ABSTRACT
Guangdong Province in China is endemic for hepatitis B virus (HBV) infection with a high prevalence of chronic HBV infection in pregnant women. Measures have been taken to reduce mother-to-child transmission (MTCT) of HBV. This study aims to analyze the trends in these preventive measures in hepatitis B surface antigen (HBsAg)-positive pregnant women from 2021 to 2023. Data were obtained from the case report forms of HBsAg-positive pregnant women and their newborns that were completed and reported in Guangdong Province through the Information System of the National Integrated Prevention of Mother-to-Child Transmission of HIV, syphilis and hepatitis B Programme from January 1, 2021, to December 31, 2023. The Cochran–Armitage test was employed to analyze trends in maternal hepatitis B e antigen (HBeAg) positivity rates across different age groups of pregnant women, antiviral treatment rates in the total and HBeAg-positive populations, and the coverage of timely birth dose of the hepatitis B vaccine (HepB-BD) and hepatitis B immunoglobulin (HBIG) among infants born to the total and HBeAg-positive pregnant women from 2021 to 2023. A total of 283,959 HBsAg-positive pregnant women and their newborns were included in the study. The HBeAg positivity rate among the HBsAg-positive pregnant women was 26.1%. The prevalence of HBeAg positivity among HBsAg-positive pregnant women in Guangdong Province experienced a declining trend from 2021 to 2023. Over the same period, the uptake of antiviral treatment increased in both the overall population and the HBeAg-positive subgroup, with the proportion of HBeAg-positive pregnant women receiving antiviral therapy rising from 23.8% in 2021 to 51.8% in 2023. The proportion of HBV-exposed newborns receiving both HepB-BD and HBIG within 12 hours of birth also increased steadily, with coverage exceeding 97% in 2023. This study highlights significant progress in reducing MTCT of hepatitis B in Guangdong Province from 2021 to 2023. HBeAg positivity among HBsAg-positive pregnant women declined, while both the uptake of antiviral therapy and the timely administration of HepB-BD and HBIG to HBV-exposed infants improved markedly. These findings underscore the important role of public health interventions while emphasizing the need for sustained efforts, particularly for young HBeAg-positive pregnant women.
KEYWORDS: Hepatitis B virus, pregnant women, mother-to-child transmission, antiviral therapy, real-world study
Introduction
Hepatitis B virus (HBV) infection remains a significant public health challenge globally, with approximately 254 million people living with chronic hepatitis B and an estimated 1.1 million deaths in 2022.1,2 Despite China’s successful efforts in reducing the hepatitis B surface antigen (HBsAg) positivity rate in the general population from 9.72% in 1992 to 5.86% in 2020, largely due to extensive vaccination campaigns and public health interventions over recent decades, around 79.75 million individuals still live with chronic hepatitis B in 2022.3,4 Notably, mother-to-child transmission (MTCT) is the primary mode of transmission in HBV-endemic regions, with a 90% risk of developing chronic HBV infection.5 Preventing MTCT is therefore pivotal to achieving the goal of hepatitis B elimination by 2030.
Universal infant immunization, including the administration of a birth dose of the hepatitis B vaccine (HepB-BD), is the most effective strategy for preventing chronic HBV infection.6 By 2022, 98% of countries worldwide have implemented universal infant vaccination against hepatitis B, achieving an 84% coverage rate for the three- to four-dose series.7 In addition, the prompt administration of hepatitis B immunoglobulin (HBIG) to exposed newborns provides passive immunization, which significantly reduces the risk of MTCT of HBV.8 Updated clinical guidelines released in 2020, along with national programs targeting the prevention of MTCT of human immunodeficiency virus, syphilis, and HBV, recommend that all infants born to HBsAg-positive mothers receive HBIG and HepB-BD as soon as possible, preferably within the first 12 hours of life.9 Despite these measures, the risk of MTCT is not entirely eliminated.10 A systematic review suggests that antiviral treatment for pregnant women infected with HBV can further reduce the risk of MTCT.11 Clinical guidelines in China recommend initiating antiviral therapy with tenofovir for pregnant women with high viral loads – defined as an HBV DNA level of >200,000 IU/mL or hepatitis B e antigen (HBeAg) positivity – between 24 and 28 weeks of gestation.12,13 HBeAg is a critical serum marker of HBV infection, reflecting high levels of viral replication and infectivity. In regions where HBV DNA testing is unavailable, HBeAg serves as a practical alternative for determining eligibility for antiviral prophylaxis.14
Guangdong Province, situated in southern China, is the most populous province in China and has a high prevalence of HBV infection, contributing more than 12% of the national disease burden.15 A survey conducted in the Pearl River Delta region of Guangdong Province revealed that the prevalence of HBsAg among the general population was 8.76%.16 This study investigates trends in interventions to prevent MTCT of HBV among HBsAg-positive pregnant women in Guangdong Province from 2021 to 2023, assessing the important role of these measures to inform future public health policies.
