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Background: 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., Methods: 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., Results: 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., Conclusions: Earlier use (within 1 hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives : China has implemented universal hepatitis B vaccination since 2002 and provided charge-free hepatitis B immunoglobulin (HBIG) to infants of HBV-infected mothers since July 2011. We aimed to compare mother-to-child transmission (MTCT) in children born before and since July 2011. Methods : In total, 5,149 children of HBV-infected mothers were tested for HBV markers. Group one contained 1,160 children born during August 2002-June 2011 and group two contained 3,989 children born during July 2011-June 2016. Results : In total, 92 (1.8%, 95% confidence interval [95%CI] 1.4-2.2) children were infected with HBV. None (0%, 95%CI 0.0-0.1) of 3,716 children of mothers with negative hepatitis B e antigen (HBeAg) was infected, whereas 92 (6.4%, 95%CI 5.2-7.8) of 1,433 children of HBeAg-positive mothers were infected (p < 0.0001). Among children of HBeAg-positive mothers, MTCT occurred in 10.3% (19/185) (95%CI 6.3-15.6) in group one and 5.8% (73/1,248) (95%CI 4.6-7.3) in group two (p = 0.02). Conclusions : Implementing charge-free active-passive immunoprophylaxis greatly reduces MTCT of HBV in children of HBeAg-positive mothers, highlighting the importance of timely administration of both hepatitis B vaccine and HBIG to prevent MTCT. The still remaining MTCT suggests that reducing maternal virus load before delivery is an additional important measure.

Background: We aimed to clarify whether presence of hepatitis B virus (HBV) markers in cord blood indicates exposure to or infection with HBV., Methods: We 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., Results: Totally 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 > 10 5  IU/ml in cord blood, four had no infection and three others were infected., Conclusion: 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., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Pregnancy is a unique physiological condition with the cellular immune functions compromised at some extents to allow the mature of growing fetus. Whether pregnancy may influence the replication of hepatitis B virus (HBV) is less studied. The present study aimed to investigate the influence of pregnancy on the replication of HBV and expression of viral antigens by comparing the levels of HBV DNA and viral antigens in pregnant and non-pregnant women., Methods: A total of 727 HBsAg-positive serum samples, collected from 214 pregnant women and 513 non-pregnant women of childbearing age, were included. Based on the pregnancy status, subjects were divided into four groups: nulliparous (n = 158), pregnant (n = 214), 7-12 months postpartum (n = 170), and 2-5 years postpartum (n = 185). The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantitatively measured with microparticle enzyme immunoassay. HBV DNA levels were detected by fluorescent real-time PCR., Results: The median ages of four groups were 25.0, 25.3, 26.2 and 29.3 years, respectively (p < 0.01). HBeAg-positive proportions were 34.2, 33.6, 35.3 and 29.2%, respectively (p = 0.624). HBV DNA levels in HBeAg-positive women were higher than those in HBeAg-negative women (7.88 vs 2.62 log IU/ml, p < 0.001). HBV DNA levels in the four groups with positive HBeAg were 7.8, 7.7, 8.0 and 8.0 log IU/ml, respectively (p = 0.057), while HBsAg titers were 4.4, 4.5, 4.6 and 4.8 log IU/ml (p = 0.086) and HBeAg titers were 3.1, 3.0, 3.1 and 3.0 log S/CO (p = 0.198). In the four groups with negative HBeAg, HBV DNA levels were 2.3, 2.6, 2.5 and 2.8 log IU/ml, respectively (p = 0.085), while HBsAg titers were 3.1, 3.3, 3.3 and 3.0 log IU/ml (p = 0.06)., Conclusions: Serum levels of HBV DNA and viral antigens showed no significant changes in nulliparous, pregnant, and postpartum women, regardless of the HBeAg status. The results indicate that pregnancy has little influence on the replication of HBV and the expression of viral antigens.

