孕期应用乙型肝炎免疫球蛋白预防乙型肝炎病毒垂直传播的预防作用

目的探讨孕期应用乙肝免疫球蛋白(HBIG)对乙肝表面抗原及e抗原双阳性孕妇乙肝母婴垂直传播的预防作用.方法外周血HBsAg阳性孕妇291例,HBsAg、HBeAg双阳性83例,分为HBIG(A组,59例)及非HBIG(B组,24例)组;所有新生儿在出生24 h内,1、6个月分别注射乙肝疫苗并检验乙肝两对半.结果 1.HBeAg阳性孕妇的外周血HBV-DNA阳性率为76.56%,显著高于HBeAg阴性孕妇(8.22%),P＜0.01;2.孕晚期应用1,2次或3次HBIG的新生儿各月龄HBsAg阳性率及HBsAb阳转率无显著差异;3.A组新生儿出生当天外周血HBsAg阳性率显著低于B组,P＜0.05;B组乙肝疫苗免疫后的6个月龄婴儿外周血HBsAb阳转率仅37.5%,显著低于A组(81.4%),P＜0.001.结论孕晚期应用HBIG可有效降低乙肝宫内感染率,提高6个月龄婴儿HBsAb阳转率.     

乙肝免疫球蛋白联合乙肝疫苗阻断乙型肝炎病毒母婴传播长期随访研究

目的研究乙肝免疫球蛋白(HBIG)联合乙肝疫苗阻断乙型肝炎病毒(HBV)母婴传播的长期效果。方法624例乙型肝炎病毒表面抗原(HBsAg)携带者母亲的婴儿随机分组,按0、1、6月龄单用乙肝疫苗20μg或出生时注射HBIG100IU,然后于1、2、7月龄接种乙肝疫苗20μg。静脉采血随访HBsAg,平均(6.34±1.71)年。结果同单用疫苗比较,HBIG联合免疫使1岁时慢性HBV感染率由17.6%降为5.0%;总慢性HBV感染率双阳性组由24.5%降至10.6%(P<0.005),单阳性组由10.7%降至3.8%(P<0.025)。双阳性组初现HBsAg阳性婴儿慢性化率也降低,在出生时HBsAg阴性而1～6个月时出现HBsAg阳性婴儿,慢性化率由40.9%降至0(P＜0.05),出生时HBsAg阳性婴儿1月龄HBsAg阴转率由26.4%提高至58.8%(P<0.05)。结论HBIG联合乙肝疫苗明显提高母婴传播阻断效果,减少慢性HBV感染率。其机理之一是减少初现HBsAg阳性婴儿的慢性化。     

国产及进口乙型肝炎免疫球蛋白阻断乙型肝炎病毒母婴垂直传播效果的研究

目的：探讨国产及进口乙型肝炎免疫球蛋白（HBIG）阻断HBeAg/或抗HBe（＋）、HBV－DNA定量PCR（＋）孕妇所生的新生儿宫内乙型肝炎病毒感染的效果。方法：于孕期第6个月起每月给予孕妇进口或国产HBIG2000IU肌注1次，预产期前5－7d再加强注射1次，新生儿娩出后3h内及第15天各肌注1次HBIG，以后按1、2、7、13个月注射基因工程乙肝疫苗10μg。结果：生后13个月时小儿HBsAg阳性率：国产HBIG组、进口HBIG Bayer组与Berna组分别为2．7％、2．2％、2．8％；抗－HBs阳性率分别为94．7％、95．6％、97．2％。13个月龄儿国产HBIG组3例、Bayer组和Berna组各1例检获HBsAg( )，乙型肝炎病毒母婴传播阻断率分别为96．9％、97．4％、96．7％。结论：国产HBIG阻断HBeAg( )孕妇新生儿宫内感染与进口HBIG一样有效，且国产HBIG安全、价廉。     

