HBeAg-positive Mothers Research Articles

Increased Protection of Earlier Use of Immunoprophylaxis in Preventing Perinatal Transmission of Hepatitis B Virus.

Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administering hepatitis B immunoglobulin (HBIG) and birth-dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg). The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase protection efficacy. We conducted a prospective, multi-center observational study in infants born to mothers with HBV infection, in whom neonatal HBIG and birth dose hepatitis B vaccine were administered within one hour after birth. The infants were followed up for HBV markers at 7-14 months of age. A total of 1140 pregnant women with HBV were enrolled, and 982 infants (9 twins) of 973 mothers were followed up at 9.6 ± 1.9 months of age. HBIG and birth-dose vaccine were administered in newborn infants within a median of 0.17 (0.02-1.0) hours after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of the 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers acquiring HBV. All 9 HBV-infected infants were born to mothers with HBV DNA >2.75 × 106 IU/mL. Maternal HBV DNA levels >2 × 106 IU/mL were an independent risk factor (odds ratio, 10.627; 95% confidence interval, 2.135-∞) for immunoprophylaxis failure. Earlier use (within 1 hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.

The role of caesarean section and nonbreastfeeding in preventing mother-to-child transmission of hepatitis B virus in HBsAg-and HBeAg-positive mothers: results from a prospective cohort study and a meta-analysis.

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother-to-child transmission (MTCT) in HBsAg- and HBeAg-positive mothers via a cohort study and a meta-analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [("HBV" or "hepatitis b" or "hepatitis b virus") and ("mother-to-infant transmission" or "vertical transmission")]. Studies were screened, and data were extracted. The fixed-effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>108 IU/mL; RR=3.03, 95% CI: 1.41-6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR=0.61) and nonbreastfeeding (RR=0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR=0.58, 95% CI: 0.46-0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR=0.74, 95% CI: 0.56-0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg- and HBeAg-positive mothers who did not receive antiviral therapy during pregnancy.

Quantitative Hepatitis B Surface Antigen Predicts Hepatitis B Transmission in Infants Born to e Antigen-positive Mothers.

This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women. Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited. In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants. Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%. Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen-positive mothers.

Reduced Mother-to-Child Transmission of Hepatitis B after Implementation of Completely Charge-Free Immunoprophylaxis in Mainland China

Background: Passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine is recommended to prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV). China has taken a policy to provide charge-free HBIG for infants of HBV-infected mothers since July 2011. We analyzed HBV infection rate in children of HBV-infected mothers born before and since July 2011 in real-life practice. Methods: Totally 5149 children of 5004 HBV-infected mothers, 1160 children born before July 2011 and 3989 children born since July 2011, across Jiangsu province, China, were followed up for HBV markers at 0⋅6-8 years age from 2009 to 2018. Findings: Totally 92 children were HBsAg positive, with an overall infection rate 1⋅79%. MTCT occurred in 0% of 3716 children of hepatitis B e antigen (HBeAg)-negative mothers, and in 6⋅42% of 1433 children of HBeAg-positive mothers (p<0⋅0001). Among 1433 children of HBeAg-positive mothers, transmission occurred in 10⋅27% born before July 2011 and 5⋅5% born since July 2011 (p=0⋅0221); HBIG and vaccine were timely administered in 76⋅47% and 92⋅67% of children born before July 2011 respectively, and in 98⋅02% and 98⋅32% of those born since July 2011 respectively (each p<0⋅0001). Among 1433 children of HBeAg-positive mothers, MTCT occurred in 75 (5⋅54%) of 1355 children with recommended immunoprophylaxis, and in 17 (21⋅79%) of 78 children not per recommended immunoprophylaxis (p<0⋅0001). The lowest HBV DNA level associated with transmission was 3⋅08ₓ106 IU/mL. Interpretation: In addition to maternal HBeAg positive, inappropriate administration of HBIG and/or hepatitis B vaccine is a critical risk for MTCT of HBV in children of HBV-infected mothers. Implementation of charge-free HBIG in infants of HBsAg-positive mothers greatly reduces transmission of HBV. Maternal HBeAg negative or HBV DNA ≤106 IU/mL requires no other interventions to prevent MTCT. Funding Statement: This study was supported by the National Health Commission of China (National Key Clinical Research Project 2011271), the National Natural Science Foundation of China (81672002), the Jiangsu Provincial Health Commission (H201537, XK201607), and the Science and Technology Department of Jiangsu Province (BK20161105), China. Declaration of Interests: The authors declare no conflict of interest. Ethical Approval Statement: The present study was approved by the institutional review board of ethics committee in each hospital. Written informed consent was from the mothers or guardians, who also signed the informed consent for children.

