Evidence map›Paper›PMID 35578268›Full record

Trial reportClinical epigenetics2022

Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms.

Miroslava Ondičová, Rachelle E Irwin, Sara-Jayne Thursby, Luke Hilman, Aoife Caffrey, Tony Cassidy, Marian McLaughlin, Diane J Lees-Murdock, Mary Ward, Michelle Murphy and 4 more

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 5 countries.

Miroslava OndičováGenomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, UK.
Rachelle E IrwinGenomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, UK.
Sara-Jayne ThursbyGenomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, UK.
Luke HilmanGenomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, UK.
Aoife CaffreyNutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.
Tony CassidyPsychology Institute, Ulster University, Coleraine, Northern Ireland, UK.
Marian McLaughlinPsychology Institute, Ulster University, Coleraine, Northern Ireland, UK.
Diane J Lees-MurdockGenomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, UK.
Mary WardNutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.
Michelle MurphyUnitat de Medicina Preventiva i Salut Pública, Facultat de Medicina i Ciències de La Salut, Universitat Rovira i Virgili, Reus, Spain.
Yvonne LamersFood, Nutrition, and Health Program, Faculty of Land and Food Systems, The University of British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.
Kristina PentievaNutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.
Helene McNultyNutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.
Colum P WalshGenomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, UK. cp.walsh@ulster.ac.uk.ORCID 0000-0001-9921-7506
University of Ulster · GBUniversitat Rovira i Virgili · ESUniversity of British Columbia · CAUppsala University · SE

Funding

Biotechnology and Biological Sciences Research Council BB/S020330/1Biotechnology and Biological Sciences Research Council ES/N000323/1
6 · The paper itself

Abstract

backgroundWe previously showed that continued folic acid (FA) supplementation beyond the first trimester of pregnancy appears to have beneficial effects on neurocognitive performance in children followed for up to 11 years, but the biological mechanism for this effect has remained unclear. Using samples from our randomized controlled trial of folic acid supplementation in second and third trimester (FASSTT), where significant improvements in cognitive and psychosocial performance were demonstrated in children from mothers supplemented in pregnancy with 400 µg/day FA compared with placebo, we examined methylation patterns from cord blood (CB) using the EPIC array which covers approximately 850,000 cytosine-guanine (CG) sites across the genome. Genes showing significant differences were verified using pyrosequencing and mechanistic approaches used in vitro to determine effects on transcription.

resultsFA supplementation resulted in significant differences in methylation, particularly at brain-related genes. Further analysis showed these genes split into two groups. In one group, which included the CES1 gene, methylation changes at the promoters were important for regulating transcription. We also identified a second group which had a characteristic bimodal profile, with low promoter and high gene body (GB) methylation. In the latter, loss of methylation in the GB is linked to decreases in transcription: this group included the PRKAR1B/HEATR2 genes and the dopamine receptor regulator PDE4C. Overall, methylation in CB also showed good correlation with methylation profiles seen in a published data set of late gestation foetal brain samples.

conclusionWe show here clear alterations in DNA methylation at specific classes of neurodevelopmental genes in the same cohort of children, born to FA-supplemented mothers, who previously showed improved cognitive and psychosocial performance. Our results show measurable differences at neural genes which are important for transcriptional regulation and add to the supporting evidence for continued FA supplementation throughout later gestation. This trial was registered on 15 May 2013 at www.isrctn.com as ISRCTN19917787.

Indexed as

DNA MethylationFolic AcidChildDietary SupplementsFemaleHumansPregnancyPregnancy Trimester, SecondPregnancy Trimester, ThirdFolic AcidDNA methylationFolic acidNeurodevelopment

Identifiers

PMID35578268
PMCPMC9112484
OpenAlexW4280535517

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.