Influencing factors of non-/low-response to hepatitis B vaccine of infants born to mothers infected with HBV
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摘要:
目的 探讨乙型肝炎(乙肝)病毒表面抗原(HBsAg)阳性母亲所生婴儿对乙肝疫苗无/弱应答发生情况以及影响因素。 方法 对2018—2021年在广州市南沙区HBsAg阳性母亲所生的全部婴儿进行追踪随访,对随访成功的婴儿检测外周血乙肝病毒血清标志物,并采用结构化问卷收集相关的可能影响婴儿乙肝疫苗无/弱应答的因素。 结果 在婴儿7~12月龄进行电话召回,共招募随访640对HBsAg阳性产妇及所生婴儿,2名(0.31%)婴儿感染乙肝病毒,婴儿对乙肝疫苗无/弱应答发生率为2.81%(18/640),其中无应答发生率为0.31%(2/640),弱应答发生率为2.50%(16/640)。 因素分析发现,HBsAg阳性产妇所生婴儿对乙肝疫苗无/弱应答与强应答组在母亲婚姻状况、文化程度、是否为HBeAg阳性、孕期HBV DNA情况、分娩方式、分娩胎龄、出生体重、婴儿性别、是否12 h内接种首剂乙肝疫苗以及乙肝免疫球蛋白方面差异均无统计学意义(P>0.05)。 HBeAg阳性或孕期HBV DNA高水平母亲,47.65%(81/170)孕期进行了抗病毒治疗,其所生婴儿12 h内接种首剂乙肝疫苗、乙肝免疫球蛋白的比例略高于HBeAg阴性或孕期HBV DNA低水平母亲所生婴儿,两组婴儿乙肝疫苗无/弱应答发生率差异无统计学意义(P>0.05)。 结论 随着消除乙肝母婴传播工作的逐步推进,HBsAg阳性产妇所生婴儿发生母婴传播、乙肝疫苗无/弱应答较以往研究明显降低。 今后应进一步强化首剂乙肝疫苗、乙肝免疫球蛋白接种时限,及对孕期HBV DNA高水平或HBeAg阳性孕妇知情告知后进行抗病毒治疗。 Abstract:Objective To investigate the incidence and influencing factors of non-/low- response to hepatitis B vaccine in infants born to HBsAg-positive mothers. Methods All infants born to HBsAg-positive women in Nansha district of Guangzhou during 2018−2021 were surveyed. Serum markers of hepatitis B virus (HBV) infection in peripheral blood were detected for the infants in follow up, and two structured questionnaires were used to collect the information about related factors that might affect non-/low-response to hepatitis B vaccine in the infants. Results A total of 640 HBsAg-positive mothers and their infants were recruited through telephone interview at 7−12 months after delivery. Two infants (0.31%) were infected with HBV. The incidence of non-/low-response to hepatitis B vaccine was 2.81% (18/640), and the incidence of non-response was 0.31% (2/640), the incidence of low-response was 2.50% (16/640). Univariate analysis found that there were no significant differences in maternal marital status, education level, HBeAg status, HBV DNA level during pregnancy, delivery mode and gestational weeks at delivery, infant birth weight, gender, and whether vaccinated the first dose of hepatitis B vaccine and hepatitis B immunoglobulin within 12 hours after birth between the infants with non-/low-response to hepatitis B vaccine and those with strong-response to hepatitis B vaccine (P>0.05). For the HBeAg-positive mothers or mothers with high levels of HBV DNA during pregnancy, 47.65% (81/170) received antiviral therapy, and the proportions of their infants who received the first dose of hepatitis B vaccine and hepatitis B immunoglobulin within 12 hours after birth were slightly higher than those of infants born to women with negative-HBeAg or low-levels of HBV DNA during pregnancy. There was no significant difference in the incidence of non-/low-response to hepatitis B vaccine between the two groups (P>0.05). Conclusion With the progress of the elimination of mother-to-child transmission of hepatitis B, the incidence rates of the mother-to-child transmission and non-/low-response to hepatitis B vaccine in infants born to HBsAg-positive women decreased significantly. In the future, the timely injections of the first dose of hepatitis B vaccine and hepatitis B immune globulin in newborns should be further strengthened, and antiviral treatment should be started for pregnant women with high levels of HBV DNA or positive-HBeAg. -
