Prenatal and birth associations of epigenetic gestational age acceleration in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort

ABSTRACT

Gestational age (GA) is an important determinant of child health and disease risk. Two epigenetic GA clocks have been developed using DNA methylation (DNAm) patterns in cord blood. We investigate the accuracy of GA clocks and determinants of epigenetic GA acceleration (GAA), a biomarker of biological ageing. We hypothesize that prenatal and birth characteristics are associated with altered GAA, thereby disrupting foetal biological ageing. We examined 372 mother-child pairs from the Center for the Health Assessment of Mothers and Children of Salinas study of primarily Latino farmworkers in California. Chronological GA was robustly correlated with epigenetic GA (DNAm GA) estimated by the Knight (r = 0.48, p < 2.2x10⁻¹⁶) and Bohlin clocks (r = 0.67, p < 2.2x10⁻¹⁶) using the Illumina 450K array in cord blood samples collected at birth. GA clock performance was robust, though slightly lower, using DNAm profiles from the Illumina EPIC array in a smaller subsample (Knight: r = 0.39, p < 3.5x10⁻⁵; Bohlin: r = 0.60, p < 7.7x10⁻¹²). After adjusting for confounders, high maternal serum triglyceride levels (Bohlin: β = −0.01 days per mg/dL, p = 0.03), high maternal serum lipid levels (Bohlin: β = −4.31x10⁻³ days per mg/dL, p = 0.04), preterm delivery (Bohlin: β = −4.03 days, p = 9.64x10⁻⁴), greater maternal parity (Knight: β = −4.07 days, p = 0.01; Bohlin: β = −2.43 days, p = 0.01), and male infant sex (Knight: β = −3.15 days, p = 3.10x10⁻³) were associated with decreased GAA.Prenatal and birth characteristics affect GAA in newborns. Understanding factors that accelerate or delay biological ageing at birth may identify early-life targets for disease prevention and improve ageing across the life-course. Future research should test the impact of altered GAA on the long-term burden of age-related diseases.

KEYWORDS:

• Epigenetic clocks
• epigenetic age
• DNA methylation age
• cord blood
• gestational age
• age acceleration

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2022.2102846

Acknowledgments

We gratefully acknowledge CHAMACOS participants and staff.

Disclosure statement

The authors declare they have no actual or potential competing financial interests.

Authors’ contributions

SD analysed and visualized the data and drafted the manuscript. K Huen assisted with the design of the data analysis, performed laboratory epigenetics analyses, and edited the manuscript. LVDL and PAC helped with epigenetic data analysis and data management. JCN edited the manuscript. K Harley, JD, BE, and NH conceived the original study, supervised initial data and sample collection, and edited the manuscript. AC conceptualized the project, developed the data analysis plan, was involved in developing study methodology and funding acquisition, and edited the manuscript. All authors read and approved the final manuscript.

Availability of data and materials

Datasets generated and analysed during the current study are available from the corresponding authors with appropriate permission from the CHAMACOS study team and investigators upon reasonable request and institutional review board approval.

Ethics approval and consent to participate

The University of California, Berkeley Committee for the Protection of Human Subjects approved all study activities. Written informed consent was obtained from the CHAMACOS mothers.

Additional information

Funding

This work was supported by the National Institutes of Health (R03AG067064; R01ES031259; R01ES026994; 1R01ES021369; P01ES009605; R01ES017054; R01DA035300; R24ES028529 and R01MD016595) and by the Environmental Protection Agency (R82670901; RD83171001; and RD83451301);US Environmental Protection Agency [R82670901, RD83171001, RD83451301].