Outcomes of the national programme on prevention of mother-to-child transmission of hepatitis B virus in China, 2016\u20132017

BackgroundIn addition to providing free hepatitis B vaccine (HBvacc) series to all infants in China since 2005, the national programme on prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) started providing free hepatitis B immunoglobulin for all new-borns born to hepatitis B surface-antigen (HBsAg) positive mothers in 2010. However, few studies have evaluated the effectiveness of the PMTCT programme. Therefore, we aimed to investigate the outcomes of the programme and identify associated factors.MethodUsing a cross-sectional study design, we collected data on 4112 pairs of HBsAg-positive mothers and their children aged 7–22 months in four representative provinces through interviews and medical record review. We tested HBsAg and hepatitis B surface antibody (anti-HBs) of children by enzyme-linked immunosorbent assay at designated maternal and child hospital laboratories. We used logistic regression to analyse factors associated with child HBsAg and anti-HBs positivity.ResultsThirty-five children were HBsAg positive, indicating the mother-to-child transmission (MTCT) rate was 0.9% (0.6–1.1%). The anti-HBs positive rate was 96.8% (96.3-97.4%). Children receiving HBvacc between 12 and 24 h of birth were 2.9 times more likely to be infected than those vaccinated in less than 12 h (adjusted odds ratio [aOR] = 2.9, 95% confidence interval [CI]: 1.4–6.3, P = 0.01). Maternal hepatitis B e-antigen (HBeAg) positivity was associated with higher MTCT rate (aOR = 79.1, 95% CI: 10.8–580.2, P < 0.001) and lower anti-HBs positive rate (aOR = 0.4, 95% CI: 0.3–0.6, P < 0.001). Children with low birth weight (LBW) were 60% less likely to be anti-HBs positive than those with normal birth weight (aOR = 0.4, 95% CI: 0.2–0.8, P = 0.01).ConclusionsThe MTCT rate was lower than the 2030 WHO elimination goal, which implies the programme is on track to achieve this target. As earlier HBvacc birth dose (HBvcc-BD) was associated with lower MTCT rate, we suggest that the PMTCT programme work with the Expanded Programme on Immunization (EPI) to modify the current recommendation for early HBvcc-BD to a requirement. Our finding that LBW was associated with lower anti-HBs positivity points to the need for further studies to understand factors associated with these risks and opportunities for program strengthening. The programme needs to ensure providing essential test to identify HBeAg-positive mothers and their infants and provide them with appropriate medical care and follow-up.

Vertically acquired occult hepatitis B virus infection may become overt after several years

To study the frequency of vertically acquired occult hepatitis B virus (HBV) infection (OBI). We investigated 44 children born to hepatitis B surface antigen (HBsAg) positive mothers. They received HBV vaccine directly after birth and at 2, 6 and 52 weeks of age; eight with HBeAg-positive mothers also received hepatitis B immunoglobulin (HBIG). HBV DNA was analyzed in blood collected at 6 weeks and 12 months of age, and HBV antibodies at 12 and 18 months of age. HBV DNA, but not HBsAg or anti-HBc, was detected at 12 months of age in three children. The viral sequences were almost identical with HBV DNA from their mothers who all were HBeAg-positive and had received tenofovir during pregnancy. Follow-up at 5-7 years age showed that one of the three children had become seropositive for HBsAg and anti-HBc. This child and one of the other two had detectable HBV DNA at the follow-up, with whole genome sequences identical to those in HBV from their mothers. Mothers-to-child transmission of HBV can, despite adequate prophylaxis, lead to OBI which may later develop into overt HBV infection. Whether such infections are of clinical importance needs to be further investigated.

