Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus

In the present study, two groups of children born to HBsAg-positive mothers were recruited. The first group was composed of 296 singleton full-term children and their 296 HBV-infected mothers. These mothers were selected based on the results of a retrospective study on the prevalence of HBsAg among pregnant women from 14 cities and rural areas across Jiangsu during 2002–2004 [10]; they were all HBsAg-positive during their pregnancy and at delivery. Serum samples (~3 ml each) from these 296 children were prospectively collected from October 2009 to March 2010, when they were at 5–7 years old. The second group was comprised of 250 children aged 1–6 years who were born to 248 HBV-infected mothers (2 pairs of twins). These children were recruited based on our invitation of 385 mothers, who were all HBsAg-positive during their pregnancy and delivered their babies in Zhenjiang Fourth People's Hospital, Jiangsu, from January 2006 to December 2010, to join this study. Blood sample (~3 ml each) was collected from each child from November 2011 to March 2012.

Each attending mother was asked to complete a questionnaire, which included demographic data of the mother and her child, the use of HBIG and first dose hepatitis B vaccine in the children. These data were all further validated by checking the hospital records. In addition, the results of HBV serologic markers and HBV DNA levels in each mother at delivery were retrieved from medical records. The use of second and third doses of hepatitis B vaccine was confirmed in 90.3% of the children by checking the children's vaccination records, and that in other instances was defined by the interview with children’s mothers.

All mothers had no coinfection with hepatitis C virus and human immunodeficiency virus, and had not received amniocentesis or anti-viral treatment before and/or during pregnancy. Those with maternal complications, such as acute hepatitis and threatening abortion, were also excluded. Totally 546 children (2 pairs of twins) born to 544 HBsAg-positive mothers were enrolled. The mothers were 23–48 years of age (mean, 31.0 ± 3.5), and the gestational ages were 35–42 weeks (39.5 ± 1.0). The children (296 boys) were 1–7 years old (4.7 ± 1.7) during follow-up; 25.1% (137/546) were born to hepatitis B e antigen (HBeAg)-positive mothers.

This study was performed according to the Declaration of Helsinki and approved by the institutional review boards of Nanjing Drum Tower Hospital and Zhenjiang Fourth People's Hospital. Each mother gave the written informed consent for the use of her child’s blood samples.

Commercial enzyme immunoassay kits (Huakang Biotech, Shenzhen; Kehua Bio-Engineering, Shanghai, China) were used for qualitative testing of HBV serologic markers, including HBsAg, antibody against hepatitis B surface antigen (anti-HBs), and antibody against hepatitis B core antigen (anti-HBc). All HBsAg-positive specimens were also tested for HBeAg and antibody against hepatitis B e antigen (anti-HBe) by EIA (Huakang Biotech; Kehua Bio-Engineering). Quantitative analysis of anti-HBs in a serum sample was further performed using a microparticle immunoassay kit (Architect system, Abbott, North Chicago). Positive and negative controls were included in each test. All samples were tested by two technicians who were unaware of the serum identity. When anti-HBs was beyond the upper detection limit (1000 mIU/ml), the specimens were retested after further dilution with 20% bovine fetal serum in phosphate-buffer saline.

Data analysis was performed using SPSS software version 17.0 (SPSS Standard version 17.0, SPSS Inc., Chicago, IL). Continuous variables normally distributed were expressed as mean ± standard deviation (SD) and compared by t-test between two groups. Quantitative data non-normally distributed were presented as median and interquartile range. Categorical variables were reported as number and percentage and compared by χ ² test or Fisher’s exact test where appropriate. A two-sided p value of <0.05 was considered as statistically significant.

Of the total 546 children, 285 (52.2%) were delivered by ECS and 261 others (47.8%) were delivered by VD. They were born to 284 and 260 mothers respectively, one pair of twin in each group. The mothers of the children in the two groups had comparable maternal and gestational ages and HBeAg-positive rates (Table 1). The children in the ECS and VD groups also had similar ages, gender ratios, feeding modes, hepatitis B vaccine coverage and administrations of HBIG (Table 1). All the children were generally in good health at the follow-up.

HBV infection was defined by the positive results of HBsAg, anti-HBc, and HBeAg. The overall rate of chronic HBV infection in the children of HBsAg-positive mothers was 2.4% (13/546), although they were all vaccinated against hepatitis B and mostly administered with HBIG within 24 hours after birth. As shown in Table 2, the rate of chronic infection and self-resolved infection, presented as HBsAg-negative and anti-HBc-positive, in the VD group was 2.3% (6/261) and 3.8% (10/261) respectively, each comparable to that in the ECS group (p = 0.904 and 0.355 respectively).

It has been demonstrated that the major risk factor responsible for mother-to-child transmission of HBV is the viral load in mothers [11]. Maternal HBeAg positivity is well correlated with the HBV DNA levels [12]. Thus, infants of HBeAg-positive mothers have an increased risk of becoming infected with HBV. In agreement with the findings, all 13 infected children in the present study were born to HBeAg-positive mothers and none of the children born to HBeAg-negative mothers was chronically infected. To clarify whether ECS may reduce the likelihood of mother-to-child transmission of HBV in these high-risk children, we compared the incidence of HBV infection in 68 children of HBeAg-positive mothers who underwent ECS with that in 69 other children of HBeAg-positive mothers who delivered vaginally. The mothers who delivered their babies by ECS had comparable HBV DNA levels with those who delivered their babies by VD (2.38 × 10⁶ vs. 2.35 × 10⁶ IU/ml, p = 0.586). Similarly, as shown in Table 3, the rates of chronic infection and self-resolved infection were both comparable between the two groups (10.3% vs. 8.7%, p = 0.750 and 5.9% vs. 13.0%, p = 0.153).

Of the 546 children who had been vaccinated against hepatitis B, 391 (71.6%) had anti-HBs ≥10 mIU/ml, which is similar to the findings in children with same ages [13]. The anti-HBs positive (≥10 mIU/ml) rate in the 291 children who were administered HBIG at birth was not different from that in those who were not administered HBIG (74.9% vs. 67.8%, p = 0.068). Furthermore, the positive rate of anti-HBs in children born by ECS was similar to that in children born by VD, even in those born to HBeAg-positive mothers (Tables 2 and 3).