First-trimester prenatal dexamethasone may alter brain structure at adult age

Prenatal treatment with dexamethasone (DEX) at first trimester appears to lead to structural alterations of the brain at old age, with an accompanying chance in gene methylation, reveals a study.

“Prenatal treatment of human disease is rare,” the investigators said. “DEX is used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in an affected female foetus.”

This study was conducted to determine whether first-trimester prenatal DEX treatment is associated with alterations in brain structure at adult age and whether these alterations correlate with DNA methylation, mood, and cognitive abilities.

The investigators compared T1-weighted and diffusion-weighted imaging scans from a single research institute between 19 first-trimester DEX-treated individuals at risk of CAH and 43 controls (age range, 16.0–26.4 years).

Individuals treated with DEX had bilateral enlargement of the amygdala, increased surface area and volume of the left superior frontal gyrus, and widespread increased radial, mean, and axial diffusivity of white matter, particularly in the superior longitudinal fasciculi and corticospinal tracts.

Increased mean and radial diffusivity in the DEX-treated group was associated with increased methylation of the promotor region of the FKBP5 gene. No group differences were seen in cognition or in scales assessing depression or anxiety. Additionally, the association between brain structure and cognition did not differ between DEX-treated and control participants.

“The findings add to the safety concerns of prenatal DEX treatment in the context of CAH,” the investigators said.