孕妇乙型肝炎病毒携带状态与母婴传播的研究

目的 :探讨孕妇乙型肝炎 (乙肝 )病毒 (HBV)携带状态与母婴传播的关系。方法 :用荧光定量PCR法检测HBV表面抗原 (HBsAg)阳性孕妇血清中HBV脱氧核糖核酸(HBVDNA)及脐血HBVDNA ,婴儿出生后 1 2h内及第 1 4天注射乙肝免疫球蛋白 ,并按0、1、6的程序全程接种乙肝疫苗 ,进行前瞻性随访研究 ,分别于婴儿 7月及 1 2月时随访 ,检测HBVDNA及乙肝血清标志物 ,婴儿 7月时未感染乙肝但抗 HBs阴性者加强注射乙肝疫苗 5μg。 结果 :HBsAg、HBeAg及抗 HBc阳性孕妇的新生儿脐血HBVDNA阳性率为1 8.37% (9/ 4 9) ;HBsAg及HBeAg双阳性者为 1 2 .50 % (2 / 1 6) ;HBsAg及抗 HBc阳性者为1 2 .50 % (3/ 2 4 ) ;HBsAg,抗 HBe和抗 HBc阳性者为 1 .37% (1 / 73) ;脐血HBVDNA阳性的新生儿均生于HBVDNA阳性的母亲 ,阳性率为 1 8.52 % (1 5/ 81 ) ,不同HBV携带状态的脐血阳性率有统计学差异。总母婴传播率为 9.78%。结论 :孕妇HBV携带状态与母婴传播有关 ,孕妇血清HBeAg阳性或HBVDNA含量高是母婴传播的重要因素之一 ,孕妇血清HBVDNA阴性者母婴垂直传播的风险极小。在新生儿、婴儿接受被动及主动全程联合免疫的条件下 ,产时、产后HBV的母婴传播可以预防     

产科消除母婴传播门诊建设在妇幼专科医院的价值

母婴传播是乙肝传播的主要方式之一,目前联合免疫是阻断乙肝母婴传播的最有效方法,但仍有8%～15%孕妇所生婴儿中存在预防接种无效,发生乙肝母婴传播,孕妇外周血中乙肝病毒(HBV)DNA载量是乙肝母婴传播的独立危险因素。目前国内外推荐妊娠晚期服用抗病毒药物减少母婴传播,但因大部分产科医务工作者未充分认识,仅少部分对乙肝孕妇进行处理并及时转诊至肝病科或感染科就诊治疗。此外,孕妇孕期多机构、多科室就诊非常不便利,并且获得信息不对称,多次就诊潜在增加乙肝相关羞辱歧视的风险,特别是对于没有肝病科或感染科的妇幼保健专科医院,如何处理管理这一人群成为难点。消除母婴传播(E)门诊的建立可健全消除母婴传播服务能力,通过整合艾梅乙患者孕期管理,为感染孕产妇提供标准化的全流程一站式服务,从而有效减少乙肝母婴传播发生。     

延迟结扎脐带对HBsAg阳性产妇母婴阻断效果及婴儿免疫应答影响的前瞻性队列研究

目的探讨HBsAg阳性产妇分娩时行延迟结扎脐带对HBV母婴阻断效果及婴儿免疫应答的影响。方法收集2017年3月至2018年9月本院产检分娩的HBsAg阳性孕妇1 200例,单双数编号,单数孕妇分娩时若母婴状况稳定则施行延迟结扎脐带(新生儿出生后1～3 min),新生儿纳入晚断脐组;双数孕妇分娩时于新生儿娩出后立刻结扎脐带,新生儿纳入对照组。全部婴儿接受HBV联合免疫,即:出生时及出生后第21天肌内注射乙型肝炎免疫球蛋白100 IU,出生时及第1、6个月接种重组酵母乙型肝炎疫苗10μg。出生时查乙肝五项及HBV-DNA,婴儿7～9个月复查乙肝五项,必要时查HBV-DNA。结果联合免疫后,晚断脐组559例(95.1%)、对照组548例(89.8%)婴儿完成7～9个月随访。晚断脐组母婴阻断成功率100%;对照组母婴阻断成功率99.82%(1/548),两组比较,差异无统计学意义(P=0.495)。晚断脐组与对照组婴儿Anti-HBs1 000 IU/ml的比例(73.2%,68.4%;P=0.083)、免疫低/无应答的比例(4.5%,5.8%;P=0.303)比较,差异均无统计学意义。晚断脐组36例、对照组29例婴儿的母亲产前HBV-DNA106IU/ml,其母婴阻断成功率、Anti-HBs1 000 IU/ml的比例、免疫低/无应答的比例(100%,96.6%,P=0.446;63.9%,65.5%,P=0.891;8.3%,10.3%,P=1)比较,差异均无统计学意义。结论延迟结扎脐带不增加HBsAg阳性产妇HBV母婴传播的风险,不影响婴儿联合免疫应答。在HBsAg阳性产妇的第三产程行延迟结扎脐带是可行的。     

