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 ß = -0.01 days per mg/dL, p = 0.03), high maternal serum lipid levels (Bohlin ß = -4.31x10-3 days per mg/dL, p = 0.04), preterm delivery (Bohlin ß = -4.03 days, p = 9.64x10-4), greater maternal parity (Knight ß = -4.07 days, p = 0.01; Bohlin ß = -2.43 days, p = 0.01), and male infant sex (Knight ß = -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.