ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 8.15 | DOI: 10.1530/ey.16.8.15

ESPEYB16 8. Adrenals New Concerns (1 abstracts)

8.15. Epigenetic alterations associated with early prenatal dexamethasone treatment

Karlsson L , Barbaro M , Ewing E , Gomez-Cabrero D & Lajic S



To read the full abstract: J Endocr Soc. 2018; 3(1): 250–263.

Prenatal treatment with dexamethasone (DEX) has been used to avoid virilization in girls with Congenital Adrenal Hyperplasia (CAH). However, it has potential short- and long-term risks and has been associated with cognitive impairments. Here, the authors investigate whether epigenetic modification of DNA during early developmental stages may be a key mediating mechanism by which prenatal DEX treatment could result in poor outcomes in the offspring by comparing genome-wide DNA methylation, from peripheral CD4+ T-cells, between prenatal DEX-treated individuals without CAH and population controls.

In total, 9672 differentially methylated probes (DMPs) were associated with DEX treatment and 7393 DMPs were associated with an interaction between DEX and sex. Associated DMPs were enriched in intergenic regions located near epigenetic markers for active enhancers. Functional enrichment of DMPs was seen in immune functioning, inflammation, and also nonimmune-related biological pathways. DEX-associated DMPs enriched near single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease, and DEX*sex interaction DMPs were enriched near SNPs associated with asthma. DMPs were also identified in genes involved in the regulation and maintenance of methylation and steroidogenesis. Methylation in the BDNF, FKBP5, and NR3C1 genes were associated with performance on several Wechsler Adult Intelligence Scale–Fourth Edition subscales.

This study highlights the importance of studying the potential risks of the prenatal DEX treatment. Furthermore, the study also indicates a possible effect on the treated individuals immune-functioning and susceptibility to future disease, which should be addressed in future studies evaluating the prenatal treatment.

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