Kim Sun Min, Romero Roberto, Lee JoonHo, Chaemsaithong Piya, Lee Min-Woo, Chaiyasit Noppadol, Lee Hyo-Jin, Yoon Bo Hyun
a Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Republic of Korea .
b Department of Obstetrics and Gynecology , Seoul Metropolitan Government-Seoul National University Boramae Medical Center , Seoul , Republic of Korea .
J Matern Fetal Neonatal Med. 2016;29(15):2414-22. doi: 10.3109/14767058.2015.1094049. Epub 2015 Dec 7.
Mid-trimester amniocentesis continues to be used for the prenatal diagnosis of chromosomal anomalies and other genetic disorders. Analysis of amniotic fluid obtained at the time of mid-trimester genetic amniocentesis identifies those patients who are at risk for early spontaneous preterm delivery. This is based on a solid body of evidence that found subclinical intra-amniotic inflammation/infection to be causally linked to early spontaneous preterm birth. Although several biomarkers have been proposed to identify intra-amniotic inflammation, the accumulated data suggest that the determination of amniotic fluid matrix metalloproteinase-8 (MMP-8), or neutrophil collagenase, is a powerful predictor of spontaneous preterm delivery. MMP-8 is released by inflammatory cells in response to microbial products or "danger signals". A rapid point-of-care test has been developed to determine MMP-8 at the bedside within 20 min, and without the requirement of laboratory equipment. The objective of this study was to determine whether an elevation of MMP-8 in the amniotic fluid, measured by a rapid point-of-care test, can identify those patients at risk for spontaneous preterm delivery after a mid-trimester genetic amniocentesis.
A case-control study was designed to obtain amniotic fluid from asymptomatic singleton pregnant women who underwent mid-trimester genetic amniocentesis. An MMP-8 bedside test was performed to analyze the amniotic fluid of 64 patients with early spontaneous preterm delivery (<30 weeks) and 128 matched controls with normal pregnancy outcomes.
(1) The MMP-8 bedside test (Yoon's MMP-8 Check™) was positive in 42.2% (27/64) of patients with spontaneous preterm delivery but in none (0/128) of the control cases (p < 0.001); (2) the MMP-8 bedside test had a sensitivity of 42.2%, and a specificity of 100% in the prediction of spontaneous preterm delivery (<30 weeks) following a mid-trimester genetic amniocentesis; and (3) among the patients with spontaneous preterm delivery, those with a positive MMP-8 bedside test had a significantly higher rate of spontaneous delivery within 2 weeks and 4 weeks of an amniocentesis [40.7% (11/27) versus 5.4% (2/37); 63.0% (17/27) versus 24.3% (9/37)] and a shorter interval-to-delivery period than those with a negative test [interval-to-delivery: median (range), 16 d (0-95 d) versus 42 d (2-91 d); p < 0.05 for each].
We conclude that 42% of patients with an early spontaneous preterm delivery (< 30 weeks) could be identified by a rapid MMP-8 bedside test at the time of their mid-trimester genetic amniocentesis. The MMP-8 bedside test is a powerful predictor of early spontaneous preterm birth in asymptomatic pregnant women.
孕中期羊膜腔穿刺术仍用于染色体异常及其他遗传性疾病的产前诊断。对孕中期遗传性羊膜腔穿刺术时获取的羊水进行分析,可识别有早期自然早产风险的患者。这是基于大量证据,这些证据发现亚临床羊膜腔内炎症/感染与早期自然早产存在因果关系。尽管已提出多种生物标志物来识别羊膜腔内炎症,但累积数据表明,测定羊水基质金属蛋白酶-8(MMP-8),即中性粒细胞胶原酶,是自然早产的有力预测指标。MMP-8由炎症细胞响应微生物产物或“危险信号”而释放。已开发出一种快速床旁检测方法,可在20分钟内在床边测定MMP-8,且无需实验室设备。本研究的目的是确定通过快速床旁检测测定的羊水中MMP-8升高是否能识别孕中期遗传性羊膜腔穿刺术后有自然早产风险的患者。
设计一项病例对照研究,从接受孕中期遗传性羊膜腔穿刺术的无症状单胎孕妇中获取羊水。对64例早期自然早产(<30周)患者和128例妊娠结局正常的匹配对照者的羊水进行MMP-8床旁检测分析。
(1)自然早产患者中42.2%(27/64)的MMP-8床旁检测(Yoon's MMP-8 Check™)呈阳性,而对照病例中无一例(0/128)呈阳性(p<0.001);(2)MMP-8床旁检测在预测孕中期遗传性羊膜腔穿刺术后自然早产(<30周)方面的敏感性为42.2%,特异性为100%;(3)在自然早产患者中,MMP-8床旁检测呈阳性者在羊膜腔穿刺术后2周和4周内的自然分娩率显著更高[40.7%(11/27)对5.4%(2/37);63.0%(17/27)对24.3%(9/37)],且分娩间隔期比检测呈阴性者短[分娩间隔期:中位数(范围),16天(0 - 95天)对42天(2 - 91天);每项p<0.05]。
我们得出结论,42%的早期自然早产(<30周)患者可在孕中期遗传性羊膜腔穿刺术时通过快速MMP-8床旁检测识别出来。MMP-8床旁检测是无症状孕妇早期自然早产的有力预测指标。