足月新生儿β地中海贫血基因携带者筛查指标及cut-off值的研究

Screening indices and their cut-off values for full-term neonates carrying β-thalassemia gene

摘要:

目的 探讨足月新生儿β地中海贫血（β地贫）基因携带者的筛查指标及其cut-off值。方法 对进行β地贫筛查（新生儿足跟血滤纸干血片血红蛋白分析和17种β珠蛋白基因突变检测）的1 193例足月新生儿的资料进行回顾性分析，将筛查指标水平与β地贫基因携带的相关性进行多因素logistic回归分析，并进行筛查指标对β地贫基因携带诊断价值的受试者工作特征曲线（ROC）分析。结果 1 193例中β地贫基因携带者638例。HbA₂为0的637例（53.39%）中携带β地贫基因的310例、β地贫基因阴性327例；HbA₂不为0的556例（46.61%）中携带β地贫基因的328例、β地贫基因阴性228例。HbA₂为0者，与β地贫基因阴性组比较，β地贫基因携带组的HbA含量较低、HbF含量较高，差异有统计学意义（P < 0.01）；HbA₂不为0者，与β地贫基因阴性组比较，β地贫基因携带组的HbA含量较低、HbF及HbA₂/HbA比较高，差异有统计学意义（P < 0.01）。HbA₂为0者，HbA、出生胎龄及两者联合对β地贫基因携带诊断的ROC曲线分析的AUC分别为0.865、0.515、0.870，其中HbA及HbA联合出生胎龄的AUC相近，均具有诊断意义（P < 0.01）。HbA₂不为0者，HbA、HbA₂/HbA比及两者联合对β地贫基因携带诊断的ROC曲线分析的AUC分别为0.943、0.885、0.978，均具有诊断意义（P < 0.01），以两者联合的AUC最大。HbA₂为0者，HbA为11.6%时对β地贫基因携带诊断的ROC曲线的AUC最大，灵敏度为85.81%、特异度为79.82%；HbA₂不为0者，HbA为16.1%~22.0%、HbA₂/HbA比 > 1.4时对β地贫基因携带诊断ROC曲线的AUC最大，灵敏度为91.38%、特异度91.89%。结论 HbA及HbA₂/HbA比是筛查足月新生儿β地贫基因携带的有效指标。

Abstract:

Objective To investigate the screening indices and their cut-off values for full-term neonates carrying β-thalassemia gene.Methods A retrospective analysis was performed for the clinical data of 1 193 full-term neonates who underwent β-thalassemia screening (hemoglobin analysis with dried blood spots on neonatal heel blood filter paper and mutation detection of 17 β-globin genes). A multivariate logistic regression analysis was used to investigate the association between screening indices and β-thalassemia gene, and the receiver operating characteristic (ROC) curve was used to analyze the value of screening indices in determining the presence or absence of β-thalassemia gene.Results Of the 1 193 neonates, 638 carried β-thalassemia gene. Of the 1 193 neonates, 637 (53.39%) had no HbA₂, among whom 310 carried β-thalassemia gene and 327 did not carry this gene; 556 (46.61%) had HbA₂, among whom 328 carried β-thalassemia gene and 228 did not carry this gene. As for the neonates without HbA₂, the β-thalassemia gene group had a significantly lower HbA level and a significantly higher HbF level than the β-thalassemia gene-negative group (P < 0.01). As for the neonates with HbA₂, the β-thalassemia gene group had a significantly lower HbA level and significantly higher HbF and HbA₂/HbA ratio than the β-thalassemia gene-negative group (P < 0.01). In the neonates without HbA₂, HbA, gestational age, and HbA combined with gestational age had an area under the ROC curve (AUC) of 0.865, 0.515, and 0.870, respectively, in determining the presence or absence of β-thalassemia gene (P < 0.01), and HbA and HbA combined with gestational age had a similar AUC and a certain diagnostic value. In the neonates with HbA₂, HbA, HbA₂/HbA ratio, and HbA combined with HbA₂/HbA ratio had an AUC of 0.943, 0.885, and 0.978, respectively, in determining the presence or absence of β-thalassemia gene. The HbA combined with HbA₂/HbA ratio had the largest AUC. In the neonates without HbA₂, HbA had the largest AUC in determining the presence or absence of β-thalassemia gene at the cut-off value of 11.6%, with a sensitivity of 85.81% and a specificity of 79.82%. In the neonates with HbA₂, an HbA of 16.1%-22.0% and an HbA₂/HbA ratio of > 1.4 had the largest AUC in determining the presence or absence of β-thalassemia gene, with a sensitivity of 91.38% and a specificity of 91.89%.Conclusions HbA and HbA₂/HbA ratio are effective indices for screening out full-term neonates carrying β-thalassemia gene.