Subclinical Intra-amniotic Inflammation Research Articles

Amniocentesis prior to cerclage: An invasive strategy to exclude patients with sub-clinical intraamniotic inflammation before treatment

Introduction: Cervical cerclage is performed in patients with cervical insufficiency to reduce risks of misscariage/extreme prematurity. Severe complications can occur if performed in patients with intraamniotic inflammation. High levels of intraamniotic interleukin-6 (IL-6) are associated with histological chorioamnionitis. In expert hands amniocentesis is considered a safe procedure which we use routinely in management of PPROM. The aim of our study is to validate our strategy – diagnostic amniocentesis prior to cerclage.

115: Subclinical intra-amniotic inflammation in the midtrimester and the subsequent development of abnormal gross motor skills in infants born either term or preterm

115: Subclinical intra-amniotic inflammation in the midtrimester and the subsequent development of abnormal gross motor skills in infants born either term or preterm

Good prognosis of cerclage in cases of cervical insufficiency when intra-amniotic inflammation/infection is ruled out

Objective: To determine if absence of sub-clinical intra-amniotic inflammation improves the prognosis of rescue cerclage in cases of bulging membranes.Methods: Cohort study with all women with bulging membranes admitted into our hospital between 2009 and 2013. Patients underwent amniocentesis to quantify amniotic glucose, leukocytes, IL-6 and leukocyte esterase levels and for microbiological culture. All patients without intra-amniotic inflammation or sub-clinical chorioamnionitis were proposed a physical examination-indicated cervical cerclage. Those who did not accept were treated with bed rest.Results: We enrolled 31 women. Median gestational age at diagnosis was 23 + 1 (21–25 + 4) weeks. Median interval until delivery was 12 (3–52.5) d. IL-6 had the highest diagnostic accuracy for good prognosis. Patients with IL6 <2.90 ng/ml were diagnosed later in pregnancy and presented a longer interval until delivery (89 versus 4 d), higher gestational age at delivery (35 + 1 versus 23 + 3 weeks) and a lower rate of prematurity (54.5% versus 100%) and perinatal mortality (0% versus 80%) than those with IL-6 ≥2.90 ng/ml. Rescue cerclage and low Il-6 were the best predictors of good outcome.Conclusion: IL-6 levels in amniotic fluid may be of clinical value for individualizing the management of patients with bulging membranes for placement of rescue cerclage.

Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (&lt;32 weeks) and late (&gt;32 weeks) preterm delivery

Intra-amniotic inflammation is traditionally defined as an elevation of amniotic fluid interleukin (IL)-6. Previous case control studies have suggested an association between an elevated midtrimester amniotic fluid IL-6 and preterm delivery, although such an association has been recently challenged. Intra-amniotic inflammation can also be defined by an elevation of the T-cell chemokine, Interferon-gamma-inducible protein (IP)-10. An elevation in amniotic fluid IP-10 has been associated with chronic chorioamnionitis, a lesion frequently found in late spontaneous preterm birth and fetal death. In contrast, an elevation in amniotic fluid IL-6 is typically associated with acute chorioamnionitis and funisitis. This study was conducted to examine the relationship between an elevation in amniotic fluid IL-6 in the midtrimester and preterm delivery at or before 32 weeks of gestation, and the amniotic fluid concentration of IP-10 and preterm delivery after 32 weeks of gestation. This cohort study included 847 consecutive women undergoing genetic midtrimester amniocentesis; in 796 cases, amniotic fluid and pregnancy outcome was available for study after exclusion of abnormal karyotype and/or fetal congenital anomalies. Spontaneous preterm delivery was defined as early (≤32 weeks) or late (after 32 completed weeks of pregnancy). The amniotic fluid and maternal blood concentrations of IL-6 and IP-10 were measured by specific immunoassays. 1) The prevalence of preterm delivery was 8.3% (66/796), while those of early and late spontaneous preterm delivery were 1.5% (n=12), and 4.5% (n=36), respectively; 2) patients who had a spontaneous preterm delivery after 32 weeks of gestation had a higher median amniotic fluid IP-10 concentration than those who delivered at term [median 713 pg/mL, inter-quartile range (IQR) 509-1427 pg/mL vs. median 589 pg/mL, IQR 402-953 pg/mL; P=0.006] and an elevation of amniotic fluid IP-10 concentration above 502 pg/mL (derived from an ROC curve) was associated with late spontaneous preterm delivery [odds ratio 3.9 (95% CI 1.6-9.9)]; 3) patients who had a spontaneous preterm delivery ≤32 weeks of gestation had a higher median amniotic fluid IL-6 concentration than those who delivered at term [median 2052 pg/mL, IQR 435-3015 pg/mL vs. median 414 pg/mL, IQR 209-930 pg/mL; P=0.006], and an elevated amniotic fluid IL-6 concentration above 1740 pg/mL (derived from an ROC curve) was associated with early spontaneous preterm delivery [odds ratio 9.5 (95% CI 2.9-31.1)]; 4) subclinical intra-amniotic inflammation, defined as an elevation of IL-6 (≥2.9 ng/mL) or IP-10 (≥2.2 ng/mL) concentration above the 95th percentile of patients who had uncomplicated term delivery (n=652 for IL-6 and n=633 for IP-10), was observed in 6.3% (50/796) and 5.8% (45/770) of cases, respectively. Although each type of inflammation is a risk factor for spontaneous preterm delivery, many patients had a term delivery without complication; 5) the amniotic fluid in the midtrimester did not contain microorganisms detectable with cultivation techniques. INTRA-amniotic inflammation is heterogeneous. Some patients have elevated amniotic fluid concentrations of IL-6, and are at risk for spontaneous preterm delivery before 32 weeks of gestation, while others have an elevated IP-10 (a chemotactic T-cell chemokine) and such patients are at risk for spontaneous preterm delivery after 32 weeks of gestation. A fraction of patients have subclinical intra-amniotic inflammation and deliver at term. The clinical significance of this condition remains to be determined.

