Prevention of intrauterine infection by hepatitis B virus with hepatitis B immune globulin: efficacy and mechanism

Objective　To evaluate the efficacy of hepatitis B immune globulin (HBIG) in preventing intrauterine infection by hepatitis B virus (HBV) and to investigate its mechanism. Methods　Forty-eight pregnant women positive for hepatitis B surface antigen (HBsAg) were randomly divided into 2 groups. The 34 women in the study group were injected with HBIG during pregnancy; the other 14 women were controls. Maternal blood samples were taken before HBIG injection and at delivery. Neonatal blood samples were taken within 24 hours after birth before HBIG and hepatitis B vaccine were given. HBsAg and antibody to HBsAg (anti-HBs) were tested by radioimmunoassay. Results　None of the 35 newborns (including 2 twins) in the study group was positive for HBsAg, but 3 (21%) in the control group were positive (P=0.02). The HBsAg titers in the women in the study group decreased after HBIG injection. Of the 35 newborns in the study group, 32 (91%) were positive for anti-HBs. Conclusion　Systematic injections of HBIG during pregnancy may prevent intrauterine HBV infection, the mechanism of which may be reduction of maternal HBV viremia and production of fetal passive immunity.     

A pilot study on the combined therapy of granulocyte-macrophage colony-stimulating factor and hepatitis B vaccine on chronic hepatitis B virus carrier children

Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac).Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM-CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM-CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four-dose schedule. HBV-DNA quantification and other HBV serological markers were tested before and after the four-dose therapy. Results Twelve children in each group completed the study. Of them, 3 children in the GM-CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment. Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM-CSF group and 10 in the HBIG group. One from each group had an HBeAg/anti-HBe seroconversion after the treatment. The quantity of HBV-DNA was significantly lower after the treatment (P=0.023) in GM-CSF group, but was not significantly reduced in HBIG group. No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group. Conclusion Combined GM-CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis.     

Relationship between heterogeneity of HBV preS/S gene and intrauterine transmission

Objective: To study the relationship of the mutation of HBV preS/S gene in HBsAg carrying pregnant women and intrauterine transmission. Methods: Polymerase chain reaction (PCR) was used to amplify HBV preS/S gene from sera of 8 HBsAg carrying pregnant women, 4 women's neonates infected with HBV, and the other's neonates non-infected with. The PCR products were cloned and 5 clones were chosen from every woman for DNA sequencing. Results: Heterogeneity of HBV preS/S gene in HBsAg carrying pregnant women having intrauterine transmission was much higher than that from having not intrauterine transmission, and the divergence rate of nucleotide sequences also higher strikingly. Conclusion: High heterogeneity of HBV preS/S gene of HBsAg positive pregnant women may be relative to high rate of intrauterine transmis-     

乙肝表面抗原阳性孕妇肌肉注射乙肝免疫球蛋白预防母婴传播的临床分析

目的 探讨经母亲对胎儿行被动免疫在预防乙型肝炎病毒(HBV)宫内感染中的作用.方法 对自孕20周起多次肌肉注射乙肝免疫球蛋白(HBIG)的乙肝表面抗原(HBsAg)(+)孕妇68例(A组)及未注射的28例HBsAg(+)孕妇(B组)采用固相放免法和套式PCR检测母血HBsAg、HBV DNA及其新生儿血HBsAg、抗HBS、HBV DNA.结果 A组70例新生儿中64例血清抗HBS(+),与B组相比差异有统计学意义(P＜0.05).A组新生儿血HBsAg、HBV DNA检出率均明显低于B组.A组孕妇用药后血HBsAg滴度及HBVDNA水平较用药前明显下降.结论 经母亲对胎儿行被动免疫可有效预防HBV宫内感染. Abstract： Objective To investigate the effect of passive immunization of fetus by infection of mother with HBIG on drevention of HBV intrauterine infection. Methods Forty-eight pregnant women with HBsAg positive were divided into two groups:group A(68 cases)were injected with HBIG during pregnancy;group B(28 cases)were followed up without injecfion of HBIG as controls. The blood samples of mothers and their infants were tested with radioimmunoassay and PCR. Results of 70 infants in group A,64(91.46%)were positive for anti-HBs(P＜0.05).The infants with HbsAg positive and HBV DNA positive in group A were fewer than those in group B(P=0.02 and ＜0.05). Conclusions Passive immunization of fetus by iniection to mother with HBsAg may prevent HBV intrauterine infection effectively.     

