential for brain scaffolding and synaptic circuitry, most notably WNT4, the PCDHG alpha\/beta clusters, and PALM. Additionally, methylation patterns in FOXF2 and CHFR suggest a potential impact on blood\u2013brain barrier integrity, while associations with FSTL3 and H6PD highlight a systemic metabolic \u2018cross-talk\u2019 influencing neurodevelopment. Although these pilot findings are hypothesis-generating and require further functional validation, this study provides pioneering evidence that neurodevelopmental alterations in the offspring of mothers with GDM are potentially associated with intrauterine epigenetic modifications detectable at birth.<\/jats:p>","DOI":"10.3390\/ijms27083571","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:14:12Z","timestamp":1776352452000},"page":"3571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association Between Maternal Gestational Diabetes, Cord Blood DNA Methylation, and Offspring Neurodevelopment"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1401-5580","authenticated-orcid":false,"given":"Nieves Luisa","family":"Gonz\u00e1lez-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, University of La Laguna (ULL), 38320 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Armas-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, University of La Laguna (ULL), 38320 La Laguna, Spain"},{"name":"Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0781-9161","authenticated-orcid":false,"given":"Enrique","family":"Gonz\u00e1lez-D\u00e1vila","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Statistics and Operations Research, Instituto de Matem\u00e1ticas y Aplicaciones (IMAULL), University of La Laguna (ULL), 38320 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-2920","authenticated-orcid":false,"given":"Jos\u00e9 Ram\u00f3n","family":"Castro-Conde","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, University of La Laguna (ULL), 38320 La Laguna, Spain"},{"name":"Department of Pediatrics, Canary Islands University Hospital, 38320 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candelaria","family":"Gonz\u00e1lez-Campo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, University of La Laguna (ULL), 38320 La Laguna, Spain"},{"name":"Department of Pediatrics, Canary Islands University Hospital, 38320 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-069X","authenticated-orcid":false,"given":"Carlos","family":"Flores","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, Instituto de Investigaci\u00f3n Sanitaria de Canarias (IISC), 38010 Santa Cruz de Tenerife, Spain"},{"name":"CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Genomics Division, Instituto Tecnol\u00f3gico y de Energ\u00edas Renovables (ITER), 38600 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-2861","authenticated-orcid":false,"given":"Jos\u00e9 Miguel","family":"Lorenzo-Salazar","sequence":"additional","affiliation":[{"name":"Genomics Division, Instituto Tecnol\u00f3gico y de Energ\u00edas Renovables (ITER), 38600 Santa Cruz de Tenerife, 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Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, University of La Laguna (ULL), 38320 La Laguna, Spain"},{"name":"Department of Obstetrics and Gynecology, Canary Islands University Hospital, 38320 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-9001","authenticated-orcid":false,"given":"Laura","family":"Tasc\u00f3n-Padr\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Prenatal Medicine, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Orribo-Morales","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, University of La Laguna (ULL), 38320 La Laguna, Spain"},{"name":"Department of Pediatrics, Canary Islands University Hospital, 38320 La Laguna, 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