Evidence map›Paper›PMID 29635492›Full record

Trial reportThe American journal of clinical nutrition2018

Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy: epigenetic analysis from a randomized controlled trial.

Aoife Caffrey, Rachelle E Irwin, Helene McNulty, J J Strain, Diane J Lees-Murdock, Breige A McNulty, Mary Ward, Colum P Walsh, Kristina Pentieva

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The American journal of clinical nutrition, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

  1. Pooled it
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  14. Effects of Gender Differences inInternational journal of genomics · 2025
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  20. Scientific opinion on the tolerable upper intake level for folate.EFSA journal. European Food Safety Authority · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Aoife CaffreyNutrition Innovation Centre for Food and Health and Genomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Rachelle E IrwinGenomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Helene McNultyNutrition Innovation Centre for Food and Health and Genomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
J J StrainNutrition Innovation Centre for Food and Health and Genomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Diane J Lees-MurdockGenomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Breige A McNultySchool of Agriculture & Food Science, University College Dublin, Dublin, Ireland.
Mary WardNutrition Innovation Centre for Food and Health and Genomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Colum P WalshGenomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Kristina PentievaNutrition Innovation Centre for Food and Health and Genomic Medicine Group, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.
University of Ulster · GBUniversity College Dublin · IE

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MR/J007773/1
6 · The paper itself

Abstract

Background: Emerging evidence suggests that maternal folate status can impact cognitive development in childhood. Folate-dependent DNA methylation may provide a biological mechanism to link folate status during pregnancy with cognition in the offspring. Objective: The objective was to investigate the effect of continued folic acid (FA) supplementation beyond the first trimester of pregnancy on DNA methylation in cord blood of epigenetically controlled genes related to brain development and function. Design: Using available cord blood samples (n = 86) from the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) trial in pregnancy, we applied pyrosequencing techniques to analyze cord blood DNA at 9 candidate loci known to be regulated by methylation, including some previously implicated in observational studies: the widely dispersed retrotransposon long interspersed nuclear element-1 (LINE-1) and 8 single-copy loci (RBM46, PEG3, IGF2, GRB10, BDNF, GRIN3B, OPCML, and APC2). Results: The newborns of mothers who received ongoing FA (400 µg/d) through the second and third trimesters, compared with placebo, had significantly lower overall DNA methylation levels at LINE-1 (56.3% ± 1.7% compared with 57.2% ± 2.1%; P = 0.024), IFG2 (48.9% ± 4.4% compared with 51.2% ± 5.1%; P = 0.021), and BDNF (2.7% ± 0.7% compared with 3.1% ± 0.8%; P = 0.003). The effect of FA treatment on DNA methylation was significant only in female offspring for IGF2 (P = 0.028) and only in males for BDNF (P = 0.012). For GRB10 and GRIN3B, we detected no effect on overall methylation; however, individual cytosine-phosphate-guanine sites showed significant DNA methylation changes in response to FA. Conclusions: Continued supplementation with FA through trimesters 2 and 3 of pregnancy results in significant changes in DNA methylation in cord blood of genes related to brain development. The findings offer a potential biological mechanism linking maternal folate status with neurodevelopment of the offspring, but this requires further investigation using a genome-wide approach. This trial was registered at www.isrctn.com as ISRCTN19917787.

Indexed as

EpigenomicsAdultBiomarkersDNA MethylationFemaleFetal BloodFolic AcidGene Expression Regulation, DevelopmentalHumansInfant, NewbornMalePregnancyPregnancy Trimester, SecondPregnancy Trimester, ThirdPrenatal Nutritional Physiological PhenomenaVitamin B 12BiomarkersFolic AcidVitamin B 12

Identifiers

PMID29635492
OpenAlexW2795568265

What OpenQuestion holds

Textmetadata
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.