乙型肝炎病毒母婴传播婴儿11例感染因素分析

目的分析11例婴儿发生HBV母婴传播的原因和时间，为采取措施进一步降低HBV母婴传播提供临床依据。 方法对2010年12月至2012年6月首都医科大学附属北京地坛医院收治的409慢性HBV感染母亲分娩的409例婴儿随访观察，所有婴儿均在出生后2 h内、15~30 d各注射乙肝免疫球蛋白（HBIG）200 IU，并按0-1-6方案接种重组酵母乙肝疫苗10 μg。采用微粒子化学发光法（CMIA）、荧光定量聚合酶链反应技术检测婴儿出生时外周静脉血的血清学标志物（HBsAg、抗-HBs、HBeAg、HBeAb、HBcAb）和HBV DNA，并于婴儿1个月、7个月~3岁随访。409例慢性HBV感染母亲按照血清HBV DNA水平高低分为3组，分别为HBV DNA阴性组147例患者（< 5 × 10²拷贝/ml）、低病毒含量组124例患者（≥ 5 × 10²~< 1.00 × 10⁶拷贝/ml）、高病毒含量组138例患者（≥ 1.00 × 10⁶拷贝/ml）。多因素Logistic回归分析喂养方式、分娩方式、母亲血清HBV DNA和HBVeAg水平对母婴传播的影响。 结果发生母婴传播的11例婴儿中，45.45%（5/11）婴儿从出生至1月龄HBsAg、HBV DNA持续阳性，1月龄时HBsAg均> 250 IU/ml、HBV DNA均> 1.00 × 10⁶拷贝/ml，免疫失败，全部进展为慢性感染，分析为宫内感染；54.55%（6/11）婴儿出生时至1个月龄无明确感染，抗-HBs均阳转，但在7月龄时5例婴儿、12月龄时1例婴儿发生HBsAg、HBV DNA阳转，分析为产后感染。HBV DNA阴性组、低病毒载量组和高病毒载量组婴儿感染率分别为0、0.81%（1/124）和7.25%（10/138），高病毒载量组较低病毒载量组婴儿感染风险高8.98倍（P = 0.01）。多因素Logistic回归分析显示母亲血清HBV DNA水平是影响母婴传播的的独立危险因素（95%CI：1.28~6.39、P = 0.01）。 结论婴儿出生后经严格主-被动联合免疫，血清高病毒载量母亲分娩婴儿仍有HBV母婴传播风险，母婴传播的原因除宫内感染外，产后感染亦是母婴传播的重要因素，特别在被动免疫消失，主动免疫尚未产生时，婴儿存在较大母婴传播风险。

Analysis of 11 infants infected through mother-to-child transmission of hepatitis B virus

ObjectiveTo investigate the causes of HBV transmission in 11 infants, and to provide clinical evidence for further HBV reduction through mother-to-child transmission. MethodsTotal of 409 infants given birth by HBV positive mothers had been observed and tracked in Beijing Ditan Hospital, Capital Medical University from December 2010 to June 2012. All the infants were given HBV immunoglobulin (HBIG) 200 IU 2 hours after birth and 15 to 30 days after birth. Meanwhile, routine HBV vaccination (recombinant yeast hepatitis B vaccine 10 μg, 0-1-6 Scheme) was given to each infant. HBV serum markers and HBV DNA were tested at birth and followed up at 1st month, 7th month until 3 years old after birth. The 409 infants were divided into three groups according to the HBV levels of their mothers: HBV negative group (< 5 × 10² copies/ml, 147 cases), HBV DNA low level group (≥ 5 × 10² - < 1 × 10⁶ copies/ml, 124 cases) and HBV DNA high level group (≥ 1 × 10⁶ copies/ml, 138 cases). The feeding method, delivery mode, mother serum HBV DNA and HBeAg level were evaluated for the impact of mother-to-child transmission by Logistic regression analysis. ResultsThere were 5 HBV positive infants who got positive HBV results from the first test (one month after birth), and kept positive in the subsequent follow-up. HBV DNA levels were higher than 1 × 10⁶ copies/ml. The transmission was considered to be intrauterine infection. The other 6 infants got HBV negative results one month after birth, and HBsAb turned to be positive. But during the follow-up, 5 cases turned to be HBV positive at the 7th month after birth and one case turned positive at the 12th month after birth. The infection time implied postpartum infection. The mother-to-child transmission rates were 0, 0.81 % (1/124) and 7.25% (10/138) in HBV DNA negative group, HBV DNA low level group and HBV DNA high level group, respectively. The relative risk of HBV transmission was 8.98 times in high HBV DNA group compared with low HBV DNA group (P = 0.01). The result of Logistic regression analysis showed that HBV DNA level of mothers was the independent risk factor for mother-to-child transmission (95%CI: 1.28-6.39, P = 0.01). ConclusionsThrough strict active-passive combined immunization of HBV, there were still risks for HBV transmission from mother to child. Besides intrauterine infection, postpartum infection was also an important reason. Especially when the passive HBsAb disappeared, meanwhile the vaccine have not establish the effective immunity, the infants were still under the risk of HBV transmission.