Speed Poster ESA-SRB-APEG-NZSE 2022

Which is the better newborn screening marker for classical CAH - 21 Deoxycortisol or 17α-hydroxyprogesterone? (#77)

Fei Lai 1 2 , Shubha Srinivasan 1 3 , Karissa Ludwig 1 3 , Adviye Tolun 1 4 , Veronica Wiley 1 2
  1. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
  2. The New South Wales Newborn Screening Programme, Sydney Children's Hospital Network, Westmead, NSW, Australia
  3. The Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, NSW, Australia
  4. NSW Biochemical Genetics Service, Sydney Children's Hospital Network, Westmead, NSW, Australia

The NSW Newborn Screening Programme commenced screening of newborns for classical congenital adrenal hyperplasia (CAH) in May 2018. All newborns born in NSW and ACT are screened for CAH using a two-tier protocol, the first tier measuring 17α-hydroxyprogesterone (17αOHP) using immunoassay followed by second-tier steroid profiling via liquid chromatography-tandem mass spectrometry (LC-MS/MS) measuring 17αOHP (MS17αOHP), androstenedione, and cortisol 1, 2. This screening algorithm gave a CAH screening positive predictive value (PPV) of 71.4%3. There were 16 (from 388,416 screened) proven cases of CAH giving an incidence of 1:24,276

The CAH screening efficacy with the addition of 21 deoxycortisol to LC-MS/MS steroid profiling was investigated to determine if it is a better disease marker compared to 17αOHP for CAH. The top 98th centile of daily immunoassay 17αOHP measurement from June 2021-February 2022 were selected (n=2762).The positive predictive value (PPV) for 17αOHP and 21 deoxycortisol as a sole indicator and part of a ratio were calculated.

There was no statistically significant effect of birth weight or gestational age (GA) on 21 deoxycortisol compared to 17αOHP. The calculated PPV, using a 95th centile concentration cut-off, showed no significant improvement when comparing 21 deoxycortisol (10.9%), against MS17αOHP (11.5%), as a sole disease marker without birth weight and GA stratification.

By combining the use of MS17αOHP concentrations of 40.1 nmol/L whole blood (WB) and MS17αOHP+A4)/cortisol of 1.2, MS17αOHP/cortisol of 1.6, and (MS17αOHP+21 deoxycortisol)/cortisol of 1.9 all newborns with CAH with gestational age (GA) >259 days were correctly identified. Screening efficacy for newborns with GA <259 days improved when the cut-off MS17αOHP WB concentration of 58.2 nmol/L in combination with (MS17αOHP + 21 deoxycortisol)/cortisol of 3.4 was used.

This study showed that the screening efficacy improved with GA stratification. No significant statistical improvement was detected by using 21 deoxycortisol as a disease marker for CAH.  

  1. Rossi C, Calton L, Brown HA, Gillingwater S, Wallace AM, Petrucci F, et al. Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med. 2011;49(4):677-84.
  2. Janzen N, Peter M, Sander S, Steuerwald U, Terhardt M, Holtkamp U, et al. Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab. 2007;92(7):2581-9.
  3. Lai F, Srinivasan S, Wiley V. Evaluation of a Two-Tier Screening Pathway for Congenital Adrenal Hyperplasia in the New South Wales Newborn Screening Programme. Int J Neonatal Screen. 2020;6(3):63.