Objective: Congenital Adrenal Hyperplasia (CAH) requires life-long replacement of cortisol. Female fetuses with classical CAH are virilized, which can be prevented by prenatal dexamethasone (DEX) treatment from gestational week 7. However, 7 out of 8 fetuses are treated unnecessarily during fetal life and are thus exposed to high prenatal glucocorticoid (GC) levels. Both prenatal exposures to high GC levels, as well as long term postnatal GC-treatment in patients with CAH are expected to affect brain development, predisposing individuals to impairments in cognition. The present study addresses effects of postnatal GC therapy in CAH, and first trimester prenatal DEX treatment in non-CAH subjects on brain structure of young adults.
Methods: 37 CAH (21 female), 43 Controls (26 female), and 19 DEX-treated non-CAH subjects (9 female), aged 1633 years, underwent MRI scanning at 3T. T1 structural images were analyzed using FreeSurfer software, obtaining estimates of neocortical volume, surface area and thickness and subcortical volumes of atlas-based regions of interest. ANOVAs were employed to assess group differences between CAH and Controls, and between DEX-treated subjects and Controls. Gender effects were estimated with an interaction between sex and group (CAH or DEX). Results were corrected for multiple comparisons (FDR). Age, total brain volume and sex were used as co-variates.
Results: CAH subjects had reduced cortical thickness of areas involved in executive function (left middle frontal gyrus) and sensory integration (right superior occipital sulcus, left intraparietal sulcus), in addition to alterations of cortical volume in areas involved in language (left superior temporal planum polare) and language-based cognitive control (left inferior frontal orbital gyrus, H-shaped sulcus). These areas include mostly left-lateralized fronto-parietal loops that are heavily involved in verbal working memory. DEX-treated subjects had increased volumes of the bilateral amygdala, a key region of the limbic system. There were no interactions with sex.
Conclusion: The present study is the first to show an effect of prenatal DEX treatment on brain structure in individuals not having CAH and exposed to DEX during early fetal life, thus proving the existence of fetal programming effects of prenatal GC treatment. In addition, we show that long-term glucocorticoid treatment affects brain structures of working memory networks in patients with CAH. Our results provide a basis for reconsidering the cost/benefit balance of prenatal DEX treatment and stress the importance of optimizing GC treatment for CAH.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology