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Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: a cohort study

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dc.contributor.authorMorales Bartolomé, Eva
dc.contributor.authorPrieto Sánchez, María Teresa
dc.contributor.authorMendiola Olivares, Jaime
dc.contributor.authorCutillas Tolín, Ana
dc.contributor.authorAdoamnei, Evdochia
dc.contributor.authorValera-Gran, Desiree
dc.contributor.authorSantaella-Pascual, Marina
dc.contributor.authorSuárez Martínez, Clara
dc.contributor.authorVioque, Jesús
dc.contributor.authorCastaños, María Jesús
dc.contributor.authorCastillo, Eva del
dc.contributor.authorGarcía-Marcos Álvarez, Luis Vicente
dc.contributor.departmentTecnología de Alimentos, Nutrición y Bromatología
dc.contributor.otherFacultad de Veterinaria
dc.date.accessioned2026-01-22T18:42:24Z
dc.date.available2026-01-22T18:42:24Z
dc.date.copyright© 2024 The Authors
dc.date.issued2024
dc.description.abstractBackground & aims: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. Methods: Data come from 325 motherechild pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015e2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. Results: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception ( 0.50; 95% CI:  0.91,  0.09; P ¼ 0.016), and from preconception up to 12 weeks of gestation ( 0.48; 95% CI:  0.88,  0.08; P ¼ 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth ( 0.77; 95% CI:  1.52,  0.02; P ¼ 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth.
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dc.format.extent8
dc.identifier.citationClinical Nutrition 43 (2024) 1191-1198
dc.identifier.doihttps://doi.org/10.1016/j.clnu.2024.04.007
dc.identifier.eissn1532-1983
dc.identifier.urihttp://hdl.handle.net/10201/191030
dc.languageeng
dc.publisherElsevier
dc.relationThis study was supported by grants from the Instituto de Salud Carlos III, Spanish Ministry of Science, Innovation and Universities, and co-funded by the European Union (Grant Numbers: CP14/00046, PIE15/00051, PI16/00422, PI19/00863, and ARADyAL network RD160006). EM was funded by Miguel Servet Fellowships (MS14/00046 and CPII19/00019) awarded by the Instituto de Salud Carlos III, Spanish Ministry of Science, Innovation and Universities, and Fondos FEDER.
dc.relation.publisherversionhttps://www.clinicalnutritionjournal.com/article/S0261-5614(24)00112-2/fulltext
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAlu
dc.subjectCord blood
dc.subjectDNA methylation
dc.subjectFolic acid
dc.subjectSupplements
dc.subject.odsObjetivo 3: Salud
dc.titleMaternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: a cohort study
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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