阻断乙型肝炎病毒宫内传播的随机对照研究

目的 最近10多年的研究表明，用乙肝疫苗主被动联合免疫能阻断母婴间乙肝病毒（HBV）传播，保护效果达到70％－90％，而宫内已感染HBV是生后免疫接种失败的主要原因，我们研究用乙肝免疫球蛋白（HBIG）多次产前注射，观察阻断HBV宫内传播的效果。方法 980例携带HBsAg孕妇随机分成两组，一组孕妇产前3个月（妊娠28周起）每4周肌注HBIG 200IU－400IU，直至临产，称HBIG组；另一组不注射为对照，称对照组。所有对象和其所生孩子出生时即采外周血，检测HBsAg、HBeAg，部分测HBV DNA，所有新生儿随访1年。结果 496例新生儿为对照组母亲所生，生后仅接种乙肝疫苗和HBIG；491例新生儿为HBIG组母亲所生，生后同样给予主被动联合免疫。结果显示对照组婴儿的宫内感染率为难4．3％；而HBIG组婴儿的宫内感染率为5．7％（x^2＝20．11，P＜0．001），宫内感染HBV的高危因素是母亲呈HBsAg、HBeAg双阳性或HBV DNA阳性。结论 研究提出产前多次肌注HBIG可有效减少HBV的宫内传播，未发现任何副作用。     

乙型肝炎病毒母婴传播和预防研究进展

乙型肝炎病毒(HBv)感染引起的相关性疾病仍是当今危害人类健康的重大问题，母婴传播是HBV的重要传播途径之一。孕妇体内HBV高复制状态是母婴传播的最危险因素，HBV自然突变或在拉米夫定以及主、被动免疫选择压力下发生突变可能是母婴传播、免疫接种失败的重要原因。乙型肝炎免疫球蛋白及乙型肝炎疫苗主、被动联合免疫，含有HBV前S2的新型乙型肝炎疫苗应用以及拉米夫定联合主、被动免疫是阻断HBV母婴传播的有效措施。母乳喂养未必会增加HBV母婴传播的危险。     

拉米夫定阻断乙型肝炎病毒母婴传播的作用

目的探讨妊娠晚期应用拉米夫定对高乙型肝炎病毒(HBV)DNA载量孕妇HBV垂直传播的阻断作用。方法血HBsAg、HBeAg阳性及HBV DNA≥1×106拷贝/mL孕妇90例,分为拉米夫定组48例与对照组42例。拉米夫定组自孕28周起口服拉米夫定。二组孕妇于孕28周、分娩前、产后6个月,其新生儿生后24h内免疫接种前、1、6个月检测HBsAg、HBeAg、HBsAb及HBV DNA。结果拉米夫定组孕妇分娩前HBV DNA显著下降(P<0.05),其新生儿出生24h内HBsAg、HBV DAN阳性率分别为16.67%、18.75%,低于对照组40.48%、45.23%(Pa<0.05);拉米夫定组6月龄儿HBsAb阳性率81.25%高于对照组59.52%(P<0.05)。二组孕妇及其新生儿未发现有不良反应。结论妊娠晚期应用拉米夫定能降低孕妇HBV DNA载量,减少HBV垂直传播率,安全有效。     

产前注射乙型肝炎免疫球蛋白预防乙型肝炎病毒宫内感染的临床研究

目的 减少新生儿宫内感染乙型肝炎病毒（ＨＢＶ）,探讨孕妇被动免疫预防ＨＢＶ宫内感染的作用。方法 将１４１例无症状ＨＢｓＡｇ（＋）孕妇随机分为两组,预防组６９例,自孕２８周起每月注射１次乙型肝炎免疫球蛋白（ＨＢＩＧ）,每次２００ ＩＵ;对照组７２例,不注射ＨＢＩＧ。在孕妇孕２８周、分娩前和新生儿出生时分别检测静脉血ＨＢｓＡｇ,ＨＢｅＡｇ和抗－ＨＢｓ,部分产妇检测乳汁ＨＢｓＡｇ,ＨＢｅＡｇ。结果 预防组新生儿血清ＨＢｓＡｇ检出率（５．８％）明显低于对照组（１６．７％）Ｐ＜０．０５;预防组新生儿抗－ＨＢｓ阳性率（３０．４％）显著高于对照组（９．７％）Ｐ＜０．０５;两组母亲乳汁ＨＢｓＡｇ检出率无显著差异。结论 产前多次肌注ＨＢＩＧ可减少携带ＨＢＶ母亲所生新生儿宫内受ＨＢＶ感染。     

