• MeSH
• 17-alpha-Hydroxyprogesterone * blood   MeSH
• Time Factors MeSH
• Fluoroimmunoassay MeSH
• Adrenal Hyperplasia, Congenital * diagnosis   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Blood Specimen Collection * MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Neonatal screening for congenital adrenal hyperplasia (CAH) identifies a certain proportion of newborns with transient moderate elevation of 17-hydroxyprogesterone (17-OHP). These children require regular follow-up until normalization of their 17-OHP levels. We investigated the possibility of reducing the individuals' recall rates by using genetic methods on their original neonatal dried blood spots. PATIENTS AND METHODS: We analysed neonatal dried blood spots from 753 subjects with transiently elevated levels of 17-OHP. The CYP21A2 gene was sequenced to detect point mutations, and the presence of CYP21A2 was further confirmed by two methods utilizing the difference between CYP21A2 and its CYP21A1P pseudogene in the sequence of exon 3 (8-bp deletion). The accuracy of the methods was verified using samples from 70 subjects with known CYP21A2 mutations and 181 healthy children. RESULT: Among the 701 successfully sequenced samples from subjects with transiently elevated 17-OHP, 670 (95%) had no point mutations or novel variants in the CYP21A2 gene. We found no individuals carrying genotypes consistent with the diagnosis of CAH (i.e. homozygotes or compound heterozygotes for point mutations, large deletions or rearrangements). However, 21 heterozygous carriers of known point mutations that cause the classic and nonclassic forms of CAH were identified. Additionally, we detected eight heterozygous and two homozygous point variants with unknown functional significance. CONCLUSION: Although CAH caused by 21-hydroxylase deficiency could be genetically excluded with a reasonable degree of confidence in 95% of the genotyped subjects that had transiently elevated 17-OHP, the performance of the tests was suboptimal when performed using dried blood spots and time-consuming in comparison with the current practice of repeated measurements of 17-OHP. The introduction of this method into clinical practice seems to be impractical at this stage.

• MeSH
• 17-alpha-Hydroxyprogesterone blood   MeSH
• Point Mutation genetics   MeSH
• Genetic Testing methods   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Neonatal Screening MeSH
• Pseudogenes genetics   MeSH
• Steroid 21-Hydroxylase genetics   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Adrenogenital Syndrome diagnosis   prevention & control   congenital   MeSH
• Humans MeSH
• Amniotic Fluid analysis   MeSH
• Prenatal Diagnosis MeSH
• Progesterone MeSH
• Radioimmunoassay methods   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH

• MeSH
• Adrenogenital Syndrome diagnosis   MeSH
• Child MeSH
• Hypertrophy diagnosis   congenital   MeSH
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Progesterone analogs & derivatives   diagnostic use   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH

The aims were to summarize the experience and to determine the performance metrics of newborn screening (NBS) for congenital adrenal hyperplasia (CAH) in the Czech Republic. 17-Hydroxyprogesterone (17OHP) was measured in NBS samples prospectively in 545,026 newborns and retrospectively in 31 CAH patients born outside the study period. A total of 2,811 screened newborns had abnormal 17OHP; CAH was confirmed in 46 probands. One patient with a severe-moderate genotype of CAH had 17OHP below the cut-off and was diagnosed clinically. This corresponds to a screening sensitivity of 98% and a false positive rate (FPR) of 0.51%. The median of 17OHP in the most severe genotypes was 484 nmol/L (n = 21); in severe/moderate, 321 nmol/L (n = 30); in moderate, 61 nmol/L (n = 20); and in mild genotypes, 31 nmol/L (n = 7). NBS is efficient to detect severe CAH but may fail to detect milder variants. However, the FPR is too high but could be improved by application of a second tier test.

• MeSH
• 17-alpha-Hydroxyprogesterone blood   MeSH
• Biomarkers blood   MeSH
• False Positive Reactions MeSH
• Genetic Markers MeSH
• Genotype MeSH
• Adrenal Hyperplasia, Congenital blood   diagnosis   genetics   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Neonatal Screening methods   MeSH
• Prospective Studies MeSH
• Retrospective Studies MeSH
• Sensitivity and Specificity MeSH
• Steroid 21-Hydroxylase genetics   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Adrenogenital Syndrome therapy   MeSH
• Child MeSH
• Glucocorticoids therapeutic use   MeSH
• Progesterone analysis   MeSH
• Check Tag
• Child MeSH

• MeSH
• 17-alpha-Hydroxyprogesterone administration & dosage   MeSH
• Anovulation MeSH
• Follicle Stimulating Hormone, Human blood   metabolism   MeSH
• Luteinizing Hormone blood   metabolism   MeSH

Posouzení proveditelnosti a přínosu novorozeneckého screeningu kongenitální adrenální hyperplazie v podmínkách České republiky.metodickým základem screeningu je měření hladin 17-hydroxyprogesteronu v suché kapce fluoroimunoassayí systémem Wallac Delfia.Cílem je jednak ověření metodiky měření a interpretace hladin 17-hydroxyprogesteronu a jednak zhodnocení včasnosti záchytu CAH-zda se skutečně bude dařit v našich podmínkách zachytit onemocnění před jeho klinickou manifestací. Výstupem grantu bude doporučení o vhodnosti či nevhodnosti provádění screeningu CAH v podmínkách České republiky.; The assement of effectivity of the neonatal screening for congenital adrenal hyperplasia in the conditions of the Czech Republic,The screening is based on the measurement of the level of 17-alfa-hydroxyprogesterone in the dried blood spot.

