scholarly journals Newborn Screening for CAH—Challenges and Opportunities

2021 ◽  
Vol 7 (1) ◽  
pp. 11
Author(s):  
Natasha L. Heather ◽  
Anna Nordenstrom
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Adrenal Hyperplasia ◽  
Challenges And Opportunities ◽  
17 Hydroxyprogesterone

Newborn screening for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone (17-OHP) as an indicator of disease was first introduced in the 1970s [...]

High frequency of non-classical congenital adrenal hyperplasia form among children with persistently elevated levels of 17-hydroxyprogesterone after newborn screening

2019 ◽  
Vol 32 (5) ◽  
pp. 499-504
Author(s):  
Patrícia S. Castro ◽  
Tatiana O. Rassi ◽  
Raquel F. Araujo ◽  
Isabela L. Pezzuti ◽  
Andresa S. Rodrigues ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Molecular Analysis ◽  
High Frequency ◽  
Clinical Status ◽  
Confirmatory Test ◽  
Adrenal Hyperplasia ◽  
Asymptomatic Children ◽  
17 Hydroxyprogesterone

Abstract Background Early diagnosis after newborn screening (NBS) for congenital adrenal hyperplasia (CAH) allows proper treatment, reducing mortality rates and preventing development of hyperandrogenic manifestations and incorrect sex assignment at birth. Despite the high NBS sensitivity to detect CAH classical forms, one of the main issues is identifying asymptomatic children who remained with increased 17-hydroxyprogesterone (17-OHP) levels. In this study, we aimed to contribute to understanding the diagnosis of these children. Methods Children with increased serum 17-OHP levels, and without disease-related clinical features during follow-up, underwent the entire CYP21A2 gene sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis (SALSA MLPA P050B CAH). Patients’ genotypes were subsequently sorted as compatible with CAH disease, and children were evaluated to determine the clinical status. Results During the study period, 106,476 newborns underwent CAH NBS. During follow-up, 328 children (0.3%) were identified as having false-positive tests and 295 were discharged after presenting with 17-OHP levels within reference values. Thirty-three remained asymptomatic and with increased serum 17-OHP levels after a mean follow-up of 3.4 years, and were subjected to molecular analysis. Seventeen out of the 33 children carried mutations: seven in the heterozygous state, nine carried non-classical genotypes and the remaining child carried a classical genotype. Conclusions We found a high frequency of non-classical CAH (NCCAH) diagnosis among children with persistent elevation of 17-OHP levels. Our findings support molecular study as decisive for elucidating diagnosis in these asymptomatic children. Molecular analysis as a confirmatory test is relevant to guide their follow-up, allows genetic counseling and avoids over treating NCCAH form.

Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels

1997 ◽  
Vol 130 (1) ◽  
pp. 128-133 ◽  
Author(s):  
David B. Allen ◽  
Gary L. Hoffman ◽  
Patrick Fitzpatrick ◽  
Ronald Laessig ◽  
Sharon Maby ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Adrenal Hyperplasia ◽  
17 Hydroxyprogesterone

scholarly journals Comparison of different preparation techniques of dried blood spot quality controls in newborn screening for congenital adrenal hyperplasia

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252091
Author(s):  
Nóra Grecsó ◽  
Anita Zádori ◽  
Ákos Baráth ◽  
Zsolt Galla ◽  
Gábor Rácz ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Dried Blood Spots ◽  
Dried Blood Spot ◽  
Adrenal Hyperplasia ◽  
Freeze Thaw ◽  
Quality Controls ◽  
17 Hydroxyprogesterone ◽  
Preparation Techniques ◽  
Blood Spot