Survey of 34 pregnant women with hepatitis A and their neonates.

Thirty-four pregnant women with hepatitis A and their neonates were investigated on serum anti-HAV IgM, ALT (GPT) and clinical manifestations (with 34 randomized controls) during the outbreak of viral hepatitis A in Shanghai. The result showed no evidence of maternal-infant transmission of hepatitis A, and no birth defect was found. Sufficient rest and proper diet for and close surveillance of the pregnant woman were suggested to ensure the well-being of mother and child. In addition, we found immune gamma-globulin given to the neonates born of mothers with hepatitis A may be beneficial to avoid horizontal transmission of hepatitis A.

     

A six-year survey of immunogenicity and efficacy of hepatitis B vaccine in infants born to HBsAg carriers.

Although the efficacy of hepatitis B vaccine is well documented, the duration of immunity of healthy infants after vaccination is unknown. 99 infants born to hepatitis B surface antigen (HBsAg)-carrier mothers were studied and found to have positive anti-HBs (titer: greater than or equal to 10 mIU/mL) after a first injection of vaccine at the ages of 1 to 6 years. The infants were randomly divided into four groups of recipients treated with the vaccine of the National Institute of Allergy and Infectious Diseases (NIAID), U.S.A. or that of the Beijing Biological Products Research Institute (BBPRI), BBPRI vaccine in combination with hepatitis B immune globulin (HBIG) and placebo. The results showed that the protective efficacy dropped considerably after 5 years with NIAID vaccine, after 3 years with BBPRI vaccine and after 4 years with BBPRI vaccine plus HBIG. This suggests that a booster injection is needed 5 years after the first injection of NIAID vaccine, 3 years after BBPRI vaccine, and 4 years after BBPRI vaccine plus HBIG.

     

Hepatitis B Immunoprophylactic Failure and Characteristics of the Hepatitis B Virus Gene in Mother-Infant Pairs in Parts of China

Objective To determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus(HBV) infected mothers and to characterize HBV genes. Methods HBV-serological testing was conducted for pregnant women and infants. The complete genomes of 30 HBV isolates were sequenced, and genetic characteristics were analyzed using MEGA 5 software. Results The immunoprophylactic failure rate for infants who had completed the scheduled hepatitis B vaccination program was 5.76%(32/556). High sequence homology(99.8%-100%) was observed in 8 of the 10 mother-infant pairs. We identified 19 subgenotype C2 strains, 9 subgenotype B2 strains, and 2 subgenotype C1 strains. Three serotypes were detected: adr(19/30), adw(9/30), and ayw(2/30). The frequency of amino acid mutation of the ‘a' determinant region was 16.67%(5/30), including that of Q129 H, F134 Y, S136 Y, and G145 E. We detected 67 amino acid mutations in the basal core promoter, precore, and core regions of the genome. Conclusion The immunoprophylactic failure rate in infants born to HBV-infected mothers is low in the regions of China examined during this study. Moreover, HBV mutation in the ‘a' determinant region could not account for immunoprophylactic failure for all infants.     

高龄孕产妇妊娠与分娩的监护及处理

目的 探讨高龄孕产妇妊娠与分娩加强监护与处理的重要性.以减少因处理不当对母婴产生的不良影响.方法 选取单胎妊娠分娩的孕妇分高龄组和非高龄组,观察两组妊娠期分娩期并发症和围生期结局.结果 两组在妊娠分娩期并发症、围生儿并发症方面差异均有统计学意义.结论 高龄孕妇妊娠分娩并发症高,增加了妊娠期及分娩期的高危状况,应加强妊娠期围生期监护,及早发现其潜在不利因素,及时处理,以保证孕产妇安全渡过围生期,达到母婴健康的目的. Abstract： Objective To investigate the importance of enhancing the monitoring and management of pregnancy and delivery in elderly pregnant women,and to reduce the harmful influence to mothers and infants due to the unsuitable treatments. Methods The pregnant women who had singleton pregnancy were divided into elderly group and non-elderly group.We observed the complications of gestation and delivery and the results of peripartum in the two groups. Results The complications of pregnancy,delivery and perinatal infants in elderly group were significantly higher than in non-elderly group. Conclusions The elderly in maternal pregnancy,the incidence of the complications of gestation and delivery was higher,which added the risk during pregnancy and delivery.For ensuring the safety of the pregnant women during perinatal period,and for the sake of the health of mothers and infants,it is significant to pay more attention to gestational and perinatal monitoring,to discover the latent adverse factors early,and to treat in time.     