Background: China has integrated hepatitis B vaccine into the Expanded Program on Immunization since 2002. We aimed to survey the seroprevalence of and immunity to hepatitis B virus (HBV) in children born from 2002 to 2014 in Jiangsu, China., Methods: Totally 3442 children (M:F=2072:1370) at the age of 7months to 12years (5.5±3.6), from five cities and rural areas across Jiangsu province, were enrolled. Blood samples were measured for HBV markers by ELISA and quantitative microparticle enzyme immunoassay. HBV DNA was tested by real-time PCR and S region was amplified by nested PCR., Results: Twelve (0.35%) children were positive for hepatitis B surface antigen (HBsAg) and 34 (0.99%) were HBsAg negative and positive for antibody against hepatitis B core antigen (anti-HBc). Totally 2542 (73.85%) children had anti-HBs levels ⩾10mIU/ml and 535 (15.54%) with 2-9.9mIU/ml. All 12 HBsAg-positive children had detectable HBV DNA with a mean level of 6.1±1.7logIU/ml (3.3-8.1logIU/ml); 8 were genotype C and 4 were genotype B. No mutation was detected in the a determinant of HBsAg. HBV DNA was not detected in all the 34 children with positive anti-HBc and negative HBsAg., Conclusion: HBsAg prevalence among children in Jiangsu born after the introduction of universal vaccination against hepatitis B has significantly decreased. No mutation of S gene is associated with vaccine failure in the cohort of children., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Hepatitis E has poor outcomes in pregnant women. Superinfection of hepatitis E virus (HEV) in patients infected with hepatitis B virus (HBV) may worsen liver disease., Objectives: To estimate the incidence and seroprevalence of HEV infection among HBV-infected pregnant women, to investigate the transplacental transfer of maternal anti-HEV IgG, and to compare the maternal and neonatal outcomes in anti-HEV positive and negative pregnant women., Study Design: Totally 391 HBV-infected pregnant women were recruited from April 2012 to October 2014. Paired mothers and infants were followed up at an average 9.8 months postpartum. Anti-HEV IgG and IgM were tested by ELISA., Results: Of the pregnant women, none was anti-HEV IgM positive and 42 (10.7%) were IgG positive. At the follow-up, 3 seronegative women converted to anti-HEV IgG positive, with an estimated incidence of 17 per 1000 person-years. No significant differences of gestational age, preterm birth rate, Apgar score and birthweight were observed between newborns of anti-HEV IgG positive and negative mothers. Of the 42 neonates born to anti-HEV IgG positive mothers, 38 (90.5%) had anti-HEV IgG in their cord blood. The neonatal and maternal anti-HEV IgG levels were positively correlated (r=0.827, p<0.05). All infants were negative for both anti-HEV IgM and IgG at the follow-up., Conclusions: HBV-infected pregnant women rarely have novel HEV infection during late pregnancy in Jiangsu, China. Maternal anti-HEV IgG efficiently transfers into the fetuses, and disappears in infants before 10 months old., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The prevalence of occult Hepatitis B virus (HBV) infection in children was considerably varied from 0.1-64% in different reports. In this study we aimed to investigate the prevalence of occult HBV infection among the children born to mothers with positive hepatitis B surface antigen (HBsAg) in Jiangsu, China. Serum samples were collected from 210 children of 207 mothers with positive HBsAg. HBV serological markers were detected by ELISA and HBV DNA was detected by nested PCR. Homology comparison of HBV sequences recovered from the child and mother was used to define the infection. Three children (1.43%) were positive for HBsAg, in whom the HBV pre S and S gene sequence in each child was identical to that in her mother. Of the 207 HBsAg-negative children, nine displayed HBV DNA positive by two nested PCR assays using primers derived from S and C genes. However, the sequence alignment showed that the sequences in each child were considerably different from those in his/her mother. Therefore, the sequences amplified from the children were very likely resultant from the cross-contaminations. Furthermore, the nine children with 'positive HBV DNA' were all negative for anti-HBc, and one had anti-HBs 3.42 mIU/ml and eight others had anti-HBs from 72 to >1000 mIU/ml, indicating that the nine children were less likely infected with HBV. Therefore, none of the 207 HBsAg-negative children of HBV-infected mothers was found to have occult HBV infection. We conclude that the prevalence of occult HBV infection in vaccinated children born to HBsAg positive mothers should be extremely low. We recommend that homology comparison of sequences recovered from the child and mother be used to define the occult HBV infection in children born to HBV infected mothers.

