【作者】 郭燕；

【导师】 杜玉开；

【作者基本信息】 华中科技大学 ， 儿少卫生与妇幼保健学， 2009， 博士

【摘要】 研究目的探讨影响乙肝母婴传播阻断干预措施选择的因素及主要干预措施的实质效果；对不同阻断措施的干预效果进行经济学评价，为选取最佳干预措施预防乙肝母婴传播提供科学依据。研究方法抽取武汉市2004年后住院分娩的、接受过系统产前检查的HBsAg阳性孕产妇及其婴儿进行回顾性现场调查研究和跟踪随访；调查方式为入户面对面问卷调查和一对一电话访谈。所有资料使用Spss10．0进行描述性分析、t检验、χ~2检验、非参数假设检验、单因素非条件logistic回归和多因素非条件logistic回归等统计学分析。研究结果1、阻断措施及效果：本研究中孕产妇HBsAg阳性率为8．67％。323例调查对象中232人(71．83％)孕期注射了HBIG，其中90．00％以上首次注射HBIG时间在孕晚期，80．00％以上注射了3次；注射HBIG的婴儿有293人(90．71％)，其中276人(94．20％)注射1次。258人(79．88％)分娩方式为剖宫产，其中29．84％因乙肝因素剖宫产；153名(47．37％)婴儿人工喂养，其中81．70％因乙肝因素人工喂养。HBsAg阳性孕产妇胎膜早破的发生率、剖宫产率和人工喂养率均高于正常组孕产妇，差异有统计学意义(P＜0．05)。323对调查的母子中，仅孕产妇在孕期注射过乙肝免疫球蛋白(HBIG)，23对(7．12％)；仅婴儿在出生后注射过HBIG(主被动免疫)，84对(26．00％)；孕产妇及其婴儿均注射过HBIG(母婴联合免疫)，209对(64．71％)；孕产妇及其婴儿均没有注射过HBIG，7对(2．17％)。阻断后宫内感染22人(6．81％)，全程接种疫苗后，10人转阴，其中3人有抗体，7人全阴。婴儿慢性感染者15人(4．64％)，其中10人为宫内感染，3人后期感染。婴儿6个月后乙肝标志物检测，154人有抗体(47．68％)。2、HBeAg与乙肝母婴传播：HBsAg阳性合并乙肝e抗原(HBeAg)阳性孕产妇63人(19．51％)。双阳组剖宫产率(90．48％)高于单阳组(77．31％)，差异有统计学意义(χ~2=5．4709，P=0．00193)；因乙肝因素剖宫产的比例双阳组(63．16％)也明显高于单阳组(20．40％)，差异有统计学意义(χ~2=38．7788，P＜0．0001)。单阳组母乳喂养比例较高(61．54％)，双阳组则多为人工喂养(84．13％)，两组喂养方式差异有统计学意义(χ~2=42．4181，P＜0．0001)。人工喂养原因中因乙肝因素者，双阳组(98．11％)明显高于单阳组(73．00％)，差异有统计学意义(Fisher’Exact Test，P＜0．0001)。双阳组宫内感染率和慢性感染率为25．40％和14．29％，明显高于单阳组的2．31％，差异有统计学意义(χ~2=42．5934，16．4303，P＜0．001)。3、影响阻断措施和效果的因素：单因素分析中与阻断方式、次数等有关的因素有孕产妇年龄、围产期职业、文化程度、家庭人均月收入、丈夫职业和文化程度、初次产前检查时间和地点、分娩时间和地点等；与阻断效果有关的有孕产妇HBV感染状态、孕期是否注射HBIG、分娩年龄、初次产前检查时间、婴儿注射HBIG次数、母乳喂养时间和分娩年份。多因素分析结果显示孕产妇分娩时年龄越大(OR=2．205)、孕产妇文化程度越高(OR=3．275)、家庭人均月收入越多(OR=1．693)、分娩时住院时间越短(OR=0．543)、分娩年份越早(OR=0．380)以及丈夫职业是员工类(公司职员／商业服务人员／工人／农民工)(OR=2．205)，孕产妇越趋向于选择孕期注射HBIG；婴儿注射HBIG次数越多(OR=3．873)、母乳喂养时间越长(OR=9．815)，婴儿6个月后越容易产生抗-HBs。4、经济学分析：减少宫内感染母婴联合阻断成本-效果比低于仅孕期阻断，减少婴儿慢性感染联合阻断成本-效果比低于仅婴儿阻断，增加抗体保护率的成本效果联合阻断优于仅孕期阻断，更优于仅婴儿阻断。三种措施挽回的DALY及成本-效用比联合阻断措施最优，敏感性分析和增量成本-效果(效用)分析后结论未变。研究结论1、近年来武汉市孕产妇乙肝病毒携带率呈现整体上升趋势。2、HBeAg阳性是影响乙肝母婴传播的重要因素，而孕产妇对其重视程度明显不足。3、HBsAg阳性孕产妇，尤其是合并HBeAg阳性者，更趋向于剖宫产和人工喂养，而本研究中亦未见剖宫产和人工喂养与否对乙肝母婴传播阻断后效果的差异有统计学意义，认为剖宫产和人工喂养并非阻断乙肝母婴传播的必要条件。4、乙肝母婴传播阻断措施的选择及效果不仅受个人、家庭因素影响，也与医疗环境息息相关。5、从经济学角度综合比较，母亲孕期注射HBIG并婴儿出生后联合注射HBIG和乙肝疫苗的母婴联合阻断措施不仅在相同总成本下能够降低较多宫内感染率和婴儿慢性感染率，挽回较多DALY，还能更有效提高婴儿抗体保护率，优于其他措施，是武汉市近几年乙肝母婴传播阻断措施中最优措施，值得推荐。更多还原

【Abstract】 ObjectivesTo explore the influential factors of choosing the blocking measures and the effects ofmain interventions. To evaluate the costs and effects of different blocking measures ofmother-to-child transmission of hepatitis B by the economic evaluation method, so as toselect the best intervention to prevent mother to child transmission of hepatitis B andprovide scientific evidence to the government and related departments to make reasonabledecisions.MethodsThe HBsAg-positive pregnant women and their children were taken out as studyobjects, who accepted prenatal care in district Maternal and Child Health Hospital ofWuhan City, from Jan 1st, 2004. Investigators who received strict training madeface-to-face or telephone interviews to these women with uniform questionnaires based ona voluntary and confidential principle. SPSS10.0 software was used to do data analysis,including descriptive analysis, t test. Chi-square test, nonparametric test, single factor andmulti-factor non-conditional logistic regression.Results1. Blocking measures and effectThe HBsAg positive rate among the pregnant women was 8.67%. 