Miller Suzanne L, Huppi Petra S, Mallard Carina
The Ritchie Centre, Hudson Institute of Medical Research, and The Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Division of Development and Growth, Department of Pediatrics, University of Geneva, Switzerland.
J Physiol. 2016 Feb 15;594(4):807-23. doi: 10.1113/JP271402. Epub 2016 Jan 5.
Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions.
胎儿生长受限(FGR)是一种严重的妊娠并发症,指胎儿因病理损害而未能充分发育至其应有的生长潜力。在高收入国家,FGR影响3%至9%的妊娠,是围产期死亡和发病的主要原因。胎盘功能不全是FGR的主要原因,可导致胎儿慢性缺氧。这种缺氧会引发胎儿的心输出量重新分布的适应性反应,以利于包括大脑在内的重要器官,因此被称为脑保护效应。尽管如此,现在很明显,脑保护效应并不能确保生长受限胎儿的大脑正常发育。在这篇综述中,我们汇集了来自人类和实验动物研究的现有证据,以描述因FGR而发生的大脑结构和功能的复杂变化。在人类和动物中,神经发育结局受FGR发病时间、FGR严重程度以及分娩时的孕周影响。FGR与全脑体积减小、皮质体积和结构改变、细胞总数减少以及髓鞘形成缺陷广泛相关。脑连接性也受损,表现为神经元迁移缺陷、树突过程减少以及长距离连接减少导致的网络效率降低。在这些结构改变之后,已有研究描述了患有FGR的学龄儿童的短期和长期功能后果,最常见的包括运动技能、认知、记忆和神经心理功能障碍方面的问题。