HBsAg阳性孕产妇其幼儿乙型肝炎疫苗免疫应答情况及其影响因素

胡妮; 李芳; 续靖宁; 张莹; 严敏; 刘存; 张磊

doi:10.16462/j.cnki.zhjbkz.2020.11.003

HBsAg阳性孕产妇其幼儿乙型肝炎疫苗免疫应答情况及其影响因素

doi: 10.16462/j.cnki.zhjbkz.2020.11.003

胡妮^{1, 2},
李芳³,
续靖宁⁴,
张莹³,
严敏¹,
刘存²,
张磊^1, ,

1.
710032 西安，空军军医大学军事预防医学系流行病学教研室，特殊作业环境危害评估与防治教育部重点实验室
2.
710054 西安，西安市疾病预防控制中心科教信息科
3.
710061 西安，西北妇女儿童医院妇女保健科
4.
710061 西安，西北妇女儿童医院产一科

基金项目:

国家自然科学基金 81102140

国家自然科学基金 81472988

详细信息

通讯作者:
张磊，E-mail:drzhanglei@fmmu.edu.cn

中图分类号: R186.7
计量
- 文章访问数: 436
- HTML全文浏览量: 270
- PDF下载量: 60
- 被引次数: 0
出版历程
- 收稿日期: 2020-05-21
- 修回日期: 2020-07-14
- 刊出日期: 2020-11-10

The immune response to hepatitis B vaccine and its influencing factors of infants born to HBsAg positive mothers

HU Ni^{1, 2},
LI Fang³,
XU Jing-ning⁴,
ZHANG Ying³,
YAN Min¹,
LIU Cun²,
ZHANG Lei^{1
, ,}

1.
Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China
2.
Science, Education and Information Section, Center for Disease Control and Prevention Xi'an 710054, China
3.
Women's Health Division, China Northwest Women and Children Hospital, Xi'an 710061, China
4.
Obstetrics, China Northwest Women and Children Hospital, Xi'an 710061, China

Funds:

National Natural Science Foundation of China 81102140

National Natural Science Foundation of China 81472988

More Information

Corresponding author: ZHANG Lei, E-mail:drzhanglei@fmmu.edu.cn

摘要

摘要: 目的获取HBsAg阳性孕产妇其幼儿乙型肝炎(乙肝)疫苗无/弱应答的概率，分析其影响因素。方法对2016年1月至2017年4月在陕西省西北妇女儿童医院分娩的284对HBsAg阳性孕产妇及其幼儿进行研究，随访幼儿乙肝疫苗接种情况及血清学标志物产生情况。结果高危幼儿无/弱应答率为10.57%(28/237)。表面抗原(HBsAg)、e抗原(HBeAg)和核心抗体(HBcAb)均阳性的孕产妇其幼儿发生乙肝疫苗免疫无/弱应答率为19.64%，高于HBsAg、e抗体(HBeAb)和HBcAb均阳性的孕产妇的幼儿，其乙肝免疫无/弱应答率为9.89%(RR=1.99，95% CI：1.01~3.92，P＜0.001)。孕期有穿刺史者其幼儿发生无/弱应答的风险是无穿刺史者的6.72倍(RR=6.72，95% CI：2.79~16.19，P=0.049)，幼儿发生乙肝疫苗无/弱应答的孕产妇白蛋白(ALB)低于强应答组(t=2.518，P=0.013)，白球比(A/G)高于强应答组(t=-5.559，P＜0.001)。结论 HBsAg阳性孕产妇幼儿是乙肝疫苗无/弱应答的重点人群，其又处于母亲为传染源的高危环境中，应重点进行抗体监测。其孕期有创检查可能会增加幼儿发生乙肝疫苗无/弱应答的概率。HBsAg、HBeAg和HBcAb均表现为阳性的孕产妇幼儿有较高的乙肝疫苗免疫无/弱应答率。
- 乙型肝炎病毒 /
- 乙肝疫苗 /
- 免疫应答
Abstract: Objective To obtain the probability of no/weak immune response to the hepatitis B vaccine of infants born to HBsAg-positive parturients, so as to analyze its influencing factors. Methods A study of 284 pairs of HBsAg-positive pregnant women and their infants who gave birth at the Northwest Women and Childre's Hospital of Shaanxi Province from January 2016 to April 2017 was carried out to follow up of infant hepatitis B vaccination and the production of serological markers. Results The rate of immune deficiency and weak response in high-risk children was 10.57%. The rate of immune deficiency and weak response in pregnant women with "HBsAg+, HBeAg+, HBcAb+" infection pattern was 19.64%, which was significantly higher than that of pregnant women in "HBsAg+, HBeAb+, HBcAb+" mode, which was 9.89% (RR=1.99, 95% CI: 1.01-3.92, P < 0.001). The risk of HBsAg-positive mothers with puncture history during pregnancy was 6.72 times higher than that of children with no puncture history (RR=6.72, 95% CI: 2.79-16.19, P=0.049). The liver function albumin (ALB) of the mothers who had immune deficiency and weak response to hepatitis B vaccine in young children was significantly lower than that in the strong response group (t=2.518, P=0.013). The liver function-to-white ratio (A/G) of the mothers who had immune deficiency and weak response to hepatitis B vaccine was significantly higher than that of the strong response group (t=-5.559, P < 0.001). Conclusions Children born to HBsAg positive mothers are at high risk of immune deficiency and weak response to Hepatitis B vaccine and intrauterine transmission of hepatitis B. Therefore, we should focus on monitoring the HBsAb production of these people. Invasive testing during pregnancy may increase the risk of immune deficiency and weak response to Hepatitis B vaccine in young children. Children have a higher hepatitis B vaccine deficiency and weak response rate when their mother's serological testing remains "HBsAg+, HBeAb+, HBcAb+" mode.
- HBV /
- Hepatitis B vaccine /
- Vaccine response

