Rose-Marie Holst

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes

Background.  Previous studies have shown an association between intra‐amniotic microbial invasion and/or inflammation and spontaneous preterm birth. The aim of this study was to investigate the occurrence of intra‐amniotic microorganisms and cytokines [interleukin (IL)‐6 and IL‐8] in a Swedish population, with low incidence of preterm birth, of women with preterm prelabor rupture of membranes and their correlation to preterm birth.

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor

Background. Previous studies indicate an association between intra‐amniotic microbial invasion and/or inflammation and spontaneous preterm birth, but there is a limited amount of data available from Europe. The aim of this study was to investigate the occurrence of intra‐amniotic microorganisms and cytokines (interleukin‐6 and interleukin‐8) in a Swedish population of women in preterm labor and their correlation with preterm birth.

Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery

Background.  Intrauterine infection and inflammation in women with preterm labor are related to adverse perinatal outcome. Due to its subclinical nature, a correct diagnosis depends on retrieval of amniotic fluid. Amniocentesis is, however, not performed as a clinical routine because of its invasiveness. Hypothetically, cytokines in the cervical fluid may represent an alternative diagnostic approach. The aim was to examine cervical interleukin (IL)‐6 and IL‐8 in relation to microbial invasion of the amniotic fluid, intra‐amniotic inflammation, and preterm birth in women in preterm labor.

Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery ☆

OBJECTIVE The purpose of this study was to evaluate the role of monocyte chemotactic protein-1 in cervical and amniotic fluid in women in preterm labor and with preterm premature rupture of membranes. STUDY DESIGN Women with singleton pregnancies (<or=34 weeks) in preterm labor (n=75 women), with preterm premature rupture of membranes (n=47 women), and at term (n=45 women) who were undergoing elective cesarean delivery were included. Cervical and amniotic fluid were sampled. RESULTS Monocyte chemotactic protein-1 in cervical and amniotic fluid was higher in women in preterm labor than in women at term. Cervical monocyte chemotactic protein-1 in women in preterm labor was associated with microbial invasion of the amniotic cavity, intra-amniotic inflammation, delivery within 7 days, and at <or=34 weeks. Amniotic monocyte chemotactic protein-1 correlated to microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes, intra-amniotic inflammation in preterm labor, preterm premature rupture of membranes, delivery within 7 days, and delivery at <or=34 weeks in women in preterm labor. CONCLUSION Monocyte chemotactic protein-1 in cervical and amniotic fluid levels are elevated in preterm labor and preterm premature rupture of membranes and correlate to intra-amniotic infection/inflammation.

Expression of cytokines and chemokines in cervical and amniotic fluid: Relationship to histological chorioamnionitis

Objective. To correlate cervical and amniotic fluid cytokines and macrophage-related chemokines to the development of histological chorioamnionitis (HCA) in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PPROM). Study design. Cervical and amniotic fluid interleukin (IL)-6, IL-8, IL-18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 from pregnant women (at ≤34 weeks of gestation) in PTL (N = 42) were analyzed and related to the subsequent occurrence of HCA or inflammatory signs in the placenta. For the patients with PPROM (N = 30) only amniotic fluid proteins were analyzed. Results. Intra-amniotic levels of IL-6, IL-8, IL-18, MCP-1, and MCP-3 were significantly higher in PTL cases with HCA compared to non-HCA controls, whereas no such relationship was obtained in the PPROM group. Cervical IL-8 and IL-6 (but not IL-18, MCP-1, MCP-2, and MCP-3) in PTL patients was associated with HCA, and at a cut-off level of 10.0 ng/mL cervical IL-8 was a strong predictor of HCA in the PTL cases (sensitivity 100%, specificity 67%, positive predictive value 63%, negative predictive value 100%). The cytokine and chemokine levels in the group with inflammatory signs were generally higher than in controls but lower compared to the concentrations in the HCA group. Conclusions. The amniotic levels of IL-6, IL-8, IL-18, and the CC-chemokines MCP-1 and MCP-3 in PTL patients all predicted HCA, whereas only IL-8 was a clinically useful marker of HCA in the cervical fluid. In addition there is indication that the levels of inflammatory proteins are related to the degree of inflammatory infiltration in placental tissue samples.

Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation and preterm delivery.

Objective To evaluate the relationship between interleukin (IL)‐18 in cervical mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm delivery and intra‐amniotic inflammation in women in preterm labour, with preterm prelabour rupture of membranes and at term.

Prediction of spontaneous preterm delivery in women with preterm labor: analysis of multiple proteins in amniotic and cervical fluids.

OBJECTIVE: To analyze whether specific proteins in amniotic and cervical fluids, alone or in combination with risk factors, can identify women in preterm labor with intact membranes who will deliver spontaneously within 7 days of sampling. METHODS: In a cohort of 89 women in preterm labor, amniotic and cervical fluids were collected between 22 and 33 weeks of gestation. Twenty-seven proteins were analyzed simultaneously using multiplex technology. Individual levels of each protein were compared and calculations performed to find associations among different proteins, background variables, and spontaneous preterm delivery within 7 days of sampling. The area under the curve (AUC) was calculated using receiver operating characteristic curve analysis, and prediction models were created based on stepwise logistic regression. RESULTS: We found two multivariable models that predicted spontaneous preterm delivery better than any single variable. One combined multivariable prediction model was based on amniotic macrophage inflammatory protein-1&bgr;, cervical interferon-&ggr;, and monocyte chemotactic protein-1. This model predicted outcome with 91% sensitivity, 84% specificity, 78% positive predictive value, and 94% negative predictive value, with a likelihood ratio of 5.6 and AUC of 0.91. An alternative, noninvasive model based on cervical length, cervical interferon-&ggr;, interleukin-6, and monocyte chemotactic protein-1 predicted delivery within 7 days with 85% sensitivity, 82% specificity, 74% positive predictive value, and 90% negative predictive value, with a likelihood ratio of 4.7 and AUC of 0.91. CONCLUSION: A combination of proteins from amniotic fluid and cervical fluid or cervical length can help determine which women will deliver preterm. LEVEL OF EVIDENCE: II

Prediction of microbial invasion of the amniotic cavity in women with preterm labour: analysis of multiple proteins in amniotic and cervical fluids

Please cite this paper as: Holst R‐M, Hagberg H, Wennerholm U‐B, Skogstrand K, Thorsen P, Jacobsson B. Prediction of microbial invasion of the amniotic cavity in women with preterm labour: analysis of multiple proteins in amniotic and cervical fluids. BJOG 2011;118:240–249.

Cervical length in women in preterm labor with intact membranes: relationship to intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm delivery

Intra‐amniotic infection, diagnosed by microbial invasion of the amniotic cavity (MIAC) and/or the presence of intra‐amniotic inflammation (IAI), is related to adverse perinatal outcome in women with preterm labor. Due to the subclinical nature of IAI, a correct diagnosis depends on amniocentesis, which is an invasive method not performed as a clinical routine. The aim of this study was to evaluate if cervical length measured by transvaginal sonography could assist in the identification of women at high risk for IAI.

Intra‐amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture

Objective. To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Design. Prospective cohort study. Setting. Evaluation of intra‐amniotic inflammation in preterm premature rupture of membranes. Population. Sixty‐six pregnant women with preterm prelabor membrane rupture at 22+0–33+6 weeks’ gestational age. Methods. Twenty‐seven amniotic fluid proteins were assayed by a multiple immunoassay. Main outcome measures. The intra‐amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. Results. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20 and 50%, respectively. There was a higher inflammatory response in women with MIAC than in those without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid interleukin (IL)‐6 and IL‐10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and a positive likelihood ratio of 3.6. There were no differences in intra‐amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Conclusion. Amniotic fluid IL‐6 and IL‐10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra‐amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.