Neonatal Screening for CAH in Sweden. Implementation and Results of Implementing Second Tier Testing

Newborn screening for Congenital adrenal hyperplasia (CAH) is effective in identifying patients with severe forms before a potentially lethal crisis but has a relatively high false positive rate. The aim of this study was to improve the national neonatal screening program in Sweden, and the positive predictive value by implementing a LC-MS/MS second-tier testing. A combination of two independent parameters, the steroid hormone ratio (androstenedione+17-hydroxyprogesterone)/cortisol and the concentration of 21-deoxycortisol and adjustment of cut-off levels resulted in an increase of the positive predictive value (PPV) from 14 % to 84 % for full-term infants. In total the false positive screening cases decreased by 88 %. CYP21A2 genotyping was used to determine the severity of CAH in identified cases. We report on the stepwise approach that was used to optimize the cut-off levels for full-term and preterm infants in order not to miss any true cases in the process.