Longitudinal Epigenetic Aging in Pregnancy and Associations With Adverse Outcomes
Danielle M Panelli1, Nicole Gladish, Nicola C Perlman
1Division of Maternal-Fetal Medicine and Obstetrics, Department of Obstetrics and Gynecology, the Department of Epidemiology and Population Health, and the Department of Psychology, Stanford University, Stanford, California.
Obstetrics and Gynecology
|July 10, 2025
Summary
Pregnancy significantly accelerates epigenetic aging, with some women aging up to 5.3 years biologically. Higher first-trimester epigenetic age, not chronological age, is linked to pregnancy complications, suggesting epigenetic clocks may indicate pregnancy health.
Area of Science:
- Epigenetics
- Molecular Biology
- Reproductive Health
Background:
- Epigenetic aging, measured by DNA methylation clocks, offers a molecular insight into biological aging.
- Understanding how pregnancy influences epigenetic aging is crucial for assessing maternal health.
Purpose of the Study:
- To investigate the relationship between pregnancy and epigenetic aging using DNA methylation clocks.
- To determine if epigenetic age in early pregnancy is associated with adverse pregnancy outcomes.
Main Methods:
- Prospective cohort study of nulliparous women (pregnant and nonpregnant).
- Blood samples collected at enrollment and postpartum/7 months later.
- Epigenetic age assessed using 11 established DNA methylation clocks.
- Within-person epigenetic age changes compared using mixed-effects models.
- Association between first-trimester epigenetic age and pregnancy complications analyzed via logistic regression.
Main Results:
- Pregnant women showed significant epigenetic age acceleration compared to nonpregnant women across six epigenetic clocks.
- Epigenetic age acceleration per 200 days ranged from 1.58 to 5.28 years.
- Each year increase in first-trimester GrimAge2 was associated with a 36% increased odds of pregnancy complications.
- Chronological age was not associated with pregnancy complications.
Conclusions:
- Pregnancy accelerates within-person epigenetic aging, with potential acceleration up to 5.3 years.
- First-trimester epigenetic age, specifically GrimAge2, is a potential biomarker for pregnancy complications.
- These findings highlight gestation's influence on biological aging and support epigenetic age as a marker for pregnancy health.
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