Background: Prenatal dexamethasone treatment (Pdex) has been used since the 1980s to prevent virilization in female offspring suspected to have congenital adrenal hyperplasia (CAH). However, due to lack of strong evidence for its best practice as well as limited data regarding long term adverse effects, use of dex is highly controversial. This study reveals the current medical practice regarding Pdex in female fetuses at risk of CAH due to 21 hydroxylase deficiency (21OHD) in Europe.
Methods: A questionnaire was designed and distributed using Microsoft Forms, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 28 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN.
Results: 36% (13/36) of the surveyed centres are currently providing Pdex. The treatment is initiated by different specialties i.e. pediatricians, obstetricians/gynecologists or geneticists. Regarding the starting point of Pdex, 15% of centres stated to initiate therapy as early as pregnancy is confirmed, 23% at 4 to 5 wpc, 31% at 6 wpc, and the rest at 7 wpc at the latest. A dose of 20µg/kg/d is used and dose distribution among the centres varies between once to thrice daily. Prenatal diagnostics are conducted at 72% (26/36) of centres, which however mainly includes chorionic villous sampling ± genotyping of the sex determining region Y from maternal blood (SRY typing) or amniocentesis and CYP21A2 genotyping. Non invasive genetic testing from maternal blood is currently offered by one centre. The total number of pregnant women who received Pdex during the first trimester of pregnancy varied from 3 to 44 per centre (median = 10, total number of treated cases n = 197), while 0 to 13 cases (median = 5, total number of treated cases n = 70) were treated for the entire gestational period. A mean of 1.6 cases are treated at each centre per year. Registries for long term follow up are only available at 46% of the centres that are using Pdex. National registries are only available in 2 of the 14 corresponding countries.
Conclusion: This study reveals a high international variability and discrepancy on the use of Pdex across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH. Evaluation of outcome and long term health of already treated cases across Europe is highly recommended.
22 Sep 2021 - 26 Sep 2021