Early origins of metabolic and overall health in young adults: An outcome-wide analysis in a general cohort population.

Introduction: Long-term consequences of impaired fetal growth are well documented for cardiometabolic outcomes. We propose an outcome-wide analysis of the association between birth weight (BW) and long-term health in a large contemporary adult cohort.

Methods: The study included 73,315 participants under 60 years with a reliable BW from the French nationwide Constances cohort. Low and high BW (LBW/HBW) were defined as BW<10th and >90th of sex-specific percentiles. Associations between BW and outcomes were analyzed with a sex-stratified modified Poisson regression adjusted for the participant's age, maternal health history, geographical origins, and parents' occupation.

Results: Mean BW (10 -90 percentile) was 3390 g (2800-4000) for men and 3247g (2680-3820) for women. In men, LBW was associated with (RR [CI95]): fasting glucose impairment (1.33 [1.16;1.52]); hypertriglyceridemia (1.27 [1.17;1.37]); high blood pressure (HBP) (1.15 [1.07;1.24]); non-alcoholic fatty liver disease NAFLD (1.13 [1.02;1.24]); high LDL-cholesterol (1.12 [1.05;1.21]); anxiety (1.12 [1.01;1.24]) and depression (1.09 [1.00;1.18]). HBW was associated with obesity (1.21 [1.08;1.35]). In women, LBW was associated with fasting glucose impairment (1.31 [1.12;1.54]); HBP (1.27 [1.16;1.4]); hypertriglyceridemia (1.20 [1.05;1.36]); anxiety (1.10 [1.03;1.17]); and asthma (1.09 [1;1.19}). HBW was associated with obesity (1.24 [1.13;1.36]) and NAFLD (1.20 [1.06;1.37). LBW and HBW were associated with a lesser likelihood of tertiary education attainment in both sexes. Participants' education level was a significant partial mediator of the association between LBW and outcomes.

Conclusion: Extreme BW is associated with long-term health. It should be considered in the personalized prevention of cardiometabolic, respiratory, and mental health conditions in adulthood, especially in socio-economically disadvantaged populations.