Maternal HBeAg positivity and viremia associated with umbilical cord blood hepatitis B viremia

Hepatitis B (HBV) transmission may result from in utero transmission. We aimed to determine the correlation between maternal serum and umbilical cord blood HBV DNA levels in infants delivered by chronic HBV-infected mothers and to describe the effect of cord blood viremia on vertical transmission. A prospective cohort of 92 chronic HBV-infected mother-and-child pairs recruited over three years was analyzed. Maternal and cord blood were tested for HBV DNA by real-time PCR. Standard immunoprophylaxis with both active and passive immunization was administered to all infants. Serological testing was performed on all infants at 9 months of age. Moderate positive correlation of the maternal HBV DNA with cord blood HBV DNA was demonstrated (r2=0.521, p=<0.001). HBeAg+ve mothers were younger with higher HBV and cord viremia. At 9 months of age, one infant was infected. Infants delivered by HBeAg positive mothers and mothers with high HBV DNA of more than 6LOG IU/mL (1 x 106 IU/mL) have increased relative risk of cord blood viremia. Maternal HBV DNA and presence of HBeAg were positively correlated to cord blood HBV DNA in infants delivered by chronic HBV-infected mothers. Our data suggest that reducing maternal viremia during the antenatal period may help to reduce cord blood viremia.

Presence of hepatitis B virus markers in umbilical cord blood: Exposure to or infection with the virus?

BackgroundWe aimed to clarify whether presence of hepatitis B virus (HBV) markers in cord blood indicates exposure to or infection with HBV. MethodsWe prospectively recruited HBsAg-positive pregnant women and their neonates 2012 through 2015. All neonates received postnatal immunoprophylaxis. The infants were followed up at 7–14 months of age. ResultsTotally 329 HBsAg-positive pregnant women and 333 neonates were enrolled. No cord blood was anti-HBc IgM positive. A total of 290 (87.1%) neonates were followed up at 7–14 months of age and 6 (2.1%) of them were infected with HBV. Of 146 neonates born to HBeAg-negative mothers, 38 (26.0%) and 30 (20.5%) had detectable HBsAg and HBV DNA in cord blood respectively, but none of 126 infants followed up was infected. Of 187 neonates born to HBeAg-positive mothers, 92 (49.2%) and 79 (42.2%) had detectable HBsAg and HBV DNA in cord blood respectively; 6 (3.7%) of 164 infants followed up were infected. Of seven neonates with HBV DNA > 105 IU/ml in cord blood, four had no infection and three others were infected. ConclusionPresence of HBsAg and/or HBV DNA, even at high levels, in cord blood just indicates exposure to, but not infection with HBV. Presence of HBV markers in cord blood cannot define intrauterine infection.

Presence of Hepatitis B Virus Markers in Umbilical Cord Blood: Exposure to or Infection with the Virus?

Background: Failure of immunoprophylaxis in the prevention of mother-to-infant transmission of hepatitis B virus (HBV) is usually attributed to in uterine infection. We aimed to clarify whether the presence of HBV markers in cord blood indicates exposure to or infection with HBV. Methods: We prospectively recruited hepatitis B surface antigen (HBsAg)-positive pregnant women and their neonates 2012 through 2015. All neonates received passive-active immunoprophylaxis after birth. The infants were followed up at 7-14 months of age. Findings: Totally 329 HBsAg-positive pregnant women and 333 neonates were enrolled. No cord blood was anti-HBc IgM positive. Of the neonates, 290 (87.1%) were followed up and 6 (2.1%) were infected with HBV. Of 146 neonates born to hepatitis B e antigen (HBeAg)-negative mothers, 38 (26.0%) and 30 (20.5%) had detectable HBsAg and HBV DNA in cord blood respectively, but none of 126 infants followed up was infected. Of 187 neonates born to HBeAg-positive mothers, 92 (49.2%) and 79 (42.2%) had detectable HBsAg and HBV DNA respectively; 6 (3.7%) of 164 infants followed up were infected. Of seven neonates with HBV DNA >10^5 IU/ml in cord blood, four had no infection and three others were infected. Interpretation: Presence of HBsAg and/or HBV DNA, even at high levels, in cord blood just indicates exposure to, but not infection with HBV. Presence of HBV markers in cord blood cannot define intrauterine infection. Funding: This work was supported by the Jiangsu Provincial Department of Health (H201537), the Science and Technology Department of Jiangsu Province (BK20161105), and the National Natural Science Foundation of China (81672002), China. Declaration of Interest: The authors have no conflict of interest to disclose. Ethical Approval: This study was approved by the institutional review board of each hospital. All methods were performed in accordance with the protocols set up based on the relevant guidelines and regulations. Written informed consent was obtained from each pregnant woman; the infant’s consent was assigned by his/her mother.