Patients with an asymptomatic short cervix (≤15 mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling

The objective of the study was to determine the frequency and clinical significance of intraamniotic inflammation in asymptomatic women with a sonographic short cervix (SCX) in the midtrimester. This cohort study included 47 asymptomatic women (14-24 weeks) with an SCX (<or=15 mm) who underwent amniocentesis. Women with multiple gestation, cerclage, or cervical dilatation greater than 2 cm were excluded. Intraamniotic inflammation was defined as an elevated amniotic fluid (AF) matrix metalloproteinase-8 concentration (>23 ng/mL). (1) intraamniotic infection was found in 4.3% of patients; (2) among patients with a negative AF culture, the prevalence of intraamniotic inflammation was 22.2%; and (3) patients with a negative AF culture, but with intraamniotic inflammation, had a higher rate of delivery within 7 days (40% vs 5.7%; P=.016) and a shorter median diagnosis-to-delivery interval than those without intraamniotic inflammation (18 vs 42 days; P=.01). Twenty-two percent of patients with a midtrimester SCX have intraamniotic inflammation. The risk of preterm delivery within 7 days for these patients is 40%.

521: One of every four patients with an asymptomatic short cervix (15mm) has subclinical intra-amniotic inflammation: implications for patient counseling and management

The clinical management of a patient with a sonographic short cervix is a common obstetrical challenge. A fraction of patients with a short cervix have evidence of intra-amniotic inflammation (Kiefer, AJOG, 2009); however, the outcome of these patients has not been characterized. The purpose of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in asymptomatic women in the mid-trimester of pregnancy with a sonographic short cervix.

Interleukin-6, but not relaxin, predicts outcome of rescue cerclage in women with cervical incompetence

Objective We investigated the potential roles of relaxin and subclinical intra-amniotic inflammation by quantitating amniotic fluid relaxin and interleukin-6 concentrations for the prediction of outcome of rescue cerclage in women with cervical incompetence. Study design Cervical incompetence was diagnosed when cervical dilatation exceeded 2 cm with intact but bulging membranes and no detectable uterine activity. Each woman underwent amniocentesis to facilitate the performance of a rescue cerclage between 15 and 27 weeks of gestation (n = 40 women). Forty-five additional women who underwent amniocentesis for chromosomal testing between 16 and 27 weeks of gestation served as a control group. All control patients were delivered of chromosomally normal infants at>37 weeks of gestation. All cases and control patients were singleton gestations. Interleukin-6 and relaxin were determined in all amniotic fluid samples by enzyme-linked immunosorbent assay. Results Amniotic fluid interleukin-6 levels were significantly higher in women with cervical incompetence than in control patients (control patients, 50.4 pg/mL [range, 19.4-97.4 pg/mL] vs cervical incompetence patients, 5459.1 pg/mL [range, 1131.4-14425.7 pg/mL] ; P < .001). In contrast to interleukin-6, relaxin levels did not differ between the 2 groups (control patients, 67.5 pg/mL [range, 35.1-153.5 pg/mL] vs cervical incompetence patients, 45.6 pg/mL [range, 30.1-75.5 pg/mL]; P = .061). There was a significant difference in interleukin-6 levels in women with shorter latencies ( P < .01 for all latency intervals that were examined: delivery within 24 hours, 3 days, 7 days, before 33 and 37 completed weeks of gestation). Linear regression analysis with the use of the latency interval from cerclage to delivery as the dependent and with interleukin-6 as the independent variable revealed a significant inverse relationship ( r = −0.62; P < .001 after log transformation of interleukin-6). There was no relationship on regression analysis between relaxin and the latency interval. Conclusion Amniotic fluid interleukin-6 is increased in patients with cervical incompetence, which suggests that subclinical inflammation may contribute to cervical incompetence. Further, an elevated interleukin-6 level predicts a cerclage short-latency interval between cerclage and delivery. In contrast with interleukin-6, amniotic fluid relaxin does not appear to contribute to cervical incompetence–induced cervical dilation.

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

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 clinically silent, 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 variety of 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/or fetal 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 pregnancy loss 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 was performed 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 with a 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 than those 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 clinical implications. 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 the procedure.

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

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.