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Article

Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation

1
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
2
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
3
Division of Research, Kaiser Permanente, Oakland, CA 94612, USA
4
Department of Public Health Sciences and the M.I.N.D. Institute, School of Medicine, University of California, Davis, CA 95616, USA
5
College of Health and Human Development, Penn State University, State College, PA 16802, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally as co-senior authors.
Int. J. Environ. Res. Public Health 2020, 17(24), 9190; https://doi.org/10.3390/ijerph17249190
Received: 5 November 2020 / Revised: 20 November 2020 / Accepted: 28 November 2020 / Published: 9 December 2020
(This article belongs to the Special Issue Environmental Epigenetics: Implications for Health and Disease)
Background: Fetal development involves cellular differentiation and epigenetic changes—complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase (MTHFR) is important for processing the nutrient folate. Hypothesis: We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns. Methods: In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal MTHFR C677T allele. Results: Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 0.03). For mothers with at least one variant allele, multivitamin intake had a null −0.06% (95% CI: −0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution (p = 0.37). Conclusions: We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy. View Full-Text
Keywords: DNA methylation; multivitamin; MTHFR; cord blood DNA methylation; multivitamin; MTHFR; cord blood
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MDPI and ACS Style

Bakulski, K.M.; Dou, J.F.; Feinberg, J.I.; Brieger, K.K.; Croen, L.A.; Hertz-Picciotto, I.; Newschaffer, C.J.; Schmidt, R.J.; Fallin, M.D. Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation. Int. J. Environ. Res. Public Health 2020, 17, 9190. https://doi.org/10.3390/ijerph17249190

AMA Style

Bakulski KM, Dou JF, Feinberg JI, Brieger KK, Croen LA, Hertz-Picciotto I, Newschaffer CJ, Schmidt RJ, Fallin MD. Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation. International Journal of Environmental Research and Public Health. 2020; 17(24):9190. https://doi.org/10.3390/ijerph17249190

Chicago/Turabian Style

Bakulski, Kelly M.; Dou, John F.; Feinberg, Jason I.; Brieger, Katharine K.; Croen, Lisa A.; Hertz-Picciotto, Irva; Newschaffer, Craig J.; Schmidt, Rebecca J.; Fallin, M. D. 2020. "Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation" Int. J. Environ. Res. Public Health 17, no. 24: 9190. https://doi.org/10.3390/ijerph17249190

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