Hormone Research in Paediatrics
Research Article
Free Access
Rajagopalan V. · Overholtzer L.N. · Kim W.S. · Wisnowski J.L. · Pickering T.A. · Fraga N.R. · Javier J. · Mackintosh L. · Mirzaian C. ·
Geffner M.E. ·
Kim M.S.
Abstract
Introduction: Patients with classical congenital adrenal hyperplasia (CAH) have prenatal and postnatal hormonal imbalances. To characterize the ontogeny of reported brain and behavior changes in older children with CAH, we aimed to study brain structure in infants with CAH compared to healthy controls.
Methods: We performed neuroimaging in 16 infants with classical CAH due to 21-hydroxylase deficiency [8 males, gestational age 38.2 ± 1.7 weeks, post-conceptional age (PCA) 42.2 ± 3.0 weeks] and 14 control infants (9 males, gestational age 38.5 ± 1.8 weeks, PCA 42.5 ± 2.4 weeks) utilizing 3-Tesla magnetic resonance imaging. Regional brain volumes were adjusted for PCA and sex, along with an additional adjustment for total brain volume (TBV), for group comparisons by regression analyses [mean, 95% confidence interval (CI)]. The degree to which each brain region was differentiated between CAH and control infants was examined by relaimpo analyses, adjusting for all other brain regions, PCA, and sex.
Results: Infants with CAH had significantly smaller thalamic volumes [8606 mm3, 95% CI (8209, 9002)] compared to age-matched control infants [9215 mm3, 95% CI (8783, 9647); β = -609; p = 0.02], which remained smaller after further adjustment for TBV. Upon further adjustment for TBV, the temporal lobe was larger in infants with CAH [66817 mm3, CI (65957, 67677)] compared to controls [65616 mm3, CI (64680, 66551); β = 1202, p = 0.03]. The brain regions most differentiated between CAH vs controls were the thalamus (22%) and parietal lobe (10%).
Conclusions: Infants with CAH exhibit smaller thalamic regions from early life, suggesting a prenatal influence on brain development in CAH. Thalamic emergence at 8-14 weeks makes the region particularly vulnerable to changes in the intrauterine environment, with potential implications for later maturing brain regions. These changes may take time to manifest, meriting longitudinal study through adolescence in CAH.
S. Karger AG, Basel
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