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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.,
Miranda Mirela C.,
Faure Cláudia,
Vallejos Carla,
Brito Vinícius N.,
Rodrigues Andresa De Santi,
Madureira Guiomar,
Mendonca Berenice B.,
Bachega Tânia A.S.S.
Publication year - 2017
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13292
Subject(s) - congenital adrenal hyperplasia , percentile , newborn screening , medicine , asymptomatic , hydroxyprogesterone , obstetrics , endocrinology , pediatrics , steroid , mathematics , hormone , statistics
Summary Introduction The 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. Objective To determine the neonatal 17‐hydroxyprogesterone (N17 OHP ) 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. Methods Neonatal 17‐hydroxyprogesterone levels from 271 810 newborns ( NB s) 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. N17 OHP was measured by an fluoroimmunoassay, and serum 17 OHP was measured by liquid chromatography‐mass spectrometry. Affected and asymptomatic NB s with persistently increased 17 OHP levels were submitted to CYP 21A2 ‐sequencing. Results Neonatal 17‐hydroxyprogesterone levels in G1 were lower than G2 in all BW groups ( P < 0·001). The FPR rate in G1/G2 was 0·2% using the 99·8th and 0·5% using the 99·5th percentile. The 99·8th percentile N17 OHP value was the best cut‐off for distinguishing between unaffected and affected NB s. Forty‐four salt wasters, and five simple virilisers were diagnosed; N17 OHP levels ranged from 93·3 to 2209·8 nmol/l, and no affected neonates with FNR were identified. The positive predictive value in G1 and G2 using the 99·8th percentile was 5·6% and 14·1%, respectively, and 2·3% and 7%, respectively, using the 99·5th percentile. Molecular tests identified two NB s with the nonclassical form among the 29 FPR . Conclusion Neonatal 17‐hydroxyprogesterone levels adjusted to sample collection age and birthweight reduced the FPR , and the use of N17 OHP values based upon the 99·8th percentile improved the NBS efficacy.