Which drugs are used for prenatal therapy of congenital adrenal hyperplasia?
**Core Concept**
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by mutations in enzymes involved in cortisol synthesis, leading to an accumulation of precursor hormones and an overproduction of androgens. Prenatal therapy aims to suppress fetal adrenal androgen production.
**Why the Correct Answer is Right**
Dexamethasone is used for prenatal therapy of CAH due to its ability to cross the placenta and reach the fetus. It acts by inhibiting the 21-hydroxylase enzyme, which is deficient in most cases of CAH. This reduces the production of androgens by the fetal adrenal glands, preventing virilization of female fetuses. Dexamethasone has a long half-life, allowing for once-daily dosing and ensuring consistent suppression of fetal adrenal androgen production.
**Why Each Wrong Option is Incorrect**
**Option A:** Hydrocortisone is used for replacement therapy in CAH, but it does not effectively cross the placenta to suppress fetal adrenal androgen production.
**Option B:** Prednisolone is metabolized by the placenta to prednisone, which then undergoes further metabolism to inactive metabolites, limiting its effectiveness in prenatal therapy.
**Option C:** Fludrocortisone is a potent mineralocorticoid, but it is not used for prenatal therapy of CAH due to its lack of glucocorticoid activity.
**Clinical Pearl / High-Yield Fact**
To prevent virilization of female fetuses with CAH, prenatal therapy with dexamethasone should be initiated between 9-16 weeks of gestation and continued until birth.
**✓ Correct Answer: D. Dexamethasone**