Elevated monocyte chemotactic protein-1 in amniotic fluid is a risk factor for pregnancy loss

Abstract

Objective: Pregnancy loss after mid-trimester amniocentesis occurs in 0.5–1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinicallysilent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide varietyof cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/orfetal death.Method: A retrospective case–control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancyloss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay(sensitivity, 18.3 pg/ml). The Kolmogorov–Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis wasperformed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1.Results:MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those witha normal pregnancy outcome (pregnancy loss, mean 2.95 ± 0.19 pg/ml vs. normal outcome, mean 2.78 ± 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis(area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7–31.1),a sensitivity of 70%, and a specificity of 76%.Conclusion: A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 thanthose who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinicalimplications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of theprocedure.