title: Nationwide neonatal screening for congenital adrenal hyperplasia in sweden: a 26-year longitudinal prospective population-based study.
abstract: OBJECTIVE
  Recent reports have questioned the rationale for neonatal screening for congenital adrenal hyperplasia (CAH) owing to low sensitivity in salt-wasting forms and a high rate of recall (ie, a positive finding resulting in a visit to a pediatrician and a second test) in preterm infants.
  
  
  OBJECTIVE
  To determine the efficiency of the neonatal screening program for CAH in Sweden over time.
  
  
  METHODS
  Longitudinal prospective population-based study in Sweden. We assessed neonatal screening for CAH from January 1, 1986, through December 31, 2011, when 2 737 932 infants (99.8%) underwent testing. The CYP21A2 genotype was investigated in 219 cases with true-positive findings (94.8%). We investigated the screening outcomes for 231 patients who had true-positive findings, 43 with late diagnosis, and 1497 infants with false-positive findings.
  
  
  METHODS
  Sensitivity of the screening for salt-wasting CAH. The most important secondary outcome measures were the positive predictive values and recall rates for full-term and preterm infants and sensitivity for milder forms of CAH.
  
  
  RESULTS
  A total of 143 patients with salt-wasting CAH were identified; none were missed. The sensitivity was lower for milder forms of the disorder (P = .04), including 79.7% for simple virilizing forms and 32.4% for nonclassic forms. The positive predictive value was higher in full-term (25.1%) than preterm (1.4%) infants and correlated with gestational age (r = 0.98; P < .001). The recall rate in full-term infants (0.03%) was lower than that in preterm infants (0.57%) (P < .001). An analysis of previously reported results from other screening programs revealed that the sensitivity of the screening was negatively correlated with the duration of follow-up (P = .03).
  
  
  CONCLUSIONS
  Screening for CAH was highly effective in detecting the salt-wasting form and thereby reducing mortality. Additional late-onset cases of CAH were detected in childhood and adolescence, reducing the sensitivity for milder forms. The positive predictive value was high despite a low recall rate in full-term infants. Further improvements are necessary to increase the effectiveness of screening among preterm infants.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden2Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gidlöf
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden4Center for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wedell
authors.affiliation: Center for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Guthenberg
authors.affiliation: Center for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden5Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: von Döbeln
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden4Center for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden6Department of Pediatric Endocrinology, Astrid Lindgren Children's Hospital, Ka.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordenström
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008137:Longitudinal Studies; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013548:Sweden
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase