About one-half of early spontaneous preterm deliveries can be identified by a rapid matrix metalloproteinase-8 (MMP-8) bedside test at the time of mid-trimester genetic amniocentesis

* This study was presented at the 35^th Annual Meeting of the Society for Maternal-Fetal Medicine, February 2–7, 2015, San Diego, CA, USA.

*

Abstract

Objective: 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.

Study design: 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.

Results: (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].

Conclusion: 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.

Keywords:

• Amniotic fluid
• intra-amniotic inflammation/infection
• point-of-care (POC) test
• preterm parturition

Declaration of interest

The test described in this article is the subject of a patent by the Seoul National University in Seoul, Republic of Korea. Dr. B. H. Yoon is listed as an inventor and has a financial interest in OBMed Co., Ltd., Seoul, Republic of Korea, the manufacturer of this test. A financial interest is defined as a potential gain or potential loss derived from the activity of this company. This research was supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI12C0768). This research was also supported, in part, by the Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS).

Notes

* This study was presented at the 35^th Annual Meeting of the Society for Maternal-Fetal Medicine, February 2–7, 2015, San Diego, CA, USA.