Hepatitis B Immunoprophylaxis rarely prevents molecularly evident subclinical HBV infection in children born to HBsAg-positive mothers
6 affiliations
- 1Department of Hepatology, Clinical School of the Second People's Hospital, Tianjin Medical University
- 2Department of Hepatology, Tianjin Second People’s Hospital
- 3Tianjin Institute of Hepatology
- 4Tianjin Integrated Traditional Chinese and Western Medicine Institute of Infectious Diseases
- 5Department of Obstetrics and Gynecology, Tianjin Second People’s Hospital
- 6Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Science Center, Memorial University of Newfoundland
Abstract
Hepatitis B virus (HBV) remains one of the most life-threatening human pathogens causing chronic hepatitis B and hepatocellular carcinoma in millions of people globally. Protective vaccines are available for decades, but their implementation is not yet universal. Mother-to-child transmission remains the prevailing route of HBV spread. Regardless of antiviral treatment of HBV-infected pregnant woman and neonatal immunoprophylaxis, HBV is transmitted at low levels to newborns as a subclinical (occult) infection at rates ranging from singular cases to the majority of the infant population examined in different centers worldwide. In the current study of 13 mother–child pairs, we applied a high-sensitivity molecular approach validated in previous studies, examination of different compartments of HBV occurrence, and testing of serial samples from infants followed for up to two years after birth to HBV-infected mothers treated or not with anti-HBV agent before parturition. All newborns received standard HBV immunoprophylaxis with HBV vaccine and hepatitis B immunoglobulin supplemented with additional doses of both during follow-up. The data showed that the majority (84.6%) of the children investigated remained HBV reactive during the 24-month follow-up after birth at levels of ≤100 HBV genome copies per microgram of DNA, indicating that the prophylactic protocol was only at a low level (~15%) effective in preventing subclinical occult infection in newborns. Nonetheless, the same protocol inhibited development of overt HBV infection for at least two years after birth. In addition, the sequencing of the 360-bp HBV preS-S genomic fragment revealed homology between infants and umbilical cord blood mononuclear cells that diverged from the corresponding sequences in maternal plasma or peripheral blood cells in 4 of the 5 mother–child pairs examined. These data from the single-center study indicate that subclinical HBV infection in infants born to HBV-infected mothers is far more frequent than that reported and argue that virus transmission to newborns could be an inevitable consequence of maternal infection with HBV. This study also uncovered previously unknown HBV genomic discrepancy between infected mothers and their infants with occult infection suggesting the fetal and/or placental origin of the viral variant detected.
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BibTeX
@article{xu2026hepatitis,
title = {{Hepatitis B Immunoprophylaxis rarely prevents molecularly evident subclinical HBV infection in children born to HBsAg-positive mothers}},
author = {Liang Xu and Qinghai Dai and Huiying Yang and Rui Su and Yanli Shi and Jing Chen and Jing Hao and Jinyu Hao and Tomasz I. Michalak},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1933288},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933288/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hepatitis B Immunoprophylaxis rarely prevents molecularly evident subclinical HBV infection in children born to HBsAg-positive mothers
AU - Liang Xu
AU - Qinghai Dai
AU - Huiying Yang
AU - Rui Su
AU - Yanli Shi
AU - Jing Chen
AU - Jing Hao
AU - Jinyu Hao
AU - Tomasz I. Michalak
PY - 2026
DA - 2026/10/16
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1933288
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933288/full
AB - Hepatitis B virus (HBV) remains one of the most life-threatening human pathogens causing chronic hepatitis B and hepatocellular carcinoma in millions of people globally. Protective vaccines are available for decades, but their implementation is not yet universal. Mother-to-child transmission remains the prevailing route of HBV spread. Regardless of antiviral treatment of HBV-infected pregnant woman and neonatal immunoprophylaxis, HBV is transmitted at low levels to newborns as a subclinical (occult) infection at rates ranging from singular cases to the majority of the infant population examined in different centers worldwide. In the current study of 13 mother–child pairs, we applied a high-sensitivity molecular approach validated in previous studies, examination of different compartments of HBV occurrence, and testing of serial samples from infants followed for up to two years after birth to HBV-infected mothers treated or not with anti-HBV agent before parturition. All newborns received standard HBV immunoprophylaxis with HBV vaccine and hepatitis B immunoglobulin supplemented with additional doses of both during follow-up. The data showed that the majority (84.6%) of the children investigated remained HBV reactive during the 24-month follow-up after birth at levels of ≤100 HBV genome copies per microgram of DNA, indicating that the prophylactic protocol was only at a low level (~15%) effective in preventing subclinical occult infection in newborns. Nonetheless, the same protocol inhibited development of overt HBV infection for at least two years after birth. In addition, the sequencing of the 360-bp HBV preS-S genomic fragment revealed homology between infants and umbilical cord blood mononuclear cells that diverged from the corresponding sequences in maternal plasma or peripheral blood cells in 4 of the 5 mother–child pairs examined. These data from the single-center study indicate that subclinical HBV infection in infants born to HBV-infected mothers is far more frequent than that reported and argue that virus transmission to newborns could be an inevitable consequence of maternal infection with HBV. This study also uncovered previously unknown HBV genomic discrepancy between infected mothers and their infants with occult infection suggesting the fetal and/or placental origin of the viral variant detected.
SN - 1664-302X
ER -