Worldwide, there are about 350 million people with chronic hepatitis B virus (HBV) infection and about one million deaths per year due to chronic hepatitis, cirrhosis, and hepatocellular carcinoma [¹,²]. Mother to child transmission of HBV is the main transmission route and contributes significantly to chronic HBV infection [³].

China used to be an area of HBV high epidemicity. About 10% of infants whose mothers were HBV positive suffered from HBV infection in their early life. It has been reported that the prevalence of Hepatitis B surface antigen (HBsAg) has been reduced from 9.75% in 1992 to 7.18% in 2006 [⁴]. In our study, we aimed to survey chronic HBV infection among pregnant women and their infants in Shenyang, China and analyze the reason for immunoprophylaxis failure.

There are more than 130 million chronic HBV carriers in China, 30%-50% of whom are thought to have acquired HBV infection from mother-to-child transmission [^5-7]. Preventing the mother-to-child transmission route can significantly decrease HBV infection among infants and can relieve the HBV disease burden. In China, 90% of HBV mother-to-child transmission can be prevented by the administration of immunoprophylaxis with HBIG and the hepatitis B vaccine [⁸,⁹]. It has been confirmed that the failure of immunoprophylaxis is mainly associated with maternal seropositivity for HBeAg and high viral load [^10-12]. It is recommended that HBsAg-positive pregnant women who are HBeAg positive and have a high viral load be given antivirals in late pregnancy to suppress virema [^13-15]. Thus, it is important to survey chronic HBV infection among pregnant women and their infants and find other reasons for immunoprophylaxis failure.

There were a total of 4,536 pregnant women aged 16 – 45 years who were enrolled in our study. We showed that the prevalence of HBsAg among pregnant women in Shenyang was 5.49%, which is lower than the overall prevalence of HBsAg among pregnant women in China (8.16%) [¹⁶]. The prevalence of HBsAg, anti-HBc and anti-HBs among pregnant women older than 20 years of age was 4.54, 5.69 and 0.61 times that among pregnant women younger than 20 years, respectively. The difference in prevalence of HBsAg, anti-HBc and anti-HBs between pregnant women older than 20 years versus younger than 20 years of age was significant. This could be related to immunoprophylaxis having been universally administered to infants since 1990, which could improve immunity against HBV and decrease HBV infection among their infants.

Among HBsAg positive pregnant women, the majority were HBeAg positive and HBVDNA positive (67.07% and 81.93%, respectively), a minority (14.86%) had a high viral load. Only 12 (4.82%) infants were HBsAg and HBVDNA positive, and their mothers were also HBeAg positive and had HBVDNA>10⁷ IU/ml, which confirmed previous reports. These HBeAg positive and high viral load pregnant women should be offered antiviral treatment during late pregnancy to prevent HBV mother-to-child transmission. There were 2 infants who were both anti-HBs and HBsAg positive. It was reported that the infants were infected with mutant strains which were transmitted from their mothers [^17-20]. We should further test sequence analysis to support it and manufacture mutant strain vaccines to prevent HBV mother-to-child transmission.

HBV has been classified into eight genotypes, designated as A-H, based on intergenotypic divergence of at least 8% in the complete nucleotide sequence or more than 4% in the S gene [^21-27]. HBV genotypes have distinct geographical distributions and correlate with the severity of liver diseases [^28-30]. Are HBV genotypes of great importance in HBV mother-to-child transmission and/or affect the immunization success with HBIG and hepatitis B vaccine? Only genotypes B and C were found among 165 pregnant women. There was a significant difference in genotypes between the pregnant women whose infants were HBV infected and those without HBV infection. Genotype C might be a risk factor for HBV mother to child transmission. It should be recommended that pregnant women who are HBeAg positive and have a high viral load be tested for HBV genotypes.

There was a significant decline in the HBsAg prevalence among pregnant women and their infants in Shenyang, which might be attributed to universal implementation of immunoprophylaxis since 1990. Genotype C might be a risk factor for HBV mother to child transmission.

The Institutional Ethics Committee of Shengjing Hospital of China Medical University approved the study (No.2010PS29K) and the study conformed to the Helsinki declaration of 1996. Informed consent was obtained from all the study subjects prior to the study.

(HBV): Hepatitis B virus; (HBsAg): Hepatitis B surface antigen; (HBeAg): Hepatitis B e antigen; (anti-HBs): Hepatitis B surface antibody; (anti-HBc): Hepatitis B core antibody; (HBIG): Hepatitis B immunoglobulin.

The authors declare that they have no competing interests.

YD and XGD designed, executed and coordinated the study. YD, QJS and LM contributed in the sample acquirement and laboratory analysis. YD and XGD participated in the drafting of the manuscript and literature search. All authors read and approved the final manuscript.

We extend our thanks to all pregnant women involved in our study.

This study was supported by China National Fund of Ministry of Science and Technology (30972612), Liaoning Provincial Fund of Provincial Department of Science and Technology (2009225010–7). And this study was also supported by Shenyang Science and Technology Program No. F10-205-1-10.