Zhang Lei, Gui Xi-en, Teter Caroline, Zhong Hairong, Pang Zhiyong, Ding Lixiong, Li Fengliang, Zhou Yun, Zhang Ling
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, No.169, Donghu Road, Wuchang District, 430071 Wuhan, Hubei Province, China; Department of Infection Control, Qingdao Municipal Hospital, Qingdao, China.
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, No.169, Donghu Road, Wuchang District, 430071 Wuhan, Hubei Province, China.
Vaccine. 2014 Oct 21;32(46):6091-7. doi: 10.1016/j.vaccine.2014.08.078. Epub 2014 Sep 18.
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.
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.
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 log₁₀copies/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 <10 IU/L, 10-500 IU/L and ≥500 IU/L was 90.3% (168/186), 90.5% (219/242) and 80.2% (89/111) respectively, p=0.011. Median titers of anti-HBs (IU/L) among infants in the three groups was 344.2, 231.9 and 161.1 respectively, p=0.020.
HBIG plus HB vaccine can effectively prevent mother-to-infant transmission of HBV, but no HBV breakthrough infection was observed in infants born to HBeAg-negative mothers who received HB vaccine with or without HBIG after birth. Antepartum injection of HBIG has no effect on preventing HBV mother-to-infant transmission. High maternal titer of anti-HBs can transplacentally impair immune response of infants towards HB vaccine.
乙型肝炎免疫球蛋白（HBIG）联合乙型肝炎疫苗（HB疫苗）进行免疫接种可有效预防乙型肝炎病毒（HBV）的围产期传播。随着HB疫苗的普遍接种，在孕妇中由HB疫苗产生的抗-HBs越来越常见，且母体抗-HBs可通过胎盘传递。本研究旨在评估乙型肝炎免疫接种对预防HBV母婴传播及婴儿对HB疫苗免疫反应的效果。
2008年至2013年，在中国15个中心开展了一项前瞻性研究。纳入完成免疫预防的HBsAg阳性孕妇及其8至12个月大的婴儿，并检测其HBV标志物（HBsAg、抗-HBs、HBeAg、抗-HBe和抗-HBc）。HBsAg阳性女性产前给予HBIG基于个人意愿。纳入HBsAg阴性孕妇及其7至24个月大接受HB疫苗系列接种的婴儿，并检测其HBV标志物。
研究了1202名HBsAg阳性母亲及其8至12个月大的婴儿，发现40名婴儿HBsAg阳性，免疫预防失败率为3.3%。免疫预防失败的婴儿均为HBV-DNA≥6 log₁₀拷贝/ml的HBeAg阳性母亲所生。在HBeAg阳性母亲的婴儿中，疫苗加HBIG组的免疫预防失败率为7.9%（29/367），显著低于仅接种疫苗组的16.9%（11/65），p = 0.021；孕妇产前是否给予HBIG，免疫预防失败率无显著差异，分别为10.3%（10/97）和9.0%（30/335），p = 0.685。HBsAg阴性孕妇中抗-HBs阳性率为56.3%（3883/6899），抗-HBs阳性母亲的脐血中抗-HBs阳性率为94.2%。完成HB疫苗系列接种后，母体抗-HBs滴度<10 IU/L组、10 - 500 IU/L组和≥500 IU/L组婴儿的抗-HBs阳性率分别为90.3%（168/186）、90.5%（219/242）和80.2%（89/111），p = 0.011。三组婴儿抗-HBs（IU/L）的中位数分别为344.2、231.9和161.1，p = 0.020。
HBIG加HB疫苗可有效预防HBV母婴传播，但出生后接受或未接受HBIG的HB疫苗接种的HBeAg阴性母亲所生婴儿未观察到HBV突破性感染。产前注射HBIG对预防HBV母婴传播无影响。母体抗-HBs高滴度可经胎盘损害婴儿对HB疫苗的免疫反应。
