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Data on clinical significance of second trimester inflammatory biomarkers in the amniotic fluid in predicting preterm delivery.

ABSTRACT: In this article second trimester amniotic fluid biomarkers are measured for correlation with preterm delivery. One additional milliliter of amniotic fluid is collected during amniocentesis for dosages of IL-6, MMP-9, CRP and glucose levels, along with maternal serum CRP and glucose. MMP-9 and Il-6 levels were measured with the corresponding Human Quantikine(R) ELISA Kit (R&D systems) according to the instructions provided by the manufacturer. Cut-off values for AF MMP-9 and IL-6 were fixed by the kit sensitivity thresholds. Data includes ROC curves for glucose (Fig. 1), IL-6 (Fig. 2) and MMP-9 (Fig. 3), aiming to search for sensitivity and specificity in the prediction of premature delivery. Statistical analyses are performed with SPSS v20.0 software. Statistical significance is determined using the Mann-Whitney and one way ANOVA test. The association with preterm delivery is performed using a two proportions test. Correlations are measured using the Pearson?'s coefficient. A p value<0.05 is considered statistically significant. The data is presented in the figures provided. Data relied on a previous publication "Prediction of preterm delivery by second trimester inflammatory biomarkers in the amniotic fluid" (A. Kesrouani, E. Chalhoub, E. El Rassy, M. Germanos, A. Khazzaka, J. Rizkallah, E. Attieh, N. Aouad, 2016) [1].

SUBMITTER: Kesrouani A

PROVIDER: S-EPMC5011160 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Data on clinical significance of second trimester inflammatory biomarkers in the amniotic fluid in predicting preterm delivery.

Kesrouani Assaad A Chalhoub Elie E El Rassy Elie E Germanos Mirna M Khazzaka Aline A Rizkallah Jamale J Attieh Elie E Aouad Norma N

Data in brief 20160824

In this article second trimester amniotic fluid biomarkers are measured for correlation with preterm delivery. One additional milliliter of amniotic fluid is collected during amniocentesis for dosages of IL-6, MMP-9, CRP and glucose levels, along with maternal serum CRP and glucose. MMP-9 and Il-6 levels were measured with the corresponding Human Quantikine(R) ELISA Kit (R&D systems) according to the instructions provided by the manufacturer. Cut-off values for AF MMP-9 and IL-6 were fixed by th ...[more]

PMID: 27626053

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Project description:IntroductionThe global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFβ, and IL-1β) in asymptomatic women with and without subsequent spontaneous preterm delivery.Material and methodsWe used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups.Clinicaltrialsgov: NCT00718705.ResultsBetween July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFβ, and IL-1β were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFβ, and IL-1β levels did not differ between the groups.ConclusionsIn amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.

Project description:BACKGROUND:Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery. OBJECTIVE:The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort. METHODS:Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls. RESULTS:Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort. CONCLUSIONS:Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.

Project description:Study questionWhich inflammation biomarkers detected in the vaginal fluid are most informative for identifying preterm delivery (PTD) risk?Summary answerElevated interleukin (IL)-6 at mid-trimester was associated with increased odds of spontaneous PTD at <35 weeks and with PTD plus histologic chorioamnionitis (HCA), and had the greatest sensitivity for detecting these two PTD subtypes.What is known alreadyMaternal and/or fetal inflammation play a role in some preterm deliveries, therefore inflammation biomarkers might help to identify women at greater risk.Study design, size, durationWe examined 1115 women from the Pregnancy Outcomes and Community Health Study, a cohort study conducted from September 1998 through June 2004, for whom data were available on mid-pregnancy inflammatory biomarkers.Participants/materials, setting, methodsAt enrollment at 16-27 weeks gestation, vaginal fluid samples were collected from a swab and 15 eluted biomarkers were measured using the Meso Scale Discovery multiplex electrochemiluminescence platform. Associations of biomarkers with PTD were examined, according to clinical circumstance, week at delivery and presence/absence of HCA. Weighted logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) adjusted for race. Sensitivity and specificity were compared between individual and multiple biomarkers, identified by a bootstrapping method.Main results and the role of chanceElevated IL-6 (>75th percentile) displayed the strongest association with spontaneous PTD <35 weeks (OR 2.3; CI 1.3-4.0) and PTD with HCA (OR 2.8; CI 1.4-6.0). The sensitivity of IL-6 to detect spontaneous PTD <35 weeks or PTD with HCA was 0.43 and 0.51, respectively, while specificity was 0.74 and 0.75, respectively. IL-6 plus IL1β, IL-6r, tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor increased specificity (range 0.84-0.88), but decreased sensitivity (range 0.28-0.34) to detect both PTD subtypes. Results were similar when a combination of IL-6 and bacterial vaginosis (BV) was explored. Thus, the use of multiple biomarkers did not detect PTD subtypes with a greater sensitivity than IL-6 alone, and IL-6 is a specific but non-sensitive marker for the detection of spontaneous PTD.Limitations, reasons for cautionOur ability to find small effect size associations between PTD and inflammation biomarkers (OR <2.0) might have been limited by the modest number of less common PTD subtypes in our population (e.g. spontaneous delivery <35 weeks, PTD accompanied by HCA) and by relatively higher variability for some cytokines, for example tumor necrosis factor-α, IL-12p70, IL-10 and granulocyte-macrophage colony-stimulating factor, that are less stable and commonly undetectable or detectable at low levels in human vaginal secretions.Wider implications of the findingsLarger studies are needed to further explore a role of inflammation biomarkers in combination with other risk factors, including specific BV-associated organisms, for the prediction of PTD subtypes.Study funding/competing interest(s)This work was supported by the National Institute of Child Health and Human Development, National Institute of Nursing, March of Dimes Foundation, Thrasher Research Foundation and Centers for Disease Control and Prevention. The authors have no conflicts of interest.

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Data on clinical significance of second trimester inflammatory biomarkers in the amniotic fluid in predicting preterm delivery.

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Data on clinical significance of second trimester inflammatory biomarkers in the amniotic fluid in predicting preterm delivery.

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