Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore.
Nutr Res Rev. 2023 Jun;36(1):60-68. doi: 10.1017/S0954422421000299. Epub 2021 Sep 16.
The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of -inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of -inositol as a preventive agent. However, the underlying molecular mechanisms by which -inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental -inositol in human parturition and explains possible underlying molecular mechanisms by which -inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal -inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal -inositol supplementation and definitively address the efficacy of -inositol prophylaxis against PTB.
早产(PTB)的发生率,即妊娠 37 周前分娩,在大多数国家都呈上升趋势。最近几项关于在孕期补充肌醇的小型临床试验主要旨在预防妊娠糖尿病,这些试验提示肌醇可能具有降低早产发生率的作用,这突显了肌醇作为预防剂的潜在作用。然而,肌醇能够发挥这种作用的潜在分子机制尚不清楚;这些机制可能通过直接影响分娩的开始和进展,或通过抑制触发或促进分娩的刺激来实现。本文提出了假说,概述了人分娩中胎盘肌醇的潜在作用,并解释了肌醇可能调节胎盘环境和抑制早产发生的潜在分子机制。我们认为,随着妊娠的进展,胎盘肌醇水平生理性下降到临界阈值,同时胎盘环境中炎症反应逐渐增强,允许自发性胎膜破裂和分娩开始。较高的胎盘肌醇水平,可能通过母体肌醇补充来促进,可能会影响脂质代谢、前列腺素的产生以及促炎细胞因子的分泌,从而整体抑制导致分娩开始和进展的促分娩胎盘环境,从而降低早产的风险。了解肌醇如何以及何时发挥作用以降低早产风险将有助于设计未来的母体肌醇补充临床试验,并明确肌醇预防早产的疗效。