In newborn screening, samples suspected for congenital adrenal hyperplasia (CAH), a potentially lethal inborn error of steroid biosynthesis, need to be confirmed using liquid chromatography–tandem mass spectrometry. Daily quality controls (QCs) for the 2nd-tier CAH assay are not commercially available and are therefore generally prepared within the laboratory. For the first time, we aimed to compare five different QC preparation approaches used in routine diagnostics for CAH on the concentrations of cortisol, 21-deoxycortisol, 11-deoxycortisol, 4-androstenedione and 17-hydroxyprogesterone in dried blood spots. The techniques from Prep1 to Prep5 were tested at two analyte concentrations by spiking aliquots of a steroid-depleted blood, derived from washed erythrocyte suspension and steroid-depleted serum. The preparation processes differed in the sequence of the preparation steps and whether freeze-thaw cycles were used to facilitate blood homogeneity. The five types of dried blood spot QCs were assayed and quantitated in duplicate on five different days using a single calibration row per day. Inter-assay variations less than 15% and concentrations within ±15% of the nominal values were considered acceptable. Results obtained by means of the four dried blood spot QC preparation techniques (Prep1, Prep2, Prep4 and Prep5) were statistically similar and remained within the ±15% ranges in terms of both reproducibility and nominal values. However, concentration results for Prep3 (spiking prior to three freeze-thaw cycles) were significantly lower than the nominal values in this setting, with differences exceeding the ±15% range in many cases despite acceptable inter-assay variations. These findings have implications for the in-house preparation of QC samples in laboratory developed tests for CAH, including 2nd-tier assays in newborn screening.

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

2017 ◽  
Vol 86 (4) ◽  
pp. 480-487 ◽  
Author(s):  
Giselle Y. Hayashi ◽  
Daniel F. Carvalho ◽  
Mirela C. de Miranda ◽  
Cláudia Faure ◽  
Carla Vallejos ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Adrenal Hyperplasia ◽  
Sample Collection ◽  
17 Hydroxyprogesterone

scholarly journals 30 Predicting gestational age improves newborn screening for congenital adrenal hyperplasia

2020 ◽  
Vol 25 (Supplement_2) ◽  
pp. e11-e11
Author(s):  
Danny Jomaa ◽  
Matthew Henderson ◽  
Steven Hawken ◽  
Pranesh Chakraborty
Keyword(s):  
Positive Predictive Value ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Gestational Age ◽  
Predictive Value ◽  
False Positive ◽  
False Positive Rate ◽  
Adrenal Hyperplasia ◽  
Positive Rate ◽  
17 Hydroxyprogesterone

Abstract Background Newborn screening for congenital adrenal hyperplasia is performed using a two-tier approach. The first tier involves comparison of neonate 17-hydroxyprogesterone levels to gestational age (GA)-based thresholds. When GA is unreported, which occurs in approximately 5% of births, birth weight (BW)-based thresholds are the only available option. However, these have a lower specificity and result in more false positive results. Recently, a predictive model was developed to estimate GA based on newborn demographics and the screening analytes measured in a blood sample. Objectives The objective of this study was to determine whether supplying a predicted GA to newborns with unreported GA, and subsequent GA-based screening, has a higher positive predictive value than BW-based screening. Design/Methods Screening data was obtained for approximately 700,000 births that occurred in Canada between 2011 and 2015. Predicted GA was calculated using a model composed of demographic and screening analyte factors. The positive predictive values of BW- and predicted GA-based screening were calculated for newborns with unreported GA. A sequential approach was then developed whereby newborns with unreported GA were first screened by BW-based screening. Newborns that screened positive were then supplied with their predicted GA and screened using GA-based thresholds. Results First-tier CAH screening using GA-based 17-hydroxyprogesterone thresholds had a higher positive predictive value than using BW-based thresholds (1.30% vs. 0.82%). In the study time period, 3.61% of newborns had an unreported GA. For these newborns, predicted GA-based screening had a higher positive predictive value than BW-based screening (0.83% vs. 0.76%) and correctly identified the 2 infants with CAH whose GA was unreported. A sequential screening approach was then used: BW-based screening and, for the screen positive population, predicted GA-based screening. This further increased the positive predictive value compared to BW-based screening (0.95% vs. 0.76%), reduced the false positive rate, and correctly identified true positive cases. Conclusion Reducing the false positive rate of CAH screening is important to prevent unnecessary second-tier screening and referrals. For newborns with unreported GA (4-5% of all births), BW-based screening is the only currently available approach. However, this approach has a poor specificity and a high false positive rate compared to GA-based screening. This study is the first to demonstrate an alternative screening strategy with a higher positive predictive value for newborns with unreported GA.

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