母亲HBV DNA载量对宫内传播及胎儿宫内窘迫的影响

The effect of maternal HBV DNA levels on HBV intrauterine transmission and fetal distress

目的明确乙型肝炎病毒(HBV)宫内传播的关键危险因素及其对胎盘及胎儿的影响。方法通过大样本前瞻性研究,对自2009年至2015年纳入的425例乙型肝炎表面抗原(HBsAg)阳性孕妇所生婴儿进行乙型肝炎免疫球蛋白及乙型肝炎疫苗联合免疫,动态监测婴儿HBV DNA载量及HBsAg定量评估宫内传播情况,采用单因素及多因素回归分析判断宫内传播的高危因素,分层分析判断母亲HBV DNA载量与胎儿宫内窘迫的关系,透射电镜观察HBV对胎盘组织的影响。结果HBV宫内感染率为2.6%(11/425),多因素分析结果显示母亲HBV DNA载量是婴儿发生宫内感染的独立危险因素(P=0.011)。母亲HBV DNA>106 IU/ml组较HBV DNA<10^(6) IU/ml组婴儿的宫内感染率明显升高(12.2%比1.8%;χ^(2)=11.275,P=0.006),宫内窘迫率也升高(24.4%比16.0%,χ^(2)=3.993,P=0.046)。透射电镜检测显示母亲HBV DNA>10^(6) IU/ml时,胎盘组织线粒体水肿及内质网扩张明显,基底膜较母亲HBV DNA<10^(6) IU/ml时增厚(960 nm比214 nm,Z=-2.782,P=0.005)。结论母亲HBV DNA>10^(6) IU/ml不仅与宫内感染有关,还和宫内窘迫发生率升高及胎盘亚微结构改变相关。为此类人群的孕期阻断治疗提供了有力的临床及组织学证据。

Aim To identify the key risk factors of intrauterine hepatitis B virus transmission(HBV)and its effect on the placenta and fetus.Methods 425 infants born to hepatitis B surface antigen(HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study.The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg.Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission.Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress.Transmission electron microscopy was used to observe HBV Effects on placental tissue.Results HBV intrauterine infection rate was 2.6%(11/425).Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants(P=0.011).Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10^(6) IU/ml than those with HBV DNA<10^(6) IU/ml(12.2%vs.1.8%;χ^(2)=11.275,P=0.006),and(24.4%vs.16.0%,χ^(2)=3.993,P=0.046).Transmission electron microscopy showed that mitochondrial edema,endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10^(6) IU/ml than that of maternal HBV DNA<10^(6) IU/ml(960 nm vs.214 nm,Z=-2.782,P=0.005)in the placental tissue.Conclusion Maternal HBV DNA>10^(6) IU/ml is associated not only with intrauterine infection,but also with increased incidence of intrauterine distress and placental sub-microstructural changes,providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.