乙型肝炎病毒母婴传播和预防研究进展

乙型肝炎病毒 (HBV)感染引起的相关性疾病仍是当今危害人类健康的重大问题 ,母婴传播是HBV的重要传播途径之一。孕妇体内HBV高复制状态是母婴传播的最危险因素 ,HBV自然突变或在拉米夫定以及主、被动免疫选择压力下发生突变可能是母婴传播、免疫接种失败的重要原因。乙型肝炎免疫球蛋白及乙型肝炎疫苗主、被动联合免疫 ,含有HBV前S2 的新型乙型肝炎疫苗应用以及拉米夫定联合主、被动免疫是阻断HBV母婴传播的有效措施。母乳喂养未必会增加HBV母婴传播的危险。     

预防乙型肝炎病毒母婴传播的随机对照研究

目的探讨乙肝免疫球蛋白（HBIG）预防乙型肝炎病毒（HBV）母婴垂直传播的效果。方法以2001年1月至2005年5月在台州医院产科初次进行妊娠健康检查,HBsAg测定阳性或HBsAg、HBeAg均阳性孕妇作为研究对象,共279例。将单纯HBsAg阳性孕妇与HBsAg、HBeAg双阳性孕妇分别应用随机数表方法随机分组,分别为单阳注射组（n=80）、单阳对照组（n=60）、双阳注射组（n=79）、双阳对照组（n=60）。单阳注射组、双阳注射组于妊娠加周开始肌肉注射HBIG 200U,每4周注射1次,直至临产。两对照组不注射HBIG。4组孕妇所产婴儿,除常规接种乙肝疫苗外,均于出生后16h内和2周肌肉注射HBIG。然后随访并测定婴儿HBsAg。结果单阳注射组、单阳对照组、双阳注射组、双阳对照组所生婴儿HBsAg感染率分别为3％、13％、10％、32％。单阳注射组与单阳对照组之间（x^2=6．07,P〈0．05）,以及双阳注射组与双阳对照组之间婴儿HBsAg感染率（x^2=10．11,P〈0．01）均有统计学意义,注射HBIG组,对单纯HBsAg阳性孕妇及HBsAg、HBeAg双阳性孕妇,出生婴儿HBsAg感染率均显著低于对照组;单阳注射组与双阳注射组之间婴儿HBsAg感染率差异亦有统计学意义,说明HBIG对单纯HBsAg阳性孕妇预防效果优于HBsAg、HBeAg双阳性孕妇。结论HBIG能有效预防母婴传播,降低HBV感染率。因此,妊娠妇女应及时进行健康检查,发现HBV感染阳性,及时采取注射HBIG等有效措施,以促进优生优育。     

胎盘Hofbauer细胞介导的乙型肝炎病毒母婴垂直传播

目的探讨胎盘Hofbauer细胞在乙型肝炎病毒（HBV）经胎盘母婴垂直传播中的作用。方法外周血HmAg和HBV-DNA均阳性孕妇175例，根据其新生儿外周血HBsAg及HBV-DNA检测结果，33例归为垂直传播组，142归为非垂直传播组；另选40例外周血ⅫBsAg和HBV-DNA均阴性母亲及其新生儿作为对照组。应用光学显微镜、透射电镜和免疫组织化学技术观察胎盘Hofbauer细胞结构变化及其与HBV感染的关系。结果1，垂直传播组和非垂直传播组Hofbauer细胞散在分布于胎盘问质中，其超微结构发生改变；对照组胎盘组织中末发现Hofbauer细胞。2．垂直传播组胎盘Hofbauer细胞总数及结合HBV的Hofbauer细胞数明显高于非垂直传播组（P=0）。3．单个或多个病毒颗粒、病毒包涵体和病毒抗原颗粒仅出现在垂直感染组胎盘Hofbauer细胞胞质空泡和细胞间隙内。结论HBV可通过胎盘Hofbauer细胞介导HBV母婴垂直传播。     

