Update on the Swedish Newborn Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Abstract

Congenital adrenal hyperplasia (CAH) was the fourth disorder added to the national Swedish neonatal screening program in 1986, and approximately 115,000 newborns are screened annually. Dried blood spot (DBS) screening with measurement of 17-hydroxyprogesterone (17OHP) is also offered to older children moving to Sweden from countries lacking a national DBS screening program. Here, we report an update on the CAH screening from January 2011 until December 2019. Results: During the study period, 1,030,409 newborns and 34,713 older children were screened. In total, 87 newborns were verified to have CAH, which gives an overall positive predictive value (PPV) of 11% and 21% for term infants. Including the five missed CAH cases identified during this period, this gives an incidence of 1:11,200 of CAH in Sweden. Among the older children, 12 of 14 recalled cases were found to be true positive for CAH. All patients were genotyped as part of the clinical follow-up and 70% of the newborns had salt wasting (SW) CAH and 92% had classic CAH (i.e., SW and simple virilizing (SV) CAH). In the group of 12 older children, none had SW CAH and two had SV CAH. Conclusion: The incidence of classic CAH is relatively high in Sweden. Early genetic confirmation with CYP21A2 genotyping has been a valuable complement to the analysis of 17OHP to predict disease severity, make treatment decisions and for the follow-up and evaluation of the screening program.

Keywords: 21-hydroxylase deficiency; CAH; CYP21A2; DBS; PPV; congenital adrenal hyperplasia; dried blood spots; neonatal screening; positive predictive value.

Figure 1

Gestational age (A) and sex (B) distribution of all recalls in the neonatal screening program for CAH in Sweden during the study period.

Figure 2

Distribution of all CAH patients’ CYP21A2 genotype groups (n = 103) (A) and correlations of the 17OHP values in the neonatal screening samples to the CYP21A2 genotype groups (B). The 17OHP level is given up to 670 nmol/L by the laboratory, which means that higher levels are reported as >670 nmol/L. Five patients are not included in graph B due to a missing genotype in one case, missing 17OHP in one case and sampling prior to 48 h in three cases.