International newborn screening practices for the early detection of congenital adrenal hyperplasia

Introduction: Newborn screening (NBS) programmes vary internationally in their approach to screening. Guidelines for congenital adrenal hyperplasia (CAH) screening recommend the use of two-tier testing and gestational age cutoffs, to minimise false positive results. The aims of this study were to describe: 1) the approaches; 2) protocols used; and 3) available outcomes for CAH screening internationally. Methods: All members of the International Society for Neonatal Screening were asked to describe their CAH NBS protocols, with an emphasis on the use of second-tier testing, 17-hydroxyprogesterone (17OHP) cutoffs and gestational age and birthweight adjustments. Where available, screening outcomes were requested. Results: Representatives from 23 screening programmes provided data. Most (n=14; 61%) recommend sampling at 48-72 hours of life. Fourteen (61%) use single-tier testing and 9 have a two-tier testing protocol. Gestational age cutoffs are used in 10 programmes, birthweight cutoffs in 3 and a combination of both in 9. One programme does not use either method of adjusting 17OHP cutoffs. Case definition of a positive test and the response to a positive test differed between programmes. Conclusions: We have demonstrated significant variation across all aspects of NBS for CAH, including timing, the use of single versus two-tier testing and cutoff interpretation. Collaboration between international screening programmes and implementation of new techniques to improve screen efficacy will facilitate ongoing expansion and quality improvement in CAH newborn screening.