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. 2022 Mar 23;186(5):K17-K24.
doi: 10.1530/EJE-21-0554.

Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe

Hanna Nowotny  1 , Uta Neumann  2 , Véronique Tardy-Guidollet  3 , S Faisal Ahmed  4 , Federico Baronio  5 , Tadej Battelino  6 , Jérôme Bertherat  7 , Oliver Blankenstein  2 , Marco Bonomi  8   9 , Claire Bouvattier  10   11 , Aude Brac de la Perrière  12 , Sara Brucker  13 , Marco Cappa  14 , Philippe Chanson  15 , Hedi L Claahsen-van der Grinten  16 , Annamaria Colao  17 , Martine Cools  18 , Justin H Davies  19 , Helmut-Günther Dörr  20 , Wiebke K Fenske  21 , Ezio Ghigo  22 , Roberta Giordano  22 , Claus H Gravholt  23 , Angela Huebner  24 , Eystein Sverre Husebye  25   26 , Rebecca Igbokwe  27 , Anders Juul  28   29 , Florian W Kiefer  30 , Juliane Léger  31 , Rita Menassa  3 , Gesine Meyer  32 , Vassos Neocleous  33   34 , Leonidas A Phylactou  33   34 , Julia Rohayem  35 , Gianni Russo  36 , Carla Scaroni  37 , Philippe Touraine  38 , Nicole Unger  39 , Jarmila Vojtková  40 , Diego Yeste  41   42   43 , Svetlana Lajic  44 , Nicole Reisch  1
Affiliations

Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe

Hanna Nowotny et al. Eur J Endocrinol. .

Abstract

Objective: To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.

Design and methods: A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN.

Results: Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4-5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France.

Conclusions: This study reveals a high international variability and discrepancy in the use of Pdex treatment 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.

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Figures

Figure 1
Figure 1
Use of Pdex treatment and prenatal diagnostics to prevent virilization in girls with CAH. (A) Pie chart depicting the percentage of included centres using or not using Pdex treatment (n = 36). (B) Selected disciplines providing Pdex treatment in the corresponding country. Multiple selections were possible (n = 31; 5 NA). (C) Daily dosing distribution of Pdex. Only centres using Pdex treatment were included (n = 13). (D) Types of prenatal diagnostics for CAH used in each corresponding country (n = 25). CVS (CYP21A2 GT + ST): CYP21A2 genotyping and sextyping between 1012 wpc; treatment is discontinued for male foetuses or notaffected females. AC (CYP21A2 GT + ST): CYP21A2 genotyping and sextyping between 1516 wpc; treatment is discontinued for male foetuses or notaffected females. SRY + CVS: SRYtyping from maternal blood (cfDNA); treatment of females only; CVS for CYP21A2 GT between 1012 wpc; treatment only continued for affected females. NIPD: massively parallel sequencing using cfDNA from maternal blood; only affected females are treated. (E) Overview of important timepoints of development of external genitalia in females. Stars are marking the starting point of Pdex treatment as indicated by each centre (n = 13).
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