Maternal CDKAL1 polygenic risk and offspring growth trajectories beyond gestational diabetes.

Saad, Khaled; Aly, Shimaa Elwardany; Elhoufey, Amira; Hussein, Wesam M; Temsah, Mohamad-Hani; Ahmad, Ahmad Roshdy; Elfarargy, Mohamed Shawky; Mahmoud, Rasha Refaat · Pediatr Res · 2026

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Abstract

Maternal CDKAL1 polygenic risk scores identify offspring at increased risk for divergent growth trajectories, persistent lean and obesity phenotypes, through pathways independent of clinically diagnosed gestational diabetes. Findings reinforce the thrifty genotype hypothesis, suggesting a context-dependent metabolic programming in which maternal genetic variation influences fetal growth adaptation to intrauterine nutrient availability. Integration of maternal genetic risk assessment into prenatal screening may enable earlier identification of children at risk for adverse growth patterns, facilitating targeted monitoring and personalized preventive strategies.