Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China.

OBJECTIVE: To evaluate prenatal maternal hepatitis B virus (HBV) screening and post-vaccination hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs) status and titers of babies born to HBsAg positive mothers, and to provide evidence for development of standard postvaccination serologic testing (PVST) strategies for babies born to HBsAg positive mothers in China. METHODS: In 2014, we conducted a baseline survey of HBV mother to child transmission (MTCT) interruption strategy implementation and PVST for babies born to HBsAg positive mothers after received 3 doses of hepatitis B vaccine (HepB) in 8 counties in 4 Provinces. Bivariate analysis and multivariable analyses modeled statistically significant predictor variables associated with infant HBsAg, anti-HBs positive, anti-HBs titer. RESULTS: Among the 1563 infants born to HBsAg positive mothers, 1025 (65.6%) maternal-infant pairs were enrolled in PVST after receiving 3 doses of HepB. 38 infants tested HBsAg positive for an HBsAg positive rate of 3.7%. Maternal hepatitis B e antigen (HBeAg) status and age of infant were significantly associated with infant HBsAg positivity. A total of 932 infants were anti-HBs positive when tested at 7-24months of age, yielding an anti-HBs positivity rate of 90.9%. Maternal HBeAg status was the factor associated with infant anti-HBs status. Amount of antigen of HepB and infant's age were most associated with anti-HBs titers. PVST performed 1-2months after the 3rd dose of HepB was associated with the highest anti-HBs level and the anti-HBs Geometric Mean Concentration (GMC) decreased as the PVST intervals prolonged. CONCLUSIONS: In China, perinatal HBV transmission is approaching the theoretical minimum possible with the current strategy of HepB coupled with HBIG administration for HBV-exposed newborns. PVST of infants born to an HBsAg positive mother is an essential strategy to ensure full protection for vaccine non-responders and appropriate medical care for those infected.

Loss of confidence in vaccines following media reports of infant deaths after hepatitis B vaccination in China.

BACKGROUND: China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported. METHODS: We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces. RESULTS: HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline. CONCLUSIONS: The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization.

An "immune barrier" is formed in the placenta by hepatitis B immunoglobulin to protect the fetus from hepatitis B virus infection from the mother.

The effect of hepatitis B immunoglobulin (HBIG) on hepatitis B virus (HBV) DNA load and its protective mechanism are not well understood. Twenty-eight hepatitis B surface antigen (HBsAg)-positive pregnant women and their newborns were assigned to an experimental (n = 12) or control group (n = 16) according to whether they received HBIG during pregnancy. HBV DNA load and markers titer of the mothers and newborns were tested. These markers and HBV DNA load in mothers of the experimental group did not fluctuate significantly and were comparable to the control. In the experimental group, there was a positive correlation between mothers and their newborns with regard to hepatitis B surface antibody titer. Immunohistochemical staining of placenta sections showed that HBsAg-positive areas mainly included trophoblastic cells and villous mesenchymal cells without HBIG colocalization, whereas HBIG-positive areas principally included villous capillary endothelial cells and villous mesenchymal cells. Additionally, compared with the control group, the positive rate and mean density of HBIG in the experimental group were remarkably higher. HBIG deposition was seen in Hofbauer cells. Thus, rather than influencing virus replication, HBIG forms an immune barrier between the mother and fetus to prevent HBV transmission.

Immunization of babies born to HBsAg positive mothers: An audit on the delivery and completeness of follow up in Norfolk and Suffolk, United Kingdom.

Perinatal transmission of hepatitis B infection has increased in the UK over the last decade. Routine antenatal screening of pregnant mothers (based on HBsAg) provides an effective means to identify 'at risk' babies. Follow up of babies born to infected mothers involves 4 doses of vaccination and/or a single dose of HBIG at birth. In this study we report the outcome of follow up of babies born to infected mothers over a 5 y period. One hundred sixty-three babies born to HBsAg positive mothers were followed up to ascertain the completeness for immunization and serological testing. Vaccination completion was 99.4% (162 of babies) at birth (1st dose), 95.6% (152 babies) for the second dose (at 1st month), 94.3 % (148 babies) for the 3rd dose (at 2nd month) and 83.4% (106 babies) for the 4th dose (at 12 months). Additionally, at 12 months 29.9% (38) of babies had their blood tested serologically to ascertain infection status; all babies receiving antigen testing were HBsAg negative. The overall vaccination coverage was good, although there is scope to improve the coverage of 4th dose. However, the proportion of children who were serologically tested for surface antigen at 12 months was considerably lower and there is a greater need to test babies concurrently at the time of giving the 4(th) dose. The proposed dried blood spot testing which will be rolled out from September 2014 should address this issue.

Perinatal hepatitis B prevention program in Shandong Province, China. Evaluation and progress.

Post-exposure prophylaxis with hepatitis B vaccine (HepB) alone is highly effective in preventing perinatal hepatitis B virus (HBV) transmission and the World Health Organization recommends administering HepB to all infants within 24 h after delivery. Maternal screening for HBsAg and administration of hepatitis B immune globulin (HBIG) in addition to HepB for infants born to HBsAg-positive pregnant women can increase the effectiveness of post-exposure prophylaxis for perinatal HBV transmission. In Shangdong Province, China which has a high prevalence of chronic HBV infection, HepB birth dose and HBIG were integrated into the routine childhood immunization program in 2002 and July 2011 respectively. We assessed progress toward implementation of these measures. Hospital-based reporting demonstrated an increase in maternal screening from 70.7% to 96.9% from 2004-2012; HepB birth dose coverage (within 24 h) remained high (96.3-97.1%) during this period. For infants with known HBsAg-positive mothers, the coverage of HBIG increased from 85.0% (before July 2011) to 92.1% (after July 2011). However, HBIG coverage in western areas of Shandong Province remained at 81.1% among infants with known HBsAg-positive mothers. Preterm/low-birth-weight and illness after birth were the most commonly reported reasons for delay in the first dose of HepB to >24 h of birth. Additional education on the safety and immune protection from HepB and HBIG might help to correct delays in administering the HepB birth dose and low HBIG coverage in the western areas of the Shandong Province.

Evaluation of policies and practices to prevent mother to child transmission of hepatitis B virus in China: results from China GAVI project final evaluation.

BACKGROUND: Mother to Child Transmission (MTCT) has remained a leading cause of HBV infection in China, accounting for 40% of total infections. Providing hepatitis B vaccine (HepB) to all infants within 24h of birth (Timely Birth Dose, TBD), and subsequent completion of at least 3 vaccine doses is key to preventing perinatal HBV infection. In 2002, with the financial support of the Global Alliance on Vaccine and Immunization (GAVI) targeted to Western region and 223 poverty-affected counties in Central region, hepatitis B vaccine was provided for free. In 2010, we evaluated the China GAVI project in terms of its activities to prevent perinatal infections. OBJECTIVE: The objectives of the evaluation were to (1) measure achievements in the China GAVI project in terms of TBD coverage, and (2) describe practices for HBsAg screening of pregnant women and HBIG use outside the GAVI China project. METHODS: We used the methods recommended by WHO to select a cluster sample of health care facilities for the purpose of an injection safety assessment. We stratified China into three regions based on economic criteria, and selected eight counties with a probability proportional to population size in each region. In each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. In each hospital, we abstracted 2002 through 2009 records to collect information regarding birth cohorts, hospitals deliveries, vaccine management, hepatitis B vaccination delivery, HBsAg screening practices and results, and HBIG administration. In addition, in all hospitals, we abstracted records regarding the delivery of TBD. RESULTS: We visited 244 facilities in the three regions, including 24 county hospitals and 220 township hospitals. We reviewed 837,409 birth summary records, 699,249 for infants born at county or township hospitals. Hospital delivery rates increased from 58% in 2002 to 93% in 2009. Surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 (+31%). Surveyed TBD coverage among children born in hospitals increased from 73% in 2002 to 98% in 2009. Between 2002 and 2009, the proportion of pregnant women screened for HBsAg increased from 64% in 2002 to 85% in 2009. In 2009, the proportion of infants born to women screened and found to be HBsAg positive who did not receive any immunization within 24h after birth ranged from 0% to 0.7% across regions. CONCLUSIONS: Increased availability of hepatitis B vaccine, along with efforts to improve hospital deliveries, increased TBD coverage in China. This decreased perinatal HBV transmission and will reduce disease burden in the future. Screening for HBsAg to guide HBIG administration has begun, but with heterogeneous immuno-prophylaxis practices and a poor system for follow up.

