Vaccine 32 (2014) 6091–6097
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine Lei Zhang a,b , Xi-en Gui a,∗ , Caroline Teter c , Hairong Zhong d , Zhiyong Pang e , Lixiong Ding f , Fengliang Li g , Yun Zhou h , Ling Zhang i a Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, No.169, Donghu Road, Wuchang District, 430071 Wuhan, Hubei Province, China b Department of Infection Control, Qingdao Municipal Hospital, Qingdao, China c Department of Medicine, Erie Family Health Center, Chicago, USA d Mother and Child Hospital, Wuxue , Huanggang, China e Centers for Disease Control and Prevention, Chongyang County, Xianning, China f Centers for Disease Control and Prevention, Xiaonan District, Xiaogan, China g Mother and Child Hospital, Tongcheng County, Xianning, China h Mother and Child Hospital, Dangyang, Yichang, China i Mother and Child Hospital, Huanggang, China
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Article history: Received 6 May 2014 Received in revised form 11 August 2014 Accepted 30 August 2014 Available online 18 September 2014 Keywords: HBV HBIG HB vaccine Mother-to-infant transmission Anti-HBs Immune response
a b s t r a c t Background: Combined immunization with hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine (HB vaccine) can effectively prevent perinatal transmission of hepatitis B virus (HBV). With the universal administration of HB vaccine, anti-HBs conferred by HB vaccine can be found increasingly in pregnant women, and maternal anti-HBs can be passed through the placenta. This study was designed to evaluate the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV and on the immune response of infants towards HB vaccine. Method: From 2008 to 2013, a prospective study was conducted in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8–12 months who completed immunoprophylaxis were enrolled in the study and tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). Antepartum administration of HBIG to HBsAg-positive women was based on individual preference. HBsAg-negative pregnant women and their infants of 7–24 months old who received HB vaccines series were enrolled and tests of their HBV markers were performed. Results: 1202 HBsAg-positive mothers and their infants aged 8–12 months were studied and 40 infants were found to be HBsAg positive with the immunoprophylaxis failure rate of 3.3%. Infants with immunoprophylaxis failure were all born to HBeAg-positive mothers of HBV-DNA ≥ 6 log10 copies/ml. Among infants of HBeAg-positive mothers, immunoprophylaxis failure rate in vaccine plus HBIG group, 7.9% (29/367), was significantly lower than the vaccine-only group, 16.9% (11/65), p = 0.021; there was no significant difference in the immunoprophylaxis failure rate whether or not antepartum HBIG was given to the pregnant woman, 10.3% (10/97) vs 9.0% (30/335), p = 0.685. Anti-HBs positive rate was 56.3% (3883/6899) among HBsAg-negative pregnant women and anti-HBs positive rate was 94.2% in cord blood of anti-HBs-positive mothers. After completing the HB vaccine series, anti-HBs positive rate among infants with maternal anti-HBs titers of 1.00 COI and antiHBc > 1.00 COI. Patient plasma was diluted up to 30 times until anti-HBs levels fell below the upper limit of detection (1000 IU/L).
HBV-DNA was performed by using PCR-Fluorescence detection kit for heptatitis B viral nucleotides (Shanghai Kehua Bio-engineering Co.,Ltd., China). The positive level was set at HBVDNA ≥ 500 copies/ml.
2.7. The principle of medical ethics The study was conducted in accordance with the ethical principles of the declaration of Helsinki and principles of good clinical practices. The study was approved by the Ethics Committee of Zhongnan Hospital affiliated with Wuhan University. Diagnostic tests were performed with written informed consent after the
In all centers, 103174 pregnant women were screened for HBsAg.
6156 (5.97%) pregnant women were positive for HBsAg.
In five of these centers, 6899 pregnant women were also screened for anti-HBs.
In four of these centers, 1202 pairs of HBsAg-positive mothers and their infants aged 8-12 months were enrolled in the follow-up study.
3883 (56.3%) pregnant women were positive for anti-HBs and negative for HBsAg.
In two of the centers, 539 pairs of HBsAg-negative mothers and their infant aged 7-24 months were enrolled in the follow-up study.
Fig. 1. The profile of samples’ collection.
