Newborn Screening for Congenital Adrenal Hyperplasia inthe Netherlands

Kamp, H.J. van der; Noordam, C.; Elvers, Bert; Baarle, Maja van; Otten, Barto J.; Verkerk, P.H.

doi:10.1542/peds.108.6.1320

Cited by 73 publications

(82 citation statements)

References 10 publications

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“…However, our findings are similar to the worldwide incidence of CAH, ranging from 1:10,870 in Mediterranean areas to 1:25,000 in Belgium [4, 18]. Moreover, it is possible that the immigration flows towards Italy in the last decade may have contributed to the variation of the incidence.…”

Section: Discussionsupporting

confidence: 86%

Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: A Report Three Years into the Program

et al. 2005

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Aims: To evaluate the incidence of congenital adrenal hyperplasia (CAH) in the Northern Italian population and the efficiency of the North-Eastern Italy screening program. To adjust cut-off levels for 17-hydroxyprogesterone (17-OHP) in relation to gestational age and birth weight, comparing the benefits in terms of reduction of recall rates with the two approaches and ultimately choosing the better of the two. Subjects and Methods: Since September 2001, blood samples from neonates born in North-Eastern Italy have been screened with a fluoroimmunoassay method for 17-OHP determination (DELFIA). A preliminary cut-off level of ≧30 nmol/l was set both for term and preterm newborns. The values of 17-OHP were analysed usingstatistical methods in relation to gestational age and birth weight in order to modify the cut-off on the basis of our data. Results: After 33 months of screening we screened 128,282 newborns and detected 6 affected babies. During the first 8 months of screening among the recalled babies, 89.6 and 78.1% were preterm and low-birth-weight newborns, respectively, with a recall rate of 2.59% for premature neonates and of 4.94% for babies with birth weights <2,500 g. We chose a new cut-off value of 50 nmol/l for preterm newborns only and, after 4 months, the recall rate was reduced to 0.83% for these infantsand to 1.83% for low-birth-weight infants. Conclusion: After 33 months of screening for CAH in North-Eastern Italy, we report an incidence of 1:21,380. In 5 out of 6 affected babies, the diagnosis was established only after a positive screening test, which prevented a severe salt-wasting crisis in these babies. The cut-off level related to gestational age led to a significant reduction in the number of false-positives among preterm babies.We therefore intend to continue with the screening program for CAH in North-Eastern Italy, keeping a gestational-age-related cut-off in the hope that our data may encourage a national screening program for CAH.

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Section: Discussionsupporting

confidence: 86%

Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: A Report Three Years into the Program

et al. 2005

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“…Newborn screening based on measuring 17-OHP by immunoassay generated a high number of false-positive results in the past [21,36]. Even the collection of samples within 24 h of life can increase the rate of false positivity.…”

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

confidence: 99%

“…After various pilot projects [15][16][17], general NBS for classic CAH was introduced as part of the NBS in many countries worldwide [7,[18][19][20][21][22][23][24]. However, in the beginning of newborn screening, many laboratories have used an immunologic method to measure 17-OHP.…”

Section: Newborn Screening For Classic Cahmentioning

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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“…By using a less stringent cut-off value for normals, i.e. 37.5 -40 nmol/l 17-OHP in blood (7,26), approximately half of our moderate CAH patients would not have been detected. An increased cut-off value is used by some groups in order to reduce the number of false-positive measurements and to avoid unnecessary stress for the parents.…”

Section: Discussionmentioning

confidence: 96%

“…Thus, the determination of the rate of false-positive measurements has been an important issue since the introduction of CAH screening (11,27). Eventually, this rate could be reduced to 0.2 -0.9% by the introduction of birth weight-or gestational age-adjusted cut-off values and by application of the DELFIA time-resolved fluoroimmunoassay (23,26). This assay currently produces the most specific, but still not accurate, estimates for 17-OHP in screening (11,28).…”

Section: Discussionmentioning

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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Newborn Screening for Congenital Adrenal Hyperplasia inthe Netherlands

Abstract: Severe salt wasting can be prevented by neonatal screening. The prevalence, specificity, and sensitivity allowed addition of screening for CAH to the routinely performed national neonatal screening program.

Cited by 73 publications

References 10 publications

Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: A Report Three Years into the Program

Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: A Report Three Years into the Program

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

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

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