Materials and methods
Study design
Data were collected from the case report forms of HBsAg-positive pregnant women and their newborns that were completed and reported in Guangdong Province through the Information System of the National Integrated Prevention of Mother-to-Child Transmission of HIV, syphilis and hepatitis B Programme, covering the period from January 1, 2021, to December 31, 2023.17 The pregnant women were categorized into four age groups (<25 y, 25–30 y, 30–35 y, and ≥35 y). Additionally, data regarding interventions to prevent MTCT were collected, which included the administration of HepB-BD, the type of hepatitis B vaccine used, HBIG for infants, as well as antiviral treatments and medications prescribed to pregnant women. The infants were classified into four groups based on HepB-BD and HBIG treatment: those who received both HepB-BD and HBIG within 12 hours, only HBIG within 12 hours, only HepB-BD within 12 hours, and both treatments after 12 hours. The HBsAg and HBeAg levels in pregnant women were assessed using enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay, or colloidal gold immunochromatography. Because the coverage of HBV DNA testing in routine practice was low, information on HBV DNA levels was unavailable for most pregnant women, and therefore HBeAg status was used as a pragmatic proxy for high viral load in this real-world setting, in line with WHO recommendations.
Statistical analysis
Data cleaning and analysis were performed using R software (version 4.4.2). Count data were expressed as frequencies. The Cochran-Mantel-Haenszel (CMH) test was used to assess differences in HBeAg positivity rates across different age groups from 2021 to 2023. The Cochran–Armitage test was employed to analyze trends over the period 2021–2023 in maternal HBeAg positivity rates across different age groups, antiviral treatment rates in the total and HBeAg-positive pregnant populations, and the coverage of timely HepB-BD and HBIG among HBV-exposed infants born to the HBeAg-positive and total HBsAg-positive pregnant women. Wilson’s method was used to calculate 95% confidence intervals.18 Two-sided tests were conducted with a significance level set at alpha = 0.05.
Results
Basic characteristics of participants
Our study included 283,959 HBsAg-positive pregnant women and their newborns from 2021 to 2023 (Table 1). Among these women, 75.4% were under the age of 35. The HBeAg positivity rate among the pregnant women was 26.1%. During pregnancy, 12.5% of the women received antiviral treatment, with tenofovir being the predominant choice (93.6%). Notably, the median gestational age at initiation of antiviral treatment was 26 weeks. According to current guidelines recommending initiation at 24–28 weeks of gestation, 39.1% of women receiving antiviral therapy started treatment earlier than 24 weeks and 45.3% started after 28 weeks, indicating that the majority received therapy outside the recommended window. Among HBV-exposed infants, the coverage of HepB-BD and HBIG without antiviral treatment was high at 87.1%, 12.5% received HepB-BD and HBIG with antiviral treatment, and 0.1% received none of the three.
Table 1.
