scholarly journals SAT-098 The Impact of 17-OHP Cutoffs Determination in a Public Newborn Screening Program for Congenital Adrenal Hyperplasia in Southern Brazil: A Three Years’ Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Cristiane Kopacek ◽  
Paloma Wiest ◽  
Simone Martins de Castro ◽  
Poli Mara Spritzer
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
False Positive ◽  
Neonatal Screening ◽  
Screening Program ◽  
Southern Brazil ◽  
Adrenal Hyperplasia ◽  
Predictive Values ◽  
Live Births ◽  
Classic Cah ◽  
Weight Groups

Abstract Congenital adrenal hyperplasia (CAH), an autosomal recessive disease, is characterized by impairment of metabolic cortisol synthesis, with or without insufficient aldosterone production. It is caused by mutations in the CYP21A2 gene in approximately 90% of all cases, leading to 21-hydroxylase deficiency and androgen precursors elevation. The main disease marker is 17-hydroxyprogesterone (17-OHP). Early diagnosis through neonatal screening (NS) allows proper treatment and reduces mortality. In Brazil, the average incidence of the classic form of CAH ranges from 1: 7,500 to 1: 18,000 live births. Objective: To determine the 17-OHP cutoffs ​​for newborn screening to diagnose Congenital Adrenal Hyperplasia (CAH) in a Public Neonatal Screening Program in Southern Brazil. Materials and Methods: A retrospective, descriptive, cross-sectional study was carried out for analysis of dried blood test results on the 17-OHP paper filter of 317,745 newborns screened by a public neonatal screening center from May 2014 to April 2017. CAH-C was defined as NB with elevation of 17-OHP confirmed by retest and/or clinical evaluation, followed by genotype study. False positive cases (FP) were characterized by absence of genital alterations and/or loss of salt, with normalization of 17-OHP levels on retest. For the determination of the cutoffs ​​according to the four weight groups (WG) (WG1 ≤1,500 g, WG2 1,501 to 2,000 g, WG3 2,001 to 2,500 g and WG4 ≥ 2,501 g), the percentiles 97.5, 98.5, 99.5 and 99.8 were calculated. Sensitivity, specificity, positive predictive values ​​(PPV), negative predictive values ​​(NPV) were performed for the four WG. Results: Based on the descriptive analysis of the data, the incidence of CAH for the state of Rio Grande do Sul was 1:15,887 live births, with 20 cases of classic CAH being diagnosed during this period, and 17-OHP values ​​ranged from 32.50 ng/mL to 733.00 ng/mL in WG 2,000 g to 2,500 g and WG ≥ 2,501 g. No confirmed cases of CAH were detected for WG ≤ 1,500 g and 1,501 g at 2,000 g until the time of analysis of this study. Most (80.73%) newborns were caucasian and prematurity rate was 9.8% of the study population. The median and average (days) of first sample collection was 5 and 5.83, while for retest was 21 and 25.97 respectively. The cutoffs change from the 99th percentile to the 98.5 for the weight group between 2,001 g and 2,500 g and to the 99.8 for the other weight groups, decreasing false positive results and increasing specificity compared to current reference values ​​to identify classic CAH cases. Conclusion: The new 17-OHP cutoffs ​​specified were, for all weight groups, higher than currently used by this screening program. The calculation of reference values ​​from local population data and the combination of percentages prove to be an important tool for proper diagnosis of CAH cases and reduction of the number of FP newborns.

scholarly journals High Reliability of Neonatal Screening for Congenital Adrenal Hyperplasia in Switzerland

2002 ◽  
Vol 87 (9) ◽  
pp. 4106-4110 ◽  
Author(s):  
Michael Steigert ◽  
Eugen J. Schoenle ◽  
Anna Biason-Lauber ◽  
Toni Torresani
Keyword(s):  
Positive Predictive Value ◽  
Congenital Adrenal Hyperplasia ◽  
Predictive Value ◽  
Neonatal Screening ◽  
Screening Program ◽  
High Reliability ◽  
Dried Blood Spots ◽  
Recall Rate ◽  
Adrenal Hyperplasia ◽  
Salt Wasting

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children’s Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.

scholarly journals Ten-year evaluation of a Neonatal Screening Program for Congenital Adrenal Hyperplasia