Different interventional criteria for chronic hepatitis B pregnant women with HBeAg(+) or HBeAg(-): Epidemiological data from Shaanxi, China.

The seroprevalence of hepatitis B virus (HBV) and its impact on pregnancy outcomes of women from Shaanxi Province (China) was assessed. Risk factors for mother-to-child transmission (MTCT) were evaluated based on HBV-related seroprevalence data.Viral markers and biochemical parameters were assessed in HBsAg-positive mothers and their infants out of 13,451 cases recruited. A pretested and structured questionnaire was used to test the general HBV knowledge. Descriptive statistics and logistic regression analysis were done to reveal possible risk factors for MTCT.The overall prevalence of HBsAg in pregnant women was 7.07% (951/13,451), and a rate as high as 9.40% was observed. Among the HBsAg-positive pregnant women, 30.49% (290/951) were HBeAg-positive, 22.08% (210/951) had HBV DNA levels >106 IU/mL and only 16.19% with a high risk of MTCT (34/210) had received antiviral treatment. The overall MTCT rate was 5.21%. Noteworthy, the risk ratio and 95% confidence interval (95% CI) of MTCT in HBeAg-negative mothers with HBV DNA levels >2 × 103 IU/mL and HBsAg >104 IU/mL was 26.062 (2.633–258.024), which was significantly higher than that of HBeAg-positive mothers with HBV DNA level >106 IU/mL. Moreover, the awareness and knowledge about HBV transmission, risk factors, and intervention for MTCT were generally lacking among HBsAg-positive mothers.As a higher HBsAg seroprevalence and a higher MTCT rate among HBeAg-negative mothers with lower HBV DNA level was observed, our study emphasizes different interventional criteria for HBeAg-positive and HBeAg-negative mothers. Extensive health education, routine screening, and immunization against HBV during pregnancy are highly warranted to minimize the possibility of perinatal transmission.

Cesarean section reduces the risk of early mother-to-child transmission of hepatitis B virus

AimsTo evaluate the effects of cesarean section (CS) on the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) among hepatitis B surface antigen (HBsAg) positive pregnant women. MethodsA prospective cohort study was performed on HBsAg-positive pregnant women who delivered from June 2012 to March 2017 at Wuhan Medical Care Center for Women and Children in Wuhan, China. Logistic regression models were used to examine the associations between mode of delivery and the presence of HBV MTCT. ResultsA total of 1384 women paired with 1407 infants were enrolled. Our study showed that the incidence of HBV MTCT was 1.0% (14/1407) in infants born to HBsAg-positive pregnant women. We observed that the infants born by CS had a smaller percentage of HBV infection than those born by vaginal delivery (VD) (0.5% vs 1.7%, P = 0.043). In the fully adjusted model, CS was significantly associated with a decreased risk of HBV MTCT (OR = 0.26; 95% CI: 0.07–0.95; P = 0.042). ConclusionOur data confirmed that CS has a protective effect on early MTCT of HBV. CS for HBeAg-positive mothers with high viral load could reduce risk of MTCT and may become a new preventive measure of HBV MTCT through research on its risk-benefit assessment.

Maternal viral load and hepatitis B virus mother-to-child transmission risk: A systematic review and meta-analysis.

The aim of this study was to assess the relationship between maternal viral load and mother-to-child transmission (MTCT) risk in hepatitis B envelope antigen (HBeAg)-positive mothers. PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)-DNA-positive and HBV-DNA-negative groups. We also examined the dose-response effect of this relationship. Twenty-one studies with 10 142 mother-child pairs were included in the studies. The mean MTCT incidence was 13.1% in the maternal HBV-DNA-positive group, compared with 4.2% in the negative group. The summary MTCT odds ratio of maternal HBV-DNA positive compared with negative was 9.895 (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random-effects model. In maternal HBV-DNA <6log10copies/mL, 6-8log10copies/mL, and >8log10 copies/mL level stratifications, the pooled MTCT incidences were 2.754% (95% CI, 1.198-4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349-13.516%; Z = 5.43, P < 0.00001), and 14.445% (95% CI, 8.317-20.572%; Z = 4.62, P < 0.00001), respectively. A significant linear dose-response association was found between maternal viral load and MTCT risk, with the points estimate of increased MTCT risk 2.705 (95% CI, 1.808-4.047) at 6log10copies/mL compared with reference (3log10copies/mL), and 7.316 (95% CI, 3.268-16.378) at 9log10 copies/mL. A significant non-linear dose-response association was also found between maternal viral load and HBV MTCT risk (model χ2 = 23.43, P < 0.00001). Our meta-analysis indicated that maternal viral load was an important risk factor for MTCT in HBeAg-positive mothers, and maternal viral load was dose-dependent with HBV MTCT incidence.

Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B

BackgroundPregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants’ receiving hepatitis B immune globulin.MethodsIn this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)–positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)–positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group).ResultsFrom January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29).ConclusionsIn a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822.)

The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China.

Antiviral therapy has been documented to reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic mothers. This large prospective cohort study conducted in China aims to delineate the maternal viral threshold for consideration of antiviral prophylaxis in settings with limited resources. A total of 1177 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current passive-active prophylaxis regimen were enrolled from community health centers in Jiangsu and Henan provinces, China. Maternal hepatitis B e antigen (HBeAg) status and viral load were tested at 36-40 weeks of gestation. Post-vaccination serologic testing was performed at 7 and 12 months of age. HBeAg-positive mothers (419/1177; 35.6%) had significantly higher viral loads, compared with HBeAg-negative mothers (758/1177; 64.4%) (8.12 vs. 2.69 log IU/mL, p < .0001). Twenty infants, born to HBeAg-positive mothers with high viral loads (median, 8.38; range: 7.82-9.22 log IU/mL), were infected at 7 months of age. In contrast, none of the HBeAg-negative mothers transmitted HBV to their offspring. After adjustment for the other risk factor, a higher maternal viral load was significantly associated with a higher risk of transmission (adjusted odds ratio, 3.78; 95% confidence interval: 1.46-9.81; p = .006). The rates of passive-active immunoprophylaxis failure were 0.0% (0/789), 0.0% (0/27), 0.0% (0/32) and 6.1% (20/329) at maternal viral loads of <5, 5-6, 6-7 and ≥7 log IU/mL, respectively. The antibody to hepatitis B surface antigen (anti-HBs) response rate was 98.4% (1138/1157) at 7 months of age. Results from this study indicate that the maternal viral threshold associated with perinatal transmission of HBV is 7 log IU/mL, which may be appropriate for consideration of antiviral prophylaxis in settings with limited resources.

Predictive value of single nucleotide polymorphisms of HLA-C and UBE2L3 in evaluating the effect of telbivudine antiviral therapy during pregnancy

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10(3) IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion: Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.

A retrospective study of hepatitis B mother-to-child transmission prevention and postvaccination serological test results of infants at risk of perinatal transmission in two counties of middle China.

Approximately, 240 million people have chronic hepatitis B worldwide, with mother-to-child-transmission (MTCT) accounting for most cases. Therefore, Henan Province, China launched a public health programme to prevent MTCT. To determine the efficacy of this health programme, a survey was carried out in Huixian and Xinan counties, which are located in northern and western Henan. All infants born in these two counties between January 1, 2013 and March 31, 2014 to a mother positive for hepatitis B surface antigen (HBsAg) were surveyed. In total, there were 438 mother-infant pairs. A blood sample was collected from all mothers and infants and the following Hepatitis B virus (HBV) markers, antibodies, and antigens were measured: HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe, and HBV-DNA. All mothers and 5.3% (23/438) of the infants were HBsAg positive. All infants received three doses of the hepatitis B vaccine (HepB) and the postvaccination serological test (PVST) showed that the appropriate interval for PVST may be 1-8months after the final HepB dose. Multivariable analysis showed that infants without a timely first and second dose of the HepB, with an HBeAg-positive mother and mothers who had not received hepatitis B immune globulin during pregnancy were implicated in MTCT. The stratified analysis using maternal HBeAg as a marker showed that maternal HBeAg may be a strong risk factor for MTCT. To prevent MTCT in middle China, several courses of action are recommended. The first is to optimize the screening method for the mother to allow HBeAg and HBsAg-positive mothers to receive medical treatment during pregnancy and a timely birth dose of the vaccine to all infants. Second, all infants with an HBsAg-positive mother should be tested for anti-HBs and HBsAg at 7-14months old and any anti-HBs-nonresponse infants should receive an additional three dosesof the vaccine.

Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus.

Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus.

Serological positive markers of hepatitis B virus in femoral venous blood or umbilical cord blood should not be evidence of in-utero infection among neonates.

