Cumulative risks predict epigenetic age in adult survivors of extremely low birth weight.

Long‐term sequelae of extremely low birth weight (ELBW; ≤1000 g) may contribute to accelerated biological aging. This hypothesis was examined by analyzing a range of risk factors with a molecular age marker in adults born at ELBW or normal birth weight (NBW; ≥2500 g). DNAm age—the weighted average of DNA methylation at 353 cytosine–phosphate–guanine (CpG) sites from across the genome—was derived from a sample of 45 ELBW (Mage = 32.35 years) and 47 NBW control (Mage = 32.44 years) adults, using the Illumina 850k BeadChip Array. At two assessments undertaken 9 years apart (at 23 and 32 years), cumulative risks were summed from six domains with potential to affect physiological and psychological health: resting respiratory sinus arrhythmia, blood pressure, basal cortisol, grip strength, body mass index, and self‐esteem. At age 32 years, cumulative risks were differentially associated with epigenetic age in ELBW survivors (interaction, p < 0.01). For each additional risk factor they possessed, ELBW survivors (B = 1.43) were biologically 2.16 years older than NBW adults (B = –0.73), by the fourth decade of life. Developmental change, epigenetic maintenance, and intervention targets are discussed. [ABSTRACT FROM AUTHOR]