Basic characteristics of HBsAg-positive pregnant women and their infants in Guangdong Province, 2021–2023.
| Variable | 2021 | 2022 | 2023 | Total |
|---|---|---|---|---|
| Overall, n | 105019 | 93829 | 85111 | 283959 |
| Age, n (%) | ||||
| <25 | 8943 (8.5) | 6185 (6.6) | 4229 (4.97) | 19357 (6.8) |
| 25–30 | 34083 (32.5) | 27976 (29.8) | 23593 (27.7) | 85652 (30.2) |
| 30–35 | 39154 (37.3) | 36133 (38.5) | 33865 (39.8) | 109152 (38.4) |
| ≥35 | 22839 (21.8) | 23534 (25.1) | 23423 (27.5) | 69796 (24.6) |
| HBeAg-positive, n (%) | 28327 (27.0) | 24484 (26.1) | 21215 (24.9) | 74026 (26.1) |
| Received HepB-BD at birth, n (%) | ||||
| Yes | 104249 (99.3) | 93570 (99.7) | 84933 (99.8) | 282752 (99.6) |
| No | 611 (0.6) | 250 (0.3) | 159 (0.2) | 1020 (0.4) |
| Treatment type, n (%) | ||||
| HepB-BD | 39 (0.0) | 34 (0.0) | 14 (0.0) | 87 (0.0) |
| HBIG | 388 (0.4) | 111 (0.1) | 66 (0.1) | 565 (0.2) |
| ART | 13 (0.0) | 20 (0.0) | 18 (0.0) | 51 (0.0) |
| HepB-BD+HBIG | 95355 (90.8) | 81615 (87.0) | 70210 (82.5) | 247180 (87.1) |
| HBIG+ART | 27 (0.0) | 9 (0.0) | 7 (0.0) | 43 (0.0) |
| HepB-BD+ART | 5 (0.0) | 3 (0.0) | 0 (0.0) | 8 (0.0) |
| HepB-BD+HBIG+ART | 8850 (8.4) | 11918 (12.7) | 14709 (17.3) | 35477 (12.5) |
| none | 183 (0.2) | 110 (0.1) | 68 (0.1) | 361 (0.1) |
| Gestational week when received ART, n (% of mothers receiving ART) | ||||
| <24 weeks | 3533 (39.7) | 4591 (38.4) | 5794 (39.3) | 13918 (39.1) |
| 24–28 weeks | 1515 (17.0) | 1972 (16.5) | 2059 (14.0) | 5546 (15.6) |
| 28–32 weeks | 2975 (33.4) | 4420 (37.0) | 5732 (38.9) | 13127 (36.9) |
| ≥32 weeks | 879 (9.9) | 969 (8.1) | 1156 (7.8) | 3004 (8.4) |
| Class of antiviral drugs, n (% of mothers receiving ART) | ||||
| Tenofovir | 8058 (90.5) | 11170 (93.5) | 14095 (95.6) | 33323 (93.6) |
| Telbivudine | 491 (5.5) | 457 (3.8) | 337 (2.3) | 1285 (3.6) |
| Lamivudine | 30 (0.3) | 34 (0.3) | 26 (0.2) | 90 (0.3) |
| Others | 323 (3.6) | 291 (2.4) | 283 (1.9) | 897 (2.5) |
Data are presented as n (% of the corresponding column total) unless otherwise specified. For “Gestational week at initiation of ART” and “Class of antiviral drugs,” percentages are calculated among mothers receiving antiviral treatment (n, % of mothers receiving ART).
Abbreviations: HBeAg, hepatitis B e antigen; HepB-BD, birth dose of the hepatitis B vaccine; HBIG, hepatitis B immunoglobulin; ART, antiviral treatment.
Trends in maternal HBeAg positivity rates by age group
The CMH test revealed statistically significant differences in HBeAg positivity rates across age groups (M2 = 929.42, P < .001). Among HBsAg-positive pregnant women, the highest prevalence of HBeAg positivity was observed in the under-25 age group (44.5%), while the lowest was found in women aged 35 and older (16.3%). Notably, the HBeAg positivity rate in the under-25 age group showed a significant increase from 2021 to 2023 (Z = 3.359, P < .001). In contrast, the 25–30 age group maintained a relatively stable positivity rate during this period, ranging from 32.7% to 33.0% (Z = −0.529, P = .597). Conversely, the HBeAg positivity rates in the 30–35 (Z = −2.747, P < .001) and ≥35 (Z = −2.785, P = .002) age groups, as well as in the total population (Z = −10.077, P < .001), showed a declining trend from 2021 to 2023 (Figure 1).
Figure 1.
