Intrauterine Transmission of Hepatitis B Cannot Be Ruled Out by A Single Negative Hepatitis B e Antigen (HBeAg) Result among Hepatitis B Surface Antigen (HBsAg) - Positive Pregnant Women

Maisuri Tadjuddin Chalid, Tina Dewi Judistiani, Rizalinda Syahril, Rina Masadah, Dwi Bahagia Febriani, Ridha Wahyuni, Turyadi Turyadi, Muh Nasrum Massi


BACKGROUND: The risk factors for intrauterine transmission of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive pregnant women are poorly understood. Numerous factors are considered to be involved, including placental barrier, obstetric environment, high viral load, and positivity of hepatitis B e antigen (HBeAg). This study was conducted to investigate the role of placenta barrier, clinical, and viral factors in intrauterine transmission of HBV.

METHODS: A cross-sectional study was conducted involving 1,353 pregnant women who underwent HBsAg screening. Eighty-four (6.2%) women were detected as HBsAg positive and were examined for HBsAg level, anti-HBs, anti-HBc, HBeAg/hepatitis B e antibody (anti-HBe) status, and HBV DNA presence in cord blood. Quantitative HBV DNA was analyzed using real-time polymerase chain reaction (PCR).

RESULTS: Eighty-four of 1,353 subjects were HBsAg-positive. HBV DNA was positive in 28/84 (33.7%) maternal sera, 19/79 (24.05%) placental specimens, and 9/83 (10.84%) in cord blood. There were significant associations between HBV DNA in maternal serum (p=0.000) and placental tissue (p=0.000) with HBV DNA in the cord blood. No clinical factors were associated with HBV DNA transmission in cord blood. Sixty percent of viral load >5.3 log10 copies/mL were found in the cord blood, of which 43.8% HBeAg positive and 3.1% HBeAg negative.

CONCLUSION: Reduced transmission via compartments established the placenta’s barrier function in mother-to-child transmission. A high maternal viral load and positive HBeAg were risk factors for intrauterine transmission, while negative HBeAg still has the possibility of transmission.

KEYWORDS: mother-to-child transmission, hepatitis B virus, intrauterine

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World Health Organization. Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Geneva: World Health Organization; 2015, article.

World Health Organization [Internet]. Hepatitis B Factsheet: World Health Organization [updated 2023 Jul 18; cited 2023 Aug 1]. Available from:

World Health Organization. Regional Office for the Western Pacific. Regional Framework for the Triple Elimination of Mother-to-child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific, 2018-2030. Manila: WHO Regional Office for the Western Pacific; 2018, article.

Ministry of Health Republic of Indonesia–National Institute of Health Research and Development (NIHRD). National Report on Basic Health Research (RISKESDAS) 2013. Jakarta: Ministry of Health; 2013, article.

Gentile I, Borgia G. Vertical transmission of hepatitis B virus: Challenges and solutions. Int J Womens Health. 2014; 6: 605-11, CrossRef.

Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive–active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat. 2012; 19(2): e18-25, CrossRef.

Cheung KW, Seto MTY, Kan ASY, Wong D, Kou KO, So PL, et al. Immunoprophylaxis failure of infants born to hepatitis B carrier mothers following routine vaccination. Clin Gastroenterol Hepatol. 2018; 16(1): 144-5, CrossRef.

Lin X, Guo Y, Zhou A, Zhang Y, Cao J, Yang M, et al. Immunoprophylaxis failure against vertical transmission of hepatitis B virus in the Chinese population: A hospital-based study and a meta-analysis. Pediatr Infect Dis J. 2014; 33(9): 897-903, CrossRef.

Liu Y, Kuang J, Zhang R, Lin S, Ding H, Liu X. Analysis about clinical data of intrauterine infection of hepatitis B virus. Zhonghua Fu Chan Ke Za Zhi. 2002; 37(8): 465-8, PMID.

Zhang SL, Yue YF, Bai GQ, Shi L, Jiang H. Mechanism of intrauterine infection of hepatitis B virus. World J Gastroenterol. 2004; 10(3): 437-8, CrossRef.

Zhang Z, Li A, Xiao X. Risk factors for intrauterine infection with hepatitis B virus. Int J Gynaecol Obstet. 2014; 125(2): 158-61, CrossRef.

Ministry of Health of the Republic of Indonesia. Indonesia Health Profile. Jakarta: Ministry of Health; 2018, article.

