Inflammatory markers as predictors of active labor onset among nulliparous women

描述（由申请人提供）：劳动护理提供者的目标通常是在“积极”劳动开始时，即，当子宫颈扩张的速度预计会增加时。然而，活跃的分娩只能根据扩张随时间的变化来回顾性地确定。报告表明，约有一半的定期签约、低风险、未经产的妇女在积极分娩前被允许分娩。这些妇女在分娩过程中更容易接受干预，包括剖宫产的风险是积极分娩的妇女的两倍多。这些数据表明，需要额外的标准，以更准确地确定劳动状态之前入院。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，炎症生物标志物在生殖组织和母体血液中变得越来越可检测。本研究的目的是确定炎症生物标志物是否有助于预测活跃分娩的发生。据推测，随着时间的推移，特异性炎症生物标志物的增加可以预测在因自然分娩而入院的低风险未经产妇女中的主动扩张状态（平均> 0.5 cm/hr，在分娩入院后的前4小时内）（n = 200）。将使用描述性比较设计来评价特定炎症生物标志物的变化率[即，白色血细胞（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]随时间的变化以及入院后前4小时内宫颈扩张量。将在分娩入院时测量炎症生物标志物，并在2小时和4小时后再次测量。将评估的随时间推移的特定炎症生物标志物变化包括入院->入院+2小时、入院->入院+4小时和入院->入院+2小时->入院+4小时。数据收集时间点之间个体炎症生物标志物的变化幅度将用于构建关于活跃分娩预测的ROC曲线。基于生物标志物变化的幅度，将以分娩分类作为因变量进行逻辑回归分析，即，积极或不积极扩张。入院时的宫颈扩张和几种常见的分娩干预将作为模型协变量纳入。同时运行多种炎症生物标志物的模型也将被考虑。如果炎症生物标志物随时间的急剧变化与活跃的分娩开始有关，则在决定“何时”让分娩妇女进入产房时可以使用这些生物标志物。最大限度地增加妇女参加积极劳动的人数是改善劳动成果的重要一步。这项研究的结果将被用来告知一个基于生理学的劳动评估协议的发展，旨在最大限度地提高妇女入院时或活跃劳动开始后的数量。随后的研究还将确定临床干预对劳动相关炎症介质的影响。 公共卫生相关性：炎症事件与启动分娩和促进分娩进展有关。因此，炎症生物标志物的测量可以预测活跃的分娩开始，目前只能回顾性地确定-通常是在已经做出入院分娩的决定后数小时。大约有一半的定期合同，低风险，未经产的妇女在积极劳动之前入院分娩，在这个高容量组的妇女更容易在劳动过程中进行干预，包括剖宫产的风险是积极劳动妇女的两倍以上。如果炎症生物标志物随时间的急性变化有效地预测活跃分娩的发生，则其测量可用于最大限度地增加活跃分娩的女性数量。更积极的短期和长期劳动力结果应该随之而来。

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.