Table_3_Extreme prematurity and perinatal risk factors related to extremely preterm birth are associated with complex patterns of regional brain volume alterations at 10 years of age: a voxel-based morphometry study.DOCX

ObjectiveStructural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group.
MethodsAt 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term.
ResultsWe found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05).
ConclusionsChildren born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.

研究目的
既往已有诸多研究针对极早早产儿开展脑结构容积差异相关探索，但针对存活性临界孕周的超早早产儿的相关研究仍相对匮乏。本团队此前曾采用基于体素的形态测量学（voxel-based morphometry, VBM）分析了足月时的超早早产儿脑结构特征。本研究旨在基于同一队列的儿童期数据，探究超早早产儿脑区灰质与白质的容积差异；同时亦旨在探讨围产期危险因素对该队列儿童脑容积的影响。

研究方法
本研究纳入了10岁龄的51例超早早产儿（出生孕周<27周0天）与38例足月出生的对照儿童，所有受试者均具备高质量的3.0特斯拉磁共振成像（magnetic resonance imaging, MRI）数据。采用基于体素的形态测量学对图像进行统计分析，所有图像均经年龄特异性模板归一化、调制及平滑处理。此外，本研究还针对存在/不存在既往证实可影响足月时脑容积差异的围产期危险因素的超早早产儿亚组，分别开展了统计分析。

研究结果
相较于对照，超早早产儿表现出颞叶灰质与白质容积降低、楔前回灰质容积降低以及前扣带束白质容积降低（所有指标均满足P<0.001，且经家族性错误率校正后的P值pfwe<0.05）。同时，超早早产儿在右侧后扣带束与枕叶区域观察到灰质与白质容积的显著升高（所有指标均满足P<0.001，且pfwe<0.05）。在本次分析的围产期危险因素中，与无脑室内出血者相比，Ⅰ-Ⅱ级脑室内出血（intraventricular hemorrhage, IVH）患儿，以及与未接受治疗或经布洛芬治疗的动脉导管未闭（patent ductus arteriosus, PDA）患儿相比，接受动脉导管未闭结扎术的患儿，在10岁龄时均表现出脑容积的显著差异（所有指标均满足P<0.001，且pfwe<0.05）。

研究结论
超早早产儿所表现出的脑容积改变模式，与既往足月时观察到的改变模式存在重叠，且多数存在容积差异的脑区均为高阶认知网络的核心枢纽。既往证实与足月时脑结构改变相关的围产期危险因素中，仅有部分与10岁龄时的脑容积改变存在关联。