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Clin Epigenetics. 2017 May 8;9:49. doi: 10.1186/s13148-017-0349-z. eCollection 2017.

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

Author information

1
Institute of Behavioral Sciences, University of Helsinki, Helsinki, 00014 Finland.
2
Helsinki Collegium of Advanced Studies, University of Helsinki, Helsinki, 00014 Finland.
3
Department of Translational Research in Psychiatry, Department of Psychiatry and Behavioral Sciences, Max-Planck Institute of Psychiatry, Munich, 80804 Germany.
4
Genetics and Molecular Biology Program, Emory University, Atlanta, 30322 GA USA.
5
Centre for Molecular Medicine and Therapeutics, BC Children's Hospital and University of British Columbia, Vancouver, V6T 1Z4 Canada.
6
HUSLAB and Department of Clinical Chemistry, Helsinki University Hospital, Helsinki, 00029 Finland.
7
National Institute for Health and Welfare, Helsinki and Oulu, Helsinki, 00271 Finland.
8
Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, 00029 Finland.
9
Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital Helsinki, Helsinki, 00029 Finland.
10
Medical and Clinical Genetics and Institute for Molecular Medicine Finland, University of Helsinki and Helsinki University Hospital, Helsinki, 00014 Finland.
11
BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ UK.
12
Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, 30322 GA USA.
13
Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA USA.
14
Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, 30322 GA USA.

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.

KEYWORDS:

Aging; Cord blood methylation; Epigenetic clock; Gestational age; Prenatal programming

PMID:
28503212
PMCID:
PMC5422977
DOI:
10.1186/s13148-017-0349-z
[Indexed for MEDLINE]
Free PMC Article

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