Screening of pregnant women for hepatitis B virus surface antigen (HBsAg) and subsequent management, Qiandongnan prefecture, Guizhou, China, 2010.

BACKGROUND: In China, in 2010, a high proportion of pregnant women were tested for hepatitis B surface antigen (HBsAg). However, the preventive actions taken following screening were unclear. We followed up infants who were born to HBsAg positive mothers to describe the management that took place after screening. METHODS: We selected eight counties with a probability proportional to population size in the Qiandongnan prefecture, Guizhou province. In each county, we selected a hospital at random. In each hospital, we (a) reviewed records to estimate the proportion of pregnant women who had been screened for HBsAg in 2010 and (b) sampled 10 screened women at random to assess management after one year in 2011. We calculated proportions and confidence intervals (CI) using standard formulae. RESULTS: Among the 7232 women who delivered in 2010 in the 8 hospitals, 98% (95% CI: 97%-99%) had been tested for HBsAg. Among 82 HBsAg women sampled for follow-up, 45 (55%; 95% CI: 44%-65%) knew they had been tested during pregnancy and 60 (73%; 95% CI: 63%-82%) knew they were HBsAg positive. The 82 infants had received three doses of hepatitis B vaccines and 79 (96%; 95% CI: 90%-99%) had received the first dose within 24h. However, only 11 infants (13%; 95% CI: 9%-25%) had received HBIG in addition to hepatitis B vaccine and 16 (20%; 95% CI: 12%-29%) had been tested for HBsAg upon completion of the vaccine series as part of their routine management. CONCLUSIONS: HBsAg testing of pregnant women was common in Qiandongnan, Guizhou, but post-screening management was limited. There is a need to ensure continuity of care through engaging women in HBsAg testing and following up infants with comprehensive management, including immunoprophylaxis and serological testing.

Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial.

Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti-HBe positive were a low-risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg-positive status and negativity for anti-HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg-positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother-to-baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother-to-child transmission of HBV infection.

Development of strategies for screening, predicting, and diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers.

This study aimed at developing strategies for screening, predicting, and diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers. A total of 1,360 infants born to 1,355 HBsAg positive mothers were followed for 1 year. All newborn infants received active and passive immunization within 24 hr after birth. Maternal and infant blood samples were collected and tested for the status of serum HBsAg, HBeAg, and HBV DNA positivity. The accuracy of infant HBsAg positivity, HBV DNA positivity, HBsAg and HBV DNA double positivity, and HBsAg and/or HBV DNA positivity at birth in the diagnosis of intrauterine HBV infection was evaluated by receiver operating characteristic curve analysis. Of 1,360 infants, 145 tested positive for HBsAg and/or HBV DNA at birth. Twenty-one (1.5%) infants, who were diagnosed with intrauterine HBV infection, showed HBsAg positivity from birth to 7 and 12 months of age. Infant HBsAg positivity at birth had the highest sensitivity in predicting intrauterine HBV infection, while neonatal HBsAg and HBV DNA double positivity had the highest specificity. These findings suggest that infants, who were born to HBsAg positive mothers and were positive for both HBsAg and HBV DNA at birth, may be at a higher risk for intrauterine HBV infection. HBsAg positivity at birth may be a good marker for screening intrauterine HBV infection. Infant HBsAg positivity both at birth and 7 months of age may be used as a diagnostic criterion to simplify diagnostic procedures and improve diagnostic efficiency.

Nucleoside plus nucleotide analogs and cessation of hepatitis B immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective.

BACKGROUND: After orthotopic liver transplantation (OLT) in chronic hepatitis B (HBV), adequate prophylaxis for recurrence of HBV in the graft is mandatory. OBJECTIVES: Evaluate safety of HBV prophylaxis with tenofovir and emtricitabine (TDF/FTC) after cessation of hepatitis B immunoglobulin (HBIG) after OLT in chronic HBV. STUDY DESIGN: In 17 consecutive patients after OLT in chronic HBV we started TDF/FTC after cessation of HBIG. All had received HBIG >6 months. 15/17 were HBsAg negative and 16/17 had undetectable HBV-DNA. RESULTS: After mean follow-up of 2 years 16/17 patients were alive, one died due to urosepsis. All 16 with undetectable HBV-DNA remained HBV-DNA negative. From 15 HBsAg negative patients at start, in one seroconversion to positive HBsAg occurred, without detectable HBV-DNA. Liver biochemistry remained within the normal ranges. There were no cases of drug discontinuation. No major side effects were reported. TDF/FTC use saves €16,262/year over standard-of-care (HBIG+LAM). This prospective follow-up study shows that in liver transplantation for chronic hepatitis B, after initial treatment including HBIG for at least 6 months combined with or followed by (dual) nucleos(t)ide analog therapy, TDF/FTC provides adequate prophylaxis against recurrent HBV infection without major side effects and leads to substantial cost savings over a regimen with HBIG. CONCLUSION: Combined prophylaxis with TDF/ETV nucleoside plus nucleotide analogs and cessation of immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective.

