原发性巨细胞病毒感染对妊娠的影响

目的　了解巨细胞病毒(CMV)感染对妊娠的影响。方法　收集确诊为原发性CMV感染并宫内传播的孕妇50例(怀51胎)。通过羊膜穿刺术和超声检查对胎儿进行评估。在孕龄21 周后,通过羊腹腔穿刺术取羊水做病毒分离培养,聚合酶链反应(PCR)分析。通过新生儿的尿液病毒分离培养或流产胎儿的组织活检确定新生儿是否感染CMV;对18例存活的新生儿进行脑超声检查、听力评估、智力发育状况评价等研究。结果　50例孕妇中33例(66%)选择终止妊娠;11 例(21.5%)超声检查异常的胎儿与宫内胎儿CMV感染有关,其中2 例继续妊娠至足月,两者均属先天性感染,其中1例出现神经功能异常。聚合酶链反应和病毒分离培养法对50例孕妇(怀51胎)进行评价的阳性预测值分别为92.0%和93.7%。17例孕妇(怀18胎)继续妊娠至足月;4例新生儿神经功能异常,其中3例产前超声检查正常;余下14例新生儿经评估证实正常。结论　羊水CMV分离培养阳性,同时PCR阳性的对象中,约94%病例被为宫内CMV感染。产前超声检查正常的胎儿中,产后出现神经功能异常的危险性为19%(3/16)。     

阻断乙肝病毒宫内感染失败的原因与对策

目的 探讨宫内感染阻断失败的原因及治疗对策.方法 选择住院分娩HBV感染的孕妇1411例及所分娩的婴儿,观察母亲不同E抗原状况、不同HBV DNA载量、不同分娩方式、抗病毒治疗情况与HBV宫内感染的关系.结果 母亲HBeAg(+)组婴儿出生时及12月龄时HBV感染率均明显高于母亲HBeAg(-)组(P=0.000,P=0.006)；母亲HBV DNA载量与婴儿出生时及12月龄时HBV感染率呈正相关；阴道分娩组婴儿出生时HBV感染率明显高于剖宫产组(P=0.000),但12月龄时两者差异无显著性(P=0.137)；母亲非抗病毒组婴儿出生时及12月龄时HBV感染率均明显高于母亲抗病毒组(P=0.042,P=0.048).结论 乙肝病毒宫内感染阻断失败主要与母亲HBV感染状况如血清HBeAg阳性、较高的HBV DNA载量等高危因素有关,而与分娩方式无关.给高病毒载量孕妇在妊娠中晚期使用抗病毒药物,可以降低母亲的HBV DNA载量,从而有效减少宫内传播.     

原发性巨细胞病毒感染对妊娠的影响

目的了解巨细胞病毒(CMV)感染对妊娠的影响。方法收集确诊为原发性CMV感染并宫内传播的孕妇50例(怀51胎)。通过羊膜穿刺术和超声检查对胎儿进行评估。在孕龄21周后，通过羊腹腔穿刺术取羊水做病毒分离培养，聚合酶链反应(PCR)分析。通过新生儿的尿液病毒分离培养或流产胎儿的组织活检确定新生儿是否感染CMV；对18例存活的新生儿进行脑超声检查、听力评估、智力发育状况评价等研究。结果50例孕妇中33例(66％)选择终止妊娠；11例(21．5％)超声检查异常的胎儿与宫内胎儿CMV感染有关，其中2例继续妊娠至足月，两者均属先天性感染，其中1例出现神经功能异常。聚合酶链反应和病毒分离培养法对50例孕妇(怀51胎)进行评价的阳性预测值分别为92．0％和93．7％。17例孕妇(怀18胎)继续妊娠至足月；4例新生儿神经功能异常，其中3例产前超声检查正常；余下14例新生儿经评估证实正常。结论羊水CMV分离培养阳性，同时PCR阳性的对象中，约94％病例被为宫内CMV感染。产前超声检查正常的胎儿中，产后出现神经功能异常的危险性为19％(3／16)。     

