Eliminating mother-to-child transmission of hepatitis B virus: practice and progress in Baoan, a national pilot district of China

Hepatitis B virus (HBV) infection is a major global public health issue, affecting an estimated 257 million people worldwide [1]. The prevalence of HBV infection varies greatly among different regions and countries, with the highest rates found in East Asia and sub-Saharan Africa. In these regions, up to 10% of the general population may be infected with HBV, compared to less than 2% in North America and Europe [2].

HBV infection is known to cause liver cirrhosis, liver cancer, and liver failure, resulting in approximately 780,000 global deaths annually [1]. Additionally, those infected with HBV have an increased risk of developing chronic infection, leading to long-term complications and further transmission. In response, the World Health Organization (WHO) has set a global target of reducing the incidence of HBV in children to less than 0.1% by 2030. The successful achievement of this target will require a combination of strategies, such as the implementation of safe and effective vaccines, improved screening and treatment access, and enhanced prevention tactics [3, 4].

Approximately 93 million Chinese are estimated to be infected with HBV, which is about a third of the global HBV burden [1]. The prevalence of HBV infection in the Chinese general population is approximately 7% [5], while chronic HBV carriers account for roughly 6.17% of pregnant women [6]. Mother-to-child transmission (MTCT) is the predominant route of HBV transmission in endemic areas, accounting for about 40–50% of all new HBV infections in China [7].

China’s efforts to combat HBV infection began in 1992 when the hepatitis B vaccine was included into the Expanded Program on Immunization (EPI). The integration of free hepatitis B immunization in 2002 further increased vaccination coverage [8, 9]. These programs have led to a significant reductions in the prevalence of HBV infection among the general population (from 9.2 to 7.2% from 1992 to 2006) and in children under 5 years old (from 0.96 to 0.32% from 2006 to 2014) [9].

In 2010, prevention of MTCT (PMTCT) work was included in the national major public health service project, expanding from solely preventing HIV to integrating strategies to prevent the transmission of HIV, syphilis, and HBV, pioneering a new global effort in PMTCT. In 2015, this important initiative was extended nationwide, ensuring that pregnant women are screened for HBV through hepatitis B surface antigen (HBsAg) and that all HBV-exposed newborns receive free administration of hepatitis B immunoglobulin (HBIG) and hepatitis B birth dose vaccine (HepB-BD) within 24 hours of birth [10, 11]. In addition, the Chinese government endorsed the 2018–2030 Asia Pacific Regional Framework for triple elimination of MTCT (EMTCT) of HIV, syphilis, and HBV in 2017, to further improve the public health system’s efforts to tackle HBV infection in China and the Asia-Pacific region [3].

Although China has made significant progress in the PMTCT of HBV in recent years, numerous challenges persist. For instance, HBV DNA testing and antiviral therapy (ART) services for HBsAg positive pregnant women need to be enhanced, and the coverage of post-vaccination serological testing (PVST) for HBV-exposed children must be increased [12]. To effectively address these challenges, extensive measures need to be implemented and carefully evaluated, particularly in high-burden areas. In September 2017, the National Health and Family Planning Commission of China launched a pilot project in Zhejiang, Guangdong, and Yunnan provinces [13], with the aim of identifying effective models for the EMTCT of HIV, syphilis and HBV in China. Baoan district, located in Shenzhen, Guangdong province, was selected as one of six pilot counties/districts [14], and was subsequently chosen for comprehensive intervention with the goal of achieving “Zero” transmission of HBV from mother-to-child in Guangdong province [15]. Baoan was appointed as a pilot area primarily because of its high prevalence of HBsAg positive among pregnant women (9.06% during 2015–2019) [16]. Additionally, Baoan has exhibited strong policy support for the implementation of interventions for all pregnant women with HBV infection.

This paper aims to evaluate the effectiveness of interventions implemented in Baoan and assess their reference for HBV prevention and control in China. Through an analysis of outcomes from the pilot initiative, the paper seeks to identify strategies that could be adopted to further improve the EMTCT of HBV in other high-burden regions of the country.

