Hepatitis B Virus Mother-to-child Transmission Research Articles

Hepatitis B virus (HBV) status of children born to HIV/HBV co‐infected women in a French hospital: a cross‐sectional study

IntroductionHuman Immunodeficiency Virus (HIV) Mother-To-Child-Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co-infected women in a developed country with a large access to cART.Materials and MethodsHIV/HBV co-infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years.ResultsForty nine (9.2%) from 530 HIV-infected women followed in the hospital were HIV/HBV co-infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost-to-follow-up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester.ConclusionsThree quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long-term protection and underlining the need of control.

Maternal transmission risk and antibody levels against hepatitis B virus e antigen in pregnant women

The generation of antibodies (anti-HBe) against hepatitis B virus (HBV) e antigen (HBeAg) often coincides with clinical remission in chronic HBV patients. We aimed to examine the effect of maternal anti-HBe in protection against HBV mother-to-child transmission (MTCT). A total of 140 chronic HBV-infected pregnant women participated in this study. Before delivery, maternal HBV serological markers and HBV viral load were determined and anti-HBe titers were semi-quantified. Neonatal hepatitis B surface antigen (HBsAg) and HBV-DNA status were determined from cord blood. The children were followed to age 1-3 years. The HBV-DNA positive rate in cord blood was 75.61% (31/41) in those who were born to mothers with serum HBV-DNA >10(6) IU/ml, which was significantly higher than in those who were born to mothers with HBV-DNA <10(6) IU/ml (3/99, 3.03%; p<0.0001). However, 10 newborns from mothers with serum HBV-DNA >10(6) IU/ml had no detectable HBV-DNA in cord blood; anti-HBe was positive with a median titer of 10 (interquartile range 10-55). A total of 84 children who received hepatitis B immune globulin (HBIG) within 12h after birth and who completed three doses of recombinant HBV vaccination were followed to age 1-3 years (up to May 2014). All 56 children who were born to mothers with serum HBV-DNA levels <10(6) IU/ml were HBsAg-negative. Five of the 22 children born to anti-HBe-negative mothers with serum HBV-DNA >10(6) IU/ml acquired an HBsAg-positive status. However, none of the six children who were born to anti-HBe-positive/weak-positive mothers with serum HBV-DNA >10(6) IU/ml acquired an HBsAg-positive status. The presence of maternal anti-HBe is protective against HBV MTCT, independent of the maternal serum HBV viral load.

Analysis of residual perinatal transmission of hepatitis B virus (HBV) and of genetic variants in human immunodeficiency virus and HBV co-infected women and their offspring

BackgroundDespite implementation of universal infant hepatitis B (HB) vaccination, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) still occurs. Limited data are available on the residual MTCT of HBV in human immunodeficiency virus (HIV)-HBV co-infected women. ObjectivesWe assessed the prevalence of HBV infection among HIV-infected pregnant women and the rate of residual MTCT of HBV from HIV-HBV co-infected women and analyzed the viral determinants in mothers and their HBV-infected children. Study designHIV-1 infected pregnant women enrolled in two nationwide perinatal HIV prevention trials in Thailand were screened for HB surface antigen (HBsAg) and tested for HBeAg and HBV DNA load. Infants born to HBsAg-positive women had HBsAg and HBV DNA tested at 4–6 months. HBV diversity within each HBV-infected mother–infant pair was analyzed by direct sequencing of amplified HBsAg-encoding gene and cloning of amplified products. ResultsAmong 3312 HIV-1 infected pregnant women, 245 (7.4%) were HBsAg-positive, of whom 125 were HBeAg-positive. Of 230 evaluable infants born to HBsAg-positive women, 11 (4.8%) were found HBsAg and HBV DNA positive at 4–6 months; 8 were born to HBeAg-positive mothers. HBV genetic analysis was performed in 9 mother–infant pairs and showed that 5 infants were infected with maternal HBV variants harboring mutations within the HBsAg “a” determinant, and four were infected with wild-type HBV present in highly viremic mothers. ConclusionsHBV-MTCT still occurs when women have high HBV DNA load and/or are infected with HBV variants. Additional interventions targeting highly viremic women are thus needed to reduce further HBV-MTCT.

Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus

Objective: This study was designed to explore if hepatitis B virus (HBV) may be transmitted via breast milk through mother-to-child transmission (MTCT), and assay the immunoprophylaxis efficacy after passive–active immunization.Method: From year 2008 to 2012, 67 720 pregnant women were screened and 1186 HBsAg-carrier mothers and their infants aged 8–12 months were followed in multi-centers of China, among whom HBV markers (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb) and HBV-DNA were measured.Results: HBsAg positive rate of pregnant women was 6.7% (4533/67 720) and infants’ immunoprophylaxis failure rate was 3.3% (39/1186). Immunoprophylaxis failure infants were all born to mothers of HBeAg positive and HBV-DNA >6 log10 copies/ml. Among infants of HBeAg positive mothers, HBV infection rate was 9.0% and HBsAg positive rate was 8.3% in breast-feeding group versus 9.2% in formula-feeding group, P = 0.761. Occurrence of perinatal HBV infection was indicated in uterus or during delivery. Different feeding patterns had no effects on HBsAb conversion of infants with the implementation of immunization.Conclusions: HBsAg prevelance rate of pregnant women enrolled was 6.7% and immunoprophylaxis failure rate of infants was 3.3%, while the infection rate reached 9.0% in infants of HBeAg positive mothers. Breast feeding did not increase the occurrence of HBV MTCT.

Breastfeeding of Newborns by Mothers Carrying Hepatitis B Virus

To perform a systematic review of prospective studies to confirm the role of breastfeeding in mother-to-child transmission (MTCT) of hepatitis B virus (HBV). A database was constructed from MEDLINE, EMBASE, Cochrane Library, National Science Digital Library, and China Biological Medicine Database and through contact with experts in this field from January 1, 1990, to August 31, 2010. All studies were peer reviewed and met the preset inclusion standards. Breastfeeding. Data regarding HBV intrauterine infection, MTCT, maternal blood and breast milk infectiousness, infant immunoprophylaxis methods and response, and adverse events. The Mantel-Haenszel fixed-effects model was used for all analyses using odds ratios and 95% confidence intervals. Ten qualified studies were included. All were clinical controlled trials, involving 751 infants in the breastfeeding group and 873 infants in the nonbreastfeeding group. As indicated by infant peripheral blood hepatitis B surface antigen or HBV DNA positivity at age 6 to 12 months, the odds ratio of MTCT of HBV in the breastfeeding group compared with that in the nonbreastfeeding group was 0.86 (95% confidence interval, 0.51-1.45) (from 8 clinical controlled trials, P = .56; I(2) = 0%, P = .99). As indicated by infant peripheral blood hepatitis B surface antibody positivity at age 6 to 12 months, the odds ratio of development of hepatitis B surface antibodies in the breastfeeding group compared with that in the nonbreastfeeding group was 0.98 (95% confidence interval, 0.69-1.40) (from 8 clinical controlled trials, P = .93; I(2) = 0%, P = .99). No adverse events or complications during breastfeeding were observed. Breastfeeding after proper immunoprophylaxis did not contribute to MTCT transmission of HBV.

A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus

To determine the therapeutic effect of lamivudine in late pregnancy for the interruption of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Studies were identified by searching available databases up to January 2011. Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials (RCTs) with lamivudine treatment in late pregnancy, and newborns or infants whose serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) or HBV DNA had been documented. The relative risks (RRs) for interruption of MTCT as indicated by HBsAg, HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval (CI) to estimate the efficacy of lamivudine treatment. Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis. The overall RR was 0.43 (95% CI, 0.25-0.76; 8 RCTs; P(heterogeneity) = 0.04) and 0.33 (95% CI, 0.23-0.47; 6 RCTs; P(heterogeneity) = 0.93) indicated by newborn HBsAg or HBV DNA. The RR was 0.33 (95% CI, 0.21-0.50; 6 RCTs; P(heterogeneity) = 0.46) and 0.32 (95% CI, 0.20-0.50; 4 RCTs; P(heterogeneity) = 0.33) indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth. The RR (lamivudine vs hepatitis B immunoglobulin) was 0.27 (95% CI, 0.16-0.46; 5 RCTs; P(heterogeneity) = 0.94) and 0.24 (95% CI, 0.07-0.79; 3 RCTs; P(heterogeneity) = 0.60) indicated by newborn HBsAg or HBV DNA, respectively. In the mothers with viral load < 10⁶ copies/mL after lamivudine treatment, the efficacy (RR, 95% CI) was 0.33, 0.21-0.53 (5 RCTs; P(heterogeneity) = 0.82) for the interruption of MTCT, however, this value was not significant if maternal viral load was > 10⁶ copies/mL after lamivudine treatment (P = 0.45, 2 RCTs), as indicated by newborn serum HBsAg. The RR (lamivudine initiated from 28 wk of gestation vs control) was 0.34 (95% CI, 0.22-0.52; 7 RCTs; P(heterogeneity) = 0.92) and 0.33 (95% CI, 0.22-0.50; 5 RCTs; P(heterogeneity) = 0.86) indicated by newborn HBsAg or HBV DNA. The incidence of adverse effects of lamivudine was not higher in the mothers than in controls (P = 0.97). Only one study reported side effects of lamivudine in newborns. Lamivudine treatment in HBV carrier-mothers from 28 wk of gestation may interrupt MTCT of HBV efficiently. Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT. HBV MTCT might be interrupted efficiently if maternal viral load is reduced to < 10⁶ copies/mL by lamivudine treatment.

Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission—a meta-analysis

To evaluate the efficacy and safety of using hepatitis B immunoglobulin (HBIG) during pregnancy to prevent hepatitis B virus (HBV) mother-to-child transmission (MTCT). We systematically reviewed the effect of HBIG in decreasing HBV MTCT from randomized controlled trials (RCTs) carried out between January 1990 and December 2008, in English and Chinese languages. Multiple databases were searched, and experts in this field were contacted. The methodological quality of each RCT was assessed by the Jadad score. We abstracted data on HBV intrauterine infection, MTCT, treatment methods, newborn immune prophylaxis methods, and adverse effects. A Mantel-Haenszel random-effects model was employed for all analyses using odds ratios (OR) and 95% confidence intervals (95% CI). Five thousand nine hundred newborns of asymptomatic hepatitis B surface antigen (HBsAg)-seropositive mothers from 37 qualified RCTs were included. Compared with the control group, newborns in the HBIG group had a lower intrauterine infection rate (indicated by HBsAg as OR 0.22, 95% CI [0.17, 0.29], from 32 RCTs; indicated by HBV DNA as OR 0.15, 95% CI [0.07, 0.30], from 13 RCTs; p<0.01 for both) and a higher protection rate (indicated by hepatitis B surface antibody (HBsAb) as OR 11.79, 95% CI [4.69, 29.61], from 15 RCTs; p<0.01). The same trend was found in MTCT by the time of 9-12 months after birth, indicated by HBsAg (OR 0.33, 95% CI [0.21, 0.51], from nine RCTs; p<0.01) and HBsAb (OR 2.49, 95% CI [1.55, 4.01], from 11 RCTs; p<0.01). HBIG appears to be safe, but a few RCTs have reported adverse events. Multiple injections of HBIG in HBV carrier mothers with a high degree of infectiousness in late pregnancy, effectively and safely prevent HBV intrauterine transmission.

Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus – a systematic review

BackgroundCaesarean section before labor or before ruptured membranes ("elective caesarean section", or ECS) has been introduced as an intervention for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Currently, no evidence that ECS versus vaginal delivery reduces the rate of MTCT of HBV has been generally provided. The aim of this review is to assess, from randomized control trails (RCTs), the efficacy and safety of ECS versus vaginal delivery in preventing mother-to-child HBV transmission.ResultsWe searched Cochrane Pregnancy and Childbirth Group's Trials Register (January, 2008), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2008, issue 1), PubMed (1950 to 2008), EMBASE (1974 to 2008), Chinese Biomedical Literature Database (CBM) (1975 to 2008), China National Knowledge Infrastructure (CNKI) (1979 to 2008), VIP database (1989 to 2008), as well as reference lists of relevant studies. Finally, four randomized trails involving 789 people were included. Based on meta-analysis, There was strong evidence that ECS versus vaginal delivery could effectively reduce the rate of MTCT of HBV (ECS: 10.5%; vaginal delivery: 28.0%). The difference between the two groups (ECS versus vaginal delivery) had statistical significance (RR 0.41, 95% CI 0.28 to 0.60, P < 0.000001). No data regarding maternal morbidity or infant morbidity according to mode of delivery were available.ConclusionECS appears to be effective in preventing MTCT of HBV and no postpartum morbidity (PPM) was reported. However, the conclusions of this review must be considered with great caution due to high risk of bias in each included study (graded C).