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

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 alpha-thalassemia and beta-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 alpha-thalassemia, 80 beta-thalassemia, and 21 alpha/beta-thalassemia cases were confirmed by molecular analysis, including 277 alpha-thalassemia silent carriers, 135 alpha-thalassemia trait carriers, 10 Hemoglobin H disease, and 80 beta-thalassemia trait carriers. The screening sensitivity, specificity, positive, and negative predictive value for alpha-thalassemia and beta-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 alpha-thalassemia genotypes (-alpha(3.7)/alpha alpha, -alpha(4.2)/alpha alpha, and alpha(WS)alpha/alpha alpha) and beta(-28)/beta(N) 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.