Long-term immunogenicity and efficacy of recombinant yeast derived hepatitis B vaccine for interruption of mother-infant transmission of hepatitis B virus.

Recombinant DNA Yeast-Derived Hepatitis B Vaccine (RYHB vaccine) is comparable to and can replace Plasma-Derived Hepatitis B Vaccine (PHB vaccine) for the prevention of mother-nfant transmission of hepatitis B virus (HBV), but the duration of immune efficacy of RYHB vaccine is not clear. This study indicates the long-term efficacy for the prevention of mother-infant transmission of HBV. One hundred and six neonates born to HBsAg-arrier mothers with HBeAg positive were randomly divided into two groups, one receiving 20 μg per dose of RYHB vaccine and the another receiving 20 μg per dose of PHB vaccine on the day of birth, at 1 month and at 6 months (three times). Physical examination and blood tests were performed for all infants at 6, 12, 24, 36, 48 and 60 months of age. The results showed that the protective efficacies at 6, 12, 24, 36, 48 and 60 months were 67%, 75%, 63%, 62%, 57% and 56%, respectively for the RYHB vaccine group and 58%, 76%, 51%, 41%, 24% and 18%, respectively for the PHB vaccine g     

海南省三亚市新型冠状病毒感染孕妇所分娩核酸阴性新生儿临床特征

Objective To explore the clinical characteristics of nucleic acid negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicron variant BA. 5.1.3) in Sanya area, and to provide evidence for understanding its clinical characteristics. Methods A retrospective analysis was performed on 14 neonates with negative nucleic acid delivered by pregnant women who tested positive for SARS-CoV-2 (Omicron variant BA.5.1.3) in Sanya Central Hospital (the Third People's Hospital of Hainan Province) from June 2022 to September 2022 (observation group, n=14). The corresponding nucleic acid-negative newborns delivered by pregnant women detected negative with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) were set as the control group (n=56), and the general data and clinical characteristics of neonates in the two groups were compared. Results There was no significant difference between the observation group and the control group in pregnancy diabetes, pregnancy induced hypertension, gestational pre-eclampsia, fetal intrauterine distress, premature rupture of membranes (P>0.05); there was no significant difference between the observation group and the control group in terms of sex, gestational age, birth weight, age, mode of delivery, birth Apgar score, heart screening, pulmonary disease, glucose 6-phosphate dehydrogenase (G6PD) deficiency, thalassemia, breast milk jaundice, hemolytic jaundice (P>0.05). The bilirubin level, blue light irradiation cases and the duration of blue light irradiation of the newborns in the observation group at 7 days after birth were higher than those in the control group (P<0.05); the ratio of blood oxygen saturation ≥ 90% in the observation group was lower than that in the control group (21.43% vs 89.29%, P<0.05), and the ratio of blood oxygen saturation occasionally<90% was higher than that in the control group (57.14% vs 10.71%, P<0.05). The ratio of blood oxygen saturation<90% had no significant difference compared with that in the control group (7.14% vs 0, P>0.05), and the ratio of blood oxygen saturation reduced to the required oxygen uptake was higher than that in the control group (14.29% vs 0, P<0.05). Conclusions The jaundice manifestation of the nucleic acid-negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) in Sanya area is relatively obvious, with blood oxygen saturation easily lower than 90% and even requiring oxygen inhalation in severe cases. © 2023 China Tropical Medicine. All rights reserved.     

拉米夫定阻断乙型肝炎病毒母婴传播的疗效观察

目的:评价妊娠中期应用拉米夫定对乙型肝炎病毒(HBV)传播的影响及安全性,寻求最佳预防宫内传播的方法。方法:拉米夫定组52例孕妇于孕20~26周开始服用拉米夫定100mg/d至分娩后,乙型肝炎免疫球蛋白(HBIG)组61例孕妇于孕28周开始使用HBIG 200 IU行宫内阻断治疗,2组新生儿出生均予主、被动联合免疫,观察新生儿宫内感染发生情况、抗病毒疗效及母婴异常情况,随访到婴儿1岁,并分别在0、1、7、12个月龄时监测其血清HBVDNA、HBsAg和抗-HBs定量变化。数据行t检验和χ2检验。结果:拉米夫定组孕妇于分娩前HBV DNA显著下降(t=18.72,P<0.05),转阴率为34.6%,肝功能异常者全部恢复正常。该组52例新生儿随访至1月龄时HBsAg或HBV DNA均为阴性,宫内感染率为0,与HBIG组宫内感染率(14.8%)相比,差异有统计学意义(χ2=9.40,P<0.05)。2组婴儿1岁时的血清抗-HBS水平无差异(t=0.71,P>0.05),拉米夫定组HBV慢性感染为0,HBIG组9例宫内感染婴儿均为HBsAg、HBeAg、抗-HBc、HBV DNA阳性,2组孕妇及婴儿均未发现不良反应。结论:对于HBV水平较高的孕妇,妊娠中期采用拉米夫定降低病毒含量,阻断HBV母婴垂直传播(宫内传播及产时传播)是行之有效的,且用药安全,未见明显不良反应。     

