SUN-159 - Early-Life Growth Trajectories and the Emergence of the PCOS Phenotype: A Longitudinal Case-Control Study

Introduction: Distinct developmental trajectories are recognized as critical determinants of cardiometabolic risk. The aim of this study was to examine the role of early-life determinants, specifically birth weight (BW), age at adiposity rebound (AR), and longitudinal BMI trajectories, in the pathogenesis of polycystic ovary syndrome (PCOS).

Methods: Consecutive adolescent patients and controls were recruited from a tertiary university hospital (Ethical Approval Protocol Number: 679/10-07-2025). To investigate potential non-linear associations between fetal growth and PCOS risk, logistic regression models with restricted cubic splines (RCS) were fitted using internal BW Z-scores (155 cases, 480 controls). Age at AR was estimated via cubic polynomial mixed-effects models and compared between cases and controls using linear regression models (103 cases, 330 controls). Finally, a linear mixed-effects model (LMM) compared WHO-standardized BMI Z-scores at birth, 5–6, 9–11, and 15–18 years to evaluate growth velocity between groups (346 cases, 764 controls).

Results: Wald statistics confirmed a significant non-linear, U-shaped association between BW Z-scores and PCOS diagnosis (p=0.036), indicating increased risk at both extremes of fetal growth. In unadjusted models, the PCOS group reached AR significantly earlier than controls (mean difference: -0.42 years; p< 0.01). However, after adjusting for BMI Z-score at age 5–6 years, this effect was substantially attenuated (mean difference: -0.20 years; p=0.22), suggesting AR timing was dependent on absolute childhood adiposity. LMM results showed that while mean BMI Z-scores were similar at birth (p=0.83), the PCOS group exhibited significantly higher BMI Z-scores at all subsequent time points (all p< 0.01). Interaction contrasts revealed that the magnitude of BMI Z-score change differed significantly between groups only during the birth to 5–6 year interval (p < 0.01), with future PCOS cases experiencing accelerated weight gain during this specific window.

Conclusions: Fetal growth extremes and rapid BMI acceleration during early childhood represent distinct developmental risk factors for PCOS. Earlier AR in PCOS patients appears to be a manifestation of accelerated early-childhood weight gain rather than an independent risk factor. These findings underscore intrauterine life and the first six years of life as the critical developmental windows for the emerging PCOS phenotype.

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