The maternal hepatitis B e antigen positivity rates among HBsAg-positive women by age group in Guangdong Province, 2021–2023.
Trends in antiviral treatment rates among total and HBeAg-positive pregnant populations
Between 2021 and 2023, 12.5% of pregnant women received antiviral treatment, while the percentage of HBeAg-positive pregnant women receiving treatment was 35.9%. Notably, the proportion of pregnant women receiving antiviral therapy in both groups showed an upward trend over the specified period. The overall percentage of pregnant women receiving antiviral therapy increased significantly from 8.5% in 2021 to 17.3% in 2023 (Z = 57.933, P < .001). Moreover, the proportion of HBeAg-positive pregnant women receiving antiviral therapy rose markedly, from 23.8% in 2021 to 51.8% in 2023 (Z = 64.311, P < .001) (Figure 2).
Figure 2.
The antiviral treatment rates in the HBeAg-positive and total HBsAg-positive pregnant populations in Guangdong Province, 2021–2023.
Abbreviation: HBeAg, Hepatitis B e antigen.
Trends in the coverage of timely HepB-BD and HBIG among HBV-exposed infants
The coverage of newborns receiving both the HepB-BD and HBIG within 12 hours was 93.5%, while 5.2% received HBIG alone and 0.3% received HepB-BD alone within the same timeframe. Additionally, 0.5% of newborns received both treatments after 12 hours. Among newborns born to HBeAg-positive mothers, 93.2% received both HepB-BD and HBIG within 12 hours, 5.4% received HBIG within 12 hours, 0.2% received HepB-BD, and 0.6% received both treatments after 12 hours.
There was a significant increase in the proportion of newborns receiving both the HepB-BD and HBIG within 12 hours of birth, rising from 87.7% in 2021 to 97.9% in 2023 (Z = 91.992, P < .001). A similar trend was observed among HBeAg-positive mothers, with rates increasing from 87.4% in 2021 to 98.1% in 2023 (Z = 48.624, P < .001) (Figure 3).
Figure 3.
The coverage of timely HepB-BD and HBIG among infants born to HBeAg-positive and total HBsAg-positive pregnant women in Guangdong Province, 2021–2023.
Abbreviations: HBeAg, Hepatitis B e antigen; HepB-BD, hepatitis B vaccine; HBIG, hepatitis B immunoglobulin.
Discussion
In our study, it was observed that HBV-exposed neonates in Guangdong Province have systematically received the timely HepB-BD and HBIG. This achievement can be attributed to the introduction of universal infant hepatitis B vaccination in 2002, followed by the implementation of a nationwide program in 2011 offering free HBIG administration to all newborns of HBV-infected mothers, with national guidelines updated in 2020 to recommend administration within 12 hours of birth, instead of the previous 24-hour window.19,20 In addition, local health authorities have progressively strengthened provider training, health education, and quality management in perinatal services, which may also have contributed to the observed increasing implementation of these interventions.21,22 There are still regional differences in the timing of antiviral treatment during pregnancy.23 In our study, the largest proportion of pregnant women (39.1%) received antiviral treatment before 24 weeks of gestation. A randomized clinical trial conducted in 2024 indicated that administering HBV vaccination to infants in conjunction with maternal tenofovir treatment initiated at week 16 was found to be non-inferior to initiating maternal tenofovir therapy at week 28 combined with HBIG and HBV vaccinations in terms of preventing MTCT of HBV.24 Moreover, later initiation after 28 weeks remains consistent with some international guidelines and clinical trials that recommend starting tenofovir between 28 and 32 weeks of gestation, with the primary goal of maximizing suppression of maternal HBV DNA at the time of delivery.25,26 This finding provides valuable insight into potential alternatives for earlier intervention, especially in regions where HBIG is not available.
