Background/Objectives: Fetal growth restriction (FGR) represents a model of adverse intrauterine programming associated with an increased risk of cardiometabolic disorders later in life. We examined the relationships between birth weight, catch-up growth, adipokine signaling, and early cardiometabolic risk in adolescents. Methods: This cross-sectional study included 80 term-born adolescents (40 FGR, 40 controls) matched for age and sex. Anthropometry, blood pressure, lipid profile, fasting glucose, adipokines (leptin, adiponectin), and ghrelin levels were assessed. Associations between birth weight, growth rate, adipokines, and cardiometabolic outcomes were analyzed. Results: Birth weight was not associated with adiposity, lipid profile, blood pressure, or glycemic status (p > 0.05). In contrast, catch-up growth in the FGR group was correlated with increased BMI (ρ = 0.680, p < 0.001), central adiposity (ρ = 0.714, p < 0.001), systolic blood pressure (ρ = 0.448, p = 0.0037) and diastolic blood pressure (ρ = 0.325, p = 0.0409). Mediation analyses showed that the current BMI largely explains the associations between catch-up growth and cardiometabolic risk, systolic blood pressure, and waist circumference (β = 2.832 kg/m2 per 1-unit increase in ΔZ; p < 0.001). The hypertensive effect of catch-up growth was amplified in overweight/obese adolescents (β = 8.13 mmHg; p = 0.006). Catch-up growth was independently associated with higher leptin (β = 220 ng/L; p = 0.022) and a higher leptin/ghrelin ratio (β = 2.330; p = 0.034). Conclusions: Postnatal growth acceleration, rather than fetal size alone, drives early cardiometabolic susceptibility following FGR through adiposity-mediated and endocrine pathways.
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