Objective: To assess the efficiency of the French national screening program for 21-hydroxylase deficiency (21-OHD). Neonatal screening for congenital adrenal hyperplasia due to 21-OHD is mainly intended to prevent death due to salt wasting but remains controversial because of the number of false-positive results and the ease with which most female cases can be identified by virilized genitalia at birth.
Design: Population-based study.
Setting: National neonatal screening program, pediatric endocrinologists nationwide, and reference center for genotyping.
Participants: All neonates screened for 21-OHD in mainland France between January 1, 1996, and December 31, 2003.
Outcome measures: Screening efficiency indicators, disease severity, contribution of screening to early diagnosis, and disease-specific mortality before and during the study period.
Results: A total of 6,012,798 neonates were screened; results in 15,407 were considered positive for 21-OHD. Three hundred eighty-three cases were identified, giving a prevalence of 1 for every 15,699 births. The positive predictive value of screening was 2.3% (95% CI, 2.1%-2.6%), with a sensitivity of 93.5% (90.9%-95.9%) and a specificity of 99.7% (99.7%-99.7%). The false-positive rate was particularly high in preterm infants, for which the positive predictive value was 0.4% (95% CI, 0.2%-0.5%). Screening allowed clinical diagnosis in 162 of 383 cases (42.3%), with the others being detected clinically or through family history. There was a trend toward declining neonatal mortality due to 21-OHD.
Conclusions: In this large population-based study, the efficiency of routine 21-OHD screening was moderate in neonates born at term and very low in preterm neonates. We recommend the discontinuation of screening, as currently performed in France, in preterm neonates.