血液系统恶性肿瘤患者巨细胞病毒和EB病毒定量检测的临床价值

目的评价实时荧光定量聚合酶链反应对血液系统恶性肿瘤患者巨细胞病毒(CMV)感染和EB病毒(EBV)感染的早期诊断价值。方法应用实时荧光定量PCR检测334例血液系统恶性肿瘤患者血液中CMV DNA和EBV DNA载量。结果 334例患者中EBV检测阳性率为13.2%,CMV检测阳性率为19.2%,DNA拷贝数介于(102~107)copy/mL之间。治疗有效者EBV DNA和CMV DNA载量迅速下降,2~3周后转阴。结论实时荧光定量PCR动态监测血液系统恶性肿瘤患者CMVDNA和EBV DNA水平对于CMV感染和EBV感染的早期诊断和疗效判断具有重要意义。     

HBeAg阳性孕妇及其婴幼儿HBV感染特征分析

目的探讨HBeAg阳性孕妇及其婴幼儿垂直感染HBV的生物特征与发展预后。方法对收集到28例HBeAg阳性孕妇及其28例婴幼儿进行乙肝5项血清学检测,采用常规病毒核酸检测(NAT)、实时荧光定量检测方法(QPCR)、巢式PCR扩增S基因的分子检测手段确认HBV DNA存在与基因分型,并追踪随访婴幼儿感染预后情况。结果 28例HBeAg阳性母亲,75%(21/28例)为大三阳HBV感染模式(HBsAg/HBeAg/抗-HBc阳性),病毒载量范围显著最高(P0.05),基因分型以B型为主(占72%);28例HBeAg阳性母亲的婴幼儿,有28.57%(8/28例)出现HBV感染,其中5例为HBsAg阴性/HBeAg阳性、3例为HBsAg阳性/HBeAg阳性,该8例婴幼儿其母亲均为大三阳HBV感染,故本研究中大三阳母亲其婴幼儿HBV感染率为38.09%(8/21)。追踪随访3例HBsAg阴性/HBeAg阳性/HBV DNA阳性婴幼儿,100%(3/3)出现HBeAg/HBV DNA均转阴而自然康复。通过比较分析发现,HBV DNA载量106IU/mL乙肝孕妇组的婴幼儿HBV感染率显著高于病毒载量106IU/mL孕妇组(P0.05)。另外获得6例HBsAg阳性孕妇脐静脉血,有50%(3/6例)出现HBeAg/HBV DNA阳性。结论 HBeAg阳性母亲群体垂直传播HBV风险性较HBsAg孕妇高,对于大三阳感染模式的高病毒载量孕妇更是如此;HBeAg可经胎盘传递给新生儿,但HBsAg阴性/HBeAg阳性婴儿在12月龄前HBeAg可转阴,而HBsAg阳性/HBeAg阳性婴幼儿感染预后有待进一步研究。     

恶性血液病患者并发病毒感染的临床研究

目的　了解恶性血液病患者EB病毒 (EBV)及巨细胞病毒 (MCV)的感染率及危险因素。方法　应用巢式聚合酶链反应 (PCR)检测患者血清中EBV DNA及CMV DNA。结果　恶性血液病患者EBV、CMV感染率为 2 3.0 %、4 7.2 % ,使用大剂量肾上腺皮质激素及有输血史者是其危险因素。结论　恶性血液病患者是病毒感染的高危人群 ,应采取相应的措施 ,以予防治     

早产儿先天性巨细胞病毒感染特点及危险因素分析

目的 调查早产儿先天性巨细胞病毒（CMV）感染状况,分析其特点及危险因素。方法 选择住院的早产儿,分别采用荧光定量PCR（FQ-PCR）法和ELISA法检测脐血血清CMV IgM与DNA。同时记录新生儿和母亲的人口学信息,采用二元多因素logistic回归分析早产儿先天性CMV感染相关影响因素。结果 共纳入1315例早产儿,血清CMV IgM和（或）CMV DNA阳性者占1.98%（26/1315）,CMV IgM阳性者占1.44%（19/1315）,血清CMV DNA阳性者占1.14%（15/1315）,CMV IgM与CMV DNA均为阳性者占0.61%（8/1315）。早产儿先天性CMV感染症状较为轻微。母亲年龄< 25岁、初次妊娠、孕期胎膜早破是早产儿先天性CMV感染的危险因素（P均< 0.05）。结论 早产儿先天性CMV感染发生率较高,以无症状感染为主。提高年轻育龄妇女对CMV的知晓率、加强早产儿先天性CMV感染的管理是很有必要的。     

联合免疫对HBV母婴传播阻断效果的观察

目的探讨不同免疫方法对乙型肝炎(乙肝)病毒(HBV)母婴传播的阻断作用。方法以HBsAg阳性孕妇及其婴儿为研究对象,按不同阻断方式分组,孕晚期孕妇及其新生儿注射乙肝免疫球蛋白(HBIG),同时对新生儿联合采用乙肝疫苗(HBVV)注射(A组,126例);仅新生儿联合使用HBIG及HBVV(B组,102例);仅新生儿进行HBVV接种(C组,215例)。检测A组孕妇血液HBV DNA含量变化,比较各组新生儿宫内感染率及1岁后感染率。结果 A组孕妇使用HBIG前后血液HBVDNA含量差异无统计学意义;A、B、C组新生儿宫内感染率分别为4.76%、4.92%和4.65%,差异无统计学意义,新生儿1年后感染率分别为5.92%、4.93%、8.3%,C组感染率与A、B组比较差异有统计学意义(P<0.05)。结论孕期使用HBIG不能降低孕妇病毒载量,对HBV宫内传播无保护作用;对新生儿联合使用HBIG及HBVV能减低HBV感染率。     

唐氏综合征筛查高危孕妇行羊水穿刺的影响因素及护理干预

目的分析唐氏综合征筛查高危孕妇行羊水穿刺的影响因素,提出护理干预措施。方法选取本院2009年11月至2011年8月收治的420例唐氏筛查高危的孕妇作为研究对象,对可能影响孕妇进行唐氏综合征羊水穿刺筛查的因素进行分析,并提出相应的护理对策。结果420例高危孕妇中360例进行羊水穿刺,年龄、家庭月收入、对唐氏筛查的了解、医生的建议、参加孕妇学校、信息可得性以及对自身健康的评价状态都是唐氏筛查的影响因素（P〈0．05）。Logistic回归分析发现年龄、医生的建议、文化程度和对筛查的了解是主要影响因素（P〈0．05）。结论高危孕妇进行唐氏筛查羊水穿刺是十分必要的,应针对其影响因素采取必要的护理干预,以提高筛查的依从性和新生儿出生质量。     

探讨乙型肝炎病毒母婴垂直传播的相关因素

目的探讨乙型肝炎病毒(HBV)在母婴垂直传播中的几个相关因素。方法采用酶联免疫吸附(ELISA)及荧光定量PCR法对产前孕妇进行HBV两对半免疫学标志联合测定和HBV DNA载量检测;新生儿分娩后取脐血检测HBV两对半免疫学测定。结果(1)乙肝表面抗原(HBsAg)阳性母亲的新生儿脐血HBsAg(或HBeAg)阳性率37.86%,阴道顺产的新生儿脐血HBsAg(或HBeAg)阳性率34.06%,剖宫产的新生儿脐血HBsAg(或HBeAg)阳性率42.86%;(2)血清HBsAg、HBeAg均阳性组88.57%孕妇血清HBV DNA≥105拷贝/ml;血清HBsAg阳性、HBeAg阴性组83.87%孕妇血清HBV DNA≤104拷贝/ml;(3)孕妇血清HBV DNA≥105拷贝/ml组新生儿脐血HBsAg(或HBeAg)阳性率65.45%,血清HBV DNA≤104拷贝/ml组新生儿脐血HBsAg(或HBeAg)阳性率17.58%。(4)HBsAg阳性孕妇在孕20周后多次肌注HBIG,一定程度上可降低HBV母婴垂直感染率。结论(1)剖宫产并不能降低HBsAg阳性母亲的新生儿脐血HB-sAg(或HBeAg)阳性率。(2)孕妇血清同时存在HBeAg阳性组血HBV DNA载量明显高于HBeAg阴性组。(3)孕妇血清HBV DNA拷贝数与新生儿脐血乙肝阳性率呈正相关,尤其当HBV DNA≥105拷贝/ml时新生儿脐血乙肝阳性率明显增高。(4)提倡对HBsAg阳性孕妇孕中晚期间隔4周多次肌注HBIG,孕期积极干预以降低胎儿宫内HBV感染。     

New developments in the diagnosis of maternal and congenital CMV infection

Recent advances in the screening of pregnant women with Cytomegalovirus (CMV) IgM, CMV IgG and CMV IgG avidity serologic tests, has led to a more accurate diagnosis of CMV infection. When serologic screening is performed early in gestation, it is possible to identify those women at risk of intrauterine transmission of the virus, i.e., those women with a primary CMV infection, who should be enrolled in prenatal diagnosis. The use of quantitative PCR on amniotic fluid from pregnant women at 21-22 weeks of gestation in prenatal diagnosis is an effective diagnostic tool to distinguish between CMV infection and CMV disease in the fetus and newborn. Quantitative PCR on peripheral blood leukocytes from CMV infected newborns can be used to monitor viral load, especially during treatment with ganciclovir. These advances in serology and quantitative virology should lead to more accurate diagnosis of maternal and congenital CMV infection.     

