Evidence map›Paper›PMID 33347560›Full record

SynthesisInternational journal of epidemiology2021

Investigating the causal effect of maternal vitamin B12 and folate levels on offspring birthweight.

Gunn-Helen Moen, Robin N Beaumont, Niels Grarup, Christine Sommer, Beverley M Shields, Deborah A Lawlor, Rachel M Freathy, David M Evans, Nicole M Warrington

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in International journal of epidemiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. 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

9 authors at 5 institutions in 4 countries.

Gunn-Helen MoenInstitute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Robin N BeaumontInstitute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Christine SommerDepartment of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
Beverley M ShieldsInstitute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK.
Deborah A LawlorPopulation Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
Rachel M FreathyInstitute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK.
David M EvansUniversity of Queensland Diamantina Institute, University of Queensland, Woolloongabba, QLD, Australia.
Nicole M WarringtonUniversity of Queensland Diamantina Institute, University of Queensland, Woolloongabba, QLD, Australia.
The University of Queensland · AUUniversity of Exeter · GBOslo University Hospital · NOUniversity of Bristol · GBUniversity of Copenhagen · DK

Funding

Metabolomic and Epigenomic Mechanisms in Developmental Overnutrition.R01DK103246 · NIDDK · UNIVERSITY OF BRISTOL · PI LAWLOR, DEBORAH ANNE · 2014 to 2018
$2.2M
Department of HealthEuropean Research Council 669545Medical Research Council MC_UU_00011/6Medical Research Council MC_UU_12013/4NIDDK NIH HHS R01 DK103246Wellcome TrustWellcome Trust 104150/Z/14/ZWellcome Trust WT104150
6 · The paper itself

Abstract

backgroundLower maternal serum vitamin B12 (B12) and folate levels have been associated with lower offspring birthweight, in observational studies. The aim of this study was to investigate whether this relationship is causal.

methodsWe performed two-sample Mendelian randomization (MR) using summary data on associations between genotype-B12 (10 genetic variants) or genotype-folate (four genetic variants) levels from: a genome-wide association study of 45 576 individuals (sample 1); and both maternal- and fetal-specific genetic effects on offspring birthweight from the latest Early Growth Genetics consortium meta-analysis with 297 356 individuals reporting their own birthweight and 210 248 women reporting their offspring's birthweight (sample 2). We used the inverse variance weighted method, and sensitivity analyses to account for pleiotropy, in addition to excluding a potentially pleiotropic variant in the FUT2 gene for B12 levels.

resultsWe did not find evidence for a causal effect of maternal or fetal B12 levels on offspring birthweight. The results were consistent across the different methods. We found a positive causal effect of maternal folate levels on offspring birthweight [0.146 (0.065, 0.227), which corresponds to an increase in birthweight of 71 g per 1 standard deviation higher folate]. We found some evidence for a small inverse effect of fetal folate levels on their own birthweight [-0.051 (-0.100, -0.003)].

conclusionsOur results are consistent with evidence from randomized controlled trials that higher maternal folate levels increase offspring birthweight. We did not find evidence for a causal effect of B12 levels on offspring birthweight, suggesting previous observational studies may have been confounded.

Indexed as

Folic AcidVitamin B 12Birth WeightFemaleGenome-Wide Association StudyHumansMendelian Randomization AnalysisFolic AcidVitamin B 12birthweightfetal genetic effectfolateMaternal genetic effectMendelian randomizationvitamin B12

Identifiers

PMID33347560
PMCPMC7938507
OpenAlexW3116544929

What OpenQuestion holds

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Registered trials

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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.