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中华实验和临床感染病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (03) : 157 -164. doi: 10.3877/cma.j.issn.1674-1358.2025.03.004

所属专题: 经典病例 文献

论著

10 250例乙型肝炎病毒垂直暴露儿童母婴传播干预效果分析
张雪1, 陈正超1, 李一辰2, 何辉2, 刘凯波1,()   
  1. 1100026 北京,首都医科大学附属北京妇产医院/北京妇幼保健院围产保健科
    2100026 北京,首都医科大学附属北京妇产医院/北京妇幼保健院儿童保健科
  • 收稿日期:2024-12-31 出版日期:2025-06-15
  • 通信作者: 刘凯波
  • 基金资助:
    国家科技部重点研发计划(No. 2023YFC2308101)

Analysis on the effectiveness of interventions to prevent mother-to-child transmission in 10 250 children exposed to hepatitis B virus vertical transmission

Xue Zhang1, Zhengchao Chen1, Yichen Li2, Hui He2, Kaibo Liu,1()   

  1. 1Department of Perinatal Health, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
    2Department of Child Health, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
  • Received:2024-12-31 Published:2025-06-15
  • Corresponding author: Kaibo Liu
引用本文:

张雪, 陈正超, 李一辰, 何辉, 刘凯波. 10 250例乙型肝炎病毒垂直暴露儿童母婴传播干预效果分析[J/OL]. 中华实验和临床感染病杂志(电子版), 2025, 19(03): 157-164.

Xue Zhang, Zhengchao Chen, Yichen Li, Hui He, Kaibo Liu. Analysis on the effectiveness of interventions to prevent mother-to-child transmission in 10 250 children exposed to hepatitis B virus vertical transmission[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2025, 19(03): 157-164.

目的

分析乙型肝炎病毒(HBV)感染孕产妇母婴传播情况,探讨在严格落实母婴传播干预措施的真实世界中HBV母婴传播率及其影响因素。

方法

采用队列研究设计,对2021年1月1日~ 2023年12月31日10 250例北京市乙型肝炎垂直暴露儿童母亲的社会经济学资料、HBV血清学标志物、HBV载量及预防母婴传播相关干预措施进行分析;采用Poisson回归分析年份、孕妇年龄与HBV表面抗原阳性率间的关系。HBV表面抗原阳性产妇及HBV暴露儿童数据来源于“国家预防艾滋病、梅毒和乙肝母婴传播信息系统”。描述8 412例(82.07%)完成血清学追访结果的HBV垂直暴露儿童疫苗全程接种后血清学标志物检测(PVST)结果及HBV母婴传播率。根据感染母亲HBV DNA载量对孕妇和暴露儿童进行分组,即高病毒载量孕妇(1 780例)和低病毒载量孕妇(8 470例),高暴露儿童(1 664例)和低暴露儿童(6 748例))。采用卡方检验和秩和检验比较两组孕妇的基本资料、胎儿结局和预防母婴传播干预措施的差异;采用卡方检验比较不同社会经济、感染状态及预防母婴传播干预措施下母婴传播率的差异。

结果

2021至2023年,北京市住院分娩产妇共403 368例,其中HBV表面抗原阳性产妇10 093例(分娩活产儿童10 250例),HBV表面抗原阳性率为2.50%(95%CI:2.45%~2.55%);随着孕妇年龄的减小,HBV表面抗原阳性率越低(RR = 0.93、P < 0.001)。高病毒载量组和低病毒载量组孕妇乙肝疫苗及时接种率(99.94%vs. 99.76%)和乙肝免疫球蛋白(HBIG)及时注射率(99.89%vs. 99.88%)均达99.50%以上,差异均无统计学意义(χ2 = 2.33、P = 0.127,χ2 = 0.00、P = 0.950)。高暴露组和低暴露组儿童乙肝疫苗接种时间分别为0.48(0.26,0.60)h和0.53(0.30,1.15)h(Z = 12.83、P < 0.001),HBIG注射时间分别为0.41(0.25,0.51)h和0.50(0.28,1.07)h(Z = 14.85、P < 0.001),差异均有统计学意义。高病毒载量组孕妇抗病毒治疗率高达96.35%(1 715/1 780),显著高于低病毒载量组(14.06%、1 191/8 470)(χ2 = 4 902.99、P < 0.001);高病毒载量组孕妇在专科医院分娩者(89.94%、1 601/1 780)显著高于低暴露组(34.90%、2 956/8 470)(χ2 = 1 805.80、P < 0.001),差异均有统计学意义。HBV母婴传播儿童共6例,母婴传播率为0.07%(95%CI:0.02%~0.16%)。不同分娩年龄、文化程度、分娩机构类型和分娩方式孕妇的HBV母婴传播率差异均无统计学意义(P均> 0.05)。HBeAg阳性孕妇的HBV母婴传播率高于HBeAg阴性孕妇(0.28%vs. 0.00%:χ2 = 17.15、P < 0.001),高病毒载量孕妇的HBV母婴传播率高于低病毒载量孕妇(0.36% vs. 0.00%:χ2 = 24.35、P < 0.001),差异均有统计学意义。

