新生儿乙型肝炎疫苗免疫低应答的影响因素分析  

Influencing factors for low response to hepatitis B vaccination in neonates

作　　者：文思敏[1] 王崇[2] 潘雨辰 赵丹[1] 王川[3] 孔菲[2] 牛俊奇[2] 姜晶[1] WEN Simin;WANG Chong;PAN Yuchen(Research Center of Clinical Epidemiology,The First Hospital of Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学第一医院临床研究部,长春130021 [2]吉林大学第一医院肝胆胰内科,长春130021 [3]北京市朝阳区妇幼保健院,北京100026

出　　处：《临床肝胆病杂志》2018年第6期1198-1203,共6页Journal of Clinical Hepatology

基　　金：十二五国家科技重大专项课题子课题(2012ZX10002001-001);吉林省卫生计生科研计划(20152003);中国肝炎防治基金会-天晴肝病基金资助课题(TQGB 20140137)

摘　　要：目的探索HBs Ag阳性母亲分娩的新生儿在接受乙型肝炎疫苗(Hep B)后发生免疫低应答的相关影响因素。方法招募了2012年7月-2015年7月参加HBV母婴传播阻断项目的 1152例HBs Ag阳性母亲分娩的新生儿,剔除了96例后,共1056例研究对象纳入分析,其中包含HBs Ag阳性/HBe Ag阴性母亲分娩的新生儿714例,HBs Ag阳性/HBe Ag阳性母亲分娩的新生儿342例。HBs Ag阳性/HBe Ag阴性和HBs Ag阳性/HBe Ag阳性母亲分娩的新生儿采用不同剂量的免疫接种方案,分别在其出生后2 h内注射10μg或20μg重组酵母Hep B,并联合100 IU乙型肝炎免疫球蛋白(HBIG),于1月龄及6月龄时再分别注射一剂10μg或20μg的Hep B。采集末次免疫后1个月的静脉血检测HBs Ag及抗-HBs水平。抗-HBs水平<100 m IU/ml为低应答者,抗-HBs水平≥100 m IU/ml为高应答者。对计量资料应用两独立样本t检验进行组间比较,计数资料应用χ2检验或Fisher精确检验进行组间比较。采用非条件logistic回归来分析新生儿Hep B免疫低应答的相关影响因素。采用协方差分析比较组间的抗-HBs水平。结果10μg方案组的免疫低应答率高于20μg方案组(5.7%vs 2.0%,χ2=7.278,P=0.007);10μg方案组母体HBV DNA载量及母亲孕期接受抗病毒治疗的比例均低于20μg方案组[(2.90±1.50)log10IU/ml vs(7.73±1.07)log10IU/ml,t=-50.297,P<0.001;0.7%vs 7.0%,χ2=34.552,P<0.001];10μg方案组新生儿的早产率高于20μg方案组(3.2%vs 1.2%,χ2=3.907,P=0.048)。10μg方案组新生儿人工喂养的比例低于20μg方案组(37.8%vs 66.4%,χ2=75.703,P<0.001)。在10μg方案组中,非条件logistic回归分析结果显示早产(比值比=3.31,95%可信区间:1.05~10.40)和人工喂养(比值比=2.67,95%可信区间:1.38~5.07)是新生儿Hep B免疫低应答的独立危险因素(P值均<0.05)。协方差分析结果显示与足月儿相比,早产儿的抗-HBs水平较低(P=0.004);与母乳喂养和混合喂养相比,人工喂养的新生儿抗-HBs水平较低(P=Objective To investigate the influencing factors for low response to hepatitis B（Hep B） vaccination in neonates born to HBs Ag-positive mothers. Methods A total of 1152 neonates born to HBs Ag-positive mothers who participated in the project of prevention of mother-to-child transmission of HBV from July 2012 to July 2015 were enrolled. After 96 neonates were excluded,1056 neonates were included in the final analysis,including 714 neonates born to HBs Ag-positive/HBe Ag-negative mothers and 342 neonates born to HBs Ag-positive/HBe Ag-positive mothers. These two groups of neonates were given immunization at different doses,i. e.,10 μg or 20 μg Hep B derived in Saccharomyces cerevisiae and 100 IU hepatitis B immunoglobulin within 2 hours after birth,followed by the injection of 10 μg or20 μg Hep B at the ages of 1 and 6 months. Venous blood samples were collected at one month after the last immunization to measure the levels of HBs Ag and anti-HBs. The neonates with anti-HBs 100 m IU/ml were classified as low responders,and those with anti-HBs ≥100 m IU/ml were classified as high responders. The two-independent-samples t test was used for comparison of continuous data between groups,and the chi-square test or the Fisher＇s exact test was used for comparison of categorical data between groups. An unconditional logistic regression analysis was used to identify the influencing factors for low response to Hep B in neonates. An analysis of covariance was used for comparison of the level of anti-HBs between groups. Results Compared with the 20 μg group,the 10 μg group had a significantly higher rate of low response（5. 7% vs 2. 0%,χ2= 7. 278,P = 0. 007）,significantly lower maternal HBV DNA load [（2. 90 ± 1. 50） log10 IU/ml vs（7. 73 ± 1. 07） log10 IU/ml,t =-50. 297,P 0. 001） ]and proportion of the mothers who received antiviral therapy during pregnancy（0. 7% vs 7. 0%,χ2= 34. 552,P 0. 001）,and a significantly higher rate of preterm birth（3. 2% vs 1. 2%,χ2= 3. 907,P =0. 048）. The 10 μg

关 键 词：肝炎疫苗 乙型 婴儿 新生 

分 类 号：R512.62[医药卫生—内科学]