Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
Departments of Neurology, Harvard Medical School, Boston, MA, USA.
Ann Neurol. 2021 Jan;89(1):143-157. doi: 10.1002/ana.25940. Epub 2020 Nov 4.
Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development.
From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables.
HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery.
Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157.
先天性心脏病（CHD）与宫内脑发育异常有关。我们应用创新性的胎儿磁共振成像（MRI）技术来确定胎儿脑基质输送减少是否会对大脑产生全面影响，还是具有特定区域的影响。我们的新设计包括两个对照组，一个有 CHD 家族史，另一个没有，以探讨共享基因和/或胎儿环境对大脑发育的贡献。
2014 年至 2018 年，我们招募了 179 名孕妇，分为 4 组：左心发育不全综合征（HLHS）或大动脉转位（TGA）的胎儿（HLHS/TGA），具有最低的胎儿脑基质输送，诊断为脑容量最低；“CHD-其他”，有其他 CHD 诊断；“CHD-相关”，健康且有 CHD 家族史；“最佳对照”，健康且无家族史。在 18 至 40 周妊娠时获得两次 MRI。随机效应回归模型评估了各组间脑容量的差异及其与血液动力学变量的关系。
HLHS/TGA 组（n=24）、CHD-其他组（50）和 CHD-相关组（34）的脑容量均明显小于最佳对照组（71）。与 CHD-相关组相比，HLHS/TGA 组的基板（-13.3%[标准误差=4.3%]，p<0.01）和中间带（-13.7%[4.3%]，p<0.01）较小，脑室带也有类似的减小趋势（-7.1%[1.9%]，p=0.07）。这些体积减小与脑基质输送减少有关。
患有 CHD 的胎儿，尤其是脑基质输送最低的胎儿，在 32 周妊娠前显示出特定区域的脑容量小和脑生长受损的模式。CHD 胎儿的大脑与 CHD-相关胎儿的大脑更为相似，而不是与最佳对照组的大脑相似，这表明遗传或环境因素也有贡献。