2014 ◽  
Vol 58 (7) ◽  
pp. 765-771 ◽  
Author(s):  
Marilza Leal Nascimento ◽  
Anísia Nhelety Baptista Cristiano ◽  
Tatiane de Campos ◽  
Masanao Ohira ◽  
Edson Cechinel ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Screening Program ◽  
Clinical Manifestations ◽  
The State ◽  
Adrenal Hyperplasia ◽  
Santa Catarina ◽  
Salt Wasting ◽  
Neonatal Screening Program ◽  
Treatment Onset

Objective Evaluate the Neonatal Screening Program (NSP) for congenital adrenal hyperplasia (CAH) of the Department of Health of the State of Santa Catarina (Secretaria de Estado da Saúde de Santa Catarina, SES/SC), and provide information to improve the program. Subjects and methods Descriptive, retrospective study of 748,395 children screened between January 2001 and December 2010. We analyzed the coverage of the NSP-SES/SC prevalence of CAH, child’s age when the first sample for 17-hydroxyprogesterone (17OHP) measurement was collected, levels of 17OHP, mean age at treatment onset and main clinical manifestations. Results The NSP-SES/SC covered 89% of the live newborns in the State. It diagnosed 50 cases of CAH, yielding an incidence of 1:14,967. Mean age at collection of the first sample was 7.3 days and mean level of 17OHP was 152.9 ng/mL. The most frequent manifestations were virilized genitalia with nonpalpable gonads, clitoromegaly and genital hyperpigmentation. In three girls, the genre established at birth was incorrect. The salt-wasting form was present in 74% of the cases. There was no occurrence of shock or death. Mean age at treatment onset in the salt-wasting form was 17.4 days compared with 54.9 days in those without the salt-wasting form of the disease. All children were treated with hydrocortisone, and those with salt-wasting CAH were also treated with fludrocortisone. Conclusions The incidence of CAH was 1 case to 14,967 live newborns. Collection of the first sample occurred outside the recommended time, resulting in delays in treatment onset.

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

2001 ◽  
Vol 55 (6) ◽  
pp. 271-277 ◽  
Author(s):  
Laura Gruñeiro-Papendieck ◽  
Laura Prieto ◽  
Ana Chiesa ◽  
Sonia Bengolea ◽  
Graciela Bossi ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Screening Program ◽  
Adrenal Hyperplasia ◽  
Recall Protocol ◽  
Neonatal Screening Program

Evaluation of the Dutch neonatal screening for congenital adrenal hyperplasia

2019 ◽  
Vol 104 (7) ◽  
pp. 653-657 ◽  
Author(s):  
Annelieke A A van der Linde ◽  
Yvonne Schönbeck ◽  
Hetty J van der Kamp ◽  
Erica L T van den Akker ◽  
Mirjam E van Albada ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
High Specificity ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Period 2 ◽  
Classic Cah ◽  
Screening Sensitivity ◽  
Simple Virilizing ◽  
Screening Result

BackgroundIn 2002, a nationwide screening for congenital adrenal hyperplasia (CAH) was introduced in the Netherlands. The aim of our study is to evaluate the validity of the neonatal screening for CAH and to assess how many newborns with salt-wasting (SW) CAH have already been clinically diagnosed before the screening result was known.MethodsRetrospective, descriptive study. The following data of patients with positive screening results since implementation of the screening programme were collected (1 January 2002 up until 31 December 2013): gestational age, sex, diagnosis, clinical presentation and contribution of screening to the diagnosis.ResultsIn the evaluated period, 2 235 931 newborns were screened. 479 children had an abnormal screening result, 133 children were diagnosed with CAH (114 SW, 14 simple virilizing (SV)), five non-classic CAH. During this period, no patients with SW CAH were missed by neonatal screening (sensitivity was 100%). After exclusion of 17 cases with missing information on diagnosis, specificity was 99.98% and positive predictive value was 24.7%. Most false positives (30%) were attributable to prematurity. Of patients with SW CAH, 68% (71/104) patients were detected by neonatal screening and 33 (33/104) were clinically diagnosed. Of girls with SW CAH, 38% (14/37) were detected by neonatal screening and 62% (23/37) were clinically diagnosed.ConclusionThe Dutch neonatal screening has an excellent sensitivity and high specificity. Both boys and girls can benefit from neonatal screening.

