Clinica chimica acta; international journal of clinical chemistry · 2025
Enhancing primary newborn screening efficiency for congenital adrenal hyperplasia with LC-MS/MS/MS.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gaudl Alexander, Lehmicke Laura, Biemann Ronald, Dittrich Julia, Ceglarek Uta
Аннотация
BACKGROUND: Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) by immunoassay (IA) suffers from analytical limitations like cross reactivity and matrix effects. Alternative tandem-mass spectrometric approaches are not suitable for high-throughput screening due to long analysis times. In this study, a rapid 1.5 min LC-MS/MS/MS (MS3) assay was applied for the first time, maturity-dependent cutoffs were determined, and the diagnostic efficiency was compared to IA for primary CAH NBS.
METHODS: 1730 selected residual dried blood samples from routine NBS (gestation week 24-41) were subjected to online-SPE-LC-MS3 quantitation of 17-Hydroxyprogesterone (17-OHP). This approach utilizes two-stage fragmentation (MS3, 17-OHP m/z 329/285/123) carried out by triple quadrupole-ion trap hybrid MS. Cutoff values were calculated depending on gestational age (GA) and birthweight (BW). Diagnostic efficiency was compared to an established IA for primary CAH screening.
RESULTS: Intermediate precision was 10-13 % with an accuracy of 99-101 % (n = 50). Cutoff values based on GA as well as BW decreased with increasing maturity and weight of the newborns, ranging from 136 nmol/L whole blood for extreme preterm babies to 15 nmol/L whole blood for term babies. Combining LC-MS3 with GA- and BW-dependent cutoffs reduced the number of false-positive results from 731 to 15, while identifying all confirmed cases of CAH.
CONCLUSION: By application of LC-MS3 and the combinatory cutoff approach, the positive predictive value for CAH-screening improved from 1% to 32%, presenting a major benefit in diagnostic efficiency over the commonly applied IA strategy. This underlines the potential of MS3 technology in clinical use.
METHODS: 1730 selected residual dried blood samples from routine NBS (gestation week 24-41) were subjected to online-SPE-LC-MS3 quantitation of 17-Hydroxyprogesterone (17-OHP). This approach utilizes two-stage fragmentation (MS3, 17-OHP m/z 329/285/123) carried out by triple quadrupole-ion trap hybrid MS. Cutoff values were calculated depending on gestational age (GA) and birthweight (BW). Diagnostic efficiency was compared to an established IA for primary CAH screening.
RESULTS: Intermediate precision was 10-13 % with an accuracy of 99-101 % (n = 50). Cutoff values based on GA as well as BW decreased with increasing maturity and weight of the newborns, ranging from 136 nmol/L whole blood for extreme preterm babies to 15 nmol/L whole blood for term babies. Combining LC-MS3 with GA- and BW-dependent cutoffs reduced the number of false-positive results from 731 to 15, while identifying all confirmed cases of CAH.
CONCLUSION: By application of LC-MS3 and the combinatory cutoff approach, the positive predictive value for CAH-screening improved from 1% to 32%, presenting a major benefit in diagnostic efficiency over the commonly applied IA strategy. This underlines the potential of MS3 technology in clinical use.