232 pregnant women (71.83%) were injected HBIG during pregnancy, and 90.00% of them began toinject in the third trimester of pregnancy. 90.00% of the pairs injected three needles. 293children were injected HBIG after birth, 94.20% of them accepted 1 needles. In the 323pregnant women, 258 (79.88%) had cesarean section, of which, 29.84% had cesareansection due to hepatitis B factors. 153 pregnant women (47.37%) developed artificialfeeding, 81.70% of which were owing to hepatitis B factors.The incidence of premature rupture of membranes, cesarean section and artificialfeeding of HBsAg positive pregnant women were higher than those of normal pregnantwomen, with statistically significant difference (P＜0.05).Among the 323 pairs of mothers and children, there were 23 pairs (7.12%) thatpregnant women without their children were injected HBIG during pregnancy. 84 pairs(26.00%) children alone were injected HBIG at birth and after birth (active and passiveimmunization). 209 pairs (64.71%) both pregnant women and their children were injectedHBIG (united maternal and child immunization). 7 pairs (2.17%) neither pregnant womennor their children were injected HBIG.Of the 323 infants, 22 (6.81%) infants suffered from intrauterine infection, 10 of themchanged to HBsAg negative after the full vaccination. 15 had HBsAg-positive at 6 monthsold (6.05%), 10 of them had been intrauterine infection. 154 (47.68%) infants hadHBsAb-positive at 6 months old.2. HBeAg and mother-to-child transmission of hepatitis B63 cases (19.51%) of HBsAg-positive pregnant women had HBeAg positive. In thesingle-positive group (only HBsAg-positive), the rate of cesarean section was 77.31%,20.40% of which were for the purpose to prevent HBV infection. And the rate of artificialfeeding was 38.46%, 73.00% of which were for the purpose to prevent HBV infection. Theintrauterine infection rate of newborns was 25.40%. The chronic HBV rate of children was14.29%. Among the double-positive group (HBsAg-positive and HBeAg-positive), the rateof cesarean section was 90.48%, 63.16% of which were for the purpose to prevent HBV infection. And the rate of artificial feeding was 84.13%, 98. 11% of which were for thepurpose to prevent HBV infection. The intrauterine infection rate of newborns was 2.31%.The chronic HBV rate of children was 2.31%. Comparing with the single-positive group,the double-positive group have significantly higher rate not only the caesarean section andthe artificial feeding (χ~2=38.7788, P＜0.0001;χ~2=42.4181, P＜0.0001), but also theintrauterine infection and the chronic HBV infection of children (χ~2=42.5934, P＜0.0001;χ~2=16.4303, P＜0.001).3. Factors of blocking measures and effectResults of single factor analysis indicated that some factors correlated to the methodsand times of blocking measures, including maternal age, perinatal occupation, educationlevel, family per capita monthly income, occupation and education level of husband, theinitial time and place of prenatal care, delivery time and location. And the effect of blockingmeasures was correlated with HBV infection status of pregnant women, injected HBIGduring pregnancy or not, birth age, the initial time of prenatal care, infant HBIG injectionfrequency, times of breast-feeding and birth year.After multi-factor analysis, we presumed that pregnancy HBIG injection was primarilyaffected by maternal age (OR=2.205), education level (OR=3.275), family per capitamonthly income (OR=1.693), birth year (OR=0.380), length of stay in hospital (OR=0.543)and husband occupation was staff occupational category (staff, business services staff,workers, migrant workers) (OR=2.205). If infants received more needles of HBIG injection(OR=3.873) and much longer breast-feeding (OR=9.815), they would be prone to haveHBsAb-positive at 6 months old.5. Economic evaluationThe cost effectiveness ratio (CER) of mother-infant combine blocking to decrease theintrauterine infection was lower than only pregnancy blocking. Comparing with the onlyinfant blocking, the total CER of mother-infant combine blocking to decrease the chronicHBV infection of children was lower, and the direct CER was higher. The CER of mother-infant combine blocking to increase the antibody protection ratio surpassed the onlypregnancy blocking and only infant blocking. Mother-infant combine blocking wasoptimization among the three measures when being evaluated by cost-utility analysis,sensitivity analysis and incremental cost effectiveness analysis.Conclusions1. Pregnant women carrying rate of hepatitis B virus showed an upward trend overall,in Wuhan City in recent years.2. Mother with HBeAg-positive is a high risk factor to the mother-to-childtransmission of HBV. However it was not given enough reconstruction by HBsAg-positivepregnant women.3. HBsAg-positive pregnant women, in particular the mergers of HBeAg-positive, tendto choose cesarean section and artificial feeding. And in this study, the effect of cesareansection and artificial feeding on preventing mother-to-child transmission of hepatitis B hadno significantly difference. Cesarean section and artificial feeding are not the necessaryconditions to prevent mother-to-child transmission of hepatitis B.4. The selection and effect of preventing mother-to-child transmission of hepatitis Bwill be affected not only by the individual, family factors, but also by the medicalenvironment.5. Comparison from an economic point of view, the measure that mothers inject HBIGduring pregnancy and their children inject HBIG and hepatitis B vaccine after birth couldreduce major rate of intrauterine infection and chronic HBV infection of children, restoremore DALY, and could more effectively improve the rate of infants` antibody protection atthe same cost. Therefore, it is superior to other measures on preventing mother-to-childtransmission of hepatitis B in Wuhan City in recent years and should be recommended.更多还原