Prevalence of Cytomegalovirus DNA in Cord Blood and Voided Urine Obtained from Pregnant Women at the End of Pregnancy

Objective

This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine.

Subjects and Methods

Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤10³ copies/µl, intermediate when the viral load = 10³−10⁴ copies/µl, and high when the viral load >10⁴ copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses.

Results

Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR.

Conclusion

This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.Key Words: Active cytomegalovirus infection, Cord blood, Maternal urine, Polymerase chain reaction, Viral load     

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection

The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0–55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4–37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5–48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy.     

广东省顺德地区6 503例孕中期羊水染色体核型结果分析

目的 探讨羊水细胞异常核型发生的频率、类型与不同产前诊断指征之间的关系,评估羊水穿刺术诊断染色体疾病的临床价值。方法 选取2009年7月～2018年7月在广东医科大学顺德妇女儿童医院产前诊断中心具有产前诊断指征的孕妇6 503例,进行羊水穿刺,胎儿羊水细胞染色体核型分析。结果①6 503例羊水细胞中,检出染色体异常核型358例,异常率5.51%。染色体数目异常264例,其中21三体128例,18三体51例,13三体20例,性染色体数目异常65例; 染色体的结构异常66例; 嵌合体28例。各产前诊断指征中,染色体异常检出率分别为3.34%,3.15%,61.95%,17.22%,37.14%,5.60%和0.62%,经χ²检验发现,高龄组与血清学筛查高风险组,高龄组与不良孕产史组,血清学筛查高风险组与不良孕产史组,差异均无统计学意义(χ2=0.147～2.279,均P>0.05); 其余各组之间两两比较,差异均有统计学意义(χ2=7.411～997.801,均P<0.01)。②2 456例高龄孕妇中,年龄35～39岁组与年龄≥40岁组胎儿染色体异常检出率分别为2.70%和5.63%,两者比较,差异有统计学意义(χ2=11.059,P<0.01)。③无创产前基因筛查(NIPT)对21三体、18三体和13三体的检测准确度分别为80.28%,75.86%和44.00%,对性染色体异常的检测准确度为55.17%,对其他染色体异常的检测准确度为22.73%。结论 ①对具有明确产前诊断指征的孕妇行羊膜腔穿刺术,进行羊水细胞染色体核型分析非常重要,可有效地检出染色体异常胎儿,避免其出生,提高人口素质。②高龄孕妇,尤其是≥40岁的高龄孕妇,进行产前诊断非常必要。③NIPT对筛查胎儿染色体疾病准确率较高,但只是筛查手段,不能完全代替羊水细胞核型分析。     

Congenital cytomegalovirus infection: patterns of fetal brain damage

Clin Microbiol Infect 2012; 18: E419-E427 ABSTRACT: Cytomegalovirus (CMV) is the most prevalent infectious agent causing neurological dysfunction in the developing brain. This study analysed the different patterns of tissue damage, particularly in the brain, of fetuses with documented CMV infection. We studied 45 fetuses at 20-21?weeks of gestation with congenital CMV infection documented by invasive positive prenatal diagnosis. At the time of amniocentesis, abnormal ultrasound findings had been recorded for 13 of the 45 fetuses (29%). Histological and immunohistochemical characterization was performed on the placenta, brain, heart, lung, liver, kidney, and pancreas. The different degrees of brain damage were correlated with tissue viral load, inflammatory response, placental functionality, and extramedullary haematopoiesis. Even though a high CMV load was detected in all amniotic fluids, brain infection occurred in only 62% of the fetuses and with different degrees of severity. Tissues with a low viral load showed a globally weak inflammatory response, and fetuses had only mild brain damage, whereas tissues with a high CMV load showed prominent infiltration of the activated cytotoxic CD8(+) T-lymphocytes responsible for immune-mediated damage. Furthermore, severe placental infection was associated with diffuse villitis and necrosis, consistent with functional impairment and possible consequent hypoxic cerebral damage. Brain injury induced by CMV congenital infection may be the result of uncontrolled viral replication, immune-mediated damage by cytotoxic CD8(+) T-lymphocytes, and, in the presence of placental insufficiency, fetal hypoxia.     