• MeSH
• 17-alpha-Hydroxyprogesterone blood   MeSH
• Adrenal Hyperplasia, Congenital diagnosis   MeSH
• Sudden Infant Death etiology   MeSH
• Neonatal Screening MeSH
• Sex Distribution MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• perinatologie a neonatologie
• endokrinologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

Cíl: Deficit 21-hydroxylázy je v České republice ze všech osmnácti screenovaných nemocí zatížen nejvyšší frekvencí falešné pozitivity ("False Positivity Rate" – FPR). Cílem této práce bylo zjistit rozdíl FPR při hodnocení screeningových hodnot 17-hydroxyprogesteronu (17OHP) dle "cut-off" vztažených k porodní hmotnosti (PH) a vůči gestačnímu věku novorozence. Metody: Analýza zahrnovala 129 175 novorozenců z období 1. 1. 2015 až 31. 12. 2017, u kterých byla dostupná data o PH i gestačním věku. 17OHP byl stanoven v suchých kapkách krve (SKK) na novorozenecké screeningové kartičce fluorescenční imunoanalytickou metodou AutoDELFIA® PerkinElmer, firmy Wallac Oy, Finsko. Pozitivní nález (tj. koncentrace 17OHP nad "cut-off" hodnotou) spustil další vyšetřovací proces. Ve většině případů se jednalo o vyžádání opakovaného odběru SKK. Pokud nedošlo k poklesu 17OHP pod "cut-off", nebo při extrémně zvýšené koncentraci (tj. jednoznačné pozitivitě) 17OHP už v prvním pravidelném odběru SKK byl proband urgentně přijat na dětské oddělení k neodkladné konfirmaci diagnózy a neodkladnému zahájení léčby. Rozdíl FPR mezi 17OHP vůči PH a gestačnímu věku byl vyhodnocen pomocí statistické metody Adjusted Wald Interval for a Difference of Proportions with Matched Pairs (software R program). Výsledky: Ve sledované kohortě mělo celkem 393 novorozenců falešně pozitivní hodnotu 17OHP nad stávajícími "cut-off" vztaženými k PH. Při použití "cut-off" hodnot dle gestačního věku počet novorozenců s falešně pozitivní hodnotou 17OHP klesl na 295 při zachování stejné schopnosti detekce pacientů. Rozdíl FPR mezi oběma skupinami byl statisticky signifikantní. Závěry: Hodnocení 17OHP vůči gestačnímu věku signifikantně sníží FPR a tím i zátěž zdravé části novorozenecké populace.

In single ventricle patients, hemoptysis is a life-threatening complication. Development of hemoptysis is associa. Objective: False positive rate (FPR) in 21-hydroxylase deficiency screening tests is the highest of all screened diseases in the Czech Republic. The aim of this study was to evaluate the FPR for 17-hydroxyprogesterone (17OHP) decision limits based on gestational age and birthweight. Methods: The study included 129,175 newborns in Bohemian region during the period 2015–2017. 17OHP was analysed using the immune-analytic method (AutoDELFIA® PerkinElmer by Wallac Oy, Finland). 411 newborns have been screened as positive newborns. FPR was compared by statistic method Adjusted Wald interval for a difference of proportions with matched pairs (Software R program). Results: The diagnosis of 21-hydroxylase deficiency was confirmed in eighteen patients, 393 findings were false positive. Our study showed a statistically significant reduction of FPR using 17OHP decision limits based on gestational age with same sensitivity. Conclusion: The evaluation of 17OHP decision limits based on gestational age reduced FPR and could decrease impacts on healthy part of population.

• Keywords
• deficit 21-hydroxylázy,
• MeSH
• 17-alpha-Hydroxyprogesterone MeSH
• False Positive Reactions * MeSH
• Adrenal Hyperplasia, Congenital * diagnosis   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Birth Weight MeSH
• Retrospective Studies MeSH
• Steroid 21-Hydroxylase analysis   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH

• MeSH
• Adult MeSH
• Gestational Age MeSH
• Hydroxyprogesterones metabolism   MeSH
• Confidence Intervals MeSH
• Adrenal Hyperplasia, Congenital diagnosis   MeSH
• Humans MeSH
• Amniotic Fluid metabolism   MeSH
• Prenatal Diagnosis MeSH
• Pregnancy Trimester, First metabolism   MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH