Department of Biomedical Engineering, Vanderbilt University, Nashville, TN.
Department of Biostatistics, Vanderbilt University, Nashville, TN.
Am J Obstet Gynecol. 2022 Aug;227(2):275.e1-275.e14. doi: 10.1016/j.ajog.2022.02.019. Epub 2022 Feb 19.
Biochemical cervical change during labor is not well understood, in part, because of a dearth of technologies capable of safely probing the pregnant cervix in vivo. The need for such a technology is 2-fold: (1) to gain a mechanistic understanding of the cervical ripening and dilation process and (2) to provide an objective method for evaluating the cervical state to guide clinical decision-making. Raman spectroscopy demonstrates the potential to meet this need, as it is a noninvasive optical technique that can sensitively detect alterations in tissue components, such as extracellular matrix proteins, lipids, nucleic acids, and blood, which have been previously established to change during the cervical remodeling process.
We sought to demonstrate that Raman spectroscopy can longitudinally monitor biochemical changes in the laboring cervix to identify spectral markers of impending parturition.
Overall, 30 pregnant participants undergoing either spontaneous or induced labor were recruited. The Raman spectra were acquired in vivo at 4-hour intervals throughout labor until rupture of membranes using a Raman system with a fiber-optic probe. Linear mixed-effects models were used to determine significant (P<.05) changes in peak intensities or peak ratios as a function of time to delivery in the study population. A nonnegative least-squares biochemical model was used to extract the changing contributions of specific molecule classes over time.
We detected multiple biochemical changes during labor, including (1) significant decreases in Raman spectral features associated with collagen and other extracellular matrix proteins (P=.0054) attributed to collagen dispersion, (2) an increase in spectral features associated with blood (P=.0372), and (3) an increase in features indicative of lipid-based molecules (P=.0273). The nonnegative least-squares model revealed a decrease in collagen contribution with time to delivery, an increase in blood contribution, and a change in lipid contribution.
Our findings have demonstrated that in vivo Raman spectroscopy is sensitive to multiple biochemical remodeling changes in the cervix during labor. Furthermore, in vivo Raman spectroscopy may be a valuable noninvasive tool for objectively evaluating the cervix to potentially guide clinical management of labor.
由于缺乏能够安全探测体内妊娠宫颈的技术,分娩过程中的生化宫颈变化尚不清楚。对这种技术的需求有两个方面:(1)获得对宫颈成熟和扩张过程的机械理解;(2)提供一种客观的方法来评估宫颈状态以指导临床决策。拉曼光谱技术具有满足这一需求的潜力,因为它是一种非侵入性的光学技术,可以灵敏地检测组织成分的变化,如细胞外基质蛋白、脂质、核酸和血液,这些成分以前已被证实会在宫颈重塑过程中发生变化。
我们试图证明拉曼光谱技术可以纵向监测分娩宫颈的生化变化,以识别即将分娩的光谱标志物。
共有 30 名处于自然或诱导分娩的孕妇参与了这项研究。在分娩过程中,使用带有光纤探头的拉曼系统,每 4 小时进行一次活体采集,直到胎膜破裂。线性混合效应模型用于确定研究人群中随分娩时间变化的峰强度或峰比的显著(P<.05)变化。非负最小二乘生化模型用于提取特定分子类别随时间的变化贡献。
我们在分娩过程中检测到多种生化变化,包括(1)与胶原蛋白和其他细胞外基质蛋白相关的拉曼光谱特征显著降低(P=.0054),归因于胶原蛋白的分散;(2)与血液相关的光谱特征增加(P=.0372);(3)指示脂质基分子的特征增加(P=.0273)。非负最小二乘模型揭示了随分娩时间的胶原蛋白贡献减少、血液贡献增加和脂质贡献变化。
我们的研究结果表明,体内拉曼光谱技术对分娩过程中宫颈的多种生化重塑变化敏感。此外,体内拉曼光谱技术可能是一种有价值的非侵入性工具,可客观评估宫颈,可能有助于指导分娩的临床管理。