ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 8.12 | DOI: 10.1530/ey.18.8.12

ESPEYB18 8. Adrenals New Concerns (2 abstracts)

8.12. First-Trimester prenatal dexamethasone treatment is associated with alterations in brain structure at adult age

Van’t Westeinde A , Karlsson L , Nordenström A , Padilla N & Lajic S

J Clin Endocrinol Metab. 2020; 105(8):dgaa340.

Here, the authors investigated whether prenatal treatment with dexamethasone (DEX) in the first trimester is associated with alterations of brain morphology on MRI scans. Observed MRI alterations were not linked to any alterations in cognitive function or mood, but were associated with DNA methylation in genes that were previously found to be differentially methylated in non-CAH DEX-treated individuals.

Prenatal treatment with glucocorticoids is used in several clinical settings. In the context of congenital adrenal hyperplasia (CAH), prenatal dexamethasone (DEX) has been used successfully in order to ameliorate the virilization of the affected female fetus. However, long term outcome, metabolic, cognitive or other, is an area for concern. Excessive exposure to glucocorticoids during prenatal development may have detrimental effects on the development of the human brain through various mechanisms, especially in glucocorticoid receptor rich regions of the brain.

In this observational study, the authors investigated brain morphology by MRI scans in adult individuals without CAH, but who had a family history of CAH and were therefore treated prenatally with DEX (n=19). They were compared to apparently healthy population controls (n=43). Prenatal DEX-exposed individuals showed bilateral enlargement of the amygdala and increased surface area and volume of the left superior frontal gyrus. Moreover, DEX-exposed individuals exhibited widespread alterations in white-matter microstructure, mainly in the superior longitudinal fasciculi and corticospinal tracts. Increased DNA methylation for one CpG site in the gene FKBP5 was significantly associated with mean radial diffusivity. DEX-exposed subjects did not exhibit any differences in measures of cognition or behavior and these outcomes were not associated with alterations in brain structure.

This study provides the first evidence that prenatal treatment with DEX is associated with alterations in brain structure that persists into adult life. Epigenetic mechanisms, here measured as differences in DNA methylation, may be an important factor in explaining how DEX exerts its effects on brain development. These findings provide new important information about prenatal with DEX.

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