A cohort study of maternal screening for congenital Toxoplasma gondii infection: 12 years' experience

Primary infection with Toxoplasma gondii (T. gondii) during pregnancy may cause congenital infection of the infant. This study evaluated whether screening using IgG avidity and multiplex-nested polymerase chain reaction (PCR) methods was effective for detecting a high-risk pregnancy for congenital T. gondii infection. In a prospective cohort study serum T. gondii IgG avidity was measured in 469 pregnant women who had a positive test for T. gondii antibody plus a positive or equivocal test for IgM. Multiplex-nested PCR for T. gondii DNA on amniotic fluid, maternal blood, and neonatal blood was performed with informed consent. Low (<30%), borderline (30–35%), and high (>35%) IgG avidity indices were found in 104 (22.2%), 30 (6.4%), and 305 (71.4%), respectively. A total of 12 cases had a positive PCR test for amniotic fluids of the prenatal amniocentesis or at birth, or neonatal blood. Seven of the 12 cases were diagnosed as having congenital T. gondii infection, and they had low IgG avidity indices. Congenital T. gondii infection screening using of IgG avidity and multiplex-nested PCR methods for pregnant women with a positive test for T. gondii antibody plus a positive or equivocal test for T. gondii IgM was useful for detecting a high-risk pregnancy and diagnosing congenital T. gondii infection.     

胎膜早破后残余羊水量对母婴的影响

目的探讨胎膜早破后残余羊水量对母婴的影响。方法对397例胎膜早破孕妇的临床资料进行回顾性分析,根据残余羊水指数（AFI）的多少分成3组,即羊水正常组（80mm〈AFI≤180mm）,羊水偏少组（50mm（AFI≤80mm）,羊水过少组（AFI≤50ram）,对不同残余羊水指数孕妇的分娩方式及胎儿窘迫、宫内感染率、新生儿发病率进行比较。结果羊水过少组较羊水偏少组及羊水正常组剖宫产率、胎儿窘迫发生率、胎儿宫内感染率、新生儿发病率高,差异有统计学意义。结论胎膜早破后残余羊水量过少会促使宫内感染率增加,影响胎儿、新生儿的生命安全,残余羊水指数可作为临床监测胎儿宫内安危的指标,予合理干预,选择正确的分娩方式,提高产科质量。     

Overview of congenitally and perinatally acquired cytomegalovirus infections: recent advances in antiviral therapy

Congenital and perinatal infection with human cytomegalovirus (CMV) are commonly encountered in newborns. In recent years there has been increased awareness of the disabilities that result from congenital CMV infection, which in turn has prompted interest in examining the potential efficacy of antiviral agents to prevent or ameliorate neurodevelopmental injury. Currently, there are three licensed systemic antivirals for the treatment of CMV: ganciclovir (Cytovene, Roche] and its prodrug valganciclovir [Valcyte, Roche); foscarnet (Foscavir, AstraZeneca); and cidofovir (Vistide, Pharmacia). A CMV-specific immunoglobulin is also available. Experience with these agents in the setting of congenital and perinatal CMV infection is very limited, but there are encouraging data from a controlled clinical trial indicating that ganciclovir therapy may be of value in limiting one form of neurodevelopmental injury caused by congenital infection, that of sensorineural hearing loss. Licensed antivirals for the treatment of CMV all share the common mechanism of targeting the viral DNA polymerase, but novel therapies that employ alternative modes of action are in development. Ultimately, the problem of perinatal CMV infection may be best controlled by the development of CMV vaccines, which could be administered to young women of childbearing age to help control this important public health problem.     

Prenatal diagnosis of cytomegalovirus infection

Prognostic value of markers of cytomegalovirus infection (CMV) in pregnant women for the neonatal status was assessed. Detection of such markers as antiCMV IgM and CMV DNA in cervical secretion by DNA dot-spot hybridization in women with a complicated course of pregnancy indicates a 5.7% risk of delivery of children with stable symptoms. Studies of antibodies to pre-early proteins (IE CMV) showed that antiCMV IgG to IE are more incident in pregnant women than antiCMV IgM; moreover, antiCMV IgG to IE but not antiCMV IgM are detected in umbilical blood. The results of detection of antiCMV IgG and IgM to IE correlated with the clinical characteristics of newborns.