BackgroundMaternal-infant transmission of hepatitis B virus(HBV) occurs even after passive-active immunization. Some scholars speculate that in-utero infection may be the main cause of immunoprophylaxis failure. However, there is a lack of evidence about the possible occurrence periods of perinatal transmission.MethodsFrom 2008 to 2012, 428 pairs of HBsAg-positive mothers and neonates were enrolled and 385 infants aged 8–12 months were followed. HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBV-DNA) were performed on all subjects.ResultsOf mothers who were positive for HBsAg, HBeAg, HBV-DNA, 35.1 %, 94.3 %, 12.7 % of their neonates were positive for those indices, respectively. Neonates’ mean titers of those indices were significantly lower than their mothers’. There were no significant differences in rates of positivity and mean titers of anti-HBe and anti-HBc between neonates and mothers. Most of the positive indices turned negative during the follow-up period. Immunoprophylaxis failed in seventeen infants: four infants had HBV-DNA > 6 log 10copies/mL both at birth and in follow-up; in six infants, mean viral load was 3.72 ± 0.17 log 10copies/mLat birth and 7.62 ± 0.14 log 10copies/mL at follow-up; seven infants were HBV-DNA negative at birth but were found to have > 6 log 10copies/mL during follow-up. Infants that were immunoprophylaxis failures were all born to HBeAg-positive mothers with HBV-DNA > 6 log 10copies/mL.ConclusionsThe placental barrier can partly prevent maternal HBsAg, HBeAg, HBV-DNA from passing through to fetus. Performing HBsAg, HBeAg, HBV-DNA once at birth can neither diagnose nor exclude maternal-infant transmission. The diagnosis of infection period depends on the dynamic changes in viral load from birth through the follow-up period but whether the infection occurred in utero, at delivery or during the neonatal period could not be determined.

Protective effect of an improved immunization practice of mother-to-infant transmission of hepatitis B virus and risk factors associated with immunoprophylaxis failure.

Although routine immunoprophylaxis has been known to reduce hepatitis B virus (HBV) transmission, immunoprophylaxis failure still occurs. The study aimed to investigate the protective efficacy of an improved immunoprophylaxis protocol to prevent mother-to-infant transmission of HBV and to explore the potential risk factors associated with immunoprophylaxis failure and low antibody response.A prospective observational cohort study was conducted from July 2012 to April 2015. A total of 863 HBsAg-positive mothers and their 871 infants (8 pairs of twins) were included in the study. Two different hepatitis B vaccine doses (20 or 10 μg) were administered to the infants based on the hepatitis B e-antigen (HBeAg) status of their mothers. Simultaneously, hepatitis B immunoglobulin (HBIG) was administered to the infants. Initial injections of HBIG and the hepatitis vaccine were given within 2 hours after birth. Rates of HBV infections among the infants were evaluated at 7 months of age. Factors associated with immunoprophylaxis failure and low responses to vaccination were analyzed by unconditional logistic regression..At 7 months of age, no immunoprophylaxis failure was observed in the 565 infants born to HBeAg-negative mothers. Among the 306 infants born to HBeAg-positive mothers, immunoprophylaxis failed in 16 infants (5.2%) of the infants and they were found to be HBsAg-positive. Further analysis showed that HBV DNA levels ≥10 IU/mL [odds ratio (OR) = 4.53, 95% confidence interval (95% CI): 1.19-17.34], delayed vaccination (OR = 4.14, 95% CI: 1.00-17.18), and inadequate initial injections (OR = 7.69, 95% CI: 1.71-34.59) were independently associated with immunoprophylaxis failure. Adequate titers of antibody to HBsAg (anti-HBs, ≥100 mIU/mL) were present in 96.5% of immunoprophylaxis-successful infants. For full-term infants, birth weights <3000 g were correlated with low immune responses to vaccination.This improved immunoprophylaxis protocol is effective in preventing perinatal transmission of HBV. Among infants with HBeAg-positive mothers, high HBV viral loads and inadequate and delayed initial injections were associated with immunoprophylaxis failure. The majority of the infants in our study produced adequate levels of protective anti-HBs titers after immunoprophylaxis. Additional efforts to further reduce perinatal transmission should be considered, especially for HBeAg-positive mothers.

Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load

BackgroundFew data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV).MethodsIn this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28.ResultsAt delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups.ConclusionsIn a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.)