Transactions of the Twenty-First Annual Meeting of the Society for Maternal-Fetal Medicine—Continued
An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery,☆☆

Presented at the Twenty-first Annual Meeting of the Society for Maternal-Fetal Medicine, Reno, Nev, February 5-10, 2001.
https://doi.org/10.1067/mob.2001.117678Get rights and content

Abstract

Objective: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. Study Design: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. Results: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. Conclusions: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications. (Am J Obstet Gynecol 2001;185:1162-7.)

Section snippets

Study design

A case-control study was designed with stored amniotic fluid obtained from women who underwent mid-trimester genetic amniocentesis. Nineteen patients with spontaneous preterm delivery before 32 weeks of gestation were matched for maternal age (within 5 years), parity (nullipara vs primipara or multipara), gestational age at amniocentesis (within 2 weeks), and year of amniocentesis (within 3 years) with 95 controls who delivered after 37 weeks of gestation (1:5 matching). Cases with abnormal

Results

The clinical characteristics of the study population are shown in Table I.

. Clinical characteristics and outcomes of study population

CharacteristicSpontaneous preterm delivery (n = 19)Term delivery (n = 95)P
Mean maternal age, y (± SD)32.8 ± 4.932.8 ± 4.3NS
Nulliparity6 (32)30 (32)NS
History of spontaneous preterm delivery1 (5)2 (2)NS
Indication for amniocentesis
 Maternal age (≥35 y)9 (47)42 (44)NS
 Risk of Down syndrome by serum marker*3 (16)27 (28)NS
 Elevated MSAFP5 (26)12 (13)NS
 Anomaly of previous baby

Comment

During the course of an inflammatory process, IL-6 and MMP-8 accumulate in body fluids (eg, crevicular, synovial, and amniotic fluid)11, 14 and, therefore, we postulate that an increased concentration of these substances in amniotic fluid is an index of the presence of intra-amniotic inflammation. Because this process is often present for weeks before preterm delivery (see Table III), inflammation must be considered chronic in nature. Inasmuch as 42% of early preterm deliveries (<32 weeks) were

References (25)

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    The matrix metalloproteinase-8 (MMP-8) and interleukin-8 concentrations were measured in the samples of stored fluid (supernatant of centrifuged amniotic fluid obtained by amniocentesis) with a commercially available enzyme-linked immunosorbent assay (ELISA; R&D Systems, Minneapolis, MN). Intraamniotic inflammation was defined when the MMP-8 concentration was >23 ng/mL, based on previous reports.26,78,88–101 The sensitivity of the test for MMP-8 was 0.058 ng/mL, and that for interleukin-8 was 0.0075 ng/mL.

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Supported by a grant (2000-N-NL-01-C-078) from the Korea Institute of Science and Technology Evaluation and Planning (KISTEP), Republic of Korea.

☆☆

Reprint requests: Bo Hyun Yoon, MD, PhD, Department of Obstetrics and Gynecology, College of Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.

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