Antenatal Diagnosis and Treatment in Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency and Congenital Adrenal Hyperplasia Screening in Newborns

Abstract

Signs of virilization, such as clitoromegaly, labio-scrotal fusion, and urogenital sinus may be observed in females with 21-hydroxylase deficiency (21-OHD) and other rare virilizing forms of congenital adrenal hyperplasia (CAH). This makes sex determination difficult, and multiple reconstructive surgeries in the postnatal period may be required. As 21-OHD is an autosomal recessive disease, the chance of any child being affected is one in four and so only one in eight will be an affected female. The primary objective of antenatal diagnosis is to identify only the affected fetus in the early gestational weeks before the onset of genital organogenesis and to treat that case. Therefore, studies aimed at antenatal diagnosis and preventing adrenal androgen exposure in the female fetus with CAH have long been of interest. Antenatal steroid treatment is considered experimental and controversial for safety reasons in recent clinical guidelines. If antenatal treatment is to be used, it is recommended that it should be performed in experienced centers that can collect data on a large number of cases which will help to define the benefits and harms of treatment better. In the postnatal period, a severe deficiency of the 21-hydroxylase enzyme leads to life-threatening adrenocortical insufficiency in both sexes and varying degrees of pathology of the external genitalia in females. This condition is also associated with high mortality in the first days of life and an increased risk of incorrect sex assignment. Neonatal screening for 21-OHD CAH effectively detects the severe forms and reduces mortality, and it is instrumental in the correct sex assignment of female cases.