P29 - PREDICT – Clinical Trial on PREnatal Dexamethasone In Congenital adrenal hyperplasia Therapy

Abstract Background/Introduction Androgen excess in females with classical congenital adrenal hyperplasia (CAH) leads to virilization of the external genitalia. Surgical interventions, such as urogenital sinus correction, carry potential long-term consequences, including psychological issues, impaired genital sensitivity, sexual dysfunction and urinary incontinence. Prenatal dexamethasone (Dex)therapy, if initiated before 6–7 weeks postconception, which is the critical window of sexual differentiation, traverses the placenta and can suppress fetal adrenal androgen production, thereby preventing or reducing virilization. Although Dex has been used for this purpose since 1984, it remains experimental, and no prospective clinical trials have systematically validated the empirically used dose of 20 μg/kg/d or defined optimal treatment duration. Pharmacokinetic modelling suggests that a lower maternal Dex dose of 7.5 μg/kg/d effectively achieves fetal HPA axis suppression in over 90% of pregnant women weighing 55–95 kg. However, Dex therapy poses potential risks for both mother and fetus and high quality evidence on its efficacy safety balance is limited. Purpose This study aims to determine whether a reduced Dex dose of 7.5 μg/kg/day is effective and non-inferior to the currently used high dose of 20 μg/kg/day in preventing prenatal virilization in females with CAH. Secondary objectives are to evaluate maternal and fetal safety, focusing on miscarriage and stillbirth rates, maternal side effects, gestational weight gain, quality of life, mental health, sleep quality, and neonatal outcomes including birth weight and length, gestational age at delivery, neurodevelopment, and congenital anomalies. Methods This is a randomized, controlled, phase II non-inferiority trial. All pregnant women at risk of carrying a fetus with classical CAH will be enrolled. Women not treated with Dex will be included in a non randomized control group for ethical reasons. Those receiving Dex will be randomized 1:1 to either 20 μg/kg/day or 7.5 μg/kg/day. Recruitment will occur from 2025 to 2031, with an interim analysis planned for 2028. Results The PREDICT trial is expected to demonstrate that the lower Dex dose reduces maternal risks without compromising efficacy in preventing virilization. Standardized treatment and follow-up will yield robust evidence on long-term maternal and child safety outcomes.