Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis
Year: 2022
Type: article
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.
Source: Clinical Epigenetics
Institutions: Erasmus MC, University Hospital Heidelberg, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Erasmus MC - Sophia Children’s Hospital, University of Bristol, MRC Integrative Epidemiology Unit, University of Exeter, Municipal Institute for Medical Research, Hospital del Mar Research Institute, Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari Sant Joan de Reus
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,190
Funders: Fundació la Marató de TV3, Wellcome Trust, Joint Programming Initiative A healthy diet for a healthy life, Deutscher Akademischer Austauschdienst, ZonMw, Generalitat de Catalunya, Dietmar Hopp Stiftung, Medical Research Council, Biotechnology and Biological Sciences Research Council, Instituto de Salud Carlos III, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Reproductive and cardio-metabolic health, Prenatal influences on childhood health: what role for mums and dads?, G2206155153, G2593619404, Does epigenetic methylation explain the gender-switch in adolescent asthma?, Born in Bradford (BiB): An international resource for exploring lifecourse determinants of health, development and social wellbeing., G3158803353, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., NutriPROGRAM: Early-life Nutritional Programming of Metabolic Health through Epigenetic Pathways, G4068037986, Accessible resource for integrated epigenomics studies (ARIES), G4314485874, G5185833053, Accessible resource for integrated epigenomics studies (ARIES), Epigenetic Epidemiology, Mendelian randomization to hypothesis-free causal inference, G7092457961, G7322992356, Epigenetic Pathways to Conduct Problem Trajectories: Early Environmental Risks, G929055435, G999822613
OpenAlex ID: W4225303634