Prenatal vitamin intake in first month of pregnancy and DNA methylation in cord blood and placenta in two prospective cohorts

Abstract

Background Prenatal vitamin use is recommended before and during pregnancies for normal fetal development. Prenatal vitamins do not have a standard formulation, but many contain calcium, folic acid, iodine, iron, omega-3 fatty acids, zinc, and vitamins A, B6, B12, and D, and usually they contain higher concentrations of folic acid and iron than regular multivitamins in the US Nutrient levels can impact epigenetic factors such as DNA methylation, but relationships between maternal prenatal vitamin use and DNA methylation have been relatively understudied. We examined use of prenatal vitamins in the first month of pregnancy in relation to cord blood and placenta DNA methylation in two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk Learning Early Signs (MARBLES) studies. Results In placenta, prenatal vitamin intake was marginally associated with −0.52% (95% CI −1.04, 0.01) lower mean array-wide DNA methylation in EARLI, and associated with −0.60% (−1.08, −0.13) lower mean array-wide DNA methylation in MARBLES. There was little consistency in the associations between prenatal vitamin intake and single DNA methylation site effect estimates across cohorts and tissues, with only a few overlapping sites with correlated effect estimates. However, the single DNA methylation sites with p-value < 0.01 (EARLI cord nCpGs = 4068, EARLI placenta nCpGs = 3647, MARBLES cord nCpGs = 4068, MARBLES placenta nCpGs = 9563) were consistently enriched in neuronal developmental pathways. Conclusions Together, our findings suggest that prenatal vitamin intake in the first month of pregnancy may be related to lower placental global DNA methylation and related to DNA methylation in brain-related pathways in both placenta and cord blood.

The one-carbon metabolism as an underlying pathway for placental DNA methylation – a systematic review

“… Global methylation: LINE-1 methylation – MethyLight Gene specific: VEGF promoter — MS-HRM Foetal side Use of milk with or without vitamin B 12 did not change VEGF promoter or LINE-1 methylation. 8 Dou (2022) – USA [ 31 ] (Subgroup of) 2 prospective cohorts Couples at increased risk for offspring with ASD. N = 70 (MARBLES cohort) + N = 88 (EARLI cohort) Maternal multivitamin use in first month of pregnancy Global methylation: Mean array methylation – MARBLES: 450K array EARLI: EPIC array Genome wide: individual CpGs – MARBLES: 450K array, EARLI: EPIC array Foetal side (MARBLES) Central full thickness biopsy (EARLI) Negative association between mean array methylation and vitamin use: −0.60% (CI −1.08, − 0.13; MARBLES); −0.52% (CI −1.04, 0.01; EARLI).…”

“…About 95% of these showed lower methylation in the vitamin group in both cohorts (average −4%). The identified CpGs were enriched in neuronal developmental pathways [ 31 ]. Schmidt et al .…”

“…CpGs associated with maternal vitamin use in the first month of pregnancy could only be identified when a less stringent FDR-corrected p-value was applied and 95% of these were hypomethylated in women who did take vitamins in the first month of pregnancy. Identified CpGs were enriched in neuronal developmental pathways [ 31 ]. A few DMRs linked to different genes could be identified based on dietary patterns reflecting differences in intake of one-carbon moieties [ 32 ] and methylation of a few CpGs associated with umbilical cord levels of SAM, SAH, and SAM:SAH, but not with RBC folate or vitamin B 12 levels in cord blood [ 42 ].…”

Prenatal Metal Exposures and Child Social Responsiveness Scale Scores in 2 Prospective Studies

“… 64 All the children, that is, the offspring of those pregnancies, were born between November 2009 and March 2012 in EARLI and between December 2006 and July 2016 in MARBLES. 65 These siblings of autistic children had 20-fold higher risk of having ASD themselves compared to the general population and were thus at “enriched risk” of ASD, providing a unique opportunity to study the complex etiology of ASD with an increased sample size from both cohorts. 66 Biological samples were collected throughout pregnancy.…”

“…The EARLI study was reviewed and approved by Human Subjects Institutional Review Boards (IRBs) from each of the 4 EARLI study sites (Johns Hopkins University, Drexel University, University of California Davis, and Kaiser Permanente) and the MARBLES study was reviewed and approved by the Human Subjects IRB from University of California Davis. 65 This secondary analysis was reviewed and approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board (IRB number: IRB00002032).…”