Prevalence of hepatitis B virus infection among pregnant women in the mountainous regions of southern China: A retrospective single‐center study

Abstract Background Hepatitis B virus (HBV) infection remains a major public health issue worldwide. Moreover, its prevalence varies significantly in different geographic areas of China. The current study aimed to assess the prevalence of HBV infection among Hakka pregnant women in Meizhou, a remote mountainous region in southern China. Methods This research was performed between January 2015 and December 2020. In total, 16,727 pregnant women receiving antenatal care at Meizhou People's Hospital were included in the analysis. All pregnant women were screened for serum HBV markers. Results The prevalence rates of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody positivity among the participants were 11.74% (n = 1964) and 48.00% (n = 8029), respectively. The overall prevalence rates of susceptibility to infection, HBV immunity, previous/occult infection, inactive HBsAg carrier, and active infection were 36.16%, 33.61%, 16.94%, 8.11%, and 2.30%, respectively. According to age distribution, the prevalence rate of HBsAg positivity elevated concomitantly with increasing age (p < 0.001). From 2015 to 2020, the prevalence rate of HBsAg positivity decreased from 14.50% to 8.19% and that of hepatitis B pre‐core antigen positivity from 4.42% to 2.31%. In addition, pregnant women with HBsAg‐positive status were more likely to present with gestational diabetes, thrombocytopenia, and anemia than those with HBsAg‐negative status. Conclusion The HBV infection rate remains high among pregnant women in the indigenous Hakka population in southern China. To prevent vertical transmission, cautious surveillance of maternal HBV infection status should be considered in Hakka pregnant women in Meizhou.


Hepatitis B virus (HBV) infection remains a major public health issue
posing a substantial socioeconomic burden. Globally, approximately 2 billion people have serologic evidence of previous or current infection with HBV, and more than 257 million have chronic HBV infection. 1 Importantly, patients with HBV who are chronic carriers are at higher risk of progression to infection-related long-term sequelae such as chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and even death. 2 In addition, the global prevalence of HBV infection varies in terms of geographic region, and it is highly endemic in resource-limited countries, particularly those in East Asia, Sub-Saharan Africa, and Western Pacific regions. 3 In 2016, the World Health Organization committed to eliminating hepatitis B, a major public health threat, by 2030. 4 HBV is transmitted between individuals via percutaneous or mucosal contact with contaminated blood and other body fluids. In highly endemic areas, the predominant route of HBV transmission is mother-to-child transmission (MTCT), accounting for approximately 90% of the global prevalence. Further, approximately 4.5 million women with chronic HBV infection give birth annually. 5 Generally, infants infected with HBV have a 80%-90% risk of progression to a chronic disease state, which further develops to liver cirrhosis and hepatocellular carcinoma in young adulthood. [6][7][8] By contrast, pregnant women with HBV are more likely to present with maternal and neonatal complications including preeclampsia, placenta previa, preterm delivery, placental separation, and gestational diabetes mellitus. [9][10][11] Despite the existence of vaccines, HBV infection remains a major obstacle to public health in China. 12 More than 86 million people are living with chronic HBV infection, and those with infection account for one-third of the infected population worldwide. 13 The overall efficacy rate of combined hepatitis B vaccine and hepatitis B immunoglobulin when used as a preventive strategy ranges from 90% to 95%. However, MTCT still occurs after passive-active immunization, and it has become the major route of HBV infection among Chinese. 14 HBV infection among women of reproductive age and pregnant women is endemic with regional variations. 15 China has a large population, and it has been implementing the national two-child policy since 2016. Therefore, antenatal screening for HBV serologic markers during pregnancy is significantly important in preventing HBV MTCT.
The economic and time costs have traditionally been a barrier that restricts follow-up treatment of MTCT in remote and mountainous areas in China. 16

| Sample collection and testing
In total, 5 ml of blood samples was collected aseptically and centrifuged to separate the serum within 3 h, and all serum specimens were evaluated within 24 h. The HBsAg, hepatitis B surface antibody (HBsAb), hepatitis B pre-core antigen (HBeAg), hepatitis B pre-core antibody (HBeAb), and hepatitis B core antibody (HBcAb) levels were evaluated using the Abbott i2000sr automatic immunoassay analyzer (Abbott Company, the USA). The markers of liver and kidney function were determined using AU5800 Automatic Analyzer (Beckman Coulter, Galway, Ireland). Complete blood count was evaluated using BC6600 plus Analyzer (Beckman Coulter, Galway, Ireland).