This study highlights significant progress in the implementation of comprehensive interventions for HBV EMTCT in Baoan district. As of 2022, 86.42% of pregnant women received early HBV screening, and over 90% of high-risk infected pregnant women received ART. The coverage of timely administration of HBIG and HepB-BD exceeded 98%, and the rate of HBV MTCT reached a record low of 0% in 2021. All national targets for the validation of HBV EMTCT have been successfully achieved, except for the coverage of PVST among high risk infants for MTCT, which currently stands at 56.15%, falling below the the target of at least 90% (Supplementary Table S5).

Despite a decreasing trend in the prevalence of maternal HBV infection in Baoan district, the current prevalence rate of 7.65% in 2022 remained relatively high when compared to the national level of 5.44% in 2020 [6]. Our findings demonstrated that maternal HBV infection in Baoan fell within the higher intermediate endemic range, which could be attributed, in part, to the historically high prevalence of HBV infection in Guangdong province. National surveys conducted in 1979 [24] and 1992 [8] among the general population reported high rates of HBV infection during the time when the women in our study were born. Notably, however, our estimate is lower than the average prevalence rate of 9.84% in 2020 reported in Guangdong province [6], which had been a long-standing high endemic region for HBV infection. The high mobility of the population in Baoan, as observed in our study, where 42.62% of HBsAg positive pregnant women originated from other provinces, partly explained this finding. Our observation supported the notion of a mixed endemic mode observed at the provincial or county level [25].

In China, EMTCT has been integrated with ANC services for pregnant women, As part of this integration, free rapid HBV screening is provided at every maternal and child health institution. However, in Baoan district, there is a challenge as some pregnant women still opt out of the free HBV screening due to the merging of free and paid services that occurs after establishing their ANC records. To address this issue, Baoan introduced the policy of “screening first, ANC registration second” in May 2018, which aims to improve screening compliance among pregnant women by identifying infections early and provide timely intervention. As a result, our study found an annual increase of 18.88% in the coverage of HBV early screening from 2018 to 2022, which, in turn, led to an increase in coverage of ART among high-risk women.

High viral load HBV infection is often observed in HBeAg positive women and increases the risk of transmission, despite vaccine prophylaxis and HBIG [26]. Antiviral prophylaxis provision has been recommended as an additional protective measure for infants born to mothers with high HBV DNA levels [26]. In 2018, Chinese experts issued guidelines suggesting that pregnant women with a viral load ≥2*10⁶IU/ml be offered TDF from week 28 of pregnancy to further reduce the risk of vertical HBV transmission [22]. Later, the viral load threshold was lower to 2*10⁵IU/ml [27]. However, the HBV viral load testing rate among HBsAg positive pregnant women is very low, likely due to the cost of the test or the lack of clear testing requirements. According to the cooperative China-WHO pilot project conducted in eight counties in four provinces of China, the HBV DNA testing rate was < 1% among HBV infected mothers [28].

Baoan serves as a typical example where routine HBV DNA testing for pregnant women with HBV infection was not conducted prior to the initiation of the EMTCT pilot project. Furthermore, infected pregnant women had to be referred to the Hepatology department for treatment, leading to low treatment compliance and high loss to follow-up. To tackle these problems, Baoan established the E clinic within the obstetrics department of all midwifery hospitals in November 2018. This clinic operates as an integrated platform that combines the management of maternal infectious diseases with antenatal care, providing one-stop free-of-charge services for pregnant women infected with hepatitis B. The services offered include viral load testing, ART, guidance on delivery methods and breastfeeding, as well as regular antenatal check-ups and follow-up throughout the entire pregnancy. Notably, our study revealed a significant annual increase of 11.90% in ART coverage among high-risk women from 2019 to 2022, which can be attributed to the successful implementation of the E clinic service mode.

The E clinic model has been recognized as the best practice for EMTCT by the World Health Organization and China. It has also been included in the Training Hub of Maternal and Child Health (MCH) for Belt and Road Initiative (BRI) Countries, as well as the EMTCT Action Plan in Guangdong Province from 2023 to 2025. Since March 2023, this model has been promoted and implemented across the entire province, resluting in the esatblisment of the E clinic in 100 MCH institutions as of December 1, 2023.

