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

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 α-thalassemia carriers in protocolⅠ 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 protocolsⅠ,Ⅱ andⅢ 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 protocolⅡ; 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 protocolⅢ, 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. Key words: Alpha-thalassemia; Prenatal diagnosis; Genetic testing