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

2009 ◽  
Vol 161 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Paolo Cavarzere ◽  
Dinane Samara-Boustani ◽  
Isabelle Flechtner ◽  
Michèle Dechaux ◽  
Caroline Elie ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
False Positive ◽  
Neonatal Screening ◽  
False Positive Rate ◽  
Clinical Signs ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Hydroxylase Gene ◽  
21 Hydroxylase Deficiency ◽  
L 14

ObjectiveNeonatal 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 (hyper-17-OHPemia) and to compare them with false positive and affected by 21-hydroxylase deficiency newborns.MethodsWe 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.ResultsThirty-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.ConclusionWe 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.

scholarly journals Neonatal screening for congenital adrenal hyperplasia in Southern Brazil: a population based study with 108,409 infants

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Cristiane Kopacek ◽  
Simone Martins de Castro ◽  
Mayara Jorgens Prado ◽  
Claudia Maria Dornelles da Silva ◽  
Luciana Amorim Beltrão ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Population Based ◽  
Southern Brazil ◽  
Adrenal Hyperplasia ◽  
Population Based Study

scholarly journals Central Precocious Puberty as a Sign of Congenital Adrenal Hyperplasia: Case Presentations

2020 ◽  
pp. 188-190
Author(s):  
R.L. Markosyan ◽  
◽  
L.V. Navasardyan ◽  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Precocious Puberty ◽  
Neonatal Screening ◽  
Screening Program ◽  
Case Reports ◽  
Central Precocious Puberty ◽  
Current Work ◽  
Endocrine Disorders ◽  
Adrenal Hyperplasia ◽  
Case Presentations

Central precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. Rarely congenital adrenal hyperplasia and/or its inappropriate treatment can be a peripheral cause of CPP. There are very few case reports of this etiology. Chronic mildly to moderately elevated adrenal androgens or intermittent hyperandrogenemia in congenital adrenal hyperplasia may trigger the precocious activation of the hypothalamic-pituitary axis, leading to CPP. In the current work, we describe 6 cases of late diagnosis of congenital adrenal hyperplasia associated with central precocious puberty. Central precocious puberty seems to be a complication of congenital adrenal hyperplasia, particularly in countries where a routine neonatal screening program for this condition is lacking. It is unclear whether these patients could avoid central precocious puberty development if the congenital adrenal hyperplasia was diagnosed in the neonatal period and appropriately treated. The current work underlines the need for congenital adrenal hyperplasia neonatal screening implementation and further investigation of the association of these two endocrine disorders.

scholarly journals Cognitive Function of Children and Adolescents With Congenital Adrenal Hyperplasia: Importance of Early Diagnosis

2020 ◽  
Vol 105 (3) ◽  
pp. e683-e691 ◽  
Author(s):  
Valeria Messina ◽  
Leif Karlsson ◽  
Tatja Hirvikoski ◽  
Anna Nordenström ◽  
Svetlana Lajic
Keyword(s):  
Early Diagnosis ◽  
Executive Functions ◽  
Congenital Adrenal Hyperplasia ◽  
Children And Adolescents ◽  
Replacement Therapy ◽  
Neonatal Screening ◽  
Screening Program ◽  
Intellectual Ability ◽  
Adrenal Hyperplasia ◽  
Population Controls

Abstract Context Patients with classic congenital adrenal hyperplasia (CAH) are treated postnatally with lifelong glucocorticoid (GC) replacement therapy. Previous results on general cognitive ability in individuals with CAH have been conflicting. Objective To evaluate long-term cognitive effects of GC replacement therapy and the impact of early diagnosis in children with CAH. Design and Setting Observational study with patients from a single research institute. Patients 32 children with CAH (mean age 11.5 years) identified through the Swedish national neonatal screening program for CAH and 52 matched population controls (mean age 10.7 years). Eleven (6 female) children with CAH who were treated prenatally with dexamethasone (DEX), (CAH-DEX) (mean age 11.7 years). Intervention GC replacement therapy, neonatal screening for CAH. Measures Cognitive abilities assessed with standardized neuropsychological tests (Wechsler scales, Span Board Test, Stroop Interference Test, NEPSY list learning). Results Children with CAH (not prenatally treated) performed equally well as population controls on a series of tests assessing general intellectual ability and executive functions. No significant differences were observed in cognitive performance between patients with different genotypes (null, non-null). Patients with salt-wasting CAH performed poorer than patients with simple virilizing CAH in a test assessing visuo-spatial working memory (P = 0.039), although the performance was within the normal range for the population. Prenatally DEX-treated girls with CAH had lower verbal intellectual ability compared with CAH girls not exposed to prenatal treatment (P = 0.037). Conclusion Children and adolescents with CAH who were diagnosed early via a neonatal screening program and treated with hydrocortisone had normal psychometric intelligence and executive functions.

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