SUN-183 - Management of newborns born to parentswith positive prenatal carrier screening for congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder that is now included in expanded prenatal carrier screening panels, which are increasingly offered before or during pregnancy. However, guidance for postnatal management of newborns born to carrier parents is lacking. This study aims to assess whether measuring serum 17-hydroxyprogesterone (17-OHP) provides additional diagnostic value in newborns with positive parental carrier screening for CAH.
We conducted a retrospective chart review of newborns for whom pediatric endocrinology was consulted in the newborn nursery or neonatal intensive care unit over a seven-year period due to parental carrier status for CAH. Data on parental pathogenic variants in the CYP21A2 gene, serum 17-OHP testing, NBS (newborn screen) results, and genetic testing outcomes were collected.
Data were collected from 99 charts. Among the parents, 88 were carriers of pathogenic variants associated with non-classical (NC)-CAH, 54 were carriers of salt-wasting (SW)-CAH variants, 9 were carriers of simple-virilizing (SV)-CAH variants, and 52 had unknown paternal genetic testing. Of the 99 newborns, 63 (63%) underwent additional serum 17-OHP testing in conjunction with newborn screening (NBS). Seven tests (11%) had either not resulted due to insufficient blood samples or were declined by parents. Among the completed tests, 2 (3.6%) resulted at the classical CAH range, and 52 (96.4%) were normal for age. Both newborns with elevated 17-OHP levels also had positive NBS results; in both cases, the parents were carriers of pathogenic variants associated with classical CAH (SW or SV). Subsequent genetic testing identified pathogenic variants consistent with SV-CAH in one patient and SW-CAH in the other. Fifteen newborns (15%) were evaluated by genetics, and 11 (11%) underwent genetic testing. Of those tested, three (27%) were diagnosed with NC-CAH, and four (36%) were identified as carriers.
Additional serum 17-OHP testing may be useful in newborns whose parents are both carriers of pathogenic variants associated with classical CAH. However, it appears to provide limited additional diagnostic value beyond NBS in cases involving parental carrier status for non-classical variants or incomplete parental carrier information. In such cases, families should be encouraged to pursue genetic testing to identify individuals with possible NC-CAH.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*