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L. Zhang et al. / Vaccine 32 (2014) 6091–6097
nature and possible consequences of the studies had been fully explained. 2.8. Statistical analysis 2 or Fisher’s exact tests were used for categorical variables. For measurement data, normal distribution of measurement data was first tested. If the result was of non-normal distribution, nonparametric tests were used for statistical calculations, expressed in terms of median (25% to 75% interquartile range, IQR). And if the result was of normal distribution, t tests or nonparametric tests were used, expressed as x¯ ± SD or median (25% to 75% IQR). SPSS 17.0 software package was used and a p value of
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine Lei Zhang a,b , Xi-en Gui a,∗ , Caroline Teter c , Hairong Zhong d , Zhiyong Pang e , Lixiong Ding f , Fengliang Li g , Yun Zhou h , Ling Zhang i a Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, No.169, Donghu Road, Wuchang District, 430071 Wuhan, Hubei Province, China b Department of Infection Control, Qingdao Municipal Hospital, Qingdao, China c Department of Medicine, Erie Family Health Center, Chicago, USA d Mother and Child Hospital, Wuxue , Huanggang, China e Centers for Disease Control and Prevention, Chongyang County, Xianning, China f Centers for Disease Control and Prevention, Xiaonan District, Xiaogan, China g Mother and Child Hospital, Tongcheng County, Xianning, China h Mother and Child Hospital, Dangyang, Yichang, China i Mother and Child Hospital, Huanggang, China
a r t i c l e
i n f o
Article history: Received 6 May 2014 Received in revised form 11 August 2014 Accepted 30 August 2014 Available online 18 September 2014 Keywords: HBV HBIG HB vaccine Mother-to-infant transmission Anti-HBs Immune response
a b s t r a c t Background: Combined immunization with hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine (HB vaccine) can effectively prevent perinatal transmission of hepatitis B virus (HBV). With the universal administration of HB vaccine, anti-HBs conferred by HB vaccine can be found increasingly in pregnant women, and maternal anti-HBs can be passed through the placenta. This study was designed to evaluate the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV and on the immune response of infants towards HB vaccine. Method: From 2008 to 2013, a prospective study was conducted in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8–12 months who completed immunoprophylaxis were enrolled in the study and tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). Antepartum administration of HBIG to HBsAg-positive women was based on individual preference. HBsAg-negative pregnant women and their infants of 7–24 months old who received HB vaccines series were enrolled and tests of their HBV markers were performed. Results: 1202 HBsAg-positive mothers and their infants aged 8–12 months were studied and 40 infants were found to be HBsAg positive with the immunoprophylaxis failure rate of 3.3%. Infants with immunoprophylaxis failure were all born to HBeAg-positive mothers of HBV-DNA ≥ 6 log10 copies/ml. Among infants of HBeAg-positive mothers, immunoprophylaxis failure rate in vaccine plus HBIG group, 7.9% (29/367), was significantly lower than the vaccine-only group, 16.9% (11/65), p = 0.021; there was no significant difference in the immunoprophylaxis failure rate whether or not antepartum HBIG was given to the pregnant woman, 10.3% (10/97) vs 9.0% (30/335), p = 0.685. Anti-HBs positive rate was 56.3% (3883/6899) among HBsAg-negative pregnant women and anti-HBs positive rate was 94.2% in cord blood of anti-HBs-positive mothers. After completing the HB vaccine series, anti-HBs positive rate among infants with maternal anti-HBs titers of 1.00 COI and antiHBc > 1.00 COI. Patient plasma was diluted up to 30 times until anti-HBs levels fell below the upper limit of detection (1000 IU/L).
HBV-DNA was performed by using PCR-Fluorescence detection kit for heptatitis B viral nucleotides (Shanghai Kehua Bio-engineering Co.,Ltd., China). The positive level was set at HBVDNA ≥ 500 copies/ml.
2.7. The principle of medical ethics The study was conducted in accordance with the ethical principles of the declaration of Helsinki and principles of good clinical practices. The study was approved by the Ethics Committee of Zhongnan Hospital affiliated with Wuhan University. Diagnostic tests were performed with written informed consent after the
In all centers, 103174 pregnant women were screened for HBsAg.
6156 (5.97%) pregnant women were positive for HBsAg.
In five of these centers, 6899 pregnant women were also screened for anti-HBs.
In four of these centers, 1202 pairs of HBsAg-positive mothers and their infants aged 8-12 months were enrolled in the follow-up study.
3883 (56.3%) pregnant women were positive for anti-HBs and negative for HBsAg.
In two of the centers, 539 pairs of HBsAg-negative mothers and their infant aged 7-24 months were enrolled in the follow-up study.
Fig. 1. The profile of samples’ collection.
6094
L. Zhang et al. / Vaccine 32 (2014) 6091–6097
nature and possible consequences of the studies had been fully explained. 2.8. Statistical analysis 2 or Fisher’s exact tests were used for categorical variables. For measurement data, normal distribution of measurement data was first tested. If the result was of non-normal distribution, nonparametric tests were used for statistical calculations, expressed in terms of median (25% to 75% interquartile range, IQR). And if the result was of normal distribution, t tests or nonparametric tests were used, expressed as x¯ ± SD or median (25% to 75% IQR). SPSS 17.0 software package was used and a p value of
