Benefits of Neonatal Screening for Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) in Sweden
Authors: Thilén Astrid , Nordenström Anna , Hagenfeldt Lars , von Döbeln Ulrika , Guthenberg Claes , Larsson Agne 
Published: August 2004

Objectives. The aim of this study was to evaluate the benefits of neonatal screening for congenital adrenal hyperplasia (CAH).

Methods. All children with CAH born in Sweden from January 1989 to December 1994 were subjected to a systematic follow-up. Clinical symptoms were recorded and laboratory data collected. The clinical diagnosis versus diagnosis by screening was investigated. The results were compared with those of a retrospective study of all patients diagnosed during 1969–1986 (before the introduction of neonatal screening).

Results. The prevalence of CAH in Sweden was 1:9800 with screening. Patients with CAH were identified earlier by screening. Half of the infants (47%) were not diagnosed at the time of recall, which was 8 days (median). In the study population, 25% of the girls and 73% of the boys were diagnosed by screening alone. The median age at the time of the definite diagnosis in boys was 21 days before screening as compared with 9 days (median) during the last part of the screening period. During the screening period, only 1 boy had a severe salt loss crisis, which occurred at the age of 8 days. Before screening, (1969–1986) 2 boys had died in the neonatal period because of an adrenal crisis. The lowest serum sodium recorded at the time of diagnosis was 124 mmol/L (median; range, 93–148) before, as compared with 134 mmol/L (median; range, 115–148) after the introduction of screening.

The number of girls who were initially considered to be boys was not reduced by screening (17% vs 18%). The period of uncertainty regarding gender attributable to virilization was shortened considerably, as well as the time it took to make a correct gender assignment: 23 days (median) before screening versus 3 days (median) with screening. The maximum time it took to make the correct gender assignment was 960 days before screening and 14 days with screening. The number of patients diagnosed late, ie, after the first year of life, decreased considerably after the introduction of screening. The false-positive rate (when a new filter paper blood sample was requested or when a child was referred to a pediatrician for follow-up) was &lt;0.05% and in about 60% of the cases, it was attributable to preterm infants. The cost of screening was US dollar 2.70 per screened infant.

Conclusion. The main benefits of screening were avoidance of serious salt loss crises, earlier correct gender assignment in virilized girls, and detection of patients who would have otherwise been missed in the neonatal period. Deaths in the neonatal period were prevented by screening. The aim of the screening program was to identify patients with the severe forms of CAH. Nevertheless, it must be considered a distinct benefit that a number of patients with milder forms of CAH were detected earlier, because earlier therapy results in decreased virilization, normalized growth and puberty, and, in all probability, an improved psychosocial situation for these children. We conclude that, in the Swedish health care system, the benefits of screening for CAH outweigh the costs.