Author(s): MARTÍNEZ-ROSALES, E., SÁNCHEZ-PARENTE, S., AMARO-GAHETE, F., ACOSTA-MANZANO, P., FLOR-ALEMANY, M., LÓPEZ-CÁNOVAS, J.L., BAENA-GARCÍA, L., APARICIO, V.A., Institution: UNIVERSITY OF GRANADA, Country: SPAIN, Abstract-ID: 2409

INTRODUCTION:
Klotho is an anti-aging protein with emerging roles in placental function, fetal growth, and neurodevelopment. Although lower Klotho concentrations have been linked to adverse pregnancy outcomes, it remains unclear whether placental Klotho is associated with health-related outcomes beyond birth. Given emerging evidence suggesting that maternal exercise may modulate placental α-Klotho expression, understanding its long-term associations is of particular interest. The aim of this study was to examine the association between placental α-Klotho and offspring health outcomes at birth and in early childhood.
METHODS:
This study was conducted within the GESTAFIT and GESTAFITOS trial. Pregnant women were allocated to a supervised, concurrent (aerobic and resistance) exercise program (3 days/week, 60 min/session, moderate-to-vigorous intensity) or to a control group from week 17 of gestation until delivery. At birth, placenta weight and placental α-Klotho concentrations were quantified. Offspring outcomes were assessed at two time points: at birth (anthropometry and cord blood gas parameters), and at approximately 4 years of age. The 4-year follow-up included anthropometry (e.g., waist circumference), body composition, cardiometabolic markers, physical fitness (handgrip strength, standing long jump, and cardiorespiratory fitness via the 20-meter shuttle run test), and cognitive function assessed with the Kaufman Brief Intelligence Test (K-BIT). Statistical analyses included Pearson correlations coefficients and multivariable linear regression models, which were adjusted for the child's age, sex, and maternal intervention group to identify independent associations.
RESULTS:
Ninety-six mother–child pairs were included at birth, and 55 children had complete data at the 4-year follow-up. Placental α-Klotho was not correlated with birth outcomes such as placenta weight and efficiency and, cord blood gas parameters. In crude models, placental α-Klotho was positively associated with waist circumference (r = 0.28, p < 0.05), handgrip strength (r = 0.37, p < 0.01), long jump (r = 0.32, p < 0.05) and all cognitive domains (p<0.05) at the 4-years follow-up. After adjustment for confounders, associations with anthropometric and fitness outcomes were no longer significant. In contrast, placental α-Klotho remained independently associated with K-BIT matrix scores (β = 4.80; 95% CI: 1.38 to 8.22; p = 0.016) and composite intelligence scores (β = 24.90; 95% CI: 4.97 to 44.82; p = 0.018).
CONCLUSION:
Higher placental α-Klotho concentrations were independently associated with better cognitive performance at 4 years of age, but not with physical growth or fitness, suggesting a potential role for placental α-Klotho in early neurodevelopment rather than general development. These findings suggest a potential role for placental α-Klotho in early neurodevelopment and support further investigation into exercise-related placental adaptations and their long-term implications for child development.