The long-term associations of perinatal obesogenic environment with offspring biological aging.

Biological age (BA), reflecting aging-related health decline beyond chronological age, varies among individuals. While previous research explored associations of maternal pregnancy-related body size with offspring health outcomes, its implications for BA in young adults remain unclear. Utilizing longitudinal data of 1148 mother-offspring pairs from the Jerusalem Perinatal Study, we analyzed associations of maternal prepregnancy BMI and gestational weight gain (GWG) with offspring using the Klemera-Doubal method (KDM)-based BA at age 32 and potential familial life-course underlying mechanisms. Maternal pregnancy-related body size, adjusted for sociodemographic/lifestyle factors was associated with offspring BA (βmaternal prepregnancy BMI = 0.183; 95% CI, 0.098-0.267; βGWG = 0.093; 95% CI, 0.021-0.165). Association of GWG with BA was largely direct (90%; 95% CI, 44%-100%), while association with maternal prepregnancy BMI was partially mediated through adolescent BMI (36%; 95% CI, 18%-75%), with both associations eliminated after adjustment for offspring adult BMI. Associations persisted after adjusting for offspring polygenic risk score for BMI (βmaternal prepregnancy BMI = 0.128; 95% CI, 0.023-0.234; βGWG = 0.102; 95% CI, 0.006-0.198), and somewhat altered after adjustment for maternal cardiometabolic conditions (βmaternal prepregnancy BMI = 0.144; 95% CI, 0.059-0.230). Impact on GWG associations was negligible. Thus, perinatal obesogenic environment contributes to offspring BA beyond sociodemographic factors and maternal cardiometabolic history, yet intergenerational transmission of obesity seems to underlie these associations. Nonetheless, the period between adolescence and young adulthood could be targeted for weight-reducing interventions, ultimately promoting healthy aging.