妊娠中期注射HBV免疫球蛋白对其宫内阻断作用

目的探讨妊娠中期开始注射乙型肝炎免疫球蛋白(HBIG)对HBsAg和HBeAg双阳性孕妇乙型肝炎病毒(HBV)的宫内阻断作用。方法将病人随机分为2组,治疗组32例,孕16周起肌注HBIG,每4周1次至分娩;对照组31例未予用药。结果治疗组孕妇HBV DNA水平比对照组显著下降(t=24.202,P<0.05),其新生儿宫内感染率明显低于对照组(χ2=5.671,P<0.05)。两组孕妇及其新生儿未发现有不良反应。结论HBsAg和HBeAg双阳性孕妇孕中期多次注射HBIG可有效减少HBV宫内感染发生率。     

HBIG阻断乙型肝炎病毒母婴传播

目的:评价HBsAg阳性母亲孕晚期肌注HBIG(乙肝免疫球蛋白)及婴儿出生后HBIG联合乙肝疫苗对HBV母婴传播及慢性化阻断的效果. 方法:历史对照组只对婴儿进行乙肝疫苗的全程免疫;HBIG组母亲孕晚期3 mo每月肌注200 u的HBIG;婴儿出生时、半月龄时分别肌注200 u的HBIG,并常规接种乙肝疫苗. 随访两组婴儿HBsAg变化情况,采用历史对照临床试验评价母亲及新生儿注射HBIG对HBV母婴传播及慢性化的阻断效果. 结果:历史对照组HBV宫内感染率5.34%,随访时婴儿HBsAg转阳率5.15%,HBV感染慢性化率87.5%;HBIG组分别为5.26%,0,18.18%. 经统计学检验,两组HBV宫内感染率无显著差异(P=1.000),但婴儿HBsAg转阳率及HBV感染慢性化率具有显著差异(P分别为0.019, 0.001). 结论:母亲孕晚期注射HBIG对阻断HBV宫内传播效果不明显;母亲及新生儿注射HBIG可显著提高乙肝疫苗对婴儿出生后HBsAg阳转及HBV感染慢性化的阻断效果.     

孕妇无症状HBsAg阳性胎儿宫内感染

目的:探讨乙型肝炎病毒宫内传播的危险因素和干预措施。 方法 :对在我院分娩的无症状 HBs Ag阳性产妇抽取静脉血和其新生儿脐血 ,检测乙型肝炎病毒标志物及乙肝 DNA。对部分大三阳孕妇孕晚期注射 HBIG,观察干预效果。结果 :大三阳孕妇乙肝 DNA阳性检出率明显高于小三阳孕妇 (P <0 .0 0 1) ,其新生儿脐血 HBs Ag阳性率也明显高于小三阳孕妇 (P<0 .0 5 ) ,大三阳孕妇孕晚期注射 HBIG可降低宫内传播。 结论 :患有大三阳的母亲对胎儿威胁最大 ,应在孕前进行治疗 ,孕晚期注射 HBIG可能有利于阻断母婴间垂直传播     

不同方法阻断乙型肝炎病毒母婴垂直传播的临床观察

目的 探讨阻断乙型肝炎病毒母婴垂直传播的方法。方法 将94例HBsAg阳性孕妇分成4组,单纯HBVac治疗组29例,单纯HBIG治疗组19例,左旋咪唑涂布剂加两者联合应用13例,未治疗组33例,均在孕26周起开始注射,孕妇和新生儿血清HBsAg,抗－HBs,HBeAg,抗－HBe,抗－HBc检测采用ELISA法。94例孕妇按分娩方式不同分别观察对乙肝病毒母婴传播的影响。结果 脐血中HBsAg阳性率,HBVac治疗组为17．24％,HBIG治疗组为5．26％,联合治疗组为0,未治疗组为21．21％。在不同的分娩方式中,急症剖宫产新生儿脐血HBsAg阳性率为0,行择期剖宫产者为10．5％,经阴道分娩者为16．9％。结论 携带HBV孕妇于孕晚期给予HBVac,HBIG和左旋咪唑涂布剂联合两者治疗后,可有效阻断HBV母婴之间传播,以联合治疗组效果最佳,剖宫产术有助于阻断HBV母婴传播。     

