First trimester prenatal dexamethasone treatment is associated with alterations in brain structure at adult age.

Prenatal treatment of human disease is rare. Dexamethasone (DEX) is used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in an affected female fetus. The safety and long-term consequences of prenatal DEX exposure on the brain are largely unknown.We investigate if first trimester prenatal DEX treatment is associated with alterations in brain structure at adult age, and if these alterations are associated with DNA methylation, mood and cognitive abilities.T1-weighted and DWI scans, from a single research institute, are compared between 19 (9 females) first trimester DEX-treated individuals, at risk of CAH but not having CAH, and 43 (26 females) controls (age range16.0 - 26.4 years).DEX-treated subjects showed bilateral enlargement of the amygdala, increased surface area and volume of the left superior frontal gyrus, and wide-spread increased radial-, mean-, and axial diffusivity of white matter, in particular in the superior longitudinal fasciculi and corticospinal tracts. In the DEX-treated group, increased mean- and radial diffusivity correlated with increased methylation of the promotor region of the FKBP5 gene. There were no group differences in cognition or in scales assessing depression or anxiety, and the relationship between brain structure and cognition did not differ between DEX-treated and controls.First trimester prenatal DEX treatment is associated with structural alterations of the brain at adult age, with an accompanying change in gene methylation. The findings add to the safety concerns of prenatal DEX treatment in the context of CAH.

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