Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis.

The Generation R Study Group, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Department of Pediatric Oncology, Hematology and Immunology, University Medical Center Heidelberg, Heidelberg, Germany. ISGlobal, Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Department of Pediatrics, Sophia's Children's Hospital, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. Bristol Medical School Population Health Sciences, University of Bristol, Bristol, UK. College of Life and Environmental Sciences, Psychology, University of Exeter, Exeter, UK. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. School of Oral and Dental Sciences, University of Bristol, Bristol, UK. Institut d'Investigació Sanitària Pere Virgili, Hospital Universitari Sant Joan de Reus, Reus, Spain. The Generation R Study Group, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. j.felix@erasmusmc.nl. Department of Pediatrics, Sophia's Children's Hospital, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. j.felix@erasmusmc.nl.

Clinical epigenetics. 2022;(1):59
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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.

Methodological quality

Publication Type : Meta-Analysis

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