Neonatal Screening Program for Congenital Adrenal Hyperplasia: Adjustments to the Recall Protocol

Gruñeiro‐Papendieck, Laura; Prieto, Laura; Chiesa, Ana; Bengolea, Sonia V.; Bossi, G; Bergadá, C

doi:10.1159/000050012

Cited by 39 publications

(26 citation statements)

References 14 publications

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“…Even the collection of samples within 24 h of life can increase the rate of false positivity. Low birth weight, prematurity and birth stress cause high 17-OHP levels [25,27,37]. Gidlof et al analysed the screening data from Sweden where 2 737 932 infants (99.8%) underwent testing between 1 January 1986 until 31 December 2011 [23].…”

Section: Problems With False-positive and False Negative-resultsmentioning

confidence: 99%

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Dörr

Odenwald²,

Nennstiel-Ratzel³

2015

IJNS

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Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessively inherited disorders of cortisol biosynthesis in the adrenal cortex. More than 95% are based on a defect in the CYP21A2 gene causing 21-hydroxylase deficiency. Newborn screening (NBS) for CAH by means of 17-hydroxy-progesterone (17-OHP) determination in dried whole blood on filter paper has been introduced as part of the NBS in many countries worldwide. The goals of CAH screening are early detection of the severe, salt-wasting form, therefore prevention of adrenal crisis or death, early detection of the simple virilizing form, and prevention or shortening of the period of incorrect gender assignment in females. Methodological problems of false-positive samples, especially in pre-term infants, can be corrected by adapting the cut-off values for 17-OHP to birth weight, gestational age and age at the time of collection and by performing a second tier screening. Despite a positive voting for newborn CAH screening by the European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society, it is obvious that the acceptance of CAH screening varies worldwide.

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Section: Problems With False-positive and False Negative-resultsmentioning

confidence: 99%

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Dörr

Odenwald²,

Nennstiel-Ratzel³

2015

IJNS

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“…In fact, hyperbilirubinemia may contribute to higher 17-OHP values due to the effect of dehydration on blood concentration (24), and neonatal stress may increase ACTH and 17-OHP levels (19). However, six simple false-positive neonates presented the same neonatal pathologies without any elevation of serum 17-OHP levels.…”

Section: Discussionmentioning

confidence: 96%

“…Therefore, the different screening programs have established 17-OHP cut-off levels in relation to gestational age (GA) (13,(16)(17)(18)(19)(20) or BW (21,22), so that the falsepositive rate could be reduced.…”

Section: Introductionmentioning

confidence: 99%

Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia

Cavarzere

Samara-Boustani²,

Flechtner³

et al. 2009

European Journal of Endocrinology

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Objective: Neonatal screening for congenital adrenal hyperplasia (CAH) is characterized by a high false-positive rate, mainly among preterm and low birth weight infants. The aims of this study were to describe a subgroup of infants with transient serum hyper-17-hydroxyprogesteronemia and to compare them with false positive and affected by 21-hydroxylase deficiency newborns. Methods: We retrospectively analyzed the clinical data of all newborns positive at CAH neonatal screening, who were referred to our hospital to confirm the diagnosis from 2002 to 2006. They were submitted to clinical investigations and blood tests to evaluate 17-hydroxyprogesterone (17-OHP), renin, and electrolyte levels. CAH-unaffected newborns with increased serum 17-OHP were submitted to strict follow-up monitoring, which included an ACTH-stimulating test and genetic analysis of the 21-hydroxylase gene, until serum 17-OHP decreased. Results: Thirty-seven newborns with gestational ages ranging from 33 to 40 weeks were studied. Eight infants (three male and five female) were affected by CAH (serum 17-OHP: 277.5 (210-921) nmol/l), 14 (ten male and four female) were false positives (17-OHP: 3.75 (0.3-8.4) nmol/l), and 15 (ten male and five female) showed a serum hyper-17-OHPemia (17-OHP: 15.9 (9.9-33) nmol/l). No mutations of the 21-hydroxylase gene were found in infants with hyper-17-OHPemia and their serum 17-OHP levels were normalized by the third month of life. Conclusion:We identified a population of infants with transient serum hyper-17-OHPemia, and no clinical signs of disease or 21-hydroxylase gene mutations. No further investigations are necessary after birth in these newborns if 17-OHP levels decrease, other confirmatory tests such as ACTH-stimulation test or genotyping analysis are necessary only if symptoms appear.

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“…In moderate forms irreversible harm may develop during prepuberty, i.e. progressive virilisation, pseudo-precocious puberty and accelerated bone maturation with reduced final height (1,(8)(9)(10). One strategy for avoiding these disadvantages has been the introduction of newborn screening for CAH, based on the measurement of the 17a-hydroxyprogesterone (17-OHP) level in blood samples collected on filter paper by means of a heel-stick (8,11,12).…”

Section: Introductionmentioning

confidence: 99%

Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia

et al. 2005

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Objective: Newborn screening based on measurement of 17a-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis; in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. Methods: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five MiddleEuropean countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. Results: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91 -1404 nmol/l) in subjects with the SW form and 40 nmol/l (4 -247 nmol/l) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 33 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. Conclusion: Newborn screening is efficient for diagnosing the SW form of CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH.European Journal of Endocrinology 152 869-874

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Neonatal Screening Program for Congenital Adrenal Hyperplasia: Adjustments to the Recall Protocol

Cited by 39 publications

References 14 publications

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia

Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia

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