乙肝免疫球蛋白阻断母婴传播机制的研究

目的　探讨乙肝孕妇妊娠中晚期注射乙肝免疫蛋白 (HBIG)阻断母婴传播的机制及预防。方法　应用荧光定量PCR检查 14例乙肝血清血指标HBeAg阳性孕妇产前血HBVDNA与妊娠中晚期注射HBIG 6 0 0U产后血HBVDNA定量对比分析 ,以及对 4 1例乙肝血清血指标HBeAg阳性的孕妇 ,产前注射 (观察组 )与未注射 (对照组 )HBIG 6 0 0U产后血、乳汁、唾液HBVDNA定性对比分析。结果　 14例HBeAg阳性孕妇HBIG注射前后血HBVDNA含量显著降低 (P <0 0 1) ,4 1例HBeAg的孕妇 ,产后HBVDNA阳性率观察组显著低于对照组分别是血 (P <0 0 1)、乳汁 (P <0 0 1)、唾液 (P <0 0 1)。结论　注射HBIG能显著降低乙肝孕妇血HBVDNA水平 ,从而有效减少孕妇HBV血、乳汁、唾液对婴儿的传播。     

拉米夫定阻断乙肝病毒母婴传播的临床研究

目的观察拉米夫定阻断乙肝病毒(HBV)母婴传播的效果和安全性.方法选择HBsAg/HBeAg双阳性,且HBV DNA阳性妇女64例,治疗组32例孕前给予拉米夫定口服,对照组32例不用任何抗病毒药物自行妊娠,婴儿出生时、1年时检测两对伴和HBV-DNA.结果治疗组妇女所产婴儿出生时、1年时检测两结伴和HBV-DNA均阴性,儿科智力/体格检查均未发现异常;对照组妇女所产婴儿出生时检测HBsAg阳性25%(8/32),HBsAg/HBeAg双阳性9.37%(3/32),HBV-DNA阳性18.75%(6/32),两组新生儿HBV感染率有显著性差异(P＜0.05).结论拉米夫定用于预防乙肝病毒(HBV)母婴传播有确切效果和近期安全性,值得临床进一步探讨.     

对乙型肝炎产妇在母乳喂养中存在的问题调查分析

本文对1997-1999年158例乙肝产妇及其分娩的164例新生儿(其中双胞胎6例)就母乳喂养与人工喂养对照随访婴儿(18个月内)HBV感染情况进行分析.结果表明,HBsAg携带者,母乳喂养与人工喂养婴儿HBV感染无明显差异,P＞0.05,提示可以母乳喂养.但母血HBsAg+、HBeAg+或ALF增高者母乳婴儿HBV感染率为82.16%-91.67%,人工喂养婴儿HBV感染率为33.33%,经统计学处理两组差异显著(P＜0.01),不宜母乳喂养,应该隔离,行人工喂养.同时作者建议开展新生儿联合应用主动免疫和被动免疫,合理指导乙肝产妇喂养婴儿,对宣传母乳喂养及防止母婴之间传播HBV有着积极的意义.     

母亲不同HBV感染状态所生新生儿树突状细胞亚群及功能研究

目的 探讨新生儿mDC、pDC频数及表面分子表达,以及母亲不同HBV感染状态对新生儿树突状细胞生物学特性的影响.方法 采集HBsAg阳性/HBeAg阳性HBV感染母亲、HBsAg阳性/HBeAg阴性HBV感染母亲以及HBV感染标志物阴性母亲所生新生儿脐带血、健康成人外周血,采用流式细胞仪检测mDC的频数及其CD86的表达、pDC的频数及其CD80、CD83、CD86表达、并采用FlowJo软件进行分析,比较各组间上述指标的差异.结果 分别采集HBsAg阳性/HBeAg阳性、HBsAg阳性/HBeAg阴性和HBV感染标志物阴性母亲所生新生儿脐带血14、12和13例,健康成人外周血7例.新生儿mDC频数(0.29±0.16)及其CD86阳性率(10.72±10.01)显著低于成年人(分别是0.81±0.17和32.13±7.46),(t=-7.86,P=0.00和t=-5.36,P=0.00)；新生儿pDC频数(0.15±0.07)以及pDC表面CD86/CD83阳性率(31.61±12.81,42.66±20.83)显著低于成年人(0.30±0.07;74.96±9.78;82.00±6.94),(t=-5.43,P =0.00;t=-8.49,P=0.00;t=-4.90,P=0.00).结论 新生儿脐带血mDC、pDC频数以及表面功能分子表达低于成人外周血,HBeAg可能降低生新生儿mDC表面CD86的表达.     

