Low birthweight is associated with epigenetic age acceleration in the first 3 years of life.

Background and objectives: The Developmental Origins of Health and Disease hypothesis posits that early life adversity is associated with poor adult health outcomes. Epidemiological evidence has supported this framework by linking low birthweight with adult health and mortality, but the mechanisms remain unclear. Accelerated epigenetic aging may be a pathway to connect early life experiences with adult health outcomes, based on associations of accelerated epigenetic aging with increased morbidity and mortality.

Methodology: Sixty-seven mother-infant dyads were recruited in the eastern Democratic Republic of Congo. Birthweight data were collected at birth, and blood samples were collected at birth and follow-up visits up to age 3. DNA methylation data were generated with the Illumina MethylationEPIC array and used to estimate epigenetic age. A multilevel model was used to test for associations between birthweight and epigenetic age acceleration.

Results: Chronological age was highly correlated with epigenetic age from birth to age 3 (r = 0.95, p < 2.2 × 10^-16). Variation in epigenetic age acceleration increased over time. Birthweight, dichotomized around 2500 g, predicted epigenetic age acceleration over the first 3 years of life (b = -0.39, p = 0.005).

Conclusions and implications: Our longitudinal analysis provides the first evidence for accelerated epigenetic aging that emerges between birth and age 3 and associates with low birthweight. These results suggest that early life experiences, such as low birthweight, may shape the trajectory of epigenetic aging in early childhood. Furthermore, accelerated epigenetic aging may be a pathway that links low birthweight and poor adult health outcomes.