PRENATAL TREATMENT OF CONGENITAL ADRENAL HYPERPLASIA

Abstract

Prenatal treatment was given to 67 fetuses at risk for classical steroid 21-hydroxylase deficiency (21OHD) congenital adrenal hyperplasia (CAH). The mothers were given dexamethasone (DEX) 1-1.5 mg/d po, computed at 20 μg/kg (pre-pregnancy weight)/day, in three divided doses. Treatment began as early as 4 weeks, continuing until birth for affected female fetuses. The diagnosis of 21OHD was established or excluded by DNA analysis using HLA-linked markers or 21OHD gene probes on the tissue provided by chorionic villus sampling (CVS). When amniocentesis was performed the diagnosis was based on the concentration of 17OHP in the supernatant and occasionally DNA was analyzed from amniotic cells. Seventeen fetuses were predicted to be affected, 10 of which were females. In every case the virilization of the genitalia of the unborn prenatally-treated females was significantly less than in the index case. No complications were observed in those fetus treated briefly and who were predicted to be unaffected. Maternal complications were observed in 6 pregnancies out of 67. These included increased appetite, weight gain, mood swings, pedal edema, and mild hypertension. None were permanent. One fetus was spontaneously aborted at 33 wks. It appears unlikely that dexamethasone was causative of the abortion since treatment with dexamethasone occurred from 10-19 weeks.In conclusion, prenatal treatment of fetuses at risk for CAH is effective and safe.