Epigenetic age and pregnancy outcomes: GrimAge acceleration is associated with shorter gestational length and lower birthweight

Background: Advanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight. Results: The sample consisted of 77 women from the Los Angeles, CA, area enrolled in the Healthy Babies Before Birth study. Whole blood samples for DNA methylation assay were obtained during the second trimester (15.6 ± 2.15 weeks gestation). Epigenetic age indices GrimAge acceleration (GrimAgeAccel), DNAm PAI-1, DNAm ADM, and DNAm cystatin C were calculated. Gestational length and birthweight were obtained from medical chart review. Covariates were maternal sociodemographic variables, gestational age at blood sample collection, and pre-pregnancy body mass index. In separate covariate-adjusted linear regression models, higher early second trimester GrimAgeAccel, b(SE) = -.171 (.056), p =.004; DNAm PAI-1, b(SE) = - 1.95 × 10-4 (8.5 × 10-5), p =.004; DNAm ADM, b(SE) = -.033 (.011), p =.003; and DNAm cystatin C, b(SE) = 2.10 × 10-5 (8.0 × 10-5), p =.012, were each associated with shorter gestational length. Higher GrimAgeAccel, b(SE) = - 75.2 (19.7), p <.001; DNAm PAI-1, b(SE) = -.079(.031), p =.013; DNAm ADM, b(SE) = - 13.8 (3.87), p =.001; and DNAm cystatin C, b(SE) = -.010 (.003), p =.001, were also associated with lower birthweight, independent of gestational length. Discussion: Higher maternal prenatal GrimAgeAccel, DNAm PAI-1, DNAm ADM, and DNAm cystatin C were associated with shorter gestational length and lower birthweight. These findings suggest that biological age, as measured by these epigenetic indices, could indicate risk for adverse pregnancy outcomes.