Key words:
- HBsAg-positive /
- Hepatitis B vaccine /
- Infant /
- Non-/low-response /
- Antiviral therapy
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表 1 HBsAg阳性母亲所生婴儿对乙肝疫苗无/弱应答的单因素分析
Table 1. Influencing factors of non - / low- response to hepatitis B vaccine in infants born to mothers infected with HBV
影响因素 无/弱应答(n=18) 强应答(n=620) 统计值 P值 婚姻状况 0.000 1.000 在婚 18 (100.00) 612 (98.71) 未婚 0(0.00) 8 (1.29) 年龄(岁,$\bar{x} \pm s $) 30.67±4.54 32.16±4.64 −1.346 0.179 文化程度 2.591 0.459 初中及以下 4(22.22) 147(23.71) 高中 7(38.89) 173(27.90) 大专及以上 5(27.78) 265(42.74) 不详 2(11.11) 35(5.65) 母亲HBeAg 0.000 1.000 阳性 4(22.22) 129(20.81) 阴性 14(77.78) 491(79.19) 孕期HBV DNA 0.638 0.727 低于检测下限 5(27.78) 161(25.97) 高于检测下限 7(38.89) 296(47.74) 未检测 6(33.33) 163(26.29) 孕期抗病毒治疗 0.436 0.509 是 4(22.22) 86(13.87) 否 14(77.78) 534(86.13) 分娩方式 1.381 0.240 剖宫产 4(22.22) 221(35.65) 自然分娩 14(77.78) 399(64.35) 分娩胎龄(d,$\bar{x} \pm s $) 275.17±6.46 273.34±8.32 0.924 0.356 早产 0(0.00) 25(4.03) 0.064 0.800 足月产 18(100.00) 595(95.97) 婴儿出生体重(g,$\bar{x} \pm s $) 3167.22±385.16 3208.20±391.50 −0.438 0.662 低出生体重 0(0.00) 12(1.94) 0.000 1.000 正常出生体重 18(100.00) 607(98.06) 婴儿性别 3.791 0.052 男性 6(33.33) 350(56.45) 女性 12(66.67) 270(43.55) 婴儿首剂乙肝疫苗接种时间(min,$\bar{x} \pm s $) 328.56±291.48 249.76±234.40 1.396 0.163 ≥12 h 0(0.00) 5(0.81) 0.000 1.000 <12 h 18(100.00) 615(99.19) 婴儿乙肝免疫球蛋白接种时间(min,$\bar{x} \pm s $) 165.72±152.14 195.31±175.20 -0.709 0.479 ≥12 h 0(0.00) 4(0.65) 0.000 1.000 <12 h 18(100.00) 616(99.35) 注:HBsAg. 乙型肝炎表面抗原,HBeAg. 乙型肝炎e抗原;括号外数据为人数,括号内数据为构成比(%) 表 2 HBsAg阳性产妇所生婴儿对乙肝疫苗无/弱应答的多因素分析
Table 2. Logistic analysis of non-/low-response to hepatitis B vaccine of infants born to HBsAg-positive mothers
因 素 aOR值(95%CI) P值 母亲HBeAg阳性 1.19(0.22~6.38) 0.836 母亲孕期抗病毒治疗 2.62(0.47~15.31) 0.286 母亲HBV DNA高于检测下限 0.49(0.13~1.91) 0.305 剖宫产 0.46(0.10~2.13) 0.317 婴儿早产 0.00(0.00~-) 0.999 婴儿低出生体重 0.00(0.00~-) 0.999 乙肝免疫球蛋白≥12 h注射 1.53(0.00~-) 1.000 乙肝首剂乙肝疫苗≥12 h注射 0.00(0.00~-) 1.000 表 3 低/高暴露风险婴儿对乙肝疫苗免疫应答情况及影响因素分析
Table 3. Immune response to hepatitis B vaccine and its influencing factors in infants at low/high exposure risk
影响因素 高暴露组(n=170) 低暴露组(n=468) 统计值 P值 免疫应答 0.000 1.000 无/弱 5(2.94) 13(2.78) 高 165(97.06) 455(97.22) 孕期抗病毒治疗 215.169 <0.001 是 81(47.65) 9(1.92) 否 89(52.35) 459(98.08) 分娩方式 1.698 0.193 剖宫产 53(31.18) 172(36.75) 自然分娩 117(68.82) 296(63.25) 分娩胎龄(d,$\bar{x} \pm s $) 273.13±7.49 273.49±8.54 0.465 0.642 早产 4(2.35) 21(4.49) 1.509 0.219 足月产 166(97.65) 447(95.51) 婴儿出生体重(g,$\bar{x} \pm s $) 3168.99±380.92 3220.78±394.19 1.477 0.140 低出生体重 3(1.78) 9(1.92) 0.000 1.000 正常出生体重 166(98.22) 459(98.08) 婴儿首剂乙肝疫苗接种时间(min,$\bar{x} \pm s $) 250.76±205.34 252.43±246.82 0.079 0.937 ≥12 h 1(0.59) 4(0.85) 0.000 1.000 <12 h 169(99.41) 464(99.15) 婴儿乙肝免疫球蛋白接种时间(min,$\bar{x} \pm s $) 196.61±165.97 193.68±177.75 −0.187 0.852 ≥12 h 0(0.00) 4(0.85) 0.412 0.521 <12 h 170(100.00) 464(99.15) 注:括号外数据为人数,括号内数据为构成比(%) -
