Preventing female virilisation in congenital adrenal hyperplasia: the controversial role of antenatal dexamethasone

Abstract

Congenital adrenal hyperplasia (CAH) refers to a group of recessively inherited disorders of cortisol production, which in the classical form results in virilisation of female fetuses. Since the 1980s, antenatal treatment with dexamethasone has been recommended in high-risk pregnancies to minimise the risk of virilising the female genitalia of affected fetuses. To be effective, this treatment requires implementation in early pregnancy, prior to the commencement of autonomous fetal adrenal androgen synthesis. Using this approach, seven of eight high-risk pregnancies are treated unnecessarily, prior to establishing the fetal gender or the confirmed diagnosis of a genetically affected pregnancy. In the face of ongoing concerns regarding potential adverse maternal-fetal effects of antenatal dexamethasone exposure, a review of this practice has been advocated by expert advisory groups. In this review, we summarise current controversies, potential improvements and future directions in the management of pregnancies at risk of CAH. In high-risk families, recent genomic advances include early prenatal diagnosis utilising noninvasive genetic techniques to minimise unnecessary dexamethasone exposure to unaffected fetuses. In affected pregnancies when families elect for antenatal treatment, optimal antenatal dosing regimens need to be defined and a standardised treatment and follow-up protocol are recommended. Establishment of a national registry with standardised follow-up will allow future families to be better informed of the risks and benefits of both treated and untreated fetal CAH.