结论

HBV暴露儿童应及时注射乙肝免疫球蛋白并接种乙肝疫苗,结合对母婴传播高风险的HBV感染孕妇在孕晚期开始抗病毒治疗,HBV母婴传播率可降低至极低水平。

Objective

To analyze the mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection in pregnant and postpartum women, and explore the MTCT rate and its influencing factors in the real-world where strict preventive interventions measures are implemented.

Methods

A cohort study was conducted on 10 250 mothers of HBV-exposed children in Beijing from January 1st, 2021 to December 31st, 2023. Socioeconomic data, HBV serological markers, HBV viral load and MTCT prevention interventions were analyzed, respectively. The relationship between year, maternal age and positivity of hepatitis B virus surface antigen (HBsAg) were analyzed by Poisson regression analysis. Data of HBsAg-positive mothers and HBV-exposed children were sourced from the National Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B Information System. Post-vaccination serological testing (PVST) results and MTCT rates were described for 8 412 (82.07%) HBV-exposed children who completed follow-up serological testing after full vaccination. Mothers and children were grouped based on the HBV DNA load of infected mothers: pregnant women with high viral load group (1 780 cases) and pregnant women with low viral load group (8 470 cases), children with high-exposure group (1 664 cases) and children with low-exposure group (6 748 cases). The differences of basic information, fetal outcomes and prevention of MTCT interventions between two groups of pregnant women were analyzed by Chi-square test and Mann-Whitney test; the differences of MTCT rates under different socioeconomic, infection status and prevention of MTCT interventions were compared by Chi-square test.

Results

From 2021 to 2023, there were a total of 403 368 deliveries in Beijing, including 10 093 HBsAg-positive delivery women (10 250 live born children were delivery women), the HBsAg positivity rate was 2.50% (95%CI: 2.45%-2.55%), with a downtrend that the younger of pregnant woman was, the lower the positive rate of HBsAg (RR = 0.93, P < 0.001). Timely vaccination rate of hepatitis B vaccine (99.94% vs. 99.76%) and timely injection rate of hepatitis B immunoglobulin (HBIG) (99.89% vs. 99.88%) of pregnant women in high viral load group and low viral load group were both higher than 99.50%, but without significant difference (χ2 = 2.33, P = 0.127; χ2 = 0.00,P = 0.950). The vaccination time of hepatitis B vaccine were 0.48 (0.26, 0.60) h and 0.53 (0.30, 1.15) h, respectively (Z = 12.83, P < 0.001); the injection time of HBIG in children with high exposure group and low exposure group were 0.41 (0.25, 0.51) h and 0.50 (0.28, 1.07) h, respectively (Z = 14.85, P < 0.001), both with significant differences. The antiviral treatment rate of pregnant women in high viral load group was 96.35% (1 715/1 780), significantly higher than that of the low viral load group (14.06%, 1 191/8 470) (χ2 = 4 902.99, P < 0.001); the proportion of pregnant women in high viral load group delivered in specialized hospitals (89.94%, 1 601/1 780) was significantly higher than that of the low exposure group (34.90%, 2 956/8 470) (χ2 = 1 805.80, P < 0.001), with significant difference. Total of 6 cases of MTCT were identified, the MTCT rate of HBV was 0.07% (95%CI: 0.02%-0.16%). Among different delivery ages, educational levels, types of delivery institutions and delivery methods, the MTCT rates of HBV were without significant difference (all P > 0.05). The MTCT rate of HBV in HBeAg positive pregnant women was higher than that of HBeAg negative pregnant women (0.28% vs. 0.00%: χ2 = 17.15, P < 0.001), and the MTCT rate of HBV in high viral load pregnant women was higher than that of low viral load pregnant women (0.36% vs. 0.00%:χ2 = 24.35, P < 0.001), both with significant differences.