[1] 崔富强, 庄辉. 我国新生儿乙型肝炎母婴阻断成就和展望[J]. 中国病毒病杂志,2019,9(5):321–326. DOI:10.16505/j.2095−0136.2019.0014.Cui FQ, Zhuang H. Achievements and prospects for preventing mother-to-child transmission of hepatitis B virus in newborns in China[J]. Chin J Viral Dis, 2019, 9(5): 321–326. DOI: 10.16505/j.2095−0136.2019.0014. [2] 李娟, 魏明伟, 朱凤才. 乙型肝炎疫苗免疫无/低应答影响因素的研究进展[J]. 中华流行病学杂志,2021,42(11):2066–2070. DOI:10.3760/cma.j.cn112338−20200910−01145.Li J, Wei MW, Zhu FC. Progress in research of influential factors for non- or low-immune response to hepatitis B vaccination[J]. Chin J Epidemiol, 2021, 42(11): 2066–2070. DOI: 10.3760/cma.j.cn112338−20200910−01145. [3] 杨志清, 郝海昀, 史晓红, 等. HBsAg阳性母亲HBV感染状况与婴儿乙肝疫苗无/弱应答的关系[J]. 中华流行病学杂志,2018,39(6):805–809. DOI:10.3760/cma.j.issn.0254−6450.2018.06.021.Yang ZQ, Hao HY, Shi XH, et al. Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants[J]. Chin J Epidemiol, 2018, 39(6): 805–809. DOI: 10.3760/cma.j.issn.0254−6450.2018.06.021. [4] 张芳, 王素萍, 史晓红, 等. 新生儿HBV血清标志物及免疫状态与乙型肝炎疫苗无/弱应答的关系[J]. 中华流行病学杂志,2016,37(8):1074–1079. DOI:10.3760/cma.j.issn.0254−6450.2016.08.004.Zhang F, Wang SP, Shi XH, et al. Relationship between the mode of HBV marker and immune status in neonates and non-/hypo-response to hepatitis B vaccine[J]. Chin J Epidemiol, 2016, 37(8): 1074–1079. DOI: 10.3760/cma.j.issn.0254−6450.2016.08.004. [5] 王斌, 许喜喜, 温海秀, 等. HBsAg阳性母亲所生婴儿乙型肝炎疫苗无/弱应答的影响因素研究[J]. 中华流行病学杂志,2017,38(7):911–915. DOI:10.3760/cma.j.issn.0254−6450.2017.07.013.Wang B, Xu XX, Wen HX, et al. Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers[J]. Chin J Epidemiol, 2017, 38(7): 911–915. DOI: 10.3760/cma.j.issn.0254−6450.2017.07.013. [6] Liu JF, Yao NJ, Chen TY, et al. FA-01-Prevalence of mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis[J]. J Hepatol, 2019, 70 Suppl 1: e123–124. DOI: 10.1016/S0618−8278(19)30217−8. [7] 中华人民共和国国家卫生和计划生育委员会办公厅. 关于印发国家免疫规划儿童免疫程序及说明(2016年版)的通知[EB/OL]. (2016-12-06)[2022-05-25]. http://www.nhc.gov.cn/cms-search/xxgk/getManuscriptXxgk.htm?id=a91fa2f3f9264cc186e1dee4b1f24084.National Health and Family Planning Commission of the People's Republic of China: Notice of printing and releasing child immunization schedule of national immunization program (2016 edition) [EB/OL]. (2016-12-06)[2022-05-25]. http://www.nhc.gov.cn/cms-search/xxgk/getManuscriptXxgk.htm?id=a91fa2f3f9264cc186e1dee4b1f24084. [8] Liu JF, Chen TY, Chen YL, et al. 2019 Chinese clinical practice guidelines for the prevention of mother-to-child transmission of hepatitis B virus[J]. J Clin Transl Hepatol, 2020, 8(4): 397–406. DOI: 10.14218/JCTH.2020.00070. [9] 广东省卫生和计划生育委员会. 