分娩方式与乙型肝炎病毒母婴传播阻断的相关性研究

目的:探讨分娩方式对乙型肝炎病毒(HBV)母婴垂直传播的影响。方法:将HBs Ag阳性孕妇及其婴儿211例,按不同分娩方式分为阴道分娩组(126例)和选择性剖宫产组(85例),两组新生儿均完成主被动联合免疫接种,检测孕妇及婴儿出生24h内、7个月、12个月龄时的外周静脉血的HBV血清学标志物、HBV DNA水平,比较两组婴儿HBV母婴阻断效果。结果:婴儿出生24h内选择性剖宫产组的HBs Ag、HBV DNA阳性率低于阴道分娩组(10.59%vs 21.43%,P0.05)。婴儿7个月龄、12个月龄时,两组的HBs Ag、HBV DNA阳性率比较,差异无统计学意义(P0.05)。孕妇HBe Ag阴性、HBV DNA≤10~(11)copies/L时,阴道分娩组和选择性剖宫产组的HBV母婴阻断失败率比较,差异无统计学意义(P0.05)。孕妇HBe Ag阳性、HBV DNA10~(11)copies/L时,选择性剖宫产组的HBV母婴阻断失败率明显低于阴道分娩组(3.45%vs 23.81%,5.25%vs 33.33%,P0.05)。结论:分娩方式与HBV母婴传播阻断有关,当孕妇HBe Ag阳性或HBV DNA10~(11)copies/L时,选择性剖宫产可能降低乙肝母婴垂直传播几率。     

剖宫分娩对乙型肝炎病毒母-婴传播的预防作用

乙型肝炎病毒(HBV)的母-婴传染在 HBV高发人群中是一严重问题。HBeAg 阳性母亲约90%的婴儿感染 HBV,如母血 HBV-DNA 亦阳性,则所有婴儿都将感染 HBV,并成为慢性携带者。HBsAg 携带者母亲中,33%的羊水、50%脐带血、71%乳汁和95%的婴儿胃内容物中有 HBsAg。HBV 可能在分娩时经口感染。剖宫分娩可减少母-婴传播,避免经生殖道分娩时摄入受感染母亲的血和分泌物,但也有认为无此作用者。作者估价了不同分娩方式对 HBeAg 阳性母亲对婴儿的影响。材料和方法:HBeAg 阳性的 HBsAg 携带者母亲所生婴儿447例,接受乙肝免疫(于出生后肌注5μg HBsAg/ml),3次/2周,然后1、2月     

