title: Cutoff levels of 17-alpha-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight.
abstract: OBJECTIVE
  In newborn screening programs for congenital adrenal hyperplasia, 17-alpha-hydroxyprogesterone (17OHP) cutoff levels are based on birth weight (BW) or on gestational age (GA). We investigated which approach would result in the greatest specificity and sensitivity.
  
  
  METHODS
  For the determination of 17OHP, a neonatal 17OHP assay was used in filter paper blood of 9492 newborns. The relationships between 17OHP and BW and between 17OHP and GA were studied by regression analysis. Reference curves with a specificity of 99.95% were constructed with the method that summarizes the distribution by three smoothed curves representing the skewness (L curve), the median (M curve), and the coefficient of variation (S curve). Median cutoff levels for BW and for GA according to the 99.95% reference curves were calculated.
  
  
  RESULTS
  Regression analysis showed that GA is a better predictor of 17OHP than BW (R(2) was 50.6 vs. 35.8%, respectively). At a specificity of 99.95%, the calculated median 17OHP cutoff level was lower for GA [12.6 microg/liter (38 nmol/liter)] than for BW [17.6 microg/liter (54 nmol/liter)], thus leading to a greater sensitivity.
  
  
  CONCLUSIONS
  This study demonstrates that GA is a better predictor of 17OHP in newborns and will result in greater specificity than BW despite the fact that the determination of GA might be less reliable than BW.
authors.affiliation: Department of Pediatrics, H-3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. H.J.van_der_Kamp@LUMC.nl
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: van der Kamp
authors.forename: Caren G M
authors.initials: CG
authors.lastname: Oudshoorn
authors.forename: Bert H
authors.initials: BH
authors.lastname: Elvers
authors.forename: Maja
authors.initials: M
authors.lastname: van Baarle
authors.forename: Barto J
authors.initials: BJ
authors.lastname: Otten
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Paul H
authors.initials: PH
authors.lastname: Verkerk
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis*; D001724:Birth Weight; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening; D012044:Regression Analysis; D012680:Sensitivity and Specificity
chemical_list: D019326:17-alpha-Hydroxyprogesterone