Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Newborn screening and its relationship to the diagnosis and treatment of the disorder

Abstract Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can be detected by newborn screening. The screening alone in 29 programs from 13 countries resulted in the diagnosis of CAH in 1 2 of affected newborns and expedited the diagnosis in 1 3 of affected newborns clinically suspected to have CAH. The benefits of newborn screening for CAH were prevention of severe adrenal crisis, its sequela, incorrect male sex assignment of severely virilized female newborns, and progressive signs of androgen excess. Screening revealed a higher incidence of CAH worldwide (1:15000 live births) compared with the case survey incidence (1:32000 live births) The false-positive rate (usually found in low birth weight and premature infants) was acceptably low (0.01–0.5%) except for three programs (0.7–2.5%). The false-negative rate of CAH screening was negligible. Prenatal diagnosis of CAH is possible by HLA typing or 21-hydroxylase B gene analysis of cultured fetal cells from chorionic villus biopsy sampling in the first trimester and from amniotic cells or hormonal analysis of amniotic fluid in the second trimester. Prenatal treatment of CAH is possible via maternal dexamethasone therapy beginning early pregnancy. However, efficacy and side effects of maternal dexamethasone therapy require further investigation.