孕晚期注射HBIG阻断HBV母婴传播的病例对照研究

目的探讨孕晚期注射乙肝免疫球蛋白（HBIG）对阻断HBV母婴传播有无作用。方法选取538例孕晚期注射HBIG和817例未注射HBIG的孕妇及其婴儿,比较两组的宫内感染率。结果（1）HBIG组和对照组的宫内感染率分别为2．2％和1．1％,两组相比差异无统计学意义（P〉0．05）;（2）当母亲同为HBeAg阳性时,两组的宫内感染率相比,差异无统计学意义（4．14％VS．4．92％,P〉0．05）;当母亲同为HBVDNA阳性时,两组的宫内感染率相比,差异仍无统计学意义（3．14％vs．3．10％,P〉0．05）;（3）进一步将孕妇血清HBVDNA按浓度高低进行分层分析,当HBVDNA浓度相同时,两组的宫内感染率相比,差异无统计学意义（P〉0．05）。结论孕期注射HBIG对阻断HBV母婴传播无明显作用,不推荐孕期使用HBIG。     

HBV感染孕妇体内病毒前C区G1896A变异与母婴垂直传播的关系

目的 分析孕妇体内乙型肝炎病毒(HBV)前C区G1896A变异对母婴垂直传播的影响.方法 收集40例本院妇产科HBeAg(-)/HBsAg( )的孕妇血标本,同时收集这些孕妇分娩时新生儿脐带血40例.荧光定量PCR(FQ-PCR)检测HBV孕妇血清和新生儿脐带血中HBV-DNA栽量,PCR-ELISA法检测孕妇血清中HBV-DNA前C区G1896A变异.分析HBV前C区G1896A变异及孕妇血清HBV-DNA载量对母婴垂直传播率的影响.结果 40例孕妇血清共检测到25例HBV前C区G1896A变异(62.5%);变异组母婴垂直传播发生率为44.0%(11/25),未变异组母婴垂直传播发生率为40.0%(6/15),二组比较无统计学差异(x2=0.0614,P＞0.05).孕妇血中HBV-DNA高载量组(≥1×105 copies/ml)母婴垂直传播发生率为62.5%(10/16),低栽量组(＜1 × 105 copies/ml)母婴垂直传播发生率为29.2%(7/24),二组相比有显著性差异(x2=4.3649,P＜0.05).结论 HBV前C区G1896A变异未增加母婴HBV垂直传播率,孕妇血清中HBV-DNA栽量升高是母婴HBV垂直传播危险因素.     

孕妇乙型肝炎HBV-M与preS1-Ag、HBV DNA的相关性及联合检测的临床价值

目的分析乙型肝炎孕妇HBV血清标志物（HBV-M）、HBV前S1抗原（preS1-Ag）及HBV DNA的相关性,探讨联合检测的临床价值。方法采用化学发光免疫分析法对375例乙型肝炎孕妇血清进行HBV-M的检测,用ELISA法检测preS1-Ag,同时采用荧光定量PCR法检测HBV DNA。结果在不同模式乙型肝炎孕妇血清中,preS1-Ag、HBeAg的检出率分别是61.87%、34.67%;在HBeAg阳性血清中,preS1-Ag检出率为90%,HBeAg阴性血清的检出率为46.94%,两者之间有统计学意义;HBV DNA与HBeAg一致性比较较差,而与preS1-Ag一致性比较较好。结论 HBVpreS1-Ag较HBeAg更敏感地反映了HBV的复制情况,HBV preS1-Ag和HBV DNA有较高的符合率,可作为HBV复制的指标,三者联合检测,可及时阻断乙肝母婴传播,降低婴儿乙肝感染率。     

HBV cccDNA在2.2.15细胞表达的动态观察

目的研究2.2.15细胞中是否存在HBVcccDNA,探讨2.2.15细胞内HBV产物的动态表达规律。方法采用PCR方法检测2.2.15细胞内cccDNA,Taqman定量PCR技术检测2.2.15细胞内及培养上清中HBVDNA含量,EIA方法检测培养上清中HBsAg、HBeAg的动态表达,并进行定量资料相关性统计学分析。结果2.2.15细胞及培养上清中存在cccDNA,2.2.15细胞培养上清中HBVDNA与HBsAg、HBeAg之间存在相关性(r=0.833,P<0.05和r=0.939,P<0.01),而细胞内HBVDNA与培养上清HBVDNA及HBsAg、HBeAg之间无相关性(r=0.024,P>0.05和r=0.177,P>0.05)。结论为阐明2.2.15细胞内HBV的复制规律提供一定依据。     