Conclusions

Timely administration of HBIG and vaccination for all HBV-exposed children, combined with antiviral treatment starting in late pregnancy for mothers with high MTCT risk, could reduce the MTCT rate of HBV to an extremely low level.

图1 HBV垂直暴露儿童入组情况
图2 不同出生年份孕妇HBV表面抗原阳性率变化趋势
表1 低病毒载量组和高病毒载量组孕妇及暴露儿童基本资料和母婴传播干预
指标 合计(10 250例) 低病毒载量组
(8 470例)
高病毒载量组
(1 780例)
统计量 P
产妇年龄(,岁) 33.17 ± 4.07 33.38 ± 4.06 32.20 ± 4.00 t = 11.17 < 0.001
产妇文化程度 [例(%)] χ2 = 27.32 < 0.001a
初中及以下 478(4.66) 399(4.71) 79(4.44)
高中/中专 892(8.70) 704(8.31) 188(10.56)
大学或大专 7 150(69.76) 5 872(69.33) 1 278(71.80)
硕士及以上 1 730(16.88) 1 495(17.65) 235(13.20)
产妇HBeAg [例(%)] χ2 = 4 601.11 < 0.001a
阴性 7 809(76.19) 7 561(89.27) 248(13.93)
阳性 2 441(23.81) 909(10.73) 1 532(86.07)
首次检测HBV DNA时孕周 [例(%)] χ2 = 5.58 0.018a
13周及以前 9 323(90.96) 7 678(90.65) 1 645(92.42)
14周及以后 927(9.04) 792(9.35) 135(7.58)
分娩机构 [例(%)] χ2 = 1 805.80 < 0.001a
非传染病专科机构 5 693(55.54) 5 514(65.10) 179(10.06)
传染病专科机构 4 557(44.46) 2 956(34.90) 1 601(89.94)
孕期抗病毒治疗 [例(%)] χ2 = 4 902.99 < 0.001a
7 344(71.65) 7 279(85.94) 65(3.65)
2 906(28.35) 1 191(14.06) 1 715(96.35)
分娩方式 [例(%)] χ2 = 2.32 0.125a
经阴道分娩 5 487(53.53) 4 505(53.19) 982(55.17)
剖宫产 4 763(46.47) 3 965(46.81) 798(44.83)
出生身长(,cm) 49.52 ± 2.16 49.59 ± 2.05 49.21 ± 2.60 t = 6.80 < 0.001
出生体重(,g) 3 230.44 ± 484.46 3 245.85 ± 477.88 3 157.12 ± 508.38 t= 7.04 < 0.001
HBIG注射 [例(%)] χ2 = 0.00 0.950a
未及时注射 12(0.12) 10(0.12) 2(0.11)
及时注射 10 238(99.88) 8 460(99.88) 1 778(99.89)
HBIG注射时间 [MP25P75),h] 0.50(0.26,0.95) 0.50(0.28,1.07) 0.41(0.25,0.51) Z = 14.85 < 0.001
乙肝疫苗接种 [例(%)] χ2 = 2.33 0.127a
未及时接种 21(0.20) 20(0.24) 1(0.06)
及时接种 10 229(99.80) 8 450(99.76) 1 779(99.94)
乙肝疫苗接种时间 [MP25P75),h] 0.53(0.30,1.00) 0.53(0.30,1.15) 0.48(0.26,0.60) Z = 12.83 < 0.001
PVST [例(%)] χ2 = 456.23 < 0.001a
未完成 1 838(17.93) 1 722(20.33) 116(6.52)
完成 8 412(82.07) 6 748(79.67) 1 664(93.48)
表2 不同社会经济状况、感染状态及相关干预措施HBV母婴传播率
表3 6例发生HBV母婴垂直传播孕妇特征及其暴露儿童干预情况
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