乙肝免疫球蛋白阻断乙肝病毒母婴传播效果研究

目的:分析乙肝免疫球蛋白对于阻断乙肝病毒母婴传播的效果。方法:病例选自我科室门诊2010年1月～2011年3月接受孕期检查的HBV携带的132例孕妇,大三阳和小三阳的孕妇于孕24周开始接受HBIG注射治疗,携带者孕妇于孕28周开始接受HBIG注射。结果:孕24周与分娩前的乙肝标志物与HBV-DNA检查结果无显著差异(P>0.05)。HBIG阻断HBV母婴传播疗效,总有效率为75.71%。而HBIG阻断HBV疗效大三阳孕妇较携带者和小三阳孕妇疗效不佳,存在明显差异。新生儿接受疫苗接种和HBIG注射后12个月,HBsAb(+)率为86.43%,与新生儿出生时HBsAb(+)率75.71%相比,有较大改善。结论:对HBV感染的孕妇在孕24周后注射HBIG,阻断乙肝病毒母婴传播效果明显,新生儿出生后采用HBIG和HBV疫苗联合阻断HBV母婴传播临床效果显著。     

孕晚期注射乙型肝炎免疫球蛋白阻断乙型肝炎病毒母婴传播的临床观察

目的：探讨HBsAg阳性和HBeAg阳性携带孕妇孕晚期应用乙型肝炎免疫球蛋白（HBIG）阻断乙型肝炎病毒（HBV）母婴传播的效果。方法：将孕妇分为双阳性组（A组）和单阳性组（B组）[HBsAg（＋）及HBeAg（＋）称为“双阳性”（A组）,HBsAg（＋）及HBeAg（-）称为“单阳性”（B组）];新生儿分为HBIG组和非HBIG组（对照组）;HBIG组孕妇孕28、32、36周各注射HBIG200IU（共3次,部分仅注射1～2次）,非HBIG组仅常规产检及监护;对两组新生儿0、6个月的静脉血作乙型肝炎两对半检测。结果：①A组孕妇的外周血HBV-DNA阳性率（76.92%）显著高于B组孕妇（8.55%）,P〈0.01;②A组孕妇所生HBIG组新生儿出生24h的HBsAg阳性率（10.64%）显著低于非HBIG组（33.33%）,P〈0.05;③A组孕妇所生HBIG组6月龄新生儿HBsAb阳转率（78.72%）明显高于非HBIG组（38.39%）,P〈0.01;B组孕妇所生HBIG组6月龄新生儿HBsAb阳转率（80.65%）高于非HBIG组（64.41%）,P〈0.05。结论：双阳性孕妇孕晚期应用HBIG可有效降低乙型肝炎宫内感染率;无论是双阳性还是单阳性孕妇,孕晚期应用HBIG可提高6月龄新生儿HBsAb阳转率。     

乙肝免疫球蛋白阻断病毒母婴传播的效果观察

目的 :探讨高效价乙肝免疫球蛋白 (HBIG)阻断乙型肝炎病毒 (HBV)母婴传播的作用机理。方法 :将5 0例HBsAg阳性的孕妇随机分成两组 ,实验组 30例 ,分别自孕 2 8周、32周、及 36周肌肉注射HBIG2 0 0IU ,分娩后 2 4h内再注射HBIG 2 0 0IU 1次 ;对照组 2 0例 ,不用HBIG。两组孕妇所生婴儿均于出生后 2 4h内肌肉注射HBIG 10 0IU 1次 ,注射乙肝疫苗的时间和剂量均按正常婴儿的操作方案进行。母儿血清HBsAg ,HBeAg和抗 HBs用固相放免法检测 ,HBV DNA用荧光定量PCR检测。结果 :实验组婴儿血清HBsAg和HBV DNA检出率明显低于对照组 (P <0 .0 5 ) ;实验组婴儿抗 HBs阳性率显著高于对照组 (P <0 .0 5 )。结论 :孕妇于孕期多次注射HBIG进行被动免疫 ,可有效地阻断乙型肝炎病毒母婴传播 ,减少婴儿HBV感染率。