Inflammatory markers as predictors of active labor onset among nulliparous women

描述(由申请人提供)：劳动保健提供者的目标通常是在“活跃”分娩开始时，即预计宫颈扩张率增加时，允许分娩妇女进入劳动单位。然而，活跃性分娩只能根据一段时间内扩张的变化来回顾确定。报告表明，大约有一半的定期收缩、低风险、未分娩的妇女在活产之前被允许分娩。这些妇女更倾向于在分娩期间进行干预，包括与进入活跃期分娩的妇女相比，剖腹产的风险高出两倍以上。这些数据表明，需要更多的标准来更准确地确定入院前的分娩状态。越来越多的证据表明，分娩的开始和进展是由炎症事件介导的，随着分娩的进展，生殖组织和母体血液中越来越多地检测到炎症生物标志物。这项研究的目的是确定炎性生物标志物是否有助于预测活跃性分娩开始。据推测，随着时间的推移，特定炎症生物标志物的增加可以预测因自然分娩而入院的低风险未分娩妇女(n=200)的主动扩张状态(分娩后4小时内平均为0.5厘米/小时)。将使用描述性比较设计来评估特定炎症生物标志物[即白细胞(WBC)计数、血清促炎细胞因子(IL-12、IL-6、IL-8、TNF-1)、C-反应蛋白(CRP)和体温]随时间的变化速度与入院后最初4小时内宫颈扩张量之间的关系。在入院时、2小时和4小时后再次测定炎症生物标志物。将评估的特定炎症生物标记物随时间的变化包括入院->入院2小时，入院->入院4小时，入院->入院2小时--入院4小时。单个炎症生物标志物在数据收集时间点之间的变化幅度将被用来构建与预测活跃分娩相关的ROC曲线。根据生物标志物变化的大小进行Logistic回归分析，以劳动力分类为因变量，即积极扩张或不积极扩张。入院时宫颈扩张和几种常见的分娩干预措施将被纳入为模型协变量。同时运行多个炎症生物标志物的模型也将被考虑。如果炎性生物标记物随时间的急剧变化与活跃性分娩有关，这些生物标记物可用于决定何时允许分娩妇女进入产房。最大限度地增加进入活跃期分娩的妇女人数是改善分娩结果的重要一步。这项研究的结果将被用来为制定基于生理的分娩评估方案提供信息，旨在最大限度地增加活跃分娩开始时或之后入院的妇女人数。随后的研究还将确定临床干预对分娩相关炎症介质的影响。 与公共卫生相关：炎症事件与启动分娩和促进分娩进程有关。因此，炎性生物标志物的测量可能预示着活跃性分娩的到来，目前，这一点只能追溯确定--通常是在已经做出入院分娩决定的几个小时后。在常规收缩、低风险、未分娩的妇女中，大约有一半是在活跃期分娩之前入院分娩的，而且这一高产量组的妇女更容易在分娩期间进行干预，包括剖腹产的风险是活跃期入院妇女的两倍以上。如果炎症生物标志物随时间的急剧变化可以有效地预测活跃期分娩开始，它们的测量可以用来最大限度地增加活跃期分娩的妇女人数。接下来应该会有更积极的短期和长期分娩结果。

DESCRIPTION (provided by applicant): Labor care providers typically aim to admit a laboring woman to the labor unit at the onset of "active" labor, i.e., when the rate of cervical dilation is anticipated to increase. However, active labor can only be determined retrospectively based on changes in dilatation over time. Reports indicate that approximately one-half of regularly contracting, low-risk, nulliparous women are admitted for labor prior to active labor. These women are more prone to intervention during labor including a more than two-fold risk of cesarean delivery compared to women admitted in active labor. These data suggest that additional criteria are needed to more accurately determine labor state prior to admission. Evidence increasingly suggests that labor onset and progression is mediated by inflammatory events and inflammatory biomarkers become increasingly detectable in reproductive tissues and maternal blood as labor advances. The purpose of this study is to determine if inflammatory biomarkers may assist in predicting active labor onset. It is hypothesized that increases in specific inflammatory biomarkers over time can predict an actively dilating state (> 0.5 cm/hr, on average, over the first 4 hrs after labor admission) among low-risk, nulliparous women admitted for spontaneous labor onset (n = 200). A descriptive, comparative design will be used to evaluate the association between rates of change in specific inflammatory biomarkers [i.e., white blood cell (WBC) count, serum pro-inflammatory cytokines (IL-12, IL-6, IL-8, TNF-1), C-reactive protein (CRP); and body temperature] over time and the amount of cervical dilation during the first 4 hrs post-admission. Inflammatory biomarkers will be measured at labor admission and again 2 hrs and 4 hrs later. Specific inflammatory biomarker changes over time that will be evaluated include admission -> admission+2hrs, admission -> admission+4hrs, and admission -> admission+2hrs -> admission+4hrs. The magnitude of change in individual inflammatory biomarkers between data collection time points will be used to construct ROC curves with respect to the prediction of active labor. Logistic regression analyses, based on the magnitude of biomarker change, will be performed with classification of labor as the dependent variable, i.e., actively or not actively dilating. Cervical dilatation at admission and several common labor interventions will be included as model covariates. Models running multiple inflammatory biomarkers simultaneously will also be considered. If acute changes in inflammatory biomarkers over time are associated with active labor onset, these biomarkers could be used when making decisions regarding "when" to admit laboring women to the labor room. Maximizing the number of women admitted in active labor is an important step toward improving labor outcomes. Findings from this study will be used to inform the development of a physiology-based labor assessment protocol aimed at maximizing the number of women admitted at or after the onset of active labor. Subsequent studies will also determine the effects that clinical interventions have on labor-associated inflammatory mediators. PUBLIC HEALTH RELEVANCE: Inflammatory events are implicated in initiating labor and propagating its progression. The measurement of inflammatory biomarkers may, therefore, be predictive of active labor onset which, at present, can only be determined retrospectively - often hours after a decision to admit for labor has already been made. Approximately one-half of regularly contracting, low-risk, nulliparous women are admitted for labor prior to active labor and women in this high-volume group are more prone to intervention during labor including a more than two-fold risk of cesarean delivery compared to women admitted in active labor. If acute changes in inflammatory biomarkers over time validly predict active labor onset, their measurement can be used to maximize the number of women admitted in active labor. More positive short- and long-term labor outcomes should follow.