Background: Many clinicians and hepatitis B virus (HBV)-infected pregnant women prefer elective caesarean section (ECS) to prevent mother-to-child transmission of HBV, since some studies found higher transmission of HBV in infants born by vaginal delivery (VD) than by cesarean section. However, other studies showed that ECS does not reduce the risk of being infected with HBV in infants. In this study, we aimed to clarify whether ECS may reduce the risk of mother-to-child transmission of HBV., Methods: Totally 546 children (1-7-year-old) born to 544 HBsAg-positive mothers from 15 cities and rural areas across Jiangsu Province, China, were enrolled. Of these children, 137 (2 pairs of twins) were born to HBeAg-positive mothers; 285 were delivered by ECS and 261 others by VD (one pair of twin in each group). HBV serologic markers were tested by enzyme or microparticle immunoassay., Results: The maternal and gestational ages, maternal HBeAg-positive rates, and children's ages, gender ratios, hepatitis B vaccine coverage and administrations of HBIG were comparable between ECS and VD groups (all p >0.05). The overall prevalence of HBsAg in the 546 children was 2.4%, with 2.5% (7/285) and 2.3% (6/261) in those born by ECS and VD respectively (p = 0.904). Further comparison of chronic HBV infection in the 137 children of HBeAg-positive mothers showed that the HBsAg-positive rates in ECS and VD groups were 10.3% (7/68) and 8.7% (6/69) respectively (p = 0.750), while the mothers had similar HBV DNA levels (2.38 × 106 vs. 2.35 × 106 IU/ml, p = 0.586). Additionally, the overall rate of anti-HBs ≥10 mIU/ml in the children was 71.6%, with 72.3% and 70.9% in those born by ECS and VD respectively (p = 0.717)., Conclusions: With the recommended immunoprophylaxis against hepatitis B, ECS does not reduce the risk of mother-to-child transmission of HBV. Therefore, ECS should not be used in HBsAg-positive pregnant women to prevent mother-to-child transmission of HBV.

Background: Many clinicians do not encourage breastfeeding in hepatitis B virus (HBV) carriers, since HBV DNA can be detected in breast milk and breast lesions may increase exposure of infants to HBV. The aim of this study was to determine whether breastfeeding may add risk for perinatal HBV transmission., Methodology/principal Findings: Totally 546 children (1-7-year-old) of 544 HBV-infected mothers were investigated, with 397 breastfed and 149 formula-fed; 137 were born to HBeAg-positive mothers. All children had been vaccinated against hepatitis B but only 53.3% received hepatitis B immune globulin (HBIG). The overall prevalence of HBsAg+, HBsAg-/anti-HBc+, and anti-HBs (≥10 mIU/ml) in children was 2.4%, 3.1%, and 71.6% respectively. The HBsAg prevalence in breast- and formula-fed children was 1.5% and 4.7% respectively (P = 0.063); the difference was likely due to the higher mothers' HBeAg-positive rate in formula-fed group (formula-fed 49.0% vs. breastfed 15.9%, P<0.001). Further logistic regression analyses showed that breastfeeding was not associated with the HBV infection in the children, adjusting for the effect of maternal HBeAg status and other factors different between the two groups., Conclusions/significance: Under the recommended prophylaxis, breastfeeding is not a risk factor for mother-to-child transmission of HBV. Therefore, clinicians should encourage HBV-infected mothers to breastfeed their infants.