妊娠期乙型肝炎的垂直传播

垂直传播即母婴传播,是指母亲所患的疾病或所带的病原因子直接传播给婴儿。妊娠期急性或慢性乙型肝炎(以下简称乙肝)或无症状的带病毒母亲,可通过垂直传播而使新生儿传染上乙型肝炎病毒(以下简称HBV)。垂直传播是乙肝的重要传播途径之一,它不仅传播率高,而且还涉及到子宫内传播所引起的免疫耐受性问题,甚至其子女终生携带病毒。新生儿感染HBV后约90％成为乙肝病毒表面抗原(HBsAg)慢性携带者,其中少数可发能为慢性活动性肝炎、肝硬化,甚至原发性肝细胞癌。乙肝垂直传播的途径一、子宫内传播:主要通过胎盘传播,依据为:1.HBsAg阳性孕妇的婴儿脐血HBsAg约半数为阳性,即使脐血HBsAg阴性的婴儿于生后120天内也有部分出现HBsAg阳性,其潜伏期与乙肝相符;若母血HBeAg阳性,表示病情处于感染状态,新生儿几乎100％HBsAg阳性。2.放射免疫法在羊水中可检出HBsAg。3.经剖宫产孕妇的新生儿HBsAg阳性,有的抗原阳性的孕妇临产时已转阴,但新生儿仍为阳性。     

丙型庚型肝炎病毒母婴传播研究

目的 研究丙型、庚型肝炎病毒(HCV、HGV)母婴传播及其影响因素。方法 2000年1月至2002年12月应用第三代ELISA法检测HCV—Ab、HGV—Ab，FQ—PCR方法检测HCV—RNA、HGV—RNA。结果 2052例普通孕妇检测抗HCV阳性22例，阳性率1．07％，其中16例HCVRNA阳性母亲所生16例婴儿有3例HCVRNA阳性，母婴传播率为18．75％。318例普通孕妇检测抗HGV阳性8例，阳性率2．52％，其中4例HGVRNA阳性母亲所生4例婴儿1例HGVRNA阳性。结论 阴道分娩过程感染可能是HCV、HGV母婴传播主要途径，孕妇临产时创旧升高是孕妇母婴传播的危险因素。     

产前抗病毒治疗对于阻断乙肝病毒母婴垂直传播作用的Meta分析

目的:评价乙肝病毒感染者孕期抗病毒治疗的疗效,探讨产前抗病毒治疗的指征。方法:对国内外12篇有关产前抗病毒治疗阻断乙肝母婴传播的文献进行Meta分析。结果:抗病毒治疗组婴儿出生时HBs Ag阳性的风险比对照组减少63%(RR=0.37,95%CI为0.22~0.62,P=0.0001),其中乙肝病毒载量≥106拷贝/ml组婴儿出生时HBsAg阳性风险减少76%(RR=0.24,95%CI为0.08~0.67,P=0.007);抗病毒治疗组婴儿6~12月龄HBsAg阳性的风险比对照组减少83%(RR=0.17,95%CI为0.11~0.27,P0.00001),其中乙肝病毒载量≥106拷贝/ml组婴儿6~12月龄HBsAg阳性风险减少89%(RR=0.11,95%CI为0.05~0.23,P0.00001);经抗病毒治疗后孕妇血清HBV DNA水平明显降低(SMD=-3.67,95%CI为-4.52~-2.82,P0.00001)。结论:产前抗病毒治疗可降低乙肝病毒感染者分娩前HBV DNA水平,其中乙肝病毒载量≥10~6拷贝/ml时抗病毒治疗,能有效阻断乙肝病毒母婴垂直传播。     

免疫阻断乙型肝炎病毒母婴传播多中心研究

目的 探讨孕产妇乙型肝炎表面抗原（HBsAg）阳性率及乙型肝炎病毒（HBV）母婴传播阻断的效果。方法 2008－2012年,通过多中心队列研究,对湖北省、山西省、广东省、新疆维吾尔自治区等地的孕产妇进行HBsAg筛查;对上述地区部分医院入院分娩的HBsAg阳性母亲及8～12个月龄婴儿进行随访观察,所有标本检测乙型肝炎血清标志物(HBsAg,HBsAb,HBeAg,HBeAb,HBcAb),部分标本检测HBV DNA。结果　筛查孕妇82214例,HBsAg阳性4924例,阳性率6.0%。随访HBsAg阳性母亲及8～12个月龄婴儿1371对,婴儿免疫阻断失败率3.1%（42/1371）,HBsAg及HBeAg双阳性母亲婴儿的免疫阻断失败率为8.2%。免疫阻断失败的婴儿其母亲均为HBeAg阳性且HBV DNA≥6 log10 copies/mL。HBeAg阳性母亲孕期注射乙型肝炎免疫球蛋白(hepatitis B immune globulin, HBIG)及未注射HBIG组,其婴儿免疫阻断失败率差异无统计学意义(8.8% vs. 8.1%, P=0.807)。结论　多中心调查显示目前孕产妇HBsAg阳性率6.0%,HBV母婴阻断失败率3.1%。HBsAg及HBeAg双阳性且HBV DNA≥6 log10 copies/mL 的孕妇应为母婴阻断的重点人群。孕妇孕期注射HBIG不能提高HBV母婴阻断效果。     