乙型肝炎病毒母婴阻断长期效果的随访研究

目的观察乙型肝炎病毒母婴阻断长期效果,探讨HBsAg阳性孕妇生产儿童发生慢性HBV感染的相关影响因素。方法随访和收集于2004--2006年在北京地坛医院出生的HBsAg阳性母亲所生,并在出生时进行200单位乙肝免疫球蛋白（HBIG）注射和经过乙肝疫苗10μg,0、1和6个月的完整免疫接种程序的儿童静脉血,采用Abbott微粒子化学发光法检测其HBsAg、抗-HBs抗体、抗-HBc抗体,分析母婴阻断和乙肝疫苗接种的长期效果及其影响因素。结果收集和调查306名儿童年龄3—6（4．84）岁,其母亲生产时HBeAg阳性198人,HBeAg阴性92人。10（3．27％）名儿童发生慢性HBV感染。除慢性HBV感染者外,其余296名儿童,20．27％抗-HBs〈10mlU／ml;44．26％抗-HBs≥10—100mlU／ml;27．03％抗-HBs≥100～1000mlU／ml和8．45％抗-HBs≥1000mlU／m,抗-HBs保护率为79．73％（236／296）。抗-HBc阳性率为7．43％（22／296）。10例感染儿童的母亲生产时HBeAg均为阳性,HBVDNA均在10。拷贝／ml以上,其中8例超过10^8拷贝／ml。结论在进行乙肝疫苗加HBIG注射的HBV母婴传播阻断措施下,HBV母婴阻断失败和慢性H13V感染发生在HBeAg阳性和高病毒载量产妇所生婴儿,在有效阻断后仍需进行抗HBs监测并加强免疫接种。     

不同剂量HBIG对母婴乙型肝炎病毒抗原抗体宫内传播的影响

目的探讨不同剂量乙肝免疫球蛋白（HBIG）对乙型肝炎病毒（HBV）抗原抗体宫内传播的影响。方法将母亲乙肝表面抗原（HBsAg）阳性的婴儿作为500例观察对象,根据出生前母亲是否用HBIG分为：观察1组：产前母亲孕末期28w、32w、36w各用200IU（蓉生）HBIG 200例;观察2组：产前母亲孕末期28w、32w、36w各用400IU（蓉生）HBIG 100例;对照1组：产前母亲孕末期不用HBIG 200例。观察生后12h内新生儿静脉血乙肝五项：HBsAg、乙型肝炎表面抗体（HBsAb）、乙型肝炎e抗原（HBeAg）、乙型肝炎e抗体（HBeAb）、乙型肝炎核心抗体（HBcAb）。结果观察1组200例新生儿HBsAg阳性1例,阳性率为0.5%,HBeAg阳性3例,（其中1例HBsAg同时阳性）阳性率为1.5%。对照组HBsAg阳性2例,阳性率为1%,HBeAg阳性8例,（其中2例HBsAg同时阳性）阳性率为4%。经统计学处理（HBsAg）χ2=0.336,P=0.562;（HBeAg）,χ2=2.337,P=0.126。观察1组与对照组生后24h内HBV抗原检测比较无显著差异。观察1组、观察2组与对照组HBsAb检测比较：观察1组新生儿HBsAb阳性率1%,观察2组新生儿HBsAb阳性率2%,对照组HBsAb阳性率1%,各组HBeAb和HBcAb检测比较,结果HBeAb和HBcAb检测母婴符合率均在97%-97.5%之间。结论孕妇HBV携带者产前孕末期用HBIG 200IU隔4w连用3次的方法对阻断乙肝病毒的宫内感染效果不显著。加大HBIG的用量400IU可基本阻断HBV垂直传播胎儿。但鉴于对照组宫内感染率仅4%,加大用量不适用所有HBV携带者孕妇,尤其是HBsAg单阳性孕妇。     

Sequence analysis of hepatitis B virus genomes from an infant with acute severe hepatitis and a hepatitis B e antigen-positive carrier mother

