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

Congenital cytomegalovirus infection in twin pregnancies: Viral load in the amniotic fluid and pregnancy outcome
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DOI:
10.1542/peds.112.2.e153
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发表时间:
2003-08-01
期刊:
影响因子:
8
通讯作者:
Landini, MP
Landini, MP
中科院分区:
医学2区
文献类型:
--
作者:
Lazzarotto, T;Gabrielli, L;Landini, MP

文献摘要

被引文献

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人巨细胞病毒(CMV)是宫内病毒感染和胎儿损伤的最常见原因,主要归因于母体原发感染。文献中报道的双胞胎先天性巨细胞病毒感染的大多数病例仅涉及一对双胞胎。我们评估了聚合酶链反应(PCR)和定量PCR对羊水(AF)的有效性,在妊娠21至22周和血清转化后至少6至8周,以预测双胎妊娠新生儿的结局。对两名双胎妊娠孕妇和1名三胎妊娠孕妇进行了评估,这些孕妇的原发性巨细胞病毒感染以免疫球蛋白(Ig) M和低IgG贪婪度和/或临床症状和肝酶值异常的存在为特征。6例胎儿/新生儿发现巨细胞病毒感染,其中3例有症状。在双绒毛膜-双绒毛膜分离胎盘的第一个双胞胎妊娠中,通过病毒分离阳性和AF病毒载量高,证明了女性双胞胎的巨细胞病毒症状感染。在房颤中,通过巨细胞病毒培养和DNA检测阴性,证明了男性胎儿未被感染。在三胎妊娠中,该妇女有一个胎盘与2个同卵双胞胎(女性)和一个异卵双胞胎(男性)的单独胎盘。定量PCR结果显示,女性房颤的基因组当量为103 GE/mL,男性房颤的基因组当量为1.9x10(5) GE/mL。两名女性双胞胎在出生时均无症状,而男性双胞胎则表现为斑点、血小板减少和脑室肿大。在最后一对双绒毛膜胎盘融合的双胞胎妊娠中,出生时诊断为先天性巨细胞病毒感染,与产前诊断相比。羊膜穿刺术时,左侧双胞胎的CMV培养和房颤DNA检测结果均为阴性,未被感染。右侧双胞胎的CMV DNA检测呈阳性,CMV DNA载量为4.9x10(4) GE/mL,房颤病毒分离呈阳性。胎盘的形态学和组织学检查有力地支持了CMV产前水平感染。这些双胎妊娠在产前诊断中显示出病毒载量的显著差异,这表明尽管暴露于相同的母体影响下,双胞胎胎儿对原发母体感染的反应可能不同。高病毒载量与先天性巨细胞病毒感染在出生时有症状相关。在这种情况下,只有一对双胞胎的胎儿感染(羊膜穿刺术)和胎盘融合,双胞胎的胎儿结局需要评估病毒从一个胎儿转移到另一个胎儿的可能性。
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 103 genome equivalents (GE)/mL of females AF and 1.9x10(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 4.9x10(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.