Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium

• Type of Material: Article
• Authors: Justina Ronkainen, University of Oulu; Anni Heiskala, University of Oulu; Florianne OL Vehmeijer, University Medical Center Rotterdam; Estelle Lowry, University of Oulu; Doretta Caramaschi, University of Bristol; Guadalupe Estrada Gutierrez, National Institute of Perinatology; Jonathan A Heiss, Icahn School of Medicine at Mount Sinai; Nadine Hummel, German Research Center for Environmental Health; Elina Keikkala, Oulu University Hospital; Tuomas Kvist, University of Helsinki; Allison Kupsco, Columbia University; Philip E Melton, Curtin University; Giancarlo Pesce, Sorbonne Universite; Munawar H Soomro, Sorbonne Universite; Marta Vives-Usano, Barcelona Institute of Science & Technology; Nour Baiz, Sorbonne Universite; Elisabeth Binder, Emory University; Darina Czamara, Max-Planck-Institute of Psychiatry; Mònica Guxens, CIBER Epidemiol & Salud Publ CIBERESP; Sanna Mustaniemi, Oulu University Hospital; Stephanie J London, National Institute of Environmental Health Sciences; Sebastian Rauschert, University of Western Australia; Marja Vääräsmäki, Oulu University Hospital; Martine Vrijheid, CIBER Epidemiología Y Salud Pública (CIBERESP); Anette-G Ziegler, Institute of Diabetes Research, Helmholtz Zentrum München; Isabella Annesi-Maesano, Sorbonne Université; Mariona Bustamante, CIBER Epidemiología Y Salud Pública (CIBERESP); Rae-Chi Huang, University of Western Australia; Sandra Hummel, Institute of Diabetes Research, Helmholtz Zentrum München; Allan C Just, Icahn School of Medicine at Mount Sinai; Eero Kajantie, Oulu University Hospital; Jari Lahti, University of Helsinki; Deborah Lawlor, University of Bristol; Katri Räikkönen, University of Helsinki; Marjo-Riitta Jarvelin, University of Oulu; Janine F Felix, University Medical Center Rotterdam; Sylvain Sebert, University of Oulu
• Language: English
• Date: 2021-01-12
• Publisher: TAYLOR & FRANCIS INC
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/15592294.2020.1864171
• Title of Journal or Parent Work: EPIGENETICS
• Volume: 17
• Issue: 1
• Start Page: 19
• End Page: 31
• Grant/Funding Information: Study-specific funding information can be found in the Supplementary Methods. JR, AH, EL, and SS were supported by the European Union’s Horizon 2020 research and innovation program [grant numbers 633595 (DynaHEALTH) and 733206 (LifeCycle)], Academy of Finland [grant number 285547 (EGEA)] and the Biocenter Oulu. ACJ was funded by the National Institute of Environmental Health Sciences [grant number R00ES023450]. AK was supported by the National Institute of Environmental Health Sciences [grant number R01ES021357]. DCa was funded by the UK Medical Research Council [grant number MC_UU_00011/7]. EKa received funding from the Horizon2020 grant for RECAP Research on Children and Adults Born Preterm [grant number 733280], Academy of Finland [grant number 315690], Foundation for Pediatric Research, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation and Sigrid Jusélius Foundation. EKe received funding from the Finnish Medical Association. MG was supported by Miguel Servet fellowship from the Institute of Health Carlos III [grant numbers MS13/00054, CP18/00018]. MVä received funding from the Research Funds of Oulu University Hospital, Juho Vainio Foundation and Signe and Ane Gyllenberg Foundation. RCH was supported by the National Health and Medical Research Council Fellowship Grants [grant number 1053384]. SJL was supported by the intramural research program of the National Institutes of Health, National Institute of Environmental Health Sciences. SM received funding from the University of Oulu Graduate School. SR was supported by National Health and Medical Research Council EU [grant number 1142858] and the Department of Health, Western Australia FutureHealth fund in connection with the European Union’s Horizon 2020 [grant number 733206].
• Keywords: DISCOVERY; ASSOCIATION; Maternal haemoglobin; Science & Technology; DNA methylation; DESIGN; pregnancy; developmental programming; Genetics & Heredity; Biochemistry & Molecular Biology; BIRTH; Life Sciences & Biomedicine; HYPOXIA
• Research Categories: Health Sciences, Public Health; Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology; Health Sciences, Obstetrics and Gynecology

Abstract

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.