Dataset Information

Newborn Screening for Cystic Fibrosis: Infant and Laboratory Factors Affecting Successful Sweat Test Completion.

ABSTRACT: Newborn screening (NBS) for Cystic Fibrosis (CF) has revolutionized the diagnosis of this inherited disease. CF NBS goals are to identify, diagnose, and initiate early CF treatment to attain better health outcomes. Abnormal CF NBS infants require diagnostic analysis via sweat chloride testing (ST). During ST, insufficient sweat volume collection causes a "quantity not sufficient" (QNS) test result and may delay CF diagnosis. The CF Foundation recommends QNS rates <10% for infants <3 months, but many CF Centers experience difficulties meeting this standard. Our quality improvement (QI) study assessed infant and laboratory factors contributing to ST success and QNS rates from 2017-2019. Infants' day of life (DOL) at successful ST completion was analyzed according to infant factors (birth weight (BW), gestational age, ethnicity, and sex). Laboratory factors and procedures affecting ST outcomes were also reviewed. At our institution, BW and gestational age were the infant factors found to significantly affect DOL at ST completion. ST education, reduced number of laboratory technicians, and direct observation during ST completion also improved ST success rates. This study supports QI measures and partnerships between CF centers and laboratory staff to identify and improve ST QNS rates while sustaining practices to ensure timely CF diagnostic testing.

SUBMITTER: Shenoy A

PROVIDER: S-EPMC7838990 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Newborn Screening for Cystic Fibrosis: Infant and Laboratory Factors Affecting Successful Sweat Test Completion.

Shenoy Ambika A Spyropoulos Dina D Peeke Kathleen K Smith Dawn D Cellucci Michael M Chidekel Aaron A

International journal of neonatal screening 20201225 1

Newborn screening (NBS) for Cystic Fibrosis (CF) has revolutionized the diagnosis of this inherited disease. CF NBS goals are to identify, diagnose, and initiate early CF treatment to attain better health outcomes. Abnormal CF NBS infants require diagnostic analysis via sweat chloride testing (ST). During ST, insufficient sweat volume collection causes a "quantity not sufficient" (QNS) test result and may delay CF diagnosis. The CF Foundation recommends QNS rates <10% for infants <3 months, but ...[more]

PMID: 33375576

Similar Datasets

Project description:The current guidelines for sweat chloride analysis identify the procedures for sweat collection, but not for chloride assay, which is usually performed by methods originally not aiming at the low concentrations of chloride found in sweat. To overcome this limitation, we set up, characterized, and adopted an original inductively coupled plasma mass spectrometry (ICP-MS) method for sweat chloride determination, which was designed for its easy use in a clinical laboratory. The method was linear in the range 8.5E-3 to 272.0E-3 mM, precision exhibited a relative standard deviation <?6%, and accuracy was in the range 99.7-103.8%. Limit of blank, limit of detection, and limit of quantitation were 2.1 mM, 3.2 mM, and 7.0 mM, respectively, which correspond to real concentrations injected into the mass spectrometer of 3.9E-3 mM for LOD and 8.5E-3 mM for LOQ. At first, the method was tested on 50 healthy volunteers who exhibited a mean chloride concentration of 15.7 mM (25-75th percentile 10.1-19.3 mM, range 2.8-37.4 mM); then, it was used to investigate two patients with suspected cystic fibrosis, who exhibited sweat chloride values of 65.6 mM and 81.2 mM, respectively. Moreover, the method was cross-validated by assaying 50 samples with chloride concentration values in the range 10-131 mM, by both ICP-MS and coulometric titration, which is the technology officially used in Tuscany for cystic fibrosis newborn screening. The reference analytical performances and the relatively low cost of ICP-MS, accompanied by the advantageous cost of a single sweat chloride assay, make this technology the best candidate to provide a top reference method for the quantification of chloride in sweat. The method that we propose was optimized and validated for sweat samples ??75 mg, which is the minimum amount requested by the international protocols. However, the method sensitivity and, in addition, the possibility to reduce the sample dilution factor, make possible the quantification of chloride even in samples weighting <?75 mg that are discarded according to the current guidelines. Graphical abstract.

Project description:The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs. However, it provides ambiguous results for intermediate sweat chloride cases while not reflecting disease progression when classifying the complex CF disease spectrum given the pleiotropic effects of gene modifiers and environment. Herein we report the first characterization of the sweat metabolome from screen-positive CF infants and identify metabolites associated with disease status that complement sweat chloride testing. Pilocarpine-stimulated sweat specimens were collected independently from two CF clinics, including 50 unaffected infants (e.g., carriers) and 18 confirmed CF cases. Nontargeted metabolite profiling was performed using multisegment injection-capillary electrophoresis-mass spectrometry as a high throughput platform for analysis of polar/ionic metabolites in volume-restricted sweat samples. Amino acids, organic acids, amino acid derivatives, dipeptides, purine derivatives, and unknown exogenous compounds were identified in sweat when using high resolution tandem mass spectrometry, including metabolites associated with affected yet asymptomatic CF infants, such as asparagine and glutamine. Unexpectedly, a metabolite of pilocarpine, used to stimulate sweat secretion, pilocarpic acid, and a plasticizer metabolite from environmental exposure, mono(2-ethylhexyl)phthalic acid, were secreted in the sweat of CF infants at significantly lower concentrations relative to unaffected CF screen-positive controls. These results indicated a deficiency in human paraoxonase, an enzyme unrelated to mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) and impaired chloride transport, which is a nonspecific arylesterase/lactonase known to mediate inflammation, bacterial biofilm formation, and recurrent lung infections in affected CF children later in life. This work sheds new light into the underlying mechanisms of CF pathophysiology as required for new advances in precision medicine of orphan diseases that benefit from early detection and intervention, including new molecular targets for therapeutic intervention.

Dataset Information

Newborn Screening for Cystic Fibrosis: Infant and Laboratory Factors Affecting Successful Sweat Test Completion.

Publications

Newborn Screening for Cystic Fibrosis: Infant and Laboratory Factors Affecting Successful Sweat Test Completion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets