C. Sow, Thao Nguyen‐Khoa, Caroline Moreau, Jean Fiet, Guillaume Bachelot, Bettina Ribault, Ophélie Chaussenery, Layla Al Zarga, Aurore Desmons, Frédéric Brioude, Dulanjalee Kariyawasam, Athanasia Stoupa, Michel Polak, Muriel Houang, Antonin Lamazière, FIRENDO Group, Jérôme Bertherat, Maria Givony, Laetitia Martinerie, Michel Polak, Patrice Rodien, Thierry Brue, Nicolas Kalfa, Corinne Vigouroux, Sophie Béliard, Coline Stordeur, Jérôme Bertherat, V Bidault, A Tabarin, A Bachelot, I Netchine, G Raverot, E Bismuth, Nathalie Jeandidier, Sara Barraud, Solange Grunenwald, Claudine Colin, Béatrice Demaret, Marguerite Helene, A Barlier, S Jaillard, I Plotton, J Brossaud, D Guenet, N de Roux, Sabine Homo-Ghenim, Fabienne Larrieu, Vincent Semeraro, Océane Ribeiro, Mickaella Heitz, Christelle Glaise, Perrine Bach, Mélanie Chevalier, Amine Boukenine
BACKGROUND: A major limitation of newborn screening (NBS) for congenital adrenal hyperplasia (CAH) is the lack of specificity of the fluoroimmunoassay (FIA) currently used for 17-hydroxyprogesterone (17OHP) determination. This issue is more pronounced in newborns, due to elevated levels of interfering compounds. Fluoroimmunoassay at our NBS centre in Ile-de-France has a false-positive rate of around 80% and a predictive positive value of 16% for first- and second-tier measurements from dried blood spots. Recently, tandem mass spectrometry (LC-MS/MS) has gained international recognition as a complementary tool to FIA testing. Currently, the most frequently used biomarkers are 17OHP and 21-deoxycortisol, used either alone or in combination with steroid ratios such as cortisol or 4-androstenedione. Concurrently, the class of 11-oxygenate-androgens-such as 11-ketotestosterone-and more recently 11-oxygenate pregnanes-such as 21-deoxycortisone-has attracted growing interest in the diagnosis of 21-hydroxylase deficiency. These derivatives result from the combined action of 11-beta hydroxysteroid dehydrogenase and 11-beta hydroxylase. METHODS: We propose a revisited LC-MS/MS steroid profile, enriched with these classes of biomarkers, to be included in the CAH NBS algorithm. This combination could be used as a multi-steroid approach implemented using a machine learning model. RESULTS: Our preliminary results suggest that these oxygenated androgen/pregnane steroids are significantly discriminative to streamline the NBS process for CAH. We have demonstrated this in 2 different NBS centres, in the greater Paris region and in Brittany, France. CONCLUSION: This new algorithm could have an important impact on reducing the number of recall and family stress related to NBS.