Intracellular-delivery of a single-chain antibody against hepatitis B core protein via cell-penetrating peptide inhibits hepatitis B virus replication in vitro.

Assembly of nucleocapsids is an attractive target for novel anti-hepatitis B virus (HBV) agents, and intracellular single-chain variable fragment (scFv) antibodies against HBV core (HBc) protein are a class of potential alternatives for this purpose; however, their application is limited by the lack of a suitable means of delivery. Owing to the favorable performance of cytoplasmic transduction peptide (CTP) in cargo delivery in hepatocytes, we purified an anti-HBc scFv fused to CTP using a previous screened sequence by a prokaryotic expression system and evaluated its efficacy in the inhibition of HBV in vitro. Our results showed that cytoplasmic translocation of the previous anti-HBc scFv was achieved by CTP in HepG2.2.15 cells. Immunoprecipitation analysis indicated the fusion protein anti-HBc scFv-CTP interacted with its target antigen HBc, and negligible cytotoxicity was observed. Moreover, the anti-HBc scFv-CTP interfered with nucleocapsid assembly and markedly reduced both the supernatant HBV DNA level and the intracellular DNA replication intermediates, with a 5.1 µM of half maximal effect concentration and a dose-dependent effect. In conclusion, this novel anti-HBc scFv fused to CTP demonstrated inhibitory activity of HBV replication in vitro and warrants further in vivo study.

The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis.

Chronic hepatitis B virus (HBV) infection poses a serious public health problem in many parts of the world. Presently, even with proper joint immunoprophylaxis, approximately 10-15% of newborns from HBV carrier mothers suffer from HBV infection through intrauterine transmission. One of the risk factors is the level of maternal viraemia. Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV. A few studies have evaluated the efficacy of telbivudine in preventing intrauterine HBV infection during late pregnancy. So we conducted this meta-analysis to arrive at an evidence-based conclusion. We searched Medline/PubMed, EMBASE, Cochrane Library, Web of Knowledge and China Biological Medicine Database from January 1990 to December 2011. Relative risks (RR) of the seropositivity rates for hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants were studied. Mean differences (MD) in maternal HBV DNA levels were reviewed. Finally two randomised controlled trials (RCTs) and four non-randomised controlled trials (NRCTs) were left for analysis which included 576 mothers in total, of whom 306 received telbivudine treatment and 270 did not receive any drug. All newborns received hepatitis B vaccine (HBVac) and hepatitis B immunoglobulin (HBIG) after birth. The seropositivity rate for HBsAg or HBV DNA was significantly lower in the telbivudine group, both at birth and at 6-12 months follow up. Meanwhile, maternal HBV DNA levels prior to delivery were significantly lower in the telbivudine group. In addition, the frequency of serum creatine kinase (CK) elevation was similar in the two groups. Our meta-analysis provides preliminary evidence that telbivudine application in late pregnancy is effective in the interruption of intrauterine HBV infection, with no significant adverse effects or complications. More high quality, well-designed, double-blinded, randomised controlled and large size clinical trials are needed for further investigation and more convincing results in the future.

Gaps in the prevention of perinatal transmission of hepatitis B virus between recommendations and routine practices in a highly endemic region: a provincial population-based study in China.

