三种α-地中海贫血产前筛查方案效果比较

Comparison of three different α-thalassemia prenatal screening strategies used in Guangdong, China

目的比较广东省常用产前α-地中海贫血（简称地贫）筛查方案的效果和成本，为地贫预防控制项目的实施和临床决策提供依据。方法采用多阶段整群抽样的方式，在广东省21个地市91家助产服务机构，选择2012年6月至12月在这些机构中住院分娩或引产的孕产妇及其配偶13284对和13369例新生儿／胎儿（子代），检测平均红细胞体积（mean cell volume，MCV）／平均红细胞血红蛋白（mean corpuscular hemoglobin，MCH）、血红蛋白A2水平及α-地贫基因。比较常见α-地贫筛查方案的筛查效能及成本。筛查方案一为基于孕妇MCV／MCH和血红蛋白A2的串联筛查。方案二为基于孕妇MCV／MCH和HbA2的并联筛查。方案三为基于孕妇夫妇双方的MCV、MCH和血红蛋白A2的串联筛查。夫妇双方如果同时携带α-地贫或血红蛋白H病，则其胎儿进行α-地贫产前诊断。采用漏诊率、灵敏度、特异度、阳性预测值和阴性预测值评价筛查效能，统计学分析采用χ^2检验。结果筛查孕妇α-地贫基因携带的灵敏度和特异度在方案一为74．82％（1352／1807）、特异度为74．11％（8506／11477），在方案二分别为89-82％（1623／1807）和48．60％（5578／11477）。1．67％（221／13284）的夫妇同时携带0【一地贫基因。对于发现同时携带d一地贫基因夫妇的漏诊率方案一、二、三分别为50．68％（112／221）、11．76％（26／221）和11．31％（25／221）。对于发现需要进行产前诊断的夫妇，漏诊率、灵敏度、特异度、阳性预测值和阴性预测值在方案一为17．46％（11／63）、82．54％（52／63）、98．35％（13003／13221）、19．26％（52／270）和99．92％（13003／13014）；在方案二为4．76％（3／63），95．24％（60／63）、88．18％（11658／13221）、3．70％（60／1623）和99．97％（11658／11661）；在方案三为3．17％（2／63）、96．83％（61／63）、59．31％（7842／13221）、1．12％（61／5440）和99．97％（7842／7844）。3种筛查方案均无重型α-地贫患儿漏诊。平均每发现1对需要进行产前诊断的夫妇，方案一、二、三所需检测费用分别为37049．23、50836．00和40321．64元。广东省育龄夫妇α-地贫基因携带率为12．75％（3387／26568）、子代为12．40％（1658／13369）。结论3种筛查方案均有较好效能。作为公共卫生项目应该综合考虑各因素以选择最适宜方案，在经济条件许可的地区建议选择方案二或方案三。

Objective To compare the effect and cost of three different α-thalassemia prenatal screening strategies used in Guangdong, China, and to provide evidence for α-thalassemia prevention. Methods In total, 13 284 hospital-delivery couples and 13 369 newborns/fetuses （offspring） from 21 counties or districts of Guangdong Province were included in this study, who were treated from June to December 2012. Mean cell volume （MCV）, mean corpuscular hemoglobin （MCH） and hemoglobin A2 （Hb A2） were detected in the couples, and 6 types of α-globin gene mutations were found in all couples and newborns. The strategies were MCV/MCH and serum Hb A2 （protocol Ⅰ ） or parallel screening based on pregnant women （protocol Ⅱ）, and serum screening based on couples （protocol Ⅲ ）. The validity and reliability of the three strategies were then compared using the Chi-square test. Results The sensitivity and the specificity of pregnant women who were et -thalassemia carriers in protocol Ⅰ were 74.82% （1 352/1 807） and 74.11% （8 506/11 477）, and were 89.82% （1 623/1 807） and 48.60%（5 578/11 477） in protocol Ⅱ , respectively. And 1.67% （221/13 284） couples were both α-thalassemia carriers by the gene test. The rate of missed diagnosis in both α-thalassemia carrier couples in protocols Ⅰ , Ⅱ and Ⅲ was 50.68% （112/221）, 11.76%（26/221） and 11.31%（25/221）, respectively. In couples who needed prenatal diagnosis, the rates of missed diagnosis, sensitivity, specificity, positive predictive value, and negative predictive value were 17.46%（11/63）, 82.54%（52/63）,98.35% （13 003/13 221）, 19.26%（52/270） and 99.92 %（13 003/13 014） in protocol Ⅰ; 4.76%（3/63）, 95.24%（60/63）, 88.18%（11 658/13 221）, 3.70%（60/1 623） and 99,97%（11 658/11 661） in protocol Ⅱ ; and 3.17%（2/63）, 96.83%（61/63）, 59.31%（7 842/13 221）, 1.12%（61/ 5 440） and 99.97%（7 842/7 844） in protocol Ⅲ , respectively. The diagnosis of severe α-thalassemia was not missed in all three screening strategies. The mean cost of protocols Ⅰ, Ⅱ and Ⅲ for detecting a couple who needed prenatal diagnosis was 37 049.23, 50 836.00 and 40 321.64 RMB, respectively. Conclusions The three screening protocols have good efficiency in screening for α-thalassemia. However, protocols Ⅱ and Ⅲ are preferred when financial conditions permit.