常规免疫预防阻断乙型肝炎病毒母婴感染的效果

目的 评价免疫预防措施在实际应用中阻断乙型肝炎病毒(hepatitis B virus,HBV)母婴感染的效果,阐明孕妇孕晚期使用乙肝免疫球蛋白(hepatitis B immunoglobulin,HBIG)能否减少HBV母婴感染.方法 将2002年7月至2004年8月江苏省14个县市的419例乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)阳性孕妇所分娩子女作为研究组,同地区同期的453例 HBsAg-孕妇分娩的子女作为对照组,于2009年10月至2010年3月期间对2组研究对象进行随访,调查母亲孕期HBIG使用情况以及子女出生后HBIG和乙型肝炎疫苗接种情况,检测儿童HBV血清标志物.率的比较采用χ2分析或者Fisher精确概率法,均数的比较采用t检验.结果研究组实际随访298例(71.12%),其中11例(3.69%) HBsAg+;而随访的328例(72.41%)对照组中,HBsAg阳性率为0.00 (χ2=12.32,P<0.01).共11例儿童HBsAg+,其母亲均为HBsAg和HBeAg同时阳性,除1例具体情况不详外,9例儿童在出生时明确没有使用HBIG或延迟接种疫苗,仅1例同时规范使用了HBIG和乙型肝炎疫苗.2组儿童抗-HBs阳性率分别为69.46%和69.21% (χ2=0.01,P=0.95).孕晚期注射HBIG的92例孕妇中,2例(2.17%)儿童HBsAg+;未使用HBIG的197例孕妇中,9例(4.57%)儿童HBsAg+ (χ2=0.98,P=0.51).结论 江苏省常规免疫预防措施在阻断母婴HBV感染方面取得了良好的效果,但对HBV携带孕妇(特别是HBeAg+者)的新生儿仍需强调及时注射HBIG.孕妇孕晚期使用HBIG不能减少母婴HBV感染.

Abstract：

Objective To assess the protective effect of vaccination in routine application on hepatitis B virus (HBV) exposed infants and to clarify whether hepatitis B immunoglobulin (HBIG) administration of pregnant women may reduce the risk of maternal-fetal transmission of HBV. Methods Serum samples of 6398 pregnant women at gestation of 15-20 weeks from 6 urban and 8 rural areas across Jiangsu province were previously tested for serologic markers of HBV by ELISA from July 2002 to August 2004. In this study, infants born to 419 HBV carrier mothers were taken as the study group, while infants born to 453 non-carrier mothers were taken as the control group by stratified random sampling. They were followed-up and screened for HBV markers during October 2009 to March 2010. Information including HBIG administration during pregnancy, HBV vaccination and HBIG administration of the infants were collected. χ2 test or Fisher′s exact method were used to compare the rates and the comparison of the means was by t test. Results The follow-up rates of the study group and control group were 71.12% (298/419) and 72.41% (328/453), respectively. Of the 298 infants born to HBV carrier mothers, 11 (3.7%) were positive for HBsAg, while none of the 328 infants born to non-carrier mothers was HBsAg positive (χ2=12.32, P<0.01). All of the 11 children were born to mothers with both HBsAg and HBeAg positive, and nine of the 11 children were not injected HBIG or not immunized with hepatitis B vaccine within 24 hours after birth, with only one received regular vaccination and detailed information was unknown in one case. The positive rates of anti-HBs in the study group and the control group were 69.46% and 69.21% respectively (χ2=0.01, P=0.95). HBsAg positive rate of the children born to pregnant women treated with HBIG during late pregnancy (n=92) was 2.17% (n=2), whereas that in the children born to women not treated with HBIG (n=197) was 4.57% (χ2=0.98, P=0.51). Conclusions The protective effect of immunoprophylaxis in routine application against perinatal HBV infection in Jiangsu province is good. Efforts are required to emphasize the importance of HBIG administration in infants born to HBV carrier mothers, especially in HBeAg positive mothers within 24 hours after delivery. Treatment of HBsAg positive pregnant women with HBIG in third trimester would not decrease the risk of maternal-fetal transmission of HBV.     

