Associations between maternal risk factors of adverse pregnancy and birth outcomes and the offspring epigenetic clock of gestational age at birth

• Type of Material: Article
• Authors: Polina Girchenko, Helsingin Yliopisto; Jari Lahti, Helsingin Yliopisto; Darina Czamara, Max Planck Institut fur Psychiatrie; Anna K. Knight, Emory University; Meaghan J. Jones, The University of British Columbia; Anna Suarez, Helsingin Yliopisto; Esa Hämäläinen, Helsinki University Central Hospital; Eero Kajantie, National Institute for Health and Welfare; Hannele Laivuori, Helsinki University Central Hospital; Pia M. Villa, Helsinki University Central Hospital; Rebecca M. Reynolds, University of Edinburgh; Michael S. Kobor, The University of British Columbia; Alicia Smith, Emory University; Elisabeth Binder, Emory University; Katri Räikkönen, Helsingin Yliopisto
• Language: English
• Date: 2017-05-08
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2017, The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13148-017-0349-z
• Title of Journal or Parent Work: Clinical Epigenetics
• ISSN: 1868-7075
• Volume: 9
• Issue: 1
• Grant/Funding Information: This work was supported by the Academy of Finland, EVO (a special state subsidy for health science research), and University of Helsinki Research Funds.
• Keywords: Epigenetic clock; Prenatal programming; Cord blood methylation; Gestational age; Aging
• Research Categories: Biology, Molecular; Health Sciences, Obstetrics and Gynecology

Abstract

Background: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results: DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjögren’s syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions: Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.