Artarini AA, Nurmalasari DR, Permanasari SC, Riani C, Tjandrawinata RR, Retnoningrum DS. T118N substitution of hepatitis B X protein reduces colony formation of HepG2 cells. Indones Biomed J. 2023; 15(1): 94-9, CrossRef.

Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal immunological adaptation during normal pregnancy. Front Immunol. 2020; 11: 575197, CrossRef.

Dunkelberg JC, Berkley EM, Thiel KW, Leslie KK. Hepatitis B and C in pregnancy: A review and recommendations for care. J Perinatol. 2014; 34(12): 882-91, CrossRef.

Liu J, Xu B, Chen T, Chen J, Feng J, Xu C, et al. Presence of hepatitis B virus markers in umbilical cord blood: Exposure to or infection with the virus? Dig Liver Dis. 2019; 51(6): 864-9, CrossRef.

Guo Z, Shi XH, Feng YL, Wang B, Feng LP, Wang SP, et al. Risk factors of HBV intrauterine transmission among HBsAg-positive pregnant women. J Viral Hepat. 2013; 20(5): 317-21, CrossRef.

Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: A case-control study. J Med Virol. 2002; 67(1): 20-6, CrossRef.

Xu DZ, Yan YP, Zou S, Choi BC, Wang S, Liu P, et al. Role of placental tissues in the intrauterine transmission of hepatitis B virus. Am J Obstet Gynecol. 2001; 185(4): 981-7, CrossRef.

Yu M, Jiang Q, Gu X, Ju L, Ji Y, Wu K, et al. Correlation between vertical transmission of hepatitis B virus and the expression of HBsAg in ovarian follicles and placenta. PLoS One. 2013; 8(1): e54246, CrossRef.

Zhang L, Gui XE, Wang B, Fan JY, Cao Q, Mullane K, et al. 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. BMC Infect Dis. 2016; 16(1): 408, CrossRef.

Sirilert S, Tongsong T. Hepatitis B virus infection in pregnancy: Immunological response, natural course and pregnancy outcomes. 2021; 10(13): 2926. J Clin Med. 2021; 10(13): 2926, CrossRef.

Piratvisuth T. Optimal management of HBV infection during pregnancy. Liver Int. 2013; 33(Suppl 1): 188-94, CrossRef.

Pan CQ, Zou HB, Chen Y, Zhang X, Zhang H, Li J, et al. Cesarean section reduces perinatal transmission of hepatitis B virus infection from hepatitis B surface antigen-positive women to their infants. Clin Gastroenterol Hepatol. 2013; 11(10): 1349-55, CrossRef.

Chen Y, Wang L, Xu Y, Liu X, Li S, Qian Q, et al. Role of maternal viremia and placental infection in hepatitis B virus intrauterine transmission. Microbes Infect. 2013; 15(5): 409-15, CrossRef.

Mavilia MG, Wu GY. Mechanisms and prevention of vertical transmission in chronic viral hepatitis. J Clin Transl Hepatol. 2017; 5(2): 119-29, CrossRef.

Navabakhsh B, Mehrabi N, Estakhri A, Mohamadnejad M, Poustchi H. Hepatitis B virus infection during pregnancy: Transmission and prevention. Middle East J Dig Dis. 2011; 3(2): 92-102, PMID.

Yang J, Zeng XM, Men YL, Zhao LS. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus – a systematic review. Virol J. 2008: 5: 100, CrossRef.

Yang M, Qin Q, Fang Q, Jiang L, Nie S. Cesarean section to prevent mother-to-child transmission of hepatitis B virus in China: A meta-analysis. BMC Pregnancy Childbirth. 2017; 17(1): 303, CrossRef.

Chang MS, Gavini S, Andrade PC, McNabb-Baltar J. Caesarean section to prevent transmission of hepatitis B: A meta-analysis. Can J Gastroenterol Hepatol. 2014; 28(8): 439-44, CrossRef.

World Health Organization. Prevention of Mother-to-child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy. Geneva: World Health Organization; 2020, article.

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016; 63(1): 261-83, CrossRef.

Livingston SE, Simonetti JP, Bulkow LR, Homan CE, Snowball MM, Cagle HH, et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology. 2007; 133(5): 1452-7, CrossRef.

Chalid MT, Turyadi, Ie SI, Sjahril R, Wahyuni R, Nasrum Massi M, Muljono DH. A cautionary note to hepatitis B e antigen (HBeAg)-negative test results in pregnant women in an area prevalent of HBeAg-negative chronic hepatitis B. J Med Virol. 2023; 95(1): e28125, CrossRef.


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