University of Oulu

Justiina Ronkainen, Anni Heiskala, Florianne O.L. Vehmeijer, Estelle Lowry, Doretta Caramaschi, Guadalupe Estrada Gutierrez, Jonathan A. Heiss, Nadine Hummel, Elina Keikkala, Tuomas Kvist, Allison Kupsco, Phillip E. Melton, Giancarlo Pesce, Munawar H. Soomro, Marta Vives-Usano, Nour Baiz, Elisabeth Binder, Darina Czamara, Mònica Guxens, Sanna Mustaniemi, Stephanie J. London, Sebastian Rauschert, Marja Vääräsmäki, Martine Vrijheid, Anette-G. Ziegler, Isabella Annesi-Maesano, Mariona Bustamante, Rae-Chi Huang, Sandra Hummel, Allan C. Just, Eero Kajantie, Jari Lahti, Deborah Lawlor, Katri Räikkönen, Marjo-Riitta Järvelin, Janine F. Felix & Sylvain Sebert (2022) Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium, Epigenetics, 17:1, 19-31, DOI: 10.1080/15592294.2020.1864171

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

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Author: Ronkainen, Justiina1; Heiskala, Anni1; Vehmeijer, Florianne O. L.2,3;
Organizations: 1Univ Oulu, Ctr Life Course Hlth Res, Oulu 90114, Finland.
2Erasmus MC, Univ Med Ctr Rotterdam, Generat R Study Grp, Rotterdam, Netherlands.
3Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands.
4Queens Univ Belfast, Sch Nat & Built Environm, Belfast, Antrim, North Ireland.
5Univ Bristol, Bristol Med Sch, Med Res Council, Populat Hlth Sci,Integrat Epidemiol Unit, Bristol, Avon, England.
6Natl Inst Perinatol, Dept Immunobiochem, Mexico City, DF, Mexico.
7Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA.
8German Res Ctr Environm Hlth, Inst Diabet Res, Helmholtz Zentrum Munchen, Munich, Germany.
9Oulu Univ Hosp, PEDEGO Res Unit, Dept Obstet & Gynecol, MRC Oulu, Oulu, Finland.
10Univ Oulu, Oulu, Finland.
11Finnish Inst Hlth & Welf, Publ Hlth Promot Unit, Helsinki, Finland.
12Finnish Inst Hlth & Welf, Publ Hlth Promot Unit, Oulu, Finland.
13Univ Helsinki, Dept Psychol & Logoped, Fac Med, Helsinki, Finland.
14Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
15Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
16Curtin Univ, Sch Pharm & Biomed Sci, Fac Hlth Sci, Bentley, WA, Australia.
17Univ Western Australia, Fac Hlth & Med Sci, Sch Biomed Sci, Crawley, Australia.
18Sorbonne Univ, Inst Pierre Louis Epidemiol & Sante Publ IPLESP, Paris, France.
19Inst Pierre Louis Epidemiol & Sante Publ IPLESP, INSERM, Epidemiol Allerg & Resp Dis Dept EPAR, Team EPAR,UMR S 1136, Paris, France.
20Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain.
21CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain.
22Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.
23ISGlobal, Barcelona, Spain.
24Univ Pompeu Fabra UPF, Barcelona, Spain.
25Erasmus MC, Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands.
26NIEHS, NIH, Dept Hlth & Human Serv, Washington, DC USA.
27Univ Western Australia, Telethon Kids Inst, Perth, WA, Australia.
28Tech Univ Munich, Forschergruppe Diabet, Klinikum Rechts Isar, Munich, Germany.
29Forschergruppe Diabet eV, Helmholtz Zentrum Munchen, Munich, Germany.
30Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
31Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland.
32Univ Helsinki, Helsinki, Finland.
33Univ Turku, Turku Inst Adv Studies, Turku, Finland.
34Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
35Imperial Coll London, Sch Med, Dept Genom Common Dis, London, England.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.8 MB)
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Language: English
Published: Informa, 2022
Publish Date: 2021-11-23


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.

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Series: Epigenetics
ISSN: 1559-2294
ISSN-E: 1559-2308
ISSN-L: 1559-2294
Volume: 17
Issue: 1
Pages: 19 - 31
DOI: 10.1080/15592294.2020.1864171
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: 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 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 Juselius 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]. MVa 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].
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.