Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening

Author(s)

Hayashi, Giselle Y. ; Carvalho, Daniel F. ; de Miranda, Mirela C. ; Faure, Claudia ; Vallejos, Carla ; Brito, Vinicius N. ; Rodrigues, Andresa De Santi ; Madureira, Guiomar ; Mendonca, Berenice B. ; Bachega, Tania A. S. S.

• Document type: Journal article
• Source: CLINICAL ENDOCRINOLOGY; v. 86, n. 4, p. 8-pg., 2017-04-01.

Abstract

IntroductionThe primary concern related to congenital adrenal hyperplasia (CAH) newborn screening (NBS) is the high rate of false-positive results (FPR) associated with prematurity; false-negative results (FNR) can also occur due to precocious sample collection. ObjectiveTo determine the neonatal 17-hydroxyprogesterone (N17OHP) normal range in newborns in Sao Paulo using different references according to age and birthweight (BW) and to establish the optimal NBS cut-off levels. MethodsNeonatal 17-hydroxyprogesterone levels from 271 810 newborns (NBs) according to sample collection time (G1: 48-<72 h and G2: 72 h) and BW (1500 g, 1501-2000 g, 2001-2500 and >2500 g) were evaluated. N17OHP was measured by an fluoroimmunoassay, and serum 17OHP was measured by liquid chromatography-mass spectrometry. Affected and asymptomatic NBs with persistently increased 17OHP levels were submitted to CYP21A2-sequencing. ResultsNeonatal 17-hydroxyprogesterone levels in G1 were lower than G2 in all BW groups (P < 0001). The FPR rate in G1/G2 was 02% using the 998th and 05% using the 995th percentile. The 998th percentile N17OHP value was the best cut-off for distinguishing between unaffected and affected NBs. Forty-four salt wasters, and five simple virilisers were diagnosed; N17OHP levels ranged from 933 to 22098 nmol/l, and no affected neonates with FNR were identified. The positive predictive value in G1 and G2 using the 998th percentile was 56% and 141%, respectively, and 23% and 7%, respectively, using the 995th percentile. Molecular tests identified two NBs with the nonclassical form among the 29 FPR. ConclusionNeonatal 17-hydroxyprogesterone levels adjusted to sample collection age and birthweight reduced the FPR, and the use of N17OHP values based upon the 998th percentile improved the NBS efficacy. (AU)

• FAPESP's process: 14/07878-4 - Improving the efficacy of congenital adrenal hyperplasia (CaH) diagnosis in the Brazilian newborn screening (NBs) program
• Grantee: Tania Aparecida Sartori Sanchez Bachega
• Support Opportunities: Regular Research Grants