Chaemsaithong Piya, Romero Roberto, Korzeniewski Steven J, Martinez-Varea Alicia, Dong Zhong, Yoon Bo Hyun, Hassan Sonia S, Chaiworapongsa Tinnakorn, Yeo Lami
a Division of Intramural Research , Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH , Bethesda, MD and Detroit , MI , USA .
b Department of Obstetrics and Gynecology , Wayne State University , Detroit , MI , USA .
J Matern Fetal Neonatal Med. 2016;29(3):349-59. doi: 10.3109/14767058.2015.1006620. Epub 2015 Sep 25.
Preterm birth is associated with 5-18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated AF IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow-based immunoassay for measurement of AF IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection and those destined to deliver spontaneously before term among women with preterm labor and intact membranes.
One-hundred thirty-six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6 ≥ 2600 pg/ml.
(1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%) and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745 pg/ml; (2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta and patients at risk of impending spontaneous preterm delivery.
A POC AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20 min - this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.
早产与5%-18%的妊娠相关，是新生儿发病和死亡的主要原因。羊水（AF）白细胞介素-6（IL-6）是识别羊膜腔内炎症的关键细胞因子，AF IL-6升高的患者有即将早产的风险。然而，传统测量方法（酶联免疫吸附测定；ELISA）的结果通常不能及时获得以指导治疗。本研究的目的是确定用于测量AF IL-6浓度的即时检验（POC）或基于侧流的免疫测定能否识别胎膜完整的早产女性中的羊膜腔内炎症和/或感染患者以及注定会在足月前自发分娩的患者。
本研究纳入了136名单胎妊娠且出现早产症状并接受羊膜腔穿刺术的女性。在诊断早产时进行羊膜腔穿刺术。测定AF革兰氏染色和AF白细胞计数。根据AF培养结果（需氧菌、厌氧菌以及生殖支原体）定义羊膜腔微生物入侵（MIAC）。通过基于侧流的免疫测定和ELISA测定AF IL-6浓度。主要结局是羊膜腔内炎症，定义为AF ELISA IL-6≥2600 pg/ml。
（1）通过POC检测测定的AF IL-6浓度在使用745 pg/ml的阈值识别羊膜腔内炎症方面具有高灵敏度（93%）、特异性（91%）和阳性似然比为10；（2）POC检测和IL-6的ELISA在识别MIAC、胎盘急性炎症病变以及有即将自发早产风险的患者方面表现相似。
POC AF IL-6检测可以识别胎膜完整的早产女性中的羊膜腔内炎症以及随后将在妊娠34周前自发分娩的女性。结果可在20分钟内获得——这具有重要的临床意义，并为羊膜腔内炎症/感染的早期诊断和治疗开辟了途径。