| Definition
As shown in Table 1

| Statistical analysis
All statistical analyses were performed using the Statistical Package for the Social Sciences software version 21.0 (IBM Inc., the USA).
Continuous variables were presented as means ± standard deviations and categorical variables as numbers and percentages.
Continuous variables were compared using the t-test for two groups or analysis of variance for more than two groups. Meanwhile, the chi-square test was utilized to analyze and compare categorical data.
A p-value of <0.05 was considered statistically significant.

| RE SULTS
Between January 2015 and December 2020, all pregnant women admitted to the antenatal units were screened. Among them, 2221 were excluded from the study. Figure 1 shows the study flow diagram. Therefore, 16,727 pregnant women were finally included in the analysis. The average age of the participants was 29.1 ± 5.3 years. Table 2 depicts the clinical characteristics of pregnant women. The participants were divided into the HBsAgpositive and HBsAg-negative groups. In total, 1964 pregnant women were HBsAg-positive, with a prevalence rate of 11.74%.
The HBsAg-positive and HBsAg-negative groups significantly differed in terms of age and marital status (p < 0.001). The HBsAg carriers were more likely to present with gestational diabetes (p = 0.011), thrombocytopenia (p < 0.001), and anemia (p = 0.004).
The association between biochemical parameters and different HBV infection statuses of pregnant women is summarized in Table 4. Pregnant women who were inactive HBsAg carriers and those with active infection had significantly higher serum glutamicpyruvic transaminase, glutamic oxaloacetic transaminase, total bile acid, total bilirubin, direct bilirubin, and creatinine levels than those with susceptibility to infection, HBV immunity, and previous/occult infection. In addition, pregnant women who were inactive HBsAg carriers and those with active infection had significantly lower albumin, prealbumin, uric acid, and hemoglobin levels and platelet count.
Laboratory parameters, including alkaline phosphatase, glutamyl transpeptidase, total protein, and globulin levels, did not differ significantly between groups. Table 4 shows the data in detail.

| DISCUSS ION
Despite the provision of vaccines, HBV infection remains a major concern worldwide, particularly in developing countries. 1 The significant progress in antiretroviral treatment caused a remarkable decline in morbidity and mortality associated with HBV infection.
However, HBV can be easily transmitted from mother to child during delivery. Antiretroviral therapy for pregnant women reduces the incidence of MTCT and maternal and child mortality. 14  showed that the prevalence rate of HBsAg positivity in the study area was 11.74%, which was similar to that in Fujian (11.39%) 22 and Anhui (10.39%). 19 However, it was higher than that in Shaanxi (7.07%), 10 Guangdong (7.69%), 18 and Zhejiang (5.88%). 23 30 Our research showed that the prevalence of HBV among pregnant women is high in Meizhou.

TA B L E 4 Association between biochemical parameters and different HBV infection statuses in pregnant women
Moreover, this further supports the notion that the prevalence of  of age may be correlated with the progressive loss of protective antibody levels against HBsAg over time. However, the seropositive rate of HBsAg or the prevalence of HBeAg decreased over time.
Notably, as there was a continuous decrease in positivity rates, our study population was assumed to benefit from routine immunization against HBV infection that was rolled out to infants and neonates in China. Nevertheless, the high prevalence rate of HBV in our study population remains a significant concern. This emphasizes the need for continuous routine antenatal HBsAg assessment among pregnant women and the implementation of appropriate measures during childbirth to reduce transmission.
The association between HBV serological outcomes and maternal complications has been contrasting. 9 pregnant women with HBV infection had a threefold increased risk for anemia compared with those with human immune viruspositive status but without HBV infection. 45 One large cohort study has found a strong association between HBV infection and incident thrombocytopenia. 46 Early detection of hepatitis B virus infection before pregnancy should be considered in clinical practice, and cautious surveillance must be performed.
The current study had several limitations that should be acknowledged. That is, it was a single-center, hospital-based, retrospective study. Therefore, selection bias might have existed, and its capability of inferences was limited. Second, data about vaccination information, educational level, monthly income, and occupation among pregnant women were not collected. Third, follow-up analysis of maternal and neonatal outcomes was not performed. surveillance of maternal HBV infection status should be recommended, and immunization programs must be strengthened.

ACK N OWLED G M ENT
We want to express our gratitude to all participants in this study.

CO N FLI C T O F I NTE R E S T
The authors declare no competing interests.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data are available upon request from the corresponding author.