Congenital Zika Virus Infection Beyond Neonatal Microcephaly
Congenital Zika Virus Infection Beyond Neonatal Microcephaly
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DOI：
10.1001/jamaneurol.2016.3720
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发表时间：
2016-12-01
期刊：
影响因子：
29
通讯作者：
Tanuri, Amilcar
中科院分区：
文献类型：
--
作者：
de Oliveira Melo, Adriana Suely;Aguiar, Renato Santana;Tanuri, Amilcar
重要性最近的研究报告称，母亲在怀孕期间感染寨卡病毒（ZIKV）的胎儿和新生儿患小头畸形的数量有所增加。据我们所知，迄今为止，大多数报告都集中在选择方面的母亲或胎儿感染和胎儿的effects.ObjectiveTo描述产前演变和围产期结果的11名新生儿谁有发育异常和神经损伤与ZIKV infection.DESIGN，SETTING，和参与者我们观察了11名婴儿先天性ZIKV感染从妊娠到6个月的状态Paraba，巴西在这项研究中，11名妇女中有10名在怀孕的前半期出现了ZIKV感染的症状，所有11名妇女都通过血清学或聚合酶链反应在几种组织中发现了感染的实验室证据。通过宫内超声检查证实脑损伤，并辅以磁共振成像。对死亡婴儿的胎盘和脑组织进行了组织学分析。ZIKV基因组在几种组织中进行了研究，并进行了测序，以进一步进行系统发育分析。主要结果和测量结果描述ZIKV先天性感染引起的主要病变。结果在11名婴儿中，7名（63.6%）为女性，分娩时的中位数（SD）母亲年龄为25（6）岁。11例新生儿死亡3例，围产儿死亡率为27.3%。出生时头周中位数（SD）为31（3）cm，低于考虑小头畸形病例的限值。在所有患者中，确定了神经功能障碍，包括小头畸形、脑体积减小、脑室扩大、小脑发育不全、无脑回畸形伴脑积水和胎儿运动不能变形序列（即，关节弯曲）。对其他小头畸形原因（如遗传性疾病、病毒和细菌感染）的有限检测结果为阴性，在母体和新生儿组织（如羊水、脐带血、胎盘和大脑）中均发现了ZIKV基因组。系统发育分析表明，宿主内的病毒变异与一些多态性与不同tissues.Conclusions和相关性的包膜基因结合的临床，实验室，影像学和病理学检查的结果提供了一个更完整的图片ZIKV感染所造成的严重损害和发育异常比以前报道。术语先天性寨卡综合征更适合指这些病例，因为小头畸形只是这种先天性畸形疾病的临床体征之一。
IMPORTANCE Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects.OBJECTIVE To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil.DESIGN, SETTING, AND PARTICIPANTS We observed 11 infants with congenital ZIKV infection from gestation to 6 monthus in the state of Paraba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis.MAIN OUTCOMES AND MEASURES Description of the major lesions caused by ZIKV congenital infection.RESULTS Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues.CONCLUSIONS AND RELEVANCE Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.