关于开展“乙肝母婴零传播”综合干预试点工作的通知[EB/OL]. (2018-08-21) [2022-05-25]. http://www.ytpp.com.cn/data/2018-08-21/50946.html.Guangdong Provincial Health and Family Planning Commission. Notice on launching the comprehensive intervention pilot work of “zero transmission of hepatitis B from mother to child”[EB/OL]. (2018-08-21)[2022-05-25]. http://www.ytpp.com.cn/data/2018-08-21/50946.html. [10] 中华人民共和国卫生健康委员会办公厅. 国家卫生健康委办公厅关于印发预防艾滋病、梅毒和乙肝母婴传播工作规范(2020年版)的通知[EB/OL]. (2020-11-12)[2022-05-25]. http://www.nhc.gov.cn/fys/s3581/202011/fc7b46b2b48b45a69bd390ae3a62d065.shtml.General Office of the Health Commission, the People’s Republic of China. Notice of of the General Office of the Health Commission about printing and issuing the specification for preventing mother to child transmission of AIDS, syphilis and hepatitis B (2020 edition) [EB/OL]. (2020-11-12)[2022-05-25]. http://www.nhc.gov.cn/fys/s3581/202011/fc7b46b2b48b45a69bd390ae3a62d065.shtml. [11] 许喜喜, 王斌, 王雪飞, 等. HBsAg阳性母亲妊娠中晚期服用替比夫定对婴儿乙型肝炎疫苗无/弱应答的影响[J]. 中华流行病学杂志,2017,38(2):168–172. DOI:10.3760/cma.j.issn.0254−6450.2017.02.007.Xu XX, Wang B, Wang XF, et al. Effect of telbivudine on infants born to HBsAg-positive mothers with non-/hypo-response to hepatitis B vaccine during their second and third trimesters of pregnancy[J]. Chin J Epidemiol, 2017, 38(2): 168–172. DOI: 10.3760/cma.j.issn.0254−6450.2017.02.007. [12] 中华医学会妇产科学分会产科学组, 中华医学会围产医学分会. 乙型肝炎病毒母婴传播预防临床指南(2020)[J]. 中华围产医学杂志,2020,23(5):289–298. DOI:10.3760/cma.j.cn113903−20200512−00445.Obstetric Subgroup, Society of Obstetrics and Gynecology, Chinese Medical Association, Chinese Society of Perinatal Medicine, Chinese Medical Association. Clinical guideline on prevention of mother-to-child transmission of hepatitis B virus (2020)[J]. Chin J Perinat Med, 2020, 23(5): 289–298. DOI: 10.3760/cma.j.cn113903−20200512−00445. [13] 郭健, 高怡, 王素萍, 等. 乙型肝炎表面抗原阳性母亲所产婴儿对乙型肝炎疫苗无或低应答的影响因素[J]. 中华传染病杂志,2014,32(8):460–463. DOI:10.3760/cma.j.issn.1000−6680.2014.08.003.Guo J, Gao Y, Wang SP, et al. The influence factors of non-responsiveness and low-responsiveness to hepatitis B vaccine of infants born to hepatitis B surface antigen positive mothers[J]. Chin J Infect Dis, 2014, 32(8): 460–463. DOI: 10.3760/cma.j.issn.1000−6680.2014.08.003. [14] Pan CQ, Zou HB, Chen Y, et al. Cesarean section reduces perinatal transmission of hepatitis B virus infection from hepatitis B surface antigen-positive women to their infants[J]. Clin Gastroenterol Hepatol, 2013, 11(10): 1349–1355. DOI: 10.1016/j.cgh.2013.04.026. [15] Hu YL, Chen J, Wen J, et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus[J]. BMC Pregnancy Childbirth, 2013, 13: 119. DOI: 10.1186/1471−2393−13−119. [16] Chen HL, Cai JY, Song YP, et al. Vaginal delivery and HBV mother to child transmission risk after immunoprophylaxis: a systematic review and a meta-analysis[J]. Midwifery, 2019, 74: 116–125. DOI: 10.1016/j.midw.2019.03.024. -

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