Prenatal treatment of congenital adrenal hyperplasia : do we have enough evidence?

The treatment of congenital adrenal hyperplasia (CAH) before birth was instituted 20 years ago in an attempt to prevent virilization of the external genitalia in affected girls. Maternally administered dexamethasone, which readily crosses the placenta unaltered, is started very early in pregnancy to ensure adequate suppression of the fetal hypothalamo-pituitary-adrenal axis. Since the diagnosis cannot be ratified until chorionic villus sampling is performed 6 weeks later, fetuses that do not require treatment (all males and unaffected females) are also exposed to high-dose glucocorticoids for an interim period. It is not known whether this induces fetal programming of metabolic changes that may manifest as disease in adult life. The expected outcome at birth in a female fetus with CAH who has been treated with adequate amounts of dexamethasone is normal-appearing genitalia or at least a significant reduction in virilization for which genitoplasty is unlikely to be required. Short-term follow-up studies in infants and children exposed to dexamethasone indicate normal growth and development. The medical treatment of CAH before birth is a unique example of the successful prevention of a major congenital malformation. However, there is a potential concern about possible long-term consequences of exposure of the fetus to glucocorticoids during early embryogenesis and beyond. This mandates the need for prenatal treatment for CAH to be undertaken only in protocol-driven clinical trials that are obliged to follow all children exposed in utero for the long term in order to collect any evidence of adverse neurodevelopmental and metabolic consequences.