ABSTRACT
BACKGROUND: Preterm prelabor rupture of membranes (PROM) is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm PROM is not broadly used in clinical practice, and therefore a shift towards a non-invasive amniotic fluid sampling method is needed. OBJECTIVE: The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of-care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intra-amniotic inflammation, and microbial-associated intra-amniotic inflammation in patients with preterm PROM. STUDY DESIGN: A prospective cohort study was conducted in women with singleton gestation complicated by preterm PROM at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive PCR analysis. Intra-amniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration ≥745 pg/mL. RESULTS: 1) It was possible to perform the point-of-care assessment of interleukin-6 in vaginal fluid in 92% (141/153) of the women, and only those women were included in the analyses. 2) The rate of microbial invasion of the amniotic cavity and intra-amniotic inflammation was 26% (36/141) and 19% (27/141), respectively. Microbial-associated intra-amniotic inflammation was identified in 12% (17/141) of the women. 3) A strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; p<0.0001). 4) The presence of microbial invasion of the amniotic cavity, intra-amniotic inflammation or microbial-associated intra-amniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. 5) A vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity [sensitivity of 53% (19/36), specificity of 89% (93/104), positive predictive value of 63% (19/30), negative predictive value of 85% (93/110), positive likelihood ratio of 5.0 (95% CI 2.5-9.5), and negative likelihood ratio of 0.5 (95% CI 0.4-0.8)], intra-amniotic inflammation [sensitivity of 74% (20/27), specificity of 91% (104/114), positive predictive value of 67% (20/30), negative predictive value of 94% (104/111), positive likelihood ratio of 8.4 (95% CI 4.5-15.9), and negative likelihood ratio of 0.3 (95%CI 0.2-0.5)], and microbial-associated intra-amniotic inflammation (sensitivity of 100% (17/17), specificity of 90% (111/124), positive predictive value of 57% (17/30), negative predictive value of 100% (111/111), positive likelihood ratio of 9.5 (95% CI 5.7-16.0), and negative likelihood ratio of 0]. CONCLUSION: The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, non-invasive, and inexpensive method for the identification of intra-amniotic inflammation and microbial-associated intra-amniotic inflammation in preterm PROM pregnancies, showing good specificity and negative predictive value.
ABSTRACT
BACKGROUND: Preterm prelabor rupture of membranes is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm prelabor rupture of membranes is not broadly used in clinical practice, and therefore, a shift toward a noninvasive amniotic fluid sampling method is needed. OBJECTIVE: The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of-care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intraamniotic inflammation, and microbial-associated intraamniotic inflammation in patients with preterm prelabor rupture of membranes. STUDY DESIGN: A prospective cohort study was conducted in women with singleton gestation complicated by preterm prelabor rupture of membranes at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive polymerase chain reaction analysis. Intraamniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration ≥745 pg/mL. RESULTS: Several results were obtained in this study. First, it was possible to perform the point-of-care assessment of interleukin-6 in vaginal fluid in 92% of the women (141 of 153), and only those women were included in the analyses. Second, the rate of microbial invasion of the amniotic cavity and intraamniotic inflammation was 26% (36 of 141) and 19% (27 of 141), respectively. Microbial-associated intraamniotic inflammation was identified in 12% of the women (17 of 141). Third, a strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; P < .0001). Fourth, the presence of microbial invasion of the amniotic cavity, intraamniotic inflammation, or microbial-associated intraamniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. Fifth, a vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity (sensitivity of 53% [19 of 36], specificity of 89% [93 of 104], positive predictive value of 63% [19 of 30], negative predictive value of 85% [93 of 110], positive likelihood ratio of 5.0 [95% confidence interval, 2.5-9.5], and negative likelihood ratio of 0.5 [95% confidence interval, 0.4-0.8]); intraamniotic inflammation (sensitivity of 74% [20/27], specificity of 91% [104/114], positive predictive value of 67% [20 of 30], negative predictive value of 94% [104 of 111], positive likelihood ratio of 8.4 [95% confidence interval, 4.5-15.9], and negative likelihood ratio of 0.3 [95% confidence interval, 0.2-0.5]); and microbial-associated intraamniotic inflammation (sensitivity of 100% [17 of 17], specificity of 90% [111 of 124), positive predictive value of 57% [17 of 30], negative predictive value of 100% [111 of 111], positive likelihood ratio of 9.5 [95% confidence interval, 5.7-16.0], and negative likelihood ratio of 0). CONCLUSION: The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, noninvasive, and inexpensive method for the identification of intraamniotic inflammation and microbial-associated intraamniotic inflammation in preterm prelabor rupture of membranes pregnancies, showing good specificity and negative predictive value.
