不同喂养方式对乙型肝炎病毒母婴传播的影响

Impact of different feeding patterns on mother-to-child transmission of hepatitis B virus

目的 探讨不同喂养方式对乙型肝炎病毒（hepatitis B virus,HBV）母婴传播的影响. 方法 2010年12月1 8日至2012年6月26日,在首都医科大学附属北京地坛医院分娩的慢性HBV感染产妇中,纳入足月单胎妊娠者,根据产妇意愿分为母乳喂养组和人工喂养组.每组根据孕妇分娩前血清HBV-DNA载量进一步分为3个亚组：HBV-DNA阴性（＜5×10^2拷贝/ml）、低病毒载量（≥5×10^2-＜1×10^6拷贝/ml）和高病毒载量（≥1×10^6拷贝/ml）.母乳喂养组共199例,3个亚组各73、62和64例;人工喂养组共210例,3个亚组各74、62和74例.新生儿出生2h内和15-30 d注射乙肝免疫球蛋白,并按“0、1、6月”方案正规接种重组酵母乙肝疫苗.采用荧光定量聚合酶链反应技术检测HBV-DNA.采用微粒子化学发光法检测HBV血清学标记物.比较母乳喂养组与人工喂养组的基本情况,及婴儿1月龄和7月龄时的免疫应答情况、7月-2岁时的感染情况.采用独立样本t检验、秩和检验、χ^2检验、Fisher精确概率法进行统计分析. 结果 HBV-DNA阴性、低病毒载量和高病毒载量的母乳喂养组与人工喂养组的乙肝e抗原阳性率分别为12.3％（9/73）与5.4％（4/74）、37.1％（23/62）与51.6％（32/62）、96.9％（62/64）与95.9％（71/74）,差异均无统计学意义（P值均＞ 0.05）.409例婴儿中,70例7月龄时未复查,但均在1-2岁时进行复查.HBV-DNA阴性、低病毒载量和高病毒载量的母乳喂养组与人工喂养组婴儿7月龄时乙肝表面抗体阳性率分别为98.4％（61/62）与100.0％（63/63）、98.2％（54/55）与98.2％（56/57）、95.7％（44/46）与92.9％（52/56）,差异均无统计学意义（P值均＞0.05）.母乳喂养组与人工喂养组婴儿感染率分别为3.0％（6/199）与2.4％（5/210）.HBV-DNA阴性组无婴儿感染;低病毒载量、高病毒载量的母乳喂养组与人工喂养组婴儿感染率分别为0.0％（0/62）与1.6％（1/62）、9.4％（6/64）与5.4％（4/74）,差异均无统计学意义（P值均＞0.05）. 结论 在联合免疫的前提下,慢性HBV感染产妇采用母乳喂养不增加婴儿感染风险.

Objective To explore the effect of different feeding patterns on mother-to-child transmission of hepatitis B virus （HBV）.Methods Chronic HBV-infected puerperae,who gave birth to a single baby at term in Beijing DiTan Hospital from December 18,2010 to June 26,2012,were recruited and separated into breast-feeding group and formula-feeding group according to the mother＇s will.Each group was then divided into three subgroups based on matemal serum HBV-DNA load before delivery：HBV-DNA negative subgroup （〈 5 × 10^2 copies/ml）,low viral load subgroup （≥ 5 × 10^2-〈 1.0 × 10^6 copies/ml） and high viral load subgroup （≥ 1.0 × 10^6 copies/ml）.A total of 199 patients in breast-feeding group were divided into three subgroups,separately including 73,62 and 64 patients,while a total of 210 patients in formula-feeding group into three subgroups,including 74,62 and 74 patients.Newborns were injected with Hepatitis B hyper-immune globulin （HBIG） within 2 h after birth and at 15 to 30 days,followed by the routine injection of recombinant yeast derived Hepatitis B vaccine in accordance with the scheme of ＂0,1,6 months＂.HBV-DNA was determined by fluorescence quantitative polymerase chain reaction,while serological markers of HBV by microsome chemiluminescence method.Comparisons were made between the breast-feeding and formula-feeding group on maternal background information,immune responses of the infants at one-month and seven-month old,the infectious status when they were between seven-month to two-year old.Statistical analysis was made with independent sample t-test,rank-sum test,χ^2 test and Fisher＇s exact test.Results The HBeAg positive rates of puerperae in the three subgroups （HBV-DNA negative,low viral load and high viral load） among women of the breast-feeding group were 12.3% （9/73）,37.1% （23/62） and 96.9%（62/64）,respectively,while 5.4% （4/74）,51.6% （32/62） and 95.9% （71/74） among the formula-feeding group.There was no significant difference between breast-feeding group and formula-feeding group （all P 〉 0.05）.Seventy of the 409 infants missed the follow-up at seven-month old,but returned between one to two years old.The anti-HBs positive rates of the three subgroups in infants of the breast-feeding group at seven-month old were 98.4% （61/62）,98.2% （54/55） and 95.7% （44/46）,while 100.0% （63/63）,98.2% （56/57） and 92.9% （52/56） in the formula-feeding group （all P 〉 0.05）.The infection rate of infants in the breast-feeding group and the formula-feeding group were 3.0% （6/199） and 2.4% （5/210） at seven-month to two-year old.Notably,infected infants was identified in HBV-DNA negative subgroup in neither the breast-feeding group nor the formula-feeding group,while 0.0% （0/62） and 9.4% （6/64） of infection rate were reported in low viral load and high viral load subgroups of the breast-feeding group and 1.6% （1/62） and 5.4% （4/74） of the formula-feeding group （both P 〉 0.05）.Conclusion With combined immunization,breast-feeding in chronic HBV infected mothers does not increase the risk of infantile infection.