联合免疫措施阻断乙型肝炎母婴传播的疗效比较

目的探讨不同剂量与时间注射乙型肝炎(乙肝)免疫球蛋白(HBIG)与乙肝疫苗阻断乙肝病毒(HBV)母婴传播的效果。方法对乙肝孕妇抽血查HBVDNA,按其载量分为A、B、C3组,每组随机分为4小组,应用不同的联合免疫阻断方法,对比其疗效。结果A、B2组在不同组间发生乙肝的阳性率与HBsAb的阳转率比较无统计学差异;C组发生乙肝的阳性率与HBsAb的阳转率比较有统计学意义。结论根据孕母HBVDNA程度不同宜采取不同方法联合免疫阻断HBV的垂直传播。     

Prevention of Vertical Transmission of Hepatitis B Virus by Yeast Recombinant Hepatitis B Vaccine

In order to prevent vertical transmission of hepatitis B virus (HBV), yeast recombinant HB vaccine at a dose of either 5 mcg or 10 mcg was administered to 185 infants born to mothers who were positive for HBs antigen (HBsAg). All of them developed antibody to HBsAg (anti-HBs) after three vaccinations. Generally, the cutaff index (COI) of anti-HBs by radioimmunoassay (RIA) was higher in the 10 mcg dosage group than in the 5 mcg dosage group. The geometric mean titer (GMT) of anti-HBs, as measured by quantitative RIA, in the former group was 2.4 times that in the latter one month after the third vaccination. The incidence of clinical reactions was only 4% in a total of 561 injections, and none of the reactiom were severe. It is conduded that recombinant HB vaccine is safe and has excellent immunogenicity for infants requiring prevention of HBV vertical transmission. It is also suggested that 10 mcg doses of the recombinant HB vaccine can provide more solid protection to high-risk infants without serious adverse reactions. ( Acta Paediutr Jpn 1989; 31: 180–185)     

妊娠晚期乙肝孕妇注射乙肝免疫球蛋白对阻断乙肝病毒母婴传播的作用

目的 探讨慢性乙肝病毒感染的孕妇于妊娠晚期注射乙肝免疫球蛋白(HBIG)对阻断乙肝病毒母婴传播的效果.方法 将慢性乙肝病毒携带者或慢性乙肝孕妇及其所生新生儿分为2组,A组孕妇于孕期第28、32及36周时分别肌肉注射HBIG 200 IU;B组孕妇未注射HBIG.分别检测两组孕妇及其所生新生儿血清乙肝病毒标志物(HBVM)及乙肝病毒DNA(HBV DNA).结果 A组孕妇378例,共分娩新生儿378例,其中新生儿血HBV DNA>500 copies/ml 17例,新生儿宫内感染发生率为4.497%;B组孕妇391例,共分娩新生儿391例,新生儿血HBVDNA>500 copies/ml 17例,新生儿宫内感染发生率为4.348%(X<'2>=0.005 6,P>0.05).血清抗-HBs阴性的孕妇所生新生儿中,A组有9例血清抗-HBs阳性,B组未见血清抗-HBs阳性(X<'2>=7.474,P<0.05).结论 给慢性乙肝病毒感染的孕妇于妊娠晚期注射HBIG 3次,每次200 IU不能明显降低新生儿发生乙肝病毒宫内感染的机会,但部分新生儿可获得血清抗-HBs.HBIG在慢性乙肝病毒感染妊娠妇女中的应用尚待进一步探讨.     

胎盘Hofbauer细胞在乙型肝炎病毒母婴垂直传播中的作用

目的 探讨胎盘Hofbauer细胞与乙型肝炎病毒（HBV）垂直传播的相关性。方法应用光学显微镜和免疫组织化学技术观察垂直传播组（母亲及新生儿HBsAg和HBV-DNA均为阳性）14例、非垂直传播组（母亲HBsAg和HBV-DNA阳性，新生儿为阴性）62例和正常对照组（母亲及新生儿HBsAg和HBV-DNA均为阴性）10例的胎盘结构变化、胎盘HBV感染与Hofbauer细胞的关系。结果1．垂直传播组和非垂直传播组孕妇胎盘组织存在坏死、水肿、绒毛动脉硬化、绒毛间质纤维化和纤维素样沉积，多形核自细胞、淋巴细胞、颗粒细胞浸润。2．垂直传播组胎盘HBsAg阳性率为100．0％；非垂直传播组为58．0％，差异具有显著性（P=0．013）。阳性信号主要出现在滋养细胞、Hofbauer细胞和血管内皮细胞。3．垂直传播组胎盘Hofbauer细胞数目明显增加，结合HBV的阳性Hofbauer细胞明显高于非垂直传播组和对照组（P均〈0．01）。结论HBV可与胎盘Hofbauer细胞结合，可能介导HBV的母婴垂直传播。     

