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

• Published in: Clinical endocrinology (Oxford) 2017-04, Vol.86 (4), p.480-487
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: 17-alpha-Hydroxyprogesterone - blood; 17-alpha-Hydroxyprogesterone - standards; Adrenal glands; Adrenal Hyperplasia, Congenital - blood; Adrenal Hyperplasia, Congenital - diagnosis; Age Factors; Birth Weight; Blood Specimen Collection - methods; Chromatography, Liquid; False Positive Reactions; Fluoroimmunoassay; Humans; Infant, Newborn; Mass Spectrometry; Medical screening; Neonatal Screening - methods; Reference Values
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.13292

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 (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. Methods Neonatal 17‐hydroxyprogesterone levels from 271 810 newborns (NBs) according to sample collection time (G1: 48–2500 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. 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 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 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 NBs 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 N17OHP values based upon the 99·8th percentile improved the NBS efficacy.