Background: Epigenetic age is one of the most accurate estimators of chronological age. However, the majority of epigenetic aging studies focus on adult aging and age-related disease, leaving a significant gap in research for pediatric populations. The offspring epigenome has been shown to be exquisitely sensitive to a broad range of maternal biopsychosocial factors, in utero. However, the extent to which these exposures effect biological aging remains unknown.
Method: DNA methylation was measured using buccal swabs taken from of 258 one year old participants of the Australian Temperament Project cohort (Generation 3). Estimates of epigenetic age (measured in years) were generated using the recently developed Pediatric-Buccal-Epigenetic (PedBE) clock algorithm (derived from 0–20-year old’s), as well as the popular multi-tissue derived Horvath clock. We tested for associations between offspring epigenetic aging and maternal mental health, substance use, and general health assessed during trimester three.
Results: After adjusting for maternal age, maternal smoking (where applicable), child sex, cell proportions and batch, higher dyadic adjustment score was associated with accelerated PedBE (b=0.19, p=0.006). Higher depression (b=-0.01, p=0.044), anxiety (b=-0.04, p=0.004), and stress (b=-0.02, p=0.037) were all associated with a slight deceleration of PedBE. Alcohol use shortly after pregnancy awareness was associated with accelerated Horvath epigenetic age (b=0.22, p=0.038), and high blood pressure during pregnancy with decelerated Horvath epigenetic age (b=-0.30, p=0.020). Smoking in the third trimester showed an acceleration in both clocks (PedBE: b=0.17, p=0.031, and Horvath: b=0.31, p=0.004). Cannabis use during third trimester also showed associated acceleration, but lost significance when adjusting for smoking.
Conclusion: Findings suggest that a broad range of biopsychosocial factors during pregnancy may impact the offspring’s epigenetic age, however further research needs to be done to replicate these findings, ascertain whether effects remain over time, and if differences are associated with measures of childhood development.