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First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age

CONTEXT: 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. OBJE...

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Autores principales: van’t Westeinde, Annelies, Karlsson, Leif, Nordenström, Anna, Padilla, Nelly, Lajic, Svetlana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304558/
https://www.ncbi.nlm.nih.gov/pubmed/32497228
http://dx.doi.org/10.1210/clinem/dgaa340
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author van’t Westeinde, Annelies
Karlsson, Leif
Nordenström, Anna
Padilla, Nelly
Lajic, Svetlana
author_facet van’t Westeinde, Annelies
Karlsson, Leif
Nordenström, Anna
Padilla, Nelly
Lajic, Svetlana
author_sort van’t Westeinde, Annelies
collection PubMed
description CONTEXT: 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. OBJECTIVE: We investigate whether 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. DESIGN, SETTING, AND PARTICIPANTS: T1-weighted and diffusion-weighted imaging scans, from a single research institute, are compared between 19 (9 women) first-trimester DEX-treated individuals, at risk of CAH but not having CAH, and 43 (26 women) controls (age range, 16.0-26.4 years). RESULTS: DEX-treated participants showed 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, 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. CONCLUSIONS: 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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spelling pubmed-73045582020-06-24 First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age van’t Westeinde, Annelies Karlsson, Leif Nordenström, Anna Padilla, Nelly Lajic, Svetlana J Clin Endocrinol Metab Clinical Research Articles CONTEXT: 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. OBJECTIVE: We investigate whether 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. DESIGN, SETTING, AND PARTICIPANTS: T1-weighted and diffusion-weighted imaging scans, from a single research institute, are compared between 19 (9 women) first-trimester DEX-treated individuals, at risk of CAH but not having CAH, and 43 (26 women) controls (age range, 16.0-26.4 years). RESULTS: DEX-treated participants showed 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, 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. CONCLUSIONS: 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. Oxford University Press 2020-06-04 /pmc/articles/PMC7304558/ /pubmed/32497228 http://dx.doi.org/10.1210/clinem/dgaa340 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Research Articles
van’t Westeinde, Annelies
Karlsson, Leif
Nordenström, Anna
Padilla, Nelly
Lajic, Svetlana
First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age
title First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age
title_full First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age
title_fullStr First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age
title_full_unstemmed First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age
title_short First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age
title_sort first-trimester prenatal dexamethasone treatment is associated with alterations in brain structure at adult age
topic Clinical Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304558/
https://www.ncbi.nlm.nih.gov/pubmed/32497228
http://dx.doi.org/10.1210/clinem/dgaa340
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