Datasheet3_Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.docx

BackgroundSARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection.
MethodsWe conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content.
ResultsA total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001.
ConclusionThis study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.

背景：严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染与围产期神经系统结局仍未完全阐明。不过，现有最新研究证据表明，母亲感染SARS-CoV-2后，新生儿可出现白质病变及神经发育受损情况。上述异常的发生机制似乎与病毒直接作用及全身炎症反应相关，可累及胶质细胞/髓鞘，并出现局部缺氧及微血管功能障碍。本研究旨在明确母亲感染SARS-CoV-2后，母婴炎症状态对新生儿中枢神经系统造成的影响。
方法：本研究于2020年6月至2021年12月开展一项纵向前瞻性队列研究，对妊娠期间暴露于SARS-CoV-2感染与未暴露的产妇所分娩新生儿进行随访。脑部影像学分析涵盖以下特定感兴趣区（regions of interest, ROIs）的多模态颅脑超声（cranial ultrasound scans, CUS）数据：包括灰阶超声、多普勒（彩色及频谱多普勒）检查，以及超声引导下脑弹性成像（剪切波模式，shear-wave mode）。感兴趣区包括：深部白质、浅表白质、胼胝体、基底节区及大脑皮质灰质。脑弹性成像用于评估脑实质硬度，该指标可间接反映大脑髓鞘组织含量。
结果：本研究共纳入219名单胎妊娠新生儿，其中201名产妇妊娠期间暴露于SARS-CoV-2感染，18名为未感染的对照新生儿。对校正胎龄后6月龄的新生儿进行神经影像学评估，共发现18例灰阶超声异常及21例多普勒血流异常。主要异常表现为：深部脑白质及基底节区（尾状核/丘脑）回声增强，以及颅内动脉血流阻力指数与搏动指数降低。脑前循环（大脑中动脉及胼周动脉）的血流波动范围较脑后循环（基底动脉）更广。剪切波超声弹性成像分析显示，SARS-CoV-2暴露组所有感兴趣区的硬度值均低于对照组，其中深部白质弹性系数尤为显著：暴露组为3.98±0.62，对照组为7.76±0.77；p<0.001。
结论：本研究进一步明确了妊娠期间SARS-CoV-2感染相关的儿童脑部结构改变。研究证实，母亲感染SARS-CoV-2可导致以深部脑白质受累为主的脑部病变，表现为局部回声增强及弹性系数降低，提示髓鞘含量存在区域性受损。影像学形态学改变可能较为隐匿，而多普勒及弹性成像等功能学检查可作为更精准识别神经系统损伤高危新生儿的有效手段。