Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels

Objective: To evaluate the efficacy and efficiency of weight-adjusted threshold levels for 17-hydroxyprogesterone (17-OHP) in screening newborn infants for 21-hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH). Design: Analysis of the number of false-positive reports and diagnoses in infants, of 21-OH-D-CAH with the use of two strategies. Before October 1993, separate criteria for definite abnormal 17-OHP levels were established and implemented for 41,846 infants on the basis of birth weight: either less than 2200 gm (17-OHP level, 90 ng/ml) or 2200 gm or more (40 ng/ml). To reduce the burden of follow-up testing in low birth weight infants, criteria for definite abnormal 17-OHP results were statistically determined for four, rather than two, birth weight divisions: 1299 gm or less (17-OHP level greater than or equal to 165 ng/ml), 1300 to 1600 gm (greater than or equal to 135 ng/ml), 1700 to 2200 gm (greater than or equal to 90 ng/ml), and more than 2200 gm (greater than or equal to 40 ng/ml). These criteria were applied to the next 149,684 infants screened, and rates of false-positive test results and of false-positive diagnoses of 21-OH-D-CAH were compared. Results: Before implementation of four-tiered weight-adjusted 17-OHP criteria, 205 definite abnormal reports yielded four confirmed cases of 21-OH-D-CAH (positive predictive value = 2%; incidence of 21-OH-D-CAH = 1 in 10,461). With the revised criteria, 61 of 149,684 infants had definite abnormal results and 14 cases of 21-OH-B-CAH were confirmed (positive predictive value, 20%; incidence of 21-OH-D-CAH, 1 in 10,692). No undetected severe cases of 21-OH-D-CAH have been subsequently reported. Conclusions: Weight-adjusted criteria for 17-OHP levels in screening for 21-OH-D-CAH markedly reduced the number of false-positive results requiring immediate follow-up testing, particularly among low birth weight infants. Increased specificity afforded by these criteria was not accompanied by diminished sensitivity in detecting severe cases. Long-term follow-up of this screened cohort will determine whether the goals of newborn screening for 21-OH-D-CAH are adequately and efficiently fulfilled by this approach.