Prevention of vertical hepatitis B transmission by hepatitis B immunoglobulin in the third trimester of pregnancy.

OBJECTIVE: To explore the possible efficacy of using hepatitis B immunoglobulin (HBIG) during the third trimester of pregnancy to prevent intrauterine transmission of hepatitis B virus (HBV). METHODS: Of 469 pregnant women testing positive for hepatitis B surface antigens (HBsAg), 126 had hepatitis B e antigen (HBeAg) and 343 did not. RESULTS: There were women who declined to be treated with HBIG in these 2 groups. Among infants born to HBeAg-positive mothers, the rates of those testing positive for HBsAg at birth and at the 6-month visit were significantly lower when the mothers had been treated with HBIG (P<0.05). Among infants born to HBeAg-negative mothers, however, no significant differences were found whether the mothers had been treated or not. Furthermore, all newborns received HBIG treatment and the first dose of a vaccination schedule within 12 h of birth. At the 6-month visit the protective anti-HBs rates were only 32.3% among infants whose mothers were HBeAg-positive and 56.2% among those whose mothers were HBeAg-negative when their mothers had not been treated with HBIG during pregnancy, whereas the corresponding rates were as high as 75.8% and 88.7% when the mothers had been treated. CONCLUSION: Maternal administration of HBIG is effective in preventing intrauterine fetal HBV infection in HBsAg-positive, HBeAg-positive pregnant women and in improving immune response to hepatitis B vaccine in infants born to HBV carriers.     

Hepatitis B and C in pregnancy

In general, pregnancy does not influence the course of hepatitis B (HBV) and C (HCV) infection. Most neonates born to mothers who suffer from acute viral hepatitis B and C are asymptomatic. Chronic hepatitis B and C infections can be transmitted to neonates. This route of transmission of HBV is a major contributing factor to the high carrier rate in endemic countries where 80–95% of infants born to HBsAg/HBeAg-positive (hepatitis B surface antigen and hepatitis B e antigen respectively) mothers are infected. Despite the availability of a immunoprophylactic vaccine, 10–15% of these infants are still infected. The possible reasons for vaccine failure include the ability of HBV antigens to induce immunotolerance and the existence of HBV variants. The factors contributing to vertical transmission of HBV and HCV are also discussed. These factors include viral load, virus variants and sensitivity of diagnostic tests. The rate of vertical transmission of HCV of less than 5% is lower compared to HBV in HCV-ribonucleic-acid-positive mothers. However, the risk of HCV transmission is increased to about 23% if the pregnant women are also human immunodeficiency virus (HIV) positive.     

Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus

Abstract

Objective: This study was designed to explore if hepatitis B virus (HBV) may be transmitted via breast milk through mother-to-child transmission (MTCT), and assay the immunoprophylaxis efficacy after passive–active immunization.

Method: From year 2008 to 2012, 67?720 pregnant women were screened and 1186 HBsAg-carrier mothers and their infants aged 8–12 months were followed in multi-centers of China, among whom HBV markers (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb) and HBV-DNA were measured.

Results: HBsAg positive rate of pregnant women was 6.7% (4533/67?720) and infants’ immunoprophylaxis failure rate was 3.3% (39/1186). Immunoprophylaxis failure infants were all born to mothers of HBeAg positive and HBV-DNA >6 log₁₀ copies/ml. Among infants of HBeAg positive mothers, HBV infection rate was 9.0% and HBsAg positive rate was 8.3% in breast-feeding group versus 9.2% in formula-feeding group, P?=?0.761. Occurrence of perinatal HBV infection was indicated in uterus or during delivery. Different feeding patterns had no effects on HBsAb conversion of infants with the implementation of immunization.

