An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia

Abstract

First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.

Keywords: CAH; brain development; dexamethasone; first trimester; prenatal treatment; treatment safety.

Figure 1

Overview of the prenatal dexamethasone treatment in pregnancies at risk for CAH. SRY analysis from maternal blood determines the sex of the fetus prior to DEX treatment. Treatment is only started if the fetus is a girl. Novel tests using whole genome sequencing (WGS) of fetal DNA obtained from maternal blood may in the future limit treatment to girls with CAH (yellow arrow). Currently, genotyping for CYP21A2 from chorionic villus sampling (CVS) is done at week 12, which determines the CAH diagnosis. DEX treatment is stopped in the case of an unaffected girl and continued until term in the case of a girl with CAH. If untreated, genitalia develop towards the male phenotype, as indicated on the right side of the figure.

Figure 2

Potential points of interference (left) and potential clinical consequences (right) of prenatal dexamethasone exposure. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Figure 3

Major steps of prenatal brain development that may be impacted by prenatal dexamethasone exposure. The yellow boxes indicate the start of DEX treatment at GW6–7 and the genotyping for CAH at GW12. Light-blue boxes indicate major events in prenatal brain development. *Although treatment currently is limited to girls because of the possibility of sex-typing prior to treatment, there are large cohorts that have received treatment before the SRY method was available and therefore contain both affected and unaffected boys. GW, gestational week.