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孕妇高 IgG 亲和指数时的巨细胞病毒 DNA 检测:诊断非原发性感染的有用工具?

Cytomegalovirus DNA detection in pregnant women with a high IgG avidity index: a valuable tool for diagnosing non-primary infections?

机构信息

Diagnostic Services Laboratory, Hellenic Pasteur Institute, Athens, Greece.

Department of Mathematical Sciences and Informatics and Health Research Institute (IdISBa), University of the Balearic Islands (UIB), Palma, Balearic Islands, Spain.

出版信息

J Matern Fetal Neonatal Med. 2022 Dec;35(25):9399-9405. doi: 10.1080/14767058.2022.2038130. Epub 2022 Feb 9.

Abstract

BACKGROUND/AIM: Congenital human cytomegalovirus infection (cCMV) is the commonest congenital infection, and it can result in hearing loss and neurodevelopmental delay. Even if primary infections are more frequent and cause more severe congenital cCMV manifestations compared to NPIs, and despite partial protection from maternal immunity, the highest birth prevalence of cCMV is observed in seropositive women with non-primary CMV infection (NPI). Given that NPI contribute significantly to the overall burden of cCMV, their accurate diagnosis of NPI remains clinically important. Considering that the serological testing for CMV infection is not always reliable, we sought to determine whether detection of CMV DNA in pregnant women with a high IgG avidity index (AI) can help diagnose NPI.

MATERIALS AND METHODS

Human CMV serology screening (IgG, IgM, and IgG AI) was performed for confirmation of CMV infection in serum samples from mainly pregnant women with indications of CMV infection due to IgG and IgM-positive samples in other laboratories. Pregnant women (or those with termination of pregnancy during the last period) with adequate IgG levels to perform IgG AI were included. Demographic data and mean gestation week at the time of screening were recorded. Serological testing was performed using CE-IVD commercial kits. CMV DNAemia detection by real time PCR (RT-PCR) was applied to confirm suspected CMV infection.

RESULTS

Nine-hundred and thirty-four pregnant women CMV IgG positive with adequate IgG titers for AI testing were included in the study. The percentage of women with a high AI was 71.8% (671/934); among them, nearly 2.4% (16/671) had presence of CMV DNA. Also, 12.4% of women (116/934) had intermediate IgG AI and 15.7% of women (147/934) had low IgG AI. The presence of CMV DNA was observed in 13.8% (16/116) and 39.5% (58/147) of the groups with intermediate and low IgG AI, respectively. A high CMV IgG AI was associated with a negative CMV PCR status (-value <.00001).

CONCLUSIONS

CMV DNA was present in 2.4% of seropositive women with high IgG AI, indicating active NPI and thus, harboring the risk of cCMV sequelae to the fetus. Moreover, the incidence of NPI may have been underestimated due to single timepoint testing. In order to detect CMV NPI in a seropositive woman, regular and frequent serology testing as well as detection of CMV DNAemia are required which render the whole diagnostic process impractical and not cost-effective.

摘要

背景/目的:先天性人类巨细胞病毒感染(cCMV)是最常见的先天性感染,可导致听力损失和神经发育迟缓。即使原发性感染比非原发性感染(NPI)更频繁且导致更严重的先天性 cCMV 表现,并且尽管母体免疫有一定的保护作用,但在 IgG 阳性且非原发性 CMV 感染的女性中,cCMV 的出生患病率最高。鉴于 NPI 对 cCMV 的总体负担有重大贡献,准确诊断 NPI 在临床上仍然很重要。鉴于 CMV 感染的血清学检测并不总是可靠,我们试图确定在 IgG 亲和力指数(AI)较高的孕妇中检测 CMV DNA 是否有助于诊断 NPI。

材料和方法

对主要因 IgG 和 IgM 阳性样本而在其他实验室有 CMV 感染指征的孕妇血清样本进行 CMV 血清学筛查(IgG、IgM 和 IgG AI),以确认 CMV 感染。纳入 IgG 水平足以进行 IgG AI 检测且有足够 IgG 水平的孕妇(或在最后阶段终止妊娠的孕妇)。记录人口统计学数据和筛查时的平均妊娠周数。使用 CE-IVD 商业试剂盒进行血清学检测。应用实时 PCR(RT-PCR)检测 CMV DNA 血症以确认疑似 CMV 感染。

结果

本研究纳入了 934 名 CMV IgG 阳性且 IgG AI 检测有足够 IgG 滴度的孕妇。高 AI 百分比为 71.8%(671/934);其中,近 2.4%(16/671)存在 CMV DNA。此外,12.4%的女性(116/934)有中等 IgG AI,15.7%的女性(147/934)有低 IgG AI。在中等 IgG AI 和低 IgG AI 组中,分别观察到 13.8%(16/116)和 39.5%(58/147)的女性存在 CMV DNA。高 CMV IgG AI 与 CMV PCR 阴性状态相关(-值<.00001)。

结论

在 IgG AI 高的血清学阳性妇女中,有 2.4%存在 CMV DNA,提示存在活动性 NPI,从而使胎儿有发生 cCMV 后遗症的风险。此外,由于单次检测,可能低估了 NPI 的发生率。为了在血清学阳性的妇女中检测 CMV NPI,需要定期频繁的血清学检测和 CMV DNA 血症检测,这使得整个诊断过程不切实际且不具有成本效益。

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