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Cited by 14Epigenetics and DNA MethylationBirth, Development, and HealthIron Metabolism and Disorders

Maternal Iron Status in Early Pregnancy and DNA Methylation in Offspring: An Epigenome-Wide Meta-Analysis

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Taeubert, M. J., de Prado-Bert, P., Geurtsen, M. L., Mancano, G., Vermeulen, M. J., Reiss, I. K. M., Caramaschi, D., Sunyer, J. +4 more·2022·Clinical Epigenetics
DOI 10.1186/s13148-022-01276-wPMC PMC9066980
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Abstract

Background: Unbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother–newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation. Results: Maternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs. Conclusion: Maternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

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  • Both iron deficiency and excess disrupt iron homeostasis, leading to altered erythropoiesis, placental dysfunction, oxidative stress, ferroptosis, and epigenetic modifications that can program offspring susceptibility to neurodevelopmental disorders and metabolic disease.

    “Both deficiency and excess disrupt iron homeostasis, leading to altered erythropoiesis, placental dysfunction, oxidative stress, ferroptosis, and epigenetic modifications that can program offspring susceptibility to neurodevelopmental disorders and metabolic disease [99,100,101,108].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [108]

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  • An association between higher early-pregnancy ferritin concentrations and lower cord blood DNA methylation at three CpGs was found to be long-lasting, remaining partially evident in older children.

    “Finally, an association between higher early-pregnancy ferritin concentrations and lower cord blood DNA methylation at three CpGs was found to be long-lasting, remaining partially evident in older children [107,108].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [108]

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Authors
Taeubert, M. J., de Prado-Bert, P., Geurtsen, M. L., Mancano, G., Vermeulen, M. J., Reiss, I. K. M., Caramaschi, D., Sunyer, J., Sharp, G. C., Julvez, J., Muckenthaler, M. U., & Felix, J. F.
Affiliations
  • Erasmus MC (NL)
  • University of Bristol (GB)
  • University of Exeter (GB)
  • Universitat Pompeu Fabra (ES)
  • University Hospital Heidelberg (DE)
Corresponding author
Felix, J. F.
ORCID
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2022-05-03
Volume
14
Issue
1
Pages
59-59
ISSN
  • 1868-7075 (ISSN-L)
  • 1868-7083
DOI
10.1186/s13148-022-01276-w
PMC
PMC9066980
OpenAlex
W4225303634
Cited by
14
References
7
Citations by year
2026: 1 · 2025: 4 · 2024: 4 · 2023: 5
FWCI
0.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Epigenetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • Explore Bristol Research (publishedVersion, cc-by)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Figshare (submittedVersion, cc-by)
  • Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
  • Figshare (cc-by)
Funders
  • Wellcome Trust (217065/Z/19/Z)
  • UK Medical Research Council Integrative Epidemiology Unit and the University of Bristol (MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8, MC_UU_00011/1, MC_UU_00011/5, MC_UU_00011/6)
  • Medical Research Council (MR/S009310/1)
  • Joint Programming Initiative A healthy diet for a healthy life (MR/S036520/1, no.529051022, no.529051023)
  • Biotechnology and Biological Sciences Research Council (BB/I025751/1, BB/I025263/1)
  • United States National Institute of Health (5RO1AI121226-02)
  • National Institute of Child and Human Development (R01HD068437)
  • Netherlands Consortium for Healthy Aging (050-060-810)
  • European Union’s Horizon 2020 research and innovation programme (733206 (LifeCycle), 874739 (LongITools), 824989 (EUCAN-Connect))
  • Deutscher Akademischer Austauschdienst
  • Dietmar Hopp Stiftung
  • Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CPII19/00015)
  • Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615, MS13/00054, CP18/00018)
  • Generalitat de Catalunya (CIRIT 1999SGR 00241)
  • Fundació la Marató de TV3 (090430)
  • EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy)
  • European Research Council (268479-BREATHE: BRain dEvelopment, Air polluTion ultrafine particles in scHool childrEn)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
maternal iron status, serum ferritin, early pregnancy, cord blood DNA methylation, CpG methylation, maternal micronutrient status, offspring health, epigenome-wide association study
MeSH terms
Epigenome, Adolescent, Child, Female, Ferritins, Humans, Infant, Newborn, Iron, Pregnancy, Prospective Studies, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study

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