It is well known that fulminant hepatitis B can occur in infants born to hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carrier mothers, whereas fulminant hepatitis and severe hepatitis are uncommon in infants born to HBeAg-positive mothers. We have encountered an infant with severe acute hepatitis B born to a HBeAg-positive mother. The aim of this study was to determine whether HBV variants contribute to the pathogenesis of fulminant hepatitis and severe hepatitis in an infant born to an HBeAg-positive mother. The nucleotide sequence of HBV genomes from the infant and his HBeAg-positive carrier mother was analyzed. All HBV isolated from the infant and his mother were subtype adr. The sequences of the cloned HBV genomes, each including a part of the X and precore/core regions, isolated from the infant were almost identical (homology of 99.1-99.9%) to those from his mother. There was no mutation in any of the 17 clones examined at nucleotides 1762 and 1764 in the core promoter, which is reported to be associated with fulminant hepatitis. A point mutation at nucleotide 1758 in the second AT-rich region of the basic core promoter was present in all clones. None of the clones had a point mutation at nucleotide 1896 of the precore region. In this study, no specific HBV variants contributing to the development of neonatal severe hepatitis were found. There is a possibility that host factors rather than viral factors play an important role in some cases of severe neonatal hepatitis B.     

Perinatal transmission of the hepatitis b virus and of the hbv-associated delta agent from mothers to offspring in northern italy

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV-associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen-antibody system, HBV-specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti-HBe in babies at birth. The data of this study indicate: 1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti-HBe-positive mothers are at a lower (P <.01) yet consistent risk of infection. 2. HBs antigenernia is usually prolonged and symptomatic in babies born to HBeAg–positive mothers while being self-limited and asymptomatic in babies born to anti-HBe-positive mothers. 3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg-positive mothers and also in two anti-HBe-positive mothers and in one HBeAg/anti-HBe-negative mother who transmitted infection to their babies. 4. High titers of anti-HBe (up to 1:10³) do not prevent HBV infection. 5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.     

Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: a case-control study in Thailand

Perinatal transmission of hepatitis B virus (HBV) has been controlled incompletely despite adequate immunoprophylaxis in infants. The aim of this study was to characterize virological factors of HBV associated with vaccine failure in Thailand. Sera of 14 infected infants (13 HBeAg‐positive and one HBeAg‐negative) with vaccine failure and their respective mothers (group M1) were tested quantitatively for HBV DNA by real‐time PCR, HBV genotypes and mutations were characterized by direct sequencing. Sera collected from 15 HBeAg‐positive (group M2) and 15 HBeAg‐negative (group M3) mothers whose infants had been vaccinated successfully served as controls. The results showed that group M1 and group M2 mothers had equal titers of HBV DNA but higher titers than group M3. All infected infants and their respective mothers had the same HBeAg status and HBV genotypes. DNA analysis in a pair of HBeAg‐negative infant and mother revealed that both were infected with an HBV precore mutant (G1896A). Escape mutants in the “a” determinant region (residues 144 and 145) were detected in two (14%) infected infants. The prevalence of BCP mutations/deletions in groups M2 and M3 was higher significantly than in group M1 (P = 0.022 and P < 0.001, respectively). In conclusion, instead of the HBeAg status, a high titer of HBV DNA in mothers was the major contributor to perinatal transmission of HBV. Escape mutants might be associated with vaccine failure in some infants. BCP mutations/deletions in mothers might contribute to the prevention of mother‐to‐infant transmission of HBV. J. Med. Virol. 84: 1177–1185, 2012. © 2012 Wiley Periodicals, Inc.     

An experimental study on developmental changes of maternal discrimination of infants in crab-eating monkeys (Macaca fascicularis)

Individually reared mother-infant dyads of crab-eating monkeys (Macaca fascicularis) were observed cross-sectionally in their mother-infant relationship. In infants aged from 0 to 5.0 months, rather drastic changes were found both at 0.5-1.0 and 2.0-3.0 months of age. For an explanation of these changes, developmental processes of discrimination between mother and infant were analyzed cross-sectionally by exchanging mother-infant combinations. The results indicated that the first 0.5 months postpartum was characterized as a behaviorally nondiscriminating stage where nipple discrimination by infants was the only exception. The latter half of the first month was the beginning of a nonaggressive discrimination stage by mothers, indicated by lipsmacking and sniffing and in infants by clinging. When infants reached the age of 2.0-3.0 months, the mothers' nonaggressive discrimination with lipsmacking decreased, and her aggressive discrimination of alien infants increased. In addition to maternal visual discrimination of infants' physical appearances, differences in infants' odor and/or their method of nipple contact were suggested to affect the mothers' differential behaviors.     