IgM Antibody to Core Antigen of Hepatitis B Virus in Vertical Transmission

Transmission of hepatitis B virus (HBV) from a mother to the child is mostly due to infection during delivery. It has been suggested, however, that intrauterine HBV infection can occur in a small number of subjects. In the present study, we examined IgM antibody to core antigen of HBV (IgM-HBcAB) in cord blood to see whether intrauterine infection could be distinguished from neonatal transmission of HBV. Infants with possible intrauterine infection, however, did not have IgM-HBcAb in cord blood. It is concluded, therefore, that examination of this antibody is not useful for such purposes. IgM-HBcAb may not be produced during the period when immune tolerance to HBV is maintained, since it was detected only in association with occurrence of liver cell injury.     

CSOG MFM Committee Guideline: Management of Hepatitis B During Pregnancy and Prevention of Mother-to-Child Transmission of Hepatitis B Virus (2020)

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is the main cause of chronic hepatitis B. The prevention of MTCT plays a critical role in control chronic hepatitis B. The main purpose of the present clinical guidelines is to aid healthcare providers in managing pregnant women with positive HBsAg and in preventing MTCT of HBV. We recommend: (1) all pregnant women require prenatal screen for hepatitis B serological markers;(2) newborn infants of mothers with negative hepatitis B surface (HBsAg) require administration of hepatitis B vaccine on a 0, 1, and 6 month-schedule;(3) newborn infants of mothers with positive HBsAg need hepatitis B immunoglobulin (HBIG) and birth dose vaccine within 12 hours (the sooner the better) after birth, followed by injection of the second and third dose of hepatitis B vaccine at the age of one and six months respectively;(4) in preterm neonates or neonates with poor health conditions born to HBsAg-positive mothers, the immunoprophylaxis measures should be appropriately taken;(5) to further reduce MTCT of HBV, pregnant women with HBV DNA levels >2×105 IU/mL or positive hepatitis B e antigen may receive oral antivirals, starting from 28 to 32 weeks of gestation and discontinuing the drug on the delivery day;(6) cesarean section is not recommended to reduce MTCT of HBV;(7) breastfeeding is recommended in infants of HBsAg-positive mothers, regardless of maternally positive hepatitis B e antigen, maternal nipple injury or bleeding, oral mucosal injury in neonates or infants;(8) breastfeeding is recommended in infants born to HBsAg-positive mothers who require continuation of antiviral therapy after delivery, and the infants should be followed up to observe whether adverse effects develop;and (9) the infants born to HBsAg-positive mothers should be tested for hepatitis B serological markers at the age of 7-12 months, and those who are negative for HBsAg and anti-HBs should receive three doses of hepatitis B vaccine on the 0, 1, and 6 month-schedule as soon as possible.     

Efficacy of HBIG and Hepatitis B Vaccine for the Prevention of HBV Transmission

The efficacy of HBIG and HB vaccine is summarized for the prophylaxis of HBV infection. Cases were divided into a “vertical” group of 130 neonates, consisting of 90 infants who received HBIG twice and then Hb vaccine from the second month after birth and HB vaccine beginning on the 5th day after birth (vertical II), and a “horizontal” group consisting of 108 infant who were given HB vaccine three times. In each case, excellent results were obtained and no adverse reaction was noted; however the number of cases who were not immunized was significantly higher and the member of chronic HBs-Ag carriers was higher in the vertical II group. the continuity of the immune state was fairly good for at least three years in the vertical I and horizontal groups. We think that in the case of the vertical group, the course of HB vaccine should be started in the second month after birth with the second inoculation of HBIG.