The American Academy of Pediatrics recommends administering both HBIG and HepB-BD within 12 h of birth [29] to ensure timely HBV post-exposure prophylaxis. China updated its national guidelines in 2020 from within 24 h of birth to within 12 h [30]. In this aspect, Baoan has pioneered the “immediate immune next to bedside” strategy since January 2018. Delivery hospitals provide free HepB-BD and HBIG to newborns who were exposed to HBV immediately in the delivery room or operating room. This has resulted in 98.61% timely HBIG coverage and 99.16% timely HepB-BD coverage.

PVST is a valuable tool for determining the HBV infection status and confirming the efficacy of the hepatitis B vaccine in HBV-exposed children. It is noteworthy that both the WHO and the US Center for Disease Control and Prevention (CDC) presently recommend PVST for infants born to HBsAg positive mothers [31‐33]. In China, PVST began in 2016 [34] and was subsequently integrated into the updated national iPMTCT guidelines in 2020 [23]. Baoan initiated free follow-up and PVST in May 2018. Unfortunately, the coverage of PVST for HBV-exposed infants in Baoan remained below 60%, which was lower than the reported 65.6% PVST coverage in four provinces of China in 2014 [35] and 67.08% in Zhejiang province between 2016 and 2020 [36].

It is noteworthy that, in contrast to PVST pilot provinces where refuse/failure of blood collection was reported as the primary cause of loss to follow-up (53.2%) [34], the lack of awareness of PVST among guardians (56.73%) was the main reason for non-compliance in Baoan district. Specifically, this refers to not knowing (44.71%), forgetting (10.68%) and not having enough time (1.34%) for the test. As PVST for HBV-exposed infants should be performed at no earlier than 6 months of age, the effectiveness of health education at the time of maternal discharge is greatly diminished due to the intervening period. This underscores the necessary for Baoan to focus on targeted publicity and education efforts aimed at raising awareness and ensuring compliance among guardians of HBV-exposed infants.

Our study findings support previous research by indicating that a lower maternal education level is a risk factor for MTCT of hepatitis B (OR = 3.76; 95%CI 1.04 ~ 13.60) [37]. This underscores the importance of targeted health education programs and interventions aimed at improving maternal knowledge and awareness of HBV transmission and prevention, particularly in vulnerable populations. However, it should be noted that low education level may not directly contribute to the risk but rather serve as an indicator for other underlying factors. These factors may include limited knowledge and awareness about MCH, restricted access to testing and treatment options, and socioeconomic pressures that impede optimal management of the infection. Therefore, caution must be exercised when interpreting our findings. Further research and comprehensive data collection are needed to gain a better understanding of the relationship between low education level and HBV MTCT.

Additionally, our study also indicated that infants born to HBeAg positive mothers are at greater risk of HBV MTCT (OR = 18.89; 95%CI 1.98 ~ 18.50). This discovery is consistent with previous studies that had established a correlation between maternal HBeAg positivity, higher levels of HBV replication, and intrauterine transmission of HBV [38]. The national guidelines for PMTCT of HBV (2020 edition) [23] recommend the use of HBeAg positivity as an alternative indicator for the administration of antivirals in HBsAg positive pregnant women. Therefore, HBeAg testing may be a convenient substitute for guiding ART in underdeveloped regions where routine HBV DNA testing may not be readily available.

In summary, this study highlights the value and significant outcomes resulting from the implementation of a comprehensive prevention strategy targeting the reduction of Hepatitis B MTCT in Baoan district, China. The establishment of a regional, multi-institutional management mechanism and the introduction of the E clinic have provided valuable insights and practical evidence for other regions to learn from. However, challenges remain, especially regarding the suboptimal coverage of PVST for HBV-exposed infants. Further research is warranted to identify and implement targeted interventions and strategies for the ultimate goal of eliminating MTCT of Hepatitis B, not only in Baoan district, but also in other areas within China and globally.