Application of an optimized interpretation model in capillary hemoglobin electrophoresis for newborn thalassemia screening

Abstract

Introduction Newborn screening is an important supplement to thalassemia control and prevention. Capillary electrophoresis (CE) technology has several advantages for thalassemia screening but with low sensitivity, especially for thalassemia carriers. This study aims to illustrate the application of an optimized interpretation model in newborn thalassemia screening by capillary hemoglobin electrophoresis. Methods Two thousand, two hundred fifty‐eight neonates selected from four regions in China were enrolled and were screened for α‐thalassemia and β‐thalassemia by capillary electrophoresis. Results were interpreted based on an optimized model integrated with multiple parameters. Molecular analysis was carried out in synchrony and used as the gold standard for the screening performance assessment. The consistency among different regions and thalassemia genotypes were also investigated. Results Among the 2258 neonates, 485 were identified to have a likely diagnosis of thalassemia, and 422 α‐thalassemia, 80 β‐thalassemia, and 21 α/β‐thalassemia cases were confirmed by molecular analysis, including 277 α‐thalassemia silent carriers, 135 α‐thalassemia trait carriers, 10 Hemoglobin H disease, and 80 β‐thalassemia trait carriers. The screening sensitivity, specificity, positive, and negative predictive value for α‐thalassemia and β‐thalassemia were 84.83%, 99.14%, 95.98%, 96.41%, and 88.75%, 98.73%, 76.34%, and 99.48%, respectively. The optimized interpretation model showed higher performance for thalassemia carriers, though some neonates with silent α‐thalassemia genotypes (‐α3.7/αα, ‐α4.2/αα, and αWSα/αα) and β‐28/βN genotype were still missed. The screening performance among different regions was comparable. Conclusions Capillary hemoglobin electrophoresis with the optimized interpretation model shows reliable performance for newborn thalassemia screening. It is applicable to large‐scale population screening.

Wooden-Tip Electrospray Mass Spectrometry Characterization of Human Hemoglobin in Whole Blood Sample for Thalassemia Screening: A Pilot Study

“…As 100 α-thalassemia, 67 βthalassemia, and 152 healthy samples were analyzed in this work, some discrete data in Figure 3f are acceptable. In the electrophoresis process of chains of Hb, there are substantial significant differences obtained from β-thalassemia compared to α-thalassemia [35][36][37][38]. Therefore, by using a simple WT-ESI-MS method in this work, our results validated the results of the electrophoresis process of chains of Hb.…”

Differences in the distribution of hemoglobin variants according to the geographic regions in a Colombian population

“…The capillary electrophoresis has also been described as having a high diagnostic performance, as for example in an analysis of the performance of neonatal thalassemia screening by capillary electrophoresis in China for α-thalassemia and β-thalassemia, in which the optimized interpretation model found a sensitivity of 84.83% and a specificity of 99.14% for α-thalassemia and a sensitivity of 88.75% and a specificity of 98.73% for β – thalassemia. 23 …”

Capillary Electrophoresis: A Three-Year Literature Review

“…CE has found extensive applications in investigating the chemical structures and isoforms in various types of proteins, − with a notable focus on Hb due to its crucial role in biological processes. Numerous CE-related studies have systematically explored the correlations between Hb’s variants, chemical modifications, and various pathological conditions, aiming to establish their significance as potential biomarkers. − To determine a suitable method for detecting various Hb variants, a comparison was conducted among CE, cation-exchange HPLC, and matrix-assisted laser desorption ionization (MALDI) techniques using 1083 blood samples from southern China. The results showed that only the CE method was able to detect the 10 most prevalent Hb variants, making it the optimal instrument for this purpose …”