First Trimester DEX Treatment Is Not Associated with Altered Brain Activity During Working Memory Performance in Adults.

Annelies Van’T Westeinde,Leif Karlsson,Marius Zimmermann,Valeria Messina,Svetlana Lajic,Nelly Padilla

doi:10.1210/clinem/dgaa611

Abstract

ContextPrenatal dexamethasone (DEX) treatment is sometimes used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in female fetuses with CAH. In boys and in fetuses not having CAH, there is no benefit of early DEX treatment and the risks of this therapy must be thoroughly investigated. High doses of prenatal glucocorticoid might alter the developmental trajectory of the brain into adulthood, even for CAH unaffected subjects treated with DEX for a short term during the first trimester.ObjectiveThe present study investigated brain activation during working memory performance in DEX-treated subjects compared with controls.Design, Setting, and ParticipantsWe tested 18 participants who were exposed to DEX during the first trimester of fetal life but did not have CAH (8 females; mean age 20.78 [standard deviation (SD), 2.67] years) and 40 control participants (24 females; mean age 20.53 [SD, 2.64]) from a single research institute. Participants underwent functional magnetic resonance imaging on a 3T scanner during a verbal and visuospatial working memory task.ResultsWe did not observe any differences in brain activity during working memory performance. However, DEX-treated subjects responded faster during the experimental condition of the verbal WM task.ConclusionsFirst trimester DEX treatment did not seem to result in altered working memory–related brain activity at adult age. Our findings contribute to the risk–benefit assessment of prenatal DEX treatment in the context of CAH.

Highlights

Congenital adrenal hyperplasia (CAH) is a genetic disorder caused by mutations in the CYP21A2 gene, resulting in a defective 21-hydroxylase enzyme necessary to produce cortisol and aldosterone [1]
Results from our follow-up study in Sweden on the psychological and somatic effects of pre- and postnatal glucocorticoid treatment show that, impairments in cognition are found in DEX-treated children compared with healthy controls, these differences seem to attenuate at adult age in children not having congenital adrenal hyperplasia (CAH) [13,14,15]
The present study assessed brain activity related to working memory performance in healthy participants who had received first-trimester DEX treatment in the context of pregnancies at risk of CAH

Summary

Introduction

Congenital adrenal hyperplasia (CAH) is a genetic disorder caused by mutations in the CYP21A2 gene, resulting in a defective 21-hydroxylase enzyme necessary to produce cortisol and aldosterone [1]. Results from our follow-up study in Sweden on the psychological and somatic effects of pre- and postnatal glucocorticoid treatment show that, impairments in cognition are found in DEX-treated children compared with healthy controls, these differences seem to attenuate at adult age in children not having CAH [13,14,15]. Despite altered structure of the brain at adult age, healthy DEX-treated subjects performed similar to nontreated controls in terms of cognition and behavior. The results will contribute to our understanding of the impact of first-trimester DEX treatment on the development of the brain until adult age Understanding of such alterations in brain function contributes to the assessment of the risks and benefits of DEX treatment in pregnancies

Objectives

Results

Conclusion