Publication: Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study
Authors
Eva Morales ; María Teresa Prieto-Sanchez ; Jaime Mendiola ; Ana Cutillas-Tolín ; Evdochia Adoamnei ; Desir ee Valera-Gran ; Carmen Martínez-Graciá ; Marina Santaella-Pascual ; Clara Suarez-Martinez ; Jesús Vioque ; María Jesús Castaños ; Eva del Castillo ; Luis García-Marcos
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Facultades de la UMU::Facultad de Veterinaria
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Publisher
Elsevier
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DOI
https://doi.org/10.1016/j.clnu.2024.04.007
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info:eu-repo/semantics/article
Description
Abstract
Background & 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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Citation
Clinical Nutrition 43 (2024) 1191e1198
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