Context: As many women with 21-hydroxylase (21-OH) deficient nonclassic adrenal hyperplasia (NCAH) carry at least one allele affected by a severe mutation of CYP21, they are at risk for giving birth to an infant with classic adrenal hyperplasia (CAH).

Objective: To determine the frequency of CAH and NCAH infants born to mothers with 21-OH deficient NCAH.

Design and Setting: International multicenter retrospective/prospective study.

Patients and Methods: The outcome of 203 pregnancies among 101 women with 21-OH deficient NCAH was reviewed. The diagnosis of 21-OH deficient NCAH was established by a basal or post-ACTH stimulation 17-hydroxyprogesterone level > 10 ng/mL (30.3 nmol/L). When possible, genotype analyses were performed to confirm CAH or NCAH in the offspring.

Results: Of the 203 pregnancies, 138 (68%) occurred before the mother's diagnosis of NCAH and 65 (32%) following the diagnosis. Spontaneous miscarriages occurred in 35/138 (25.4%) pregnancies before the maternal diagnosis of NCAH, and in only 4/65 (6.2%) of pregnancies after the diagnosis (P < 0.002). Four (2.5%; 95% CI: 0.7-6.2%) of the 162 livebirths were diagnosed with CAH. To date 24 (14.8%; 95% CI: 9.0-20.6%) children -13 girls and 11 boys- have been diagnosed with NCAH. The distribution of NCAH children and their mothers varied significantly by ethnicity (P < 0.0001, for both).

Conclusions: The risk of a mother with 21-OH deficient NCAH for giving birth to a child affected with CAH is 2.5%; at least 14.8% of children born to these mothers have NCAH.