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

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Abstract

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 ≥165 ng/ml), 1300 to 1600 gm (≥135 ng/ml), 1700 to 2200 gm (≥90 ng/ml), and more than 2200 gm (≥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-D–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. (J Pediatr 1997;130:128-33)

Section snippets

METHODS

In March 1993, screening for CAH was added to the battery of tests routinely performed on approximately 70,000 newborn infants each year in Wisconsin. Dried whole blood samples, collected on filter paper at the time of hospital discharge, were assayed for 17-OHP by polyclonal antibody radioimmunoassay (Neonatal 17-OH Progesterone Kit; Diagnostic Products Corp.). Electronic processing of the raw data from a gamma counter (model 1290, TM Analytic, Inc., Elk Grove Village, Ill.) produced a

RESULTS

Results are summarized in Table III.

. Implementation of multitiered versus two-tiered weight-adjusted criteria for CAH screening in newborn infants

Empty CellEmpty CellInfant birth weight*Empty CellEmpty Cell
Strategy (n)Abnormal report classification<2200 gm≥2200 gmPositive predictive value of testCAH Incidence
Two-tiered criteria (oneDefinite58 (0)153 (4)2%1:10,461
LBW division) [41,846]Possible161 (0)0 (0)0%
Retrospective application ofDefinite6 (0)5 (2)18%1:10,461
multitiered criteria (i.e. 3
LBW divisions) to initialPossible27 (0)113 (2)

DISCUSSION

The development of an assay for the 17-OHP concentration using a heel-stick capillary blood specimen impregnated on filter paper made screening for 21-OH-D–CAH possible. 5 A pilot newborn screening program in Alaska first demonstrated the feasibility of newborn screening for CAH. 6 Experience gleaned from this and other early programs suggests that early diagnosis and treatment of affected but symptom-free boys can be accomplished with filter-paper newborn screening. 7 However, although pilot

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Reprint requests: David B. Allen, MD, H4/448 CSC—Pediatrics, 600 Highland Ave., Madison, WI 53792.

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