Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine & Texas Children's Hospital, Houston, TX.
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Cediul-Cedifetal, Barranquilla, Colombia.
Am J Obstet Gynecol. 2018 Apr;218(4):440.e1-440.e36. doi: 10.1016/j.ajog.2018.01.012. Epub 2018 Jan 17.
Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly and manifests as a number of signs and symptoms that are detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited.
Main objectives of this study conducted on fetuses and infants with confirmed congenital Zika virus infection and detected brain abnormalities were (1) to assess the prevalence of microcephaly and the frequency of the anomalies that include a detailed description based on ultrasound and magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging, and computed tomography imaging postnatally, (2) to provide quantitative measures of fetal and infant brain findings by magnetic resonance imaging with the use of volumetric analyses and diffusion-weighted imaging, and (3) to obtain additional information from placental and fetal histopathologic assessments and postnatal clinical evaluations.
This is a longitudinal cohort study of Zika virus-infected pregnancies from a single institution in Colombia. Clinical and imaging findings of patients with laboratory-confirmed Zika virus infection and fetal brain anomalies were the focus of this study. Patients underwent monthly fetal ultrasound scans, neurosonography, and a fetal magnetic resonance imaging. Postnatally, infant brain assessment was offered by the use of ultrasound imaging, magnetic resonance imaging, and/or computed tomography. Fetal head circumference measurements were compared with different reference ranges with <2 or <3 standard deviations below the mean for the diagnosis of microcephaly. Fetal and infant magnetic resonance imaging images were processed to obtain a quantitative brain volumetric assessment. Diffusion weighted imaging sequences were processed to assess brain microstructure. Anthropometric, neurologic, auditory, and visual assessments were performed postnatally. Histopathologic assessment was included if patients opted for pregnancy termination.
All women (n=214) had been referred for Zika virus symptoms during pregnancy that affected themselves or their partners or if fetal anomalies that are compatible with congenital Zika virus syndrome were detected. A total of 12 pregnant patients with laboratory confirmation of Zika virus infection were diagnosed with fetal brain malformations. Most common findings that were assessed by prenatal and postnatal imaging were brain volume loss (92%), calcifications (92%), callosal anomalies (100%), cortical malformations (89%), and ventriculomegaly (92%). Results from fetal brain volumetric assessment by magnetic resonance imaging showed that 1 of the most common findings associated with microcephaly was reduced supratentorial brain parenchyma and increased subarachnoid cerebrospinal fluid. Diffusion weighted imaging analyses of apparent diffusion coefficient values showed microstructural changes. Microcephaly was present in 33.3-58.3% of the cases at referral and was present at delivery in 55.6-77.8% of cases. At birth, most of the affected neonates (55.6-77.8%) had head circumference measurements >3 standard deviations below the mean. Postnatal imaging studies confirmed brain malformations that were detected prenatally. Auditory screening results were normal in 2 cases that were assessed. Visual screening showed different anomalies in 2 of the 3 cases that were examined. Pathologic results that were obtained from 2 of the 3 cases who opted for termination showed similar signs of abnormalities in the central nervous system and placental analyses, including brain microcalcifications.
Congenital microcephaly is not an optimal screening method for congenital Zika virus syndrome, because it may not accompany other evident and preceding brain findings; microcephaly could be an endpoint of the disease that results from progressive changes that are related to brain volume loss. Long-term studies are needed to understand the clinical and developmental relevance of these findings.
先天性寨卡病毒（ZIKV）感染可在存在和不存在小头畸形的情况下被检测到，并表现出许多临床上和神经影像学检测到的体征和症状。然而，迄今为止，用于诊断和预后的定性和定量方法仍很有限。
本研究对经证实感染先天性寨卡病毒且存在脑异常的胎儿和婴儿进行了研究，其主要目的是：（1）评估小头畸形的发生率和包括详细超声和磁共振成像描述的异常频率，在胎儿中，在出生后进行超声、磁共振成像和计算机断层扫描成像；（2）通过磁共振成像提供胎儿和婴儿脑发现的定量测量，使用容积分析和弥散加权成像；（3）从胎盘和胎儿组织病理学评估以及产后临床评估中获得其他信息。
这是哥伦比亚一家单一机构对寨卡病毒感染妊娠的纵向队列研究。本研究的重点是实验室确诊寨卡病毒感染且胎儿脑异常的患者的临床和影像学发现。患者每月接受胎儿超声检查、神经超声检查和胎儿磁共振成像检查。在出生后，通过超声成像、磁共振成像和/或计算机断层扫描对婴儿脑进行评估。胎儿头围测量值与不同的参考范围进行比较，<2 或 <3 个标准差低于平均值用于诊断小头畸形。对胎儿和婴儿磁共振成像图像进行处理，以获得定量脑容积评估。处理弥散加权成像序列以评估脑微观结构。在出生后进行了人体测量、神经学、听觉和视觉评估。如果患者选择终止妊娠，则包括组织病理学评估。
所有女性（n=214）在怀孕期间均因寨卡病毒症状而被转诊，或因与先天性寨卡病毒综合征相符的胎儿异常而被转诊。12 名孕妇经实验室证实感染寨卡病毒，被诊断为胎儿脑畸形。产前和产后影像学最常见的发现是脑体积损失（92%）、钙化（92%）、胼胝体异常（100%）、皮质畸形（89%）和脑室扩大（92%）。磁共振成像胎儿脑容积评估结果显示，与小头畸形最常见的相关发现之一是幕上脑实质减少和蛛网膜下腔脑脊液增加。表观扩散系数值的弥散加权成像分析显示微观结构变化。在转诊时，小头畸形的发生率为 33.3%-58.3%，在分娩时为 55.6%-77.8%。出生时，大多数受影响的新生儿（55.6%-77.8%）的头围测量值低于平均值 3 个标准差。产后影像学研究证实了产前发现的脑畸形。对 2 例接受评估的患儿进行了听力筛查，结果正常。对 3 例接受检查的患儿中的 2 例进行了视力筛查，发现了不同的异常。对 3 例选择终止妊娠的患儿中的 2 例进行了病理检查，结果显示中枢神经系统和胎盘分析中存在类似的异常迹象，包括脑微钙化。
先天性小头畸形不是先天性寨卡病毒综合征的最佳筛查方法，因为它可能不伴有其他明显和先前的脑发现；小头畸形可能是与脑体积损失相关的进行性变化的结果，是疾病的终点。需要进行长期研究，以了解这些发现的临床和发育相关性。
