Prenatal stress and its relationship with inflammaging and cognitive performance in young adulthood

Prenatal stress has adverse effects on the offspring, which may be driven by inflammatory pathways. However, it is not clear whether prenatal stress might have time-specific effects on epigenetic signatures of chronic low-grade inflammation, accelerated epigenetic aging, and cognition in young adulthood. A follow-up of the ELSPAC prenatal birth cohort (n = 178) revealed that early prenatal stress (GW 1–20) was associated with chronic low-grade inflammation, premature epigenetic aging (GrimAge), and faster pace of aging (DunedinPACE) in young adulthood independently of sex, chronological age, BMI, cigarette smoking, recent stress, birth weight, maternal education, and later prenatal stress (GW 20–40). Moreover, the epigenetic inflammatory scores mediated the relationship between early prenatal stress and premature aging (GrimAge), as well as accelerated pace of aging (DunedinPACE). Importantly, faster pace of aging (DunedinPACE) mediated the relationship between early prenatal stress and lower IQ, suggesting early prenatal stress has long-term effects on inflammation, aging, and cognition.