Romero Roberto, Kadar Nicholas, Miranda Jezid, Korzeniewski Steven J, Schwartz Alyse G, Chaemsaithong Piya, Rogers Wade, Soto Eleazar, Gotsch Francesca, Yeo Lami, Hassan Sonia S, Chaiworapongsa Tinnakorn
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH , Bethesda, MD and Detroit , MI .
J Matern Fetal Neonatal Med. 2014 May;27(8):757-69. doi: 10.3109/14767058.2013.844123. Epub 2013 Dec 16.
Intra-amniotic infection/inflammation are major causes of spontaneous preterm labor and delivery. However, diagnosis of intra-amniotic infection is challenging because most are subclinical and amniotic fluid (AF) cultures take several days before results are available. Several tests have been proposed for the rapid diagnosis of microbial invasion of the amniotic cavity (MIAC) or intra-amniotic inflammation. The aim of this study was to examine the diagnostic performance of the AF Mass Restricted (MR) score in comparison with interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8) for the identification of MIAC or inflammation.
AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n = 100). Intra-amniotic inflammation was defined as >100 white blood cells/mm(3) (WBCs) in AF; MIAC was defined as a positive AF culture. AF IL-6 and MMP-8 were determined using ELISA. The MR score was obtained using the Surface-Enhanced Laser Desorption Ionization Time of Flight (SELDI-TOF) mass spectrometry. Sensitivity and specificity were calculated and logistic regression models were fit to construct receiver-operating characteristic (ROC) curves for the identification of each outcome. The McNemar's test and paired sample non-parametric statistical techniques were used to test for differences in diagnostic performance metrics.
(1) The prevalence of MIAC and intra-amniotic inflammation was 34% (34/100) and 40% (40/100), respectively; (2) there were no significant differences in sensitivity of the three tests under study (MR score, IL-6 or MMP-8) in the identification of either MIAC or intra-amniotic inflammation (using the following cutoffs: MR score >2, IL-6 >11.4 ng/mL, and MMP-8 >23 ng/mL); (3) there was no significant difference in the sensitivity among the three tests for the same outcomes when the false positive rate was fixed at 15%; (4) the specificity for IL-6 was not significantly different from that of the MR score in identifying either MIAC or intra-amniotic inflammation when using previously reported thresholds; and (5) there were no significant differences in the area under the ROC curve when comparing the MR score, IL-6 or MMP-8 in the identification of these outcomes.
IL-6 and the MR score have equivalent diagnostic performance in the identification of MIAC or intra-amniotic inflammation. Selection from among these three tests (MR score, IL-6 and MMP-8) for diagnostic purposes should be based on factors such as availability, reproducibility, and cost. The MR score requires a protein chip and a SELDI-TOF instrument which are not widely available or considered "state of the art". In contrast, immunoassays for IL-6 can be performed in the majority of clinical laboratories.
羊膜腔内感染/炎症是自发性早产和分娩的主要原因。然而，羊膜腔内感染的诊断具有挑战性，因为大多数病例为亚临床感染，羊水（AF）培养需要数天才能得出结果。已经提出了几种用于快速诊断羊膜腔微生物入侵（MIAC）或羊膜腔内炎症的检测方法。本研究的目的是比较AF质量限制（MR）评分与白细胞介素-6（IL-6）和基质金属蛋白酶-8（MMP-8）在识别MIAC或炎症方面的诊断性能。
收集单胎妊娠且有早产症状的患者的羊水样本（n = 100）。羊膜腔内炎症定义为羊水中白细胞（WBC）>100个/mm³；MIAC定义为羊水培养阳性。采用酶联免疫吸附测定法（ELISA）测定羊水IL-6和MMP-8。使用表面增强激光解吸电离飞行时间（SELDI-TOF）质谱法获得MR评分。计算敏感性和特异性，并拟合逻辑回归模型以构建用于识别每种结局的受试者操作特征（ROC）曲线。采用McNemar检验和配对样本非参数统计技术检验诊断性能指标的差异。
（1）MIAC和羊膜腔内炎症的发生率分别为34%（34/100）和40%（40/100）；（2）在所研究的三项检测（MR评分、IL-6或MMP-8）中，在识别MIAC或羊膜腔内炎症方面（使用以下临界值：MR评分>2、IL-6>11.4 ng/mL和MMP-8>23 ng/mL），敏感性无显著差异；（3）当假阳性率固定为15%时，三项检测对相同结局的敏感性无显著差异；（4）在使用先前报道的临界值识别MIAC或羊膜腔内炎症时，IL-6的特异性与MR评分的特异性无显著差异；（5）在比较MR评分、IL-6或MMP-8识别这些结局时，ROC曲线下面积无显著差异。
IL-6和MR评分在识别MIAC或羊膜腔内炎症方面具有同等的诊断性能。从这三项检测（MR评分、IL-6和MMP-8）中选择用于诊断目的应基于可获得性、可重复性和成本等因素。MR评分需要蛋白质芯片和SELDI-TOF仪器，这些设备并不广泛可用或被视为“先进技术”。相比之下，大多数临床实验室都可以进行IL-6的免疫测定。