HTML全文

表 1 2016-2017陕西HBsAg阳性产妇的社会人口学特征

Table 1. Social demographic characteristics of HBsAg positive parturients in Shaanxi from 2016 to 2017

指标	人数	构成比(%)
幼儿性别
男	142	53.58
女	123	46.42
民族
汉	262	98.87
其他	3	1.13
文化程度
初中以下	9	3.43
本科以下	2	0.76
本科及以上	251	94.71
生产方式
足月	136	51.32
早产	129	48.68
年龄(岁)
20~	58	21.89
30~	191	72.08
≥40	16	6.04
孕产史
有	139	52.45
无	126	47.55
家庭感染史
有	18	6.79
无	247	93.21

下载: 导出CSV

表 2 2016-2017陕西HBsAg阳性产妇HBV感染模式及对应幼儿乙肝疫苗应答情况

Table 2. HBsAg-positive maternal HBV infection patterns and corresponding hepatitis B vaccine responses in young children in Shaanxi from 2016 to 2017

HBV感染模式	N	乙肝疫苗应答			χ²值	P值	RR(95% CI)值
HBV感染模式	N	应答	无应答	无应答率(%)	χ²值	P值	RR(95% CI)值
模式一	56	45	11	19.64	3.874	0.049	1.99(1.01~3.92)
模式二	192	173	19	9.89	3.874	0.049	1.99(1.01~3.92)
注：HBV模式一是指HBsAg、HBeAg和HBcAb均为阳性；HBV感染模式二HBsAg、HBeAb、HBcAb均为阳性。

下载: 导出CSV

表 3 2016-2017陕西HBsAg阳性产妇产前肝功检查情况(x±s)

Table 3. Results of HBsAg positive maternal liver function test in Shaanxi from 2016 to 2017 (x±s)

指标	产妇 (N=265)	体检人群 (N=2 496)	t值	P值
ALT(μmol/L)	17.23±12.63	29.59±12.97	-15.228	＜0.001
AST(μmol/L)	25.59±11.88	24.66±9.46	1.498	0.134
TP(g/L)	57.51±7.42	76.19±3.96	-66.997	＜0.001
ALB(g/L)	31.46±6.33	48.00±2.87	-78.328	＜0.001
DBIL(μmol/L)	10.48±9.06	11.95±3.18	-5.730	＜0.001
A/G	1.57±2.77	1.73±0.28	-2.981	0.003

下载: 导出CSV

表 4 2016-2017年陕西幼儿免疫应答情况与HBsAg母亲肝功能指标的比较(x±s)

Table 4. Comparison of the immune response of young children in Shaanxi from 2016 to 2017 and the liver function indexes of HBsAg mothers (x±s)

指标	强应答组	无/弱应答组	t值	P值
ALT(μmol/L)	16.80±12.08	21.33±16.72	-1.571	0.118
AST(μmol/L)	25.21±11.00	29.14±18.25	-1.444	0.150
TP(g/L)	57.71±7.51	55.64±6.36	-1.219	0.224
ALB(g/L)	37.71±5.91	27.24±6.31	2.518	0.013
DBIL(μmol/L)	10.55±9.44	9.80±4.04	0.362	0.717
A/G	1.23±1.92	4.54±8.58	-5.559	＜0.001

下载: 导出CSV

参考文献(14)