A systematic review calculated the HBeAg positivity rate among HBsAg-positive pregnant women from 2016 to 2021 to be 25.8%, closely aligning with the 26.1% reported in our study.27 The spontaneous loss of HBeAg with advancing age results in a higher prevalence of HBeAg among younger HBsAg-positive mothers and a decrease in the overall HBeAg positivity rate in the HBsAg-positive pregnant population.28,29 Notably, the elevated prevalence of HBeAg positivity among the young maternal population under 25 y old from 2021 to 2023 is likely attributable to Guangdong Province hosting the largest floating population in China, primarily composed of a young labor force.30 Floating populations often experience higher hepatitis B prevalence due to limited access to healthcare services, weakened immunity, and increased opportunities for contact with hepatitis B carriers.31 This trend underscores the necessity for antiviral therapy within this demographic.
The uptake of antiviral therapy among HBsAg-positive pregnant women in Guangdong Province has significantly increased from 2021 to 2023, aligning with recent survey data.32 Furthermore, a larger proportion of HBeAg-positive pregnant women received antiviral therapy compared to the overall pregnant women, aligning with trends reported in previous studies.33 This trend may be attributed to the perception among patients that HBeAg positivity indicates a more severe condition, thereby enhancing their willingness to pursue treatment. However, a gap exists between the current situation and the World Health Organization’s recommendations, which state that HBsAg-positive pregnant women with high HBV DNA levels or positive HBeAg should receive antiviral treatment to minimize the risk of intrauterine transmission.34 A survey conducted among pregnant women with hepatitis B in Zhejiang Province, China, revealed that the primary reason for not receiving medication during pregnancy was apprehension regarding the safety of the medication for the fetus.35 These findings underscore the necessity for further educational initiatives aimed at informing women about the long-term consequences of HBV infection in infants and the importance of preventing MTCT.36 Additionally, the implementation of HBV DNA testing in Guangdong Province was suboptimal, revealing the challenges in real-world settings for obtaining quantitative HBV viral load data and determining eligibility for preventive treatment or testing, particularly in grassroots healthcare facilities. Therefore, HBeAg testing is still the best proxy for identifying the high viral load pregnant women.37
Although these analyses provide a comprehensive understanding of the current situation and progress in reducing MTCT of HBV in Guangdong Province, this study acknowledges several limitations. First, our study may not adequately include cases originating from primary care settings or remote areas. The reported addresses correspond to the locations of the testing facilities rather than the patients’ places of residence or birth. Consequently, these factors may influence the actual prevalence of HBeAg positivity. Second, variations in the test kits used by local hospitals may result in differences in sensitivity and specificity, potentially influencing the reported rates of HBeAg positivity. Third, our routine dataset does not contain complete and reliable information on migrant status for all participants and therefore does not support a robust multivariable analysis including this factor; in addition, although this study examined differences in HBeAg positivity rates across age groups, it did not consider other potential confounding factors, such as maternal lifestyle, nutritional status, socioeconomic status, and health policies pertaining to hepatitis B vaccination.
Conclusion
Our study revealed significant improvements in the prevention of MTCT of HBV in Guangdong Province from 2021 to 2023. The uptake of antiviral treatment for HBeAg-positive women increased substantially, reaching over 50% in 2023. Additionally, the timely administration of HepB-BD and HBIG to HBV-exposed infants showed a marked increase, with coverage rates surpassing 97% by 2023. These trends highlight the important role of ongoing public health efforts and intervention measures in reducing the risk of MTCT of HBV, particularly through timely antiviral treatment and immunization of newborns. Continued efforts are needed to ensure sustained access to these interventions, particularly for young HBeAg-positive pregnant women.
Biographies
Fuqiang Cui serves as Director and Professor in the Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, China. He is chairman of the Hepatitis Prevention and Control Branch of China Vaccine Industry Association, member of the Expert Steering Committee of China Vaccinology Training Project of Bill Gates Foundation, deputy editor of Journal of Medical Virology.
Fenghua Liu serves as Vice Dean at the Guangdong Women and Children Hospital, Guangdong Province, China.
Funding Statement
This work was supported by the National Key Research and Development Program of China [No. 2023YFC2308100].
Disclosure statement
No potential conflict of interest was reported by the author(s).
Consent to publish
The participant has consented to the submission of the research to the journal.
Data availability statement
The datasets analyzed during the current study are not publicly available.
Ethical approval
This study was reviewed by Guangdong Women and Children Hospital, and an exemption from ethical review was granted for the use of public database data.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets analyzed during the current study are not publicly available.