Gaps in the prevention of perinatal transmission of hepatitis B virus between recommendations and routine practices in a highly endemic region: a provincial population-based study in China

During August 2002 to July 2004, serum samples from 19 904 pregnant women aged 20–42 years, at 15–20 weeks of gestation, from 6 cities (urban) and 8 counties (rural area) across Jiangsu Province, China, were collected in a study on the provincial prevalence of birth defects [13]. The samples were stored at −30°C. These pregnant women had been selected to represent the pregnant women population in Jiangsu and all delivered their infants in hospitals. Jiangsu Province is located in the east of China, and is one of the six financially prosperous provinces in China and has the densest population with more than 76 million inhabitants. There are approximately 500 000 live births per year. Recently, we retrospectively measured the HBV serologic markers in the 6398 sera, which were randomly selected from above samples, and 429 (6.7%) were positive for hepatitis B surface antigen (HBsAg) [14]. Of the 429 HBsAg positive sera, 10 were negative for antibody against hepatitis B core antigen (anti-HBc) and either hepatitis B e antigen (HBeAg) or anti-HBe. The positivity of HBsAg in these 10 samples was validated by retesting with Architect HBsAg Reagents (Abbott, North Chicago, USA) and by detection of HBV DNA [14]; we speculated that these 10 women were in the incubation period of HBV infection when the sera were collected. Thus, we excluded these 10 women from the study and planned to follow up the children of 419 HBsAg positive women, of whom 125 (29.8%) were also positive for HBeAg [14]. Because of the “one family one child policy” in China, the target population was the 419 children born from February 2003 to December 2004 (Figure 1). As control subjects, 453 children born to HBsAg negative mothers in the same areas and same period of time were randomly selected (Figure 1).

During October 2009 and March 2010, we invited these mothers and their children to participate in the present investigation as an “add-on” part of the project on the provincial prevalence of birth defects [13]. Each attending mother was asked to complete a questionnaire, which included demographic data of the mother and her child, screening for HBsAg during pregnancy, and use of hepatitis B vaccine and HBIG in the child. Nearly half of the HBsAg screening in pregnant women and the HBIG administration in infants were validated by checking the hospital discharge records. The use of hepatitis B vaccine was evidenced in 83.7% children by the vaccination record cards. Furthermore, ~3 ml of blood was collected from each child after obtaining the consent from the child’s mother.

This study followed the ethical guidelines of the Declaration of Helsinki, and was approved by the institutional review boards of Nanjing Drum Tower Hospital and Jiangsu Family Planning Institute. The pregnant women consented to participate in the birth defect study conducted from August 2002 to July 2004 [13] and their serum samples were used in this study; the mothers consented to be interviewed and consented to their children's participation in this follow-up study.

All serum samples were tested by commercial ELISA kits for the presence of HBsAg, antibody to HBsAg (anti-HBs), and anti-HBc. HBsAg was tested with an ELISA kit (Huakang Biotech, Shenzhen, China), and anti-HBs and anti-HBc were quantitatively tested with microparticle enzyme immunoassay (AxSYM AUSAB, Abbott, North Chicago, USA). Quantitative levels of anti-HBs were expressed in international units.

HBV infection was defined by the presence of HBsAg. The presence of anti-HBc in the absence of HBsAg represented resolved HBV infection. Timely vaccination referred to receipt of the first dose of the vaccine within 24 hours after birth.

Data were analyzed using SPSS version 13 (SPSS Inc., Chicago, USA). Statistical comparisons of continuous variables between maternal HBsAg positive and negative groups were analyzed by t-test. A χ ² test was used to analyze and compare categorical data. A P value of <0.05 was considered statistically significant.

Of the 419 invited mothers with positive HBsAg, 298 (71.1%) mothers and their children participated in the study, while 328 (72.4%) of the 453 invited mothers who were negative for HBsAg and their children attended the investigation (Figure 1); the follow-up rates were comparable in these two groups (P > 0.05). Additionally, the follow-up rate of children born to HBV carrier mothers with positive HBeAg was also similar to that of children of carrier mothers with negative HBeAg (72.0% vs. 70.7%, Figure 1). The demographic data, vaccination coverage, status of HBV infection, and anti-HBs responses in children are shown in Table 1. Almost all infants in the both groups were vaccinated and the positive rates of anti-HBs were comparable. Of the children born to HBsAg positive mothers, 11 (3.7%) were HBsAg positive, demonstrating the HBV infection, and 16 (5.4%) were HBsAg negative but anti-HBc positive, indicating past resolved infection, whereas none of the children born to HBsAg negative mothers was infected with HBV and only 0.9% had the resolved infection.

Since recommended immunoprophylaxis against hepatitis B in infants born to HBsAg positive mothers requires the timely use of hepatitis B vaccine and HBIG, we particularly paid attention to collecting the data about the preventive measures used in the routine practices (Table 2). Although prenatal HBsAg screening is recommended for all pregnant women in China, the test was not done in nearly a third of the pregnant women in cities and more than half in rural areas. Consequently, only 37.6% of the HBV-exposed infants received HBIG after birth, and the use of HBIG in HBV-exposed infants was less frequently in rural areas than in cities (55.7% vs. 32.0%, P <0.001). In other words, 62.4% of the infants born to HBV carrier mothers were not administered with HBIG in Jiangsu Province from February 2003 to December 2004. This was a substantial gap in the prevention of HBV infection. Additionally, the first dose of the vaccine was delayed in 15.1% of the HBV-exposed infants.

Of the 298 children born to HBV carrier mothers, 11 were infected with HBV and 16 experienced resolved infections (Table 1). To clarify the factors responsible for the infections, we analyzed the HBeAg status in their mothers and the immunoprophylactic measures used in these children. All 11 children infected with HBV and 12 of 16 children with the resolved infection were born to HBeAg positive mothers. These results are in agreement with the previous reports that children born to HBV carrier mothers with positive HBeAg are much more frequently to be infected than those born to HBeAg negative HBV carrier mothers [15, 16]. On the other hand, of the 11 children infected with HBV, only one received timely administration of both HBIG and hepatitis B vaccine, and 10 others did not receive HBIG or received delayed hepatitis B vaccine (Table 3). Of the 16 children with the resolved infections, 9 were not administered with HBIG and one was given the first dose of vaccine 40 days after birth (Table 3). The results demonstrated that the infections in children born to HBV carrier mothers were mostly attributed to the inadequate implementation of the immunoprophylaxis.