巨细胞病毒抗体阳性孕妇母婴传播高危群体的鉴别新方法研究

Primary or recurrent infection of cytomegalovirus in pregnant woman leads to congenital infection in newborn and results in the permanent sequelae in 15~20% of the latter. The dogma that congenitally infected children who are born to women with preexisting antibodies have normal outcomes has led to inattention to congenital CMV in developing countries. Emerging data from highly seropositive populations, which are usually in developing countries, however, suggest that not only is the rate of congenital CMV infection higher than in developed countries but it is an important cause of hearing loss. The utility of traditional IgM and IgG detection in pregnant is wildly questioned for their low sensitivity and specificity in detecting maternal recurrent CMV infection. It is urgently needed to develop new method to identify population with high-risk of intrauterine transmission. Using a recombinant PP150 antigen of CMV, we had detected the anti-CMV IgG levels in serial sera collected from a natural population. The results showed that the baseline antibody level is closely associated with the risk of recurrent CMV infection (risk ratio=11.1, 95%CI 7.7-14.3). The findings suggest the potential usage of quantifying maternal anti-PP150 IgG levels in predicting the risk of congenital infection. In this project, we plan to establish a longitudinal cohort of women who are in their early phase of pregnancy. The cohort will be prospectively followed up for the occurrence of active CMV infection during their pregnancy and also the occurrence of congenital infection in their newborns. The primary object is to validate the value of baseline anti-PP150 levels in prediction the risk of congenital infection. The second object is to develop an easily-operate assay to quantitative the anti-PP150 levels based on chemical luminescent principle.

孕期巨细胞病毒（CMV）的新发或再发感染导致新生儿先天感染并影响其神经发育，造成约15~20%患儿出现耳聋、智障等永久性缺陷。过去曾认为我国等CMV高流行区由于大多数妇女孕前已有抗体，因此先天感染威胁较小。然而近年来研究发现阳性孕妇中约1%出现新生儿先天感染。传统的IgM和IgG抗体检测用于孕妇再发感染诊断的灵敏度和特异度广受质疑，亟需发展鉴别母婴传播高危群体的新方法。本课题组曾利用CMV PP150抗原对自然人群系列血清进行IgG抗体检测，发现再发感染风险与基线抗体水平密切相关（RR=11.1，95%CI 7.7-14.3），提示用于鉴别CMV母婴传播高危群体的可能性。本课题拟建立孕早期孕妇队列并随访孕期活动性感染和新生儿先天感染情况，探讨与基线抗体水平的相关性，研究这一新方法对母婴传播高危群体的预测价值，并发展出可便捷定量的化学发光法试剂，为CMV先天感染的防控提供新思路和新工具。

孕期巨细胞病毒（CMV）的新发或再发感染导致新生儿先天感染并影响其神经发育，造成约15~20%患儿出现耳聋、智障等永久性缺陷。本研究主要目的是建立孕早期孕妇队列并随访孕期活动性巨细胞病毒（Cytomegalovirus, CMV）感染和新生儿先天性CMV感染情况，探讨其与基线抗体水平的相关性，并研究这一新方法对母婴传播高危群体的预测价值。项目2014年启动，以“巨细胞病毒抗体阳性孕妇母婴传播高危群体的鉴别新方法研究”为核心，首先启动预实验“在校女大学生巨细胞病毒活动性感染的流行病学研究“和”新生儿巨细胞病毒感染的流行病学调查“，并基于其主要结果结论，进一步开展”巨细胞病毒母婴传播风险队列研究“进行母婴传播高危群体预测的探索。研究发现中国河南省先天性CMV感染率为1.31%。绝大多数孕妇(95.8%)在怀孕早期已感染CMV，孕早期孕妇低抗体水平是新生儿先天性CMV感染的危险因素。孕早期母亲抗体水平、新生儿身长及胎数，具有预测先天性CMV感染发生的潜在价值。研究期间所获成果已申请通过中国知识产权局及美国专利商标局专利，发表三篇SCI文章，拟继续撰写发表若干篇SCI文章。研究本身及所获成果已加深了对公众特别是科研开展地区对先天性CMV感染的认知及重视，为CMV在中国的流行情况提供了重要的数据支持，并为将来拟定防控策略提供了科学线索。