Interventions with depressed mothers and their infants: modifying interactive behaviours

BACKGROUND: Postpartum depression (PPD) has a prevalence ranging from 3% to 30% and is associated with serious infant growth and developmental problems. Interventions directed at improving maternal mood have been unsuccessful in producing changes in observed face-to-face interactions between mother and infant. The Keys to Caregiving (KTC) is an intervention program that helps parents to understand and respond to infant behaviours, with a goal of increasing positive affective expressions in infants. In this pilot study, KTC was used with mothers suffering from mild to moderate PPD and their infants. METHODS: PPD was confirmed by scores on the Edinburgh Postnatal Depression Scale and the Beck Depression Inventory. Eleven dyads completed the study. KTC was carried out in 5 weekly group sessions, beginning at infant age of 3 months. Dyads were videotaped prior to and after KTC, using the Face-to-Face Still-Face paradigm, which assesses infants' responses during normal play and the effects of the Still-Face perturbation. The tapes were scored for infant facial emotion expressions. RESULTS: After intervention, infants displayed a marked increase in Interest and Joy when interacting face-to-face with their mothers, even though mothers' depression ratings did not change. LIMITATIONS: This pilot study is limited by lack of control dyads, however, it provides the foundation necessary for a full trial. CONCLUSIONS: This study suggests that intervention that focuses on what mothers do with their infants instead of how they feel can be effective in increasing infants' positive responsiveness and improving infant outcomes. Such interventions can be an essential component of treatment when mothers present with postpartum depression.     

Mobile surrogate mothers and the development of exploratory behavior and radius of action in infant long-tailed macaques (Macaca fascicularis).

One of the effects of rearing young monkeys on surrogate mothers is a delay in the development of exploratory behavior. An important question is which difference between mother and surrogate mother caused this delay. We hypothesized that the mothers' carrying the infant through the environment promotes the development of exploratory behavior and the radius of action of infant macques. Using surrogate mothers, we reared 9 infants in a peer group with immobile surrogates and 10 infants in another peer group with mobile surrogates. During the 3rd to the 6th month, we observed each infant for 30 min weekly, collecting observational data on several behavioral parameters and on time spent in several areas in the cage. Results showed that exploratory behavior and an increase in radius of action developed more rapidly in the mobile-reared infants.     

Mothers' depressive symptoms and children's facial emotions: examining the depression-inhibition hypothesis

Vibrant expression of emotion is the principal means infants and young children use to elicit appropriate and timely caregiving, stimulation, and support. This study examined the depression-inhibition hypothesis: that declines in mothers' support as their depressive symptoms increase inhibit children's emotional communication. Ninety-four mothers and their 14- to 27-month-olds interacted in a university playroom. Based on microanalytic coding of discrete facial displays, results supported three components of the hypothesis. (a) As mothers' depressive symptoms increased, children displayed less facial emotion (more flat affect, less joy, less sadness, less negative). (b) Mothers' low emotional and behavioral support predicted children's low facial communication and mediated relations between mothers' depressive symptoms and children's infrequent emotion. (c) Children who were passive with mothers behaviorally expressed emotion infrequently. Children's passivity mediated relations between mothers' depressive symptoms and children's infrequent emotion displays. Contrary to modeling and contagion theories, mothers' facial displays did not mediate relations between their depressive symptoms and children's facial displays. Nor were the outcomes children experienced regulating their facial displays. Rather, findings suggest that, even when depressive symptoms are modest, young children inhibit emotion as mothers' depressive symptoms increase to withdraw from unresponsive mothers, which may adversely affect children's subsequent relationships and competencies.     

乙型肝炎病毒母婴传播的早期筛选

作者对100名入院产妇静脉血及100份新生儿脐血行母婴配对HBV检测,结果发现产妇HBV阳性54人,脐血HBV阳性52人,阳性率分别为54.0%、52.%.产妇及脐血HBV96.296%呈母婴配对阳性.同时发现100名产妇孕期保健卡中HBV正常60人,产时HBV阳性检出34人,再检阳性率占56.67%;不正常4人,产时HBV阳性4人,再检阳性率100%,未查36人,产时HBV阳性16人,再检阳性率44.44%,提示存有母婴传播高危因素.为提高围产期母婴保健质量,预防产时交叉感染,作者提出了建议.     

Absence of hepatitis B virus (HBV) DNA in children born after exposure of their mothers to HBV during in vitro fertilization.

During in vitro fertilization, 22 human embryos were exposed to hepatitis B virus (HBV) in contaminated human serum present in the culture medium. All mothers experienced hepatitis B during the first trimester of pregnancy, and two had hepatitis B surface antigen and HBV DNA, as determined by PCR, at the time of delivery. No HBV DNA was found in serum or lymphocytes from the exposed 22 infants. HBV DNA was also absent from one infant at autopsy.