Abstract
Results of studies examining hippocampal subfield development and age-related differences are conflicting. This study aimed to investigate age- and sex-related volumetric differences and asymmetry in hippocampal subfields in childhood and adolescence. In this retrospective study, we included 443 individuals (200 females) with normal radiological anatomy between the ages of 2 and 18 years who had a brain MRI between 2012 and 2023. We obtained absolute and relative volumes of CA1-3, CA4-DG, and subiculum with Kulaga-Yoskovitz segmentation of volBrain HIPS in 3D-T1-weighted MRIs. We compared the volumetric data of developmental periods with SPSS (ver.28). Total hippocampal volume was consistent with quadratic models in females and sigmoid (absolute) and inverse (relative) models in males. CA1-3 showed age-related differences best characterized by sigmoid, CA4-DG by cubic and quadratic, and subiculum by cubic and power models. Total hippocampus and CA1-3 volumes were significantly smaller in the toddler period than in other periods (p < 0.05). While the absolute volume of the Subiculum increased significantly in all developmental periods, its relative volume increased significantly only in adolescence. CA4-DG relative volume did not differ between developmental periods (p > 0.05). In absolute volume, hippocampal structures differed between the sexes, but only CA4-DG had sexual dimorphism in relative volume (p < 0.05). In the 2–18 age group, the subiculum had left > right asymmetry, while other hippocampal subfields were lateralized to the right. This study demonstrated that hippocampal subfields exhibited heterogeneity in terms of age-related differences, with the subiculum being more sensitive to age-related factors, and CA4-DG showed a proportional increase with brain development.