Newlife Birth Defects Research Centre and Developmental Biology & Cancer Programme, Institute of Child Health, University College London, London, United Kingdom.
Birth Defects Res. 2017 Jan 30;109(2):68-80. doi: 10.1002/bdra.23533.
Susceptibility to neural tube defects (NTDs), such as anencephaly and spina bifida is influenced by genetic and environmental factors including maternal nutrition. Maternal periconceptional supplementation with folic acid significantly reduces the risk of an NTD-affected pregnancy, but does not prevent all NTDs, and "folic acid non-responsive" NTDs continue to occur. Similarly, among mouse models of NTDs, some are responsive to folic acid but others are not. Among nutritional factors, inositol deficiency causes cranial NTDs in mice while supplemental inositol prevents spinal and cranial NTDs in the curly tail (Grhl3 hypomorph) mouse, rodent models of hyperglycemia or induced diabetes, and in a folate-deficiency induced NTD model. NTDs also occur in mice lacking expression of certain inositol kinases. Inositol-containing phospholipids (phosphoinositides) and soluble inositol phosphates mediate a range of functions, including intracellular signaling, interaction with cytoskeletal proteins, and regulation of membrane identity in trafficking and cell division. Myo-inositol has been trialed in humans for a range of conditions and appears safe for use in human pregnancy. In pilot studies in Italy and the United Kingdom, women took inositol together with folic acid preconceptionally, after one or more previous NTD-affected pregnancies. In nonrandomized cohorts and a randomized double-blind study in the United Kingdom, no recurrent NTDs were observed among 52 pregnancies reported to date. Larger-scale fully powered trials are needed to determine whether supplementation with inositol and folic acid would more effectively prevent NTDs than folic acid alone. Birth Defects Research 109:68-80, 2017. © 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.
神经管缺陷（NTDs）的易感性，如无脑畸形和脊柱裂，受遗传和环境因素的影响，包括母体营养。母亲在受孕前补充叶酸可显著降低 NTD 妊娠的风险，但不能预防所有的 NTDs，并且“叶酸无反应性”NTDs 仍在发生。同样，在 NTD 的小鼠模型中，有些对叶酸有反应，而有些则没有。在营养因素中，肌醇缺乏会导致小鼠出现颅 NTD，而补充肌醇可预防卷曲尾（Grhl3 低聚物）小鼠、高血糖或诱导型糖尿病的啮齿动物模型以及叶酸缺乏诱导的 NTD 模型中的脊髓和颅 NTD。在缺乏某些肌醇激酶表达的小鼠中也会发生 NTD。含有肌醇的磷脂（磷酸肌醇）和可溶的肌醇磷酸盐介导多种功能，包括细胞内信号转导、与细胞骨架蛋白相互作用以及调节运输和细胞分裂中的膜特性。肌醇已在人类中进行了一系列疾病的临床试验，似乎对人类妊娠安全。在意大利和英国的初步研究中，女性在受孕前与叶酸一起服用肌醇，此前曾有一次或多次 NTD 受影响的妊娠。在非随机队列和英国的一项随机双盲研究中，迄今为止报告的 52 例妊娠中没有观察到复发性 NTD。需要更大规模的、充分有效的试验来确定补充肌醇和叶酸是否比单独补充叶酸更有效地预防 NTD。出生缺陷研究 109:68-80, 2017. © 2016 作者 出生缺陷研究 由 Wiley 期刊出版公司出版