Conclusions: HBsAg prevelance rate of pregnant women enrolled was 6.7% and immunoprophylaxis failure rate of infants was 3.3%, while the infection rate reached 9.0% in infants of HBeAg positive mothers. Breast feeding did not increase the occurrence of HBV MTCT.     

乙型肝炎表面抗原与乙型肝炎e抗原阴性孕妇乙型肝炎病毒宫内感染的研究

目的 探讨应用套式PCR方法检测乙型肝炎表面抗原(HBsAg)及乙型肝炎e抗原(HBeAg)阴性孕妇乙型肝炎病毒(HBV)宫内感染的状况。方法 选择HBsAg与HBeAg阴性,其他HBV血清标志物阳性孕妇及其新生儿24例作为病例组,同期HBV血清标志物全部阴性孕妇及其新生儿16例作为对照组。采用套式PCR方法检测两组孕妇及其新生儿的血清及外周血单个核细胞(PBMC)中HBV-DNA。结果(1)病例组24例孕妇中,血清HBV-DNA阳性8例,阳性率为33％;PBMC中HBV-DNA阳性10例,阳性率为42％r。其中血清与PBMC均阳性3例,总阳性率为63％r(15／24)。(2)病例组24个新生儿中,血清HBV-DNA阳性3例,阳性率为13％,PBMC中HBV-DNA阳性6例,阳性率为25％。其中血清与PBMC均阳性1例,宫内感染率为33％(8／24)。(3)病例组24例孕妇中,血清阴性而PBMC阳性共7例,其新生儿4例发生宫内感染,感染率为4／7。(4)对照组16例孕妇及其新生儿血清及PBMC中HBV-DNA全部阴性。结论 HBsAg及HBeAg阴性孕妇也可发生HBV宫内感染,采用灵敏度高的套式PCR方法检测孕妇及其新生儿血清及PBMC中HBV-DNA,对诊断HBV宫内感染具有重要临床意义。     

Hepatitis B vaccine inhibiting vertical transmission of hepatitis B virus]

A survey of hepatitis B virus infection was carried out among 1,947 pregnant women. The results showed that 215 women were HBsAg positive, a rate of 10.7%. Among the 38 serum samples reexamined, 10 were positive both for HBsAg and HBeAg (26.3%). In order to evaluate the effect of hepatitis B vaccine on inhibiting vertical transmission, all infants of the 38 women positive for HBsAg were given hepatitis B vaccine 40 micrograms. by injection 7 months after the immunization, HBsAg was found absent in 31 of them, but all the infants had produced anti-HBsAg antibody. The positive rate of anti-HBsAg antibody in infants whose mothers had both positive HBsAg and HBeAg was 50%, whereas in infants whose mothers had only positive HBsAg it was 92.9% (chi 2 = 6.38 P less than 0.05).     

妊娠合并乙型肝炎病毒感染围分娩期管理

对乙型肝炎(乙肝)病毒感染孕妇采取合理的围分娩期管理以阻断母婴垂直传播是降低我国慢性乙肝感染率的关键。新生儿出生后及时注射乙肝免疫球蛋白,并按照0、1、6方案接种乙肝疫苗,可有效阻断乙肝的围分娩期传播。孕妇在晚孕期进行抗病毒治疗可能通过降低母体病毒水平而减少围分娩期传播风险,但抗病毒药物对胎儿的安全性仍需进一步验证。     

胎盘乙型肝炎病毒感染与宫内传播的关系

目的 探讨乙型肝炎病毒（ＨＢＶ）宫内传播的危险因素,并追踪ＨＢＶ经胎盘传播的途径和胎儿宫内感染的时间,方法 共收集了乙型肝炎表面抗原（ＨＢｓＡｇ）携带孕妇１３１例,其中孕早期人工流产胎盘２４例,孕中期引产胎盘和胎儿各６例,足月分娩胎盘和新生儿各１０１例。孕妇和新生儿血清ＨＢｓＡｇ和ＨＢＶ ＤＮＡ检测分别采用酶联免疫吸附试验和聚酶链反应法。