[1]	李凡, 王廷材, 刘冰, 等.甘肃省武威市学龄前儿童乙肝疫苗接种和免疫效果调查[J].中华疾病控制杂志, 2012, 16(6):524-576. http://zhjbkzzz_cn.xml-journal.net/article/id/JBKZ201206021 Li F, Wang TC, Liu B, et al. HBV vaccination and immunization effects of preschool children in Wuwei, Gansu Province[J]. Chin J Dis Control Prev, 2012, 16(6):524-576. http://zhjbkzzz_cn.xml-journal.net/article/id/JBKZ201206021
[2]	杨汝沛, 王津涛, 李柯, 等.成都市2002-2005年出生儿童乙肝疫苗首针及时接种率及影响因素[J].中华疾病控制杂志, 2009, 13(3):267-269. Yang RP, Wang JT, Li K, et al. Analysis on timely birth dose coverage rate of hepatitis B vaccine and influential factors among children born between 2002 and 2005 in Chengdu[J]. Chin J Dis Control Prev, 2009, 13(3):267-269.
[3]	张磊, 邵中军. HBV宫内传播研究在乙型肝炎防控工作中发挥着重要的作用[J].中华流行病学杂志, 2019, 40(9):9-12. DOI: 10.3760/cma.j.issn.1055-1058.2019.09.000. Zhang L, Shao ZJ. Important role of study on intrauterine transmission of HBV in prevention and control of hepatitis B[J]. Chin J Epidemiol, 2019, 40(9):9-12. DOI: 10.3760/cma.j.issn.1055-1058.2019.09.000.
[4]	Isolani AP, Sversuti CS. Protection against hepatitis B by the Butang^® recombinant vaccine in newborn children in South Brazil[J]. Mem Inst Oswaldo Cruz, 2006, 101(5):551-553. DOI: 10.1590/S0074-02762006000500012.
[5]	Krawczyk A, Ludwig C, Jochum C, et al. Induction of a robust T- and B-cell immune response in non- and low-responders to conventional vaccination against hepatitis B by using a third generation PreS/S vaccine[J]. Vaccine, 2014, 32(39):5077-5082. DOI: 10.1016/j.vaccine.2014.06.076.
[6]	王静, 冯玉岭, 刘明晖, 等. HBsAg阳性母亲所生婴儿联合免疫后乙型肝炎表面抗体的动态变化[J].中华肝脏病杂志, 2013, 21(8):580-583. DOI: 10.3760/cma.j.issn.1007-3418.2013.08.005. Wang J, Feng YL, Liu MH, et al. Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein titer in infants born to mothers with positivity for hepatitis B surface antigen[J]. Chin J Hepatol, 2013, 21(8):580-583. DOI: 10.3760/cma.j.issn.1007-3418.2013.08.005.
[7]	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.
[8]	胡妮, 续靖宁, 李芳, 等.西安市HBsAg阳性产妇HBV宫内传播的流行病学研究[J].中华流行病学杂志, 2019, 40(9):13-18. DOI: 10.3760/cma.j.issn.1059-1064.2019.09. Hu N, Xu JN, Li F, et al. Epidemiology study of intrauterine transmission of HBV in HBsAg-positive parturients in Xi'an[J]. Chin J Epidemiol, 2019, 40(9):13-18. DOI: 10.3760/cma.j.issn.1059-1064.2019.09.
[9]	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.
[10]	郝建珍, 胡玉红, 易为, 等.羊水穿刺对HBVDNA阴性的慢性乙型肝炎病毒感染孕妇母婴垂直传播的影响[J].中华妇产科杂志, 2011, 46(10):778-779. DOI: 10.3760/cma.j.issn.0529-567x.2011.10.016. Hao JZ, Hu YH, Yi W, et al. The effect of amniocentesis on the vertical transmission of HBV DNA negative chronic hepatitis B virus infection in pregnant women[J]. Chin J Obstet Gynecol, 2011, 46(10):778-779. DOI: 10.3760/cma.j.issn.0529-567x.2011.10.016.
[11]	Yi W, Pan CQ, Hao JZ, et al. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers[J]. J Hepatol, 2014, 60(3):523-529. DOI: 10.1016/j.jhep.2013.11.008.
[12]	白玉炫, 张淑萍.乙肝五项指标组合模式及分析[J].职业与健康, 2001, 17(6):43. DOI: 10.3969/j.issn.1004-1257.2001.06.035. Bai YX, Zhang SP. The combination model and analysis of five indexes of hepatitis B[J]. Occupation and Health, 2001, 17(6):43. DOI: 10.3969/j.issn.1004-1257.2001.06.035.
[13]	江红秀, 韩国荣, 王翠敏, 等.乙型肝炎病毒e抗原阳性孕妇所生婴儿联合免疫接种后乙型肝炎病毒血清学标志物的动态变化[J].中华肝脏病杂志, 2011, 19(11):818-822. DOI: 10.3760/cma.j.issn.1007-3418.2011.11.007. Jiang HX, Han GR, Wang CM, et al. Abstract efficacy of combined vaccine for the prevention of HBV transmission in highly viremic HBeAg+ mothers and the HBV markers' dynamic change of babies in follow-up[J]. Chin J Hepatol, 2011, 19(11):818-822. DOI: 10.3760/cma.j.issn.1007-3418.2011.11.007.
[14]	刘智昱, 李夏雨, 颜雪梅, 等.应用巢式病例对照探讨HBV围生期传播的影响因素[J].中南大学学报(医学版), 2007, 32(3):451-454. DOI: 10.3321/j.issn:1672-7347.2007.03.017. Liu ZY, Li XY, Yan XM, et al. Using nested case control to explore the influencing factors of HBV perinatal transmission[J]. J Cent South Univ (Med Sci), 2007, 32(3):451-454. DOI: 10.3321/j.issn:1672-7347.2007.03.017.