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双胎妊娠中的先天性巨细胞病毒感染:羊水病毒载量与妊娠结局

Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome.

作者信息

Lazzarotto Tiziana, Gabrielli Liliana, Foschini Maria Pia, Lanari Marcello, Guerra Brunella, Eusebi Vincenzo, Landini Maria Paola

机构信息

Section of Microbiology, Department of Clinical and Experimental Medicine, St Orsola Malpighi General Hospital, University of Bologna, Bologna, Italy.

出版信息

Pediatrics. 2003 Aug;112(2):e153-7. doi: 10.1542/peds.112.2.e153.

Abstract

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks' gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 10(3) genome equivalents (GE)/mL of females AF and 1.9 x 10(5) GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 x 10(4) GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.

摘要

人巨细胞病毒(CMV)是病毒宫内感染和胎儿损伤的最常见原因,这在很大程度上归因于母亲的原发性感染。文献报道的双胞胎先天性CMV感染病例大多仅涉及1个胎儿。我们评估了在妊娠21至22周且血清转化后至少6至8周时,对羊水(AF)进行聚合酶链反应(PCR)和定量PCR以预测双胎妊娠新生儿结局的有效性。对2例双胎妊娠孕妇和1例三胎妊娠孕妇进行了评估,她们因存在免疫球蛋白(Ig)M和低IgG亲和力和/或存在临床症状及肝酶值异常而被定义为原发性CMV感染。在6例胎儿/新生儿中发现了CMV感染,其中3例有症状。在第一例双绒毛膜双羊膜囊双胎妊娠中,通过羊水病毒分离阳性和高病毒载量证实了女性胎儿的CMV症状性感染。羊水CMV培养和DNA检测均为阴性,表明男性胎儿未感染。在三胎妊娠中,该孕妇有一个胎盘,其中有2个单卵双胎(女性),另一个单独的胎盘中有一个异卵双胎(男性)。定量PCR结果显示,女性羊水的病毒载量为10³基因组当量(GE)/mL,男性羊水的病毒载量为1.9×10⁵ GE/mL。出生时,两个女性胎儿均无症状,而男性胎儿出现瘀点、血小板减少和脑室扩大。在最后一例双绒毛膜胎盘融合的双胎妊娠中,与产前诊断相反,出生时诊断出两个胎儿均有先天性CMV感染。在羊膜穿刺术时,左侧胎儿羊水CMV培养和DNA检测结果均为阴性,表明未感染。右侧胎儿羊水CMV DNA检测阳性,CMV DNA载量为4.9×10⁴ GE/mL,病毒分离阳性,表明感染了CMV。胎盘的形态学和组织学检查有力地支持了CMV感染的产前水平传播。这些双胎妊娠在产前诊断记录的病毒载量数量上有显著差异,表明双胎胎儿尽管受到相同的母体影响,但对母亲原发性感染的反应可能不同。高病毒载量与出生时出现症状的先天性CMV感染相关。在这种情况下,当仅1个胎儿(羊膜穿刺术时)感染且胎盘融合时,需要评估两个胎儿的结局,以确定病毒从一个胎儿转移到另一个胎儿的可能性。

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