BACKGROUND: Hepatitis B virus (HBV) infection is endemic in China; perinatal transmission is the main source of chronic HBV infection. Simultaneous administration of hepatitis B immune globulin (HBIG) and hepatitis B vaccine is highly effective to prevent perinatal transmission of HBV; however, the effectiveness also depends on full adherence to the recommended protocols in daily practice. In the present investigation, we aimed to identify gaps in immunoprophylaxis of perinatal transmission of HBV between recommendations and routine practices in Jiangsu Province, China. METHODS: Totally 626 children from 6 cities and 8 rural areas across Jiangsu Province, China, born from February 2003 to December 2004, were enrolled; 298 were born to mothers with positive hepatitis B surface antigen (HBsAg) and 328 were born to HBsAg-negative mothers. Immunoprophylactic measures against hepatitis B were retrospectively reviewed for about half of the children by checking medical records or vaccination cards and the vaccine status was validated for most of children. RESULTS: Of 298 children born to HBV carrier mothers, 11 (3.7%) were HBsAg positive, while none of 328 children born to non-carrier mothers was HBsAg positive (P < 0.01). The rates of anti-HBs ≥ 10 mIU/ml in children of carrier and non-carrier mothers were 69.5% and 69.2% respectively (P = 0.95). The hepatitis B vaccine coverage in two groups was 100% and 99.4% respectively (P = 0.50), but 15.1% of HBV-exposed infants did not receive the timely birth dose. Prenatal HBsAg screening was performed only in 156 (52.3%) of the carrier mothers. Consequently, only 112 (37.6%) of HBV-exposed infants received HBIG after birth. Furthermore, of the 11 HBV-infected children, only one received both HBIG and hepatitis B vaccine timely, seven missed HBIG, two received delayed vaccination, and one missed HBIG and received delayed vaccination. CONCLUSIONS: There are substantial gaps in the prevention of perinatal HBV infection between the recommendations and routine practices in China, which highlights the importance of full adherence to the recommendations to eliminate perinatal HBV infection in the endemic regions.

[Chronic HBV infection in a two year-old girl in spite of correct HBV vaccination after birth]. / Kronisk HBV-infektion hos en toårig pige trods korrekt HBV-vaccination efter fødslen.

Our case story is about a two year-old girl who, despite full vaccination with neonatal hepatitis B immunoglobulin and hepatitis B vaccination and revaccination with hepatitis B vaccine at one, two and 12 months of age, got chronic hepatitis B presumably due to intrauterine mother-to-child transmission. Her mother was known to be HBsAg and HBeAg positive with genotype C and a viral load of one billion IU/ml. It is important that children with HBV infection are detected and seen in a special department. Post-vaccination screening of children from HBsAg positive mothers should be considered.

Prevention of perinatal hepatitis B virus transmission in the Netherlands, 2003-2007: children of Chinese mothers are at increased risk of breakthrough infection.

BACKGROUND: In the Netherlands, different hepatitis B vaccination schedules have been used for children born to HBV-infected mothers. All schedules included a birth dose of hepatitis B immunoglobuline (HBIg). We assessed determinants of perinatal HBV transmission and determinants of anti-HBs titers in infants born to HBsAg positive mothers. METHODS: We included infants born to HBV infected mothers between 1.1.2003 and 30.6.2007, using national databases and a separate database for Amsterdam. Risk factors for perinatal transmission and determinants of the anti-HBs titer were studied using logistic and linear regression, respectively. RESULTS: Of 2657 infants registered in the national database, 91% were registered to have received HBIg and at least three hepatitis B vaccinations. In Amsterdam, this coverage among 413 children at risk was higher (96%, p<0.01). Serological test results for 2121 infants (80%) indicated that 13 (0.6%) were HBsAg positive. A mother of Chinese descent was the only risk factor for perinatal HBV infection identified (RR 9.1, 95% CI 3.1-26.8). Receiving a birth dose of hepatitis B vaccine later than in the first week of life was not associated with an increased risk of perinatal HBV infection. A shorter period between last vaccination and testing, and having received more doses of hepatitis B vaccine were independently associated with a higher anti-HBs titer. CONCLUSIONS: Infants born to Chinese mothers were at increased risk of perinatal HBV infection. All HBsAg positive pregnant women of Chinese origin should be assessed to determine whether there is an indication for anti-viral treatment during pregnancy. Among infants who received HBIg at birth, we did not detect an increased risk of perinatal HBV infection when the first dose of hepatitis B vaccine was administered after the first week of life.

A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection.

BACKGROUND & AIMS: In the Asia-Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10-30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. METHODS: Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10(7) copies/ml mothers received telbivudine 600 mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200 IU of HBIg within 12 h postpartum and recombinant HBV vaccine of 20 µg at 0, 1, and 6 months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. RESULTS: Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p=0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. CONCLUSIONS: Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population.