海南省孕前及孕期地中海贫血筛查方案评价及优化研究

目的对海南省免费孕前及孕期地中海贫血筛查方案进行评价,为地贫筛查流程的优化提供理论依据。方法2020年11月—2021年7月对海南省19个市县参与海南省居民地中海贫血流行病学调查的10396例海南户籍成人进行调查,所有人均进行血常规检测、血红蛋白电泳检测及地贫基因检测。通过受试者工作特征曲线和灵敏度等筛检试验指标,判断平均红细胞体积(mean corpuscular volume,MCV)、平均红细胞血红蛋白含量(mean corpuscular he⁃moglobin,MCH)和血红蛋白2型(haemoglobin adult type 2,HbA2)筛查地贫的最佳诊断界值,并评估不同地贫基因携带者初筛方案的诊断效能。结果使用海南省现有MCV单指标地贫初筛方案,即MCV<82 fL时进行地贫基因检查,诊断地贫基因携带者的漏诊率较高(34.06%),灵敏度较低(65.94%)。海南省MCV筛查α-地贫和β-地贫的最佳截断值分别为84.45 fL和79.05 fL;MCH筛查α-地贫和β-地贫的最佳截断值分别为27.95 pg和25.15 pg。HbA2筛查α-地贫的最佳截断值为小于2.55%,筛查β-地贫则为大于3.35%。地贫初筛时使用本研究推荐截断值的“HbA2或MCH或MCV联合筛查方案”具有较好的性能,灵敏度(92.96%)和阴性预测值(92.67%)最高,漏诊率(7.04%)最低,与现有方案比较差异有统计学意义(P<0.05)。结论目前海南省地贫筛查流程有漏诊可能,联合使用MCV、MCH和HbA2筛查地贫,采用本地适宜的地贫初筛指标截断值,可以改善地贫漏报的发生,提高诊断效能。

Evaluation and optimization of pre-pregnancy and pregnancy thalassaemia screening programmes in Hainan Province;

Objective To evaluate the free thalassaemia screening programme for preconception and pregnancy in Hainan Province, and to provide a theoretical basis for optimizing the screening process for thalassaemia. Methods From November 2020 to July 2021, a survey was conducted on 10 396 adults with Hainan household registration who participated in the Epidemiological Survey of Thalassemia in Hainan Residents in 19 cities and counties of Hainan Province. All of them underwent routine blood tests, haemoglobin electrophoresis tests and genetic tests for thalassaemia. The optimal diagnostic cutoff values for mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and haemoglobin adult type 2 (HbA2) were determined using screening test indexes such as receiver operating characteristic curve and sensitivity. The diagnostic effectiveness of different primary screening programs for thalassemia gene carriers was evaluated. Results Using the existing MCV single-indicator thalassemia primary screening protocol in Hainan Province, where individuals with MCV<82 fL undergo thalassemia gene testing, resulted in a high missed diagnosis rate (34.06%) and low sensitivity (65.94%). The optimal cut-off values for MCV screening for alpha-and beta-thalassaemia were 84.45 fL and 79.05 fL, respectively; the optimal cut-off values for MCH screening for alpha-and beta-thalassaemia were 27.95 pg and 25.15 pg, respectively. The optimal cut-off value for HbA2 screening for alpha-thalassaemia was less than 2.55% and greater than 3.35% for beta-thalassaemia. The combined HbA2 or MCH or MCV screening protocol with the cut-off values recommended in this study had a better performance in primary screening for thalassemia, with the highest sensitivity (92.96%) and negative predictive value (92.67%) and the lowest underdiagnosis rate (7.04%), statistically significant differences compared with the existing protocol (P<0.05). Conclusions The current process of screening for thalassemia in Hainan Province may lead to missed diagnoses. The combined use of MCV, MCH and HbA2 for thalassemia screening, adopting locally suitable cutoff values for primary screening indicators, can improve the incidence of missed reporting of thalassemia and enhance diagnostic effectiveness. © 2023 Editorial Department of China Tropical Medicine. All rights reserved.