Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the Pregnancy And Childhood Epigenetics Consortium

Justiina Ronkainen, Anni Heiskala, Florianne O.L. Vehmeijer, Estelle Lowry, Doretta Caramaschi, Guadalupe Estrada Gutiérrez, 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 MustaniemiStephanie 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

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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-analysed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 child and 1,962 adolescent whole-blood samples derived from ten cohorts. DNA methylation was measured using Illumina Infinium Methylation450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for 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.
Original languageEnglish
Early online date17 Dec 2020
Publication statusEarly online date - 17 Dec 2020


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