Amniotic fluid soluble Toll-like receptor 4 in pregnancies complicated by preterm prelabor rupture of the membranes

Objective: To determine amniotic fluid soluble Toll-like receptor 4 (sTLR4) levels in women with preterm prelabor rupture of the membranes according to the presence of microbial invasion of the amniotic cavity and histological chorioamnionitis and its relation to neonatal outcome. Methods: One hundred two women with singleton pregnancies with a gestational age between 24?+?0 and 36?+?6 weeks were included in a prospective cohort study. Amniocenteses were performed, and the concentrations of sTLR4 in the amniotic fluid were determined using sandwich enzyme-linked immunosorbent assay technique. Results: Women with the presence of microbial invasion of the amniotic cavity had higher sTLR4 levels [median 54.2?ng/mL, interquartile range (IQR) 10.15–289.9] than those without this condition (median 18.1?ng/mL, IQR 8.1–29.9; p?=?0.001). Women with the presence of histological chorioamnionitis had a higher sTLR4 level (median 28.0?ng/mL, IQR 11.15–178.1) compared with women without histological chorioamnionitis (median 13.0?ng/mL, IQR 7.8–28.7; p?=?0.003). A mixed linear model was used to adjust for confounders. The difference was found only between women with and without microbial invasion of the amniotic cavity in this model. Conclusions: Microbial invasion of the amniotic cavity was associated with higher amniotic fluid sTLR4 levels independent of confounders.     

Amniotic fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine amniotic fluid soluble Toll-like receptor 2 (sTLR2) levels in PPROM according to the presence of microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis (HCA), and both these conditions. To test the cutoff level of 222.7?ng/mL, as proposed in our previous study, in order to distinguish women with both MIAC and HCA. Methods: 169 women with a gestational age between 24+0 and 36+6 weeks were included in a prospective cohort study. Amniocenteses were performed, and sTLR2 in the amniotic fluid were determined using ELISA. Results: Women with MIAC had higher sTLR2 levels (median 113.2?ng/mL) than those without MIAC (median 47.1 ng/mL; p < 0.0001). Women with HCA did not have a higher sTLR2 level (median 52.6?ng/mL) compared with women without HCA (median 47.1?ng/mL; p = 0.23). Women with both MIAC and HCA had higher sTLR2 levels (median: 311.3?ng/mL) than other women (17.5?ng/mL; p < 0.0001). The cutoff level 222.7?ng/mL had a sensitivity of 63%, a specificity of 98%, and a likelihood ratio of 40.3 for the prediction of both MIAC and HCA. Conclusions: Amniotic fluid sTLR2 is a promising predictor of both MIAC and HCA with high specificity in PPROM.     

Ureaplasma species and Mycoplasma hominis in cervical fluid of pregnancies complicated by preterm prelabor rupture of membranes

Objective: To evaluate Ureaplasma species and Mycoplasma hominis DNA in the cervical fluid and their association with microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).

Study design: A prospective study of 68 women with singleton pregnancies complicated by PPROM between 24^0/7 and 36^6/7 weeks was conducted. Cervical fluid and amniotic fluid were collected from all women at the time of admission. The Ureaplasma species and Mycoplasma hominis DNA in the cervical fluid were identified using specific real-time PCR.

Results: Ureaplasma species and Mycoplasma hominis DNA were identified in 59% (40/69) of the cervical fluid samples. Women with the presence of Ureaplasma species DNA with and without Mycoplasma hominis DNA in the cervical fluid had a higher rate of MIAC alone [35% (14/40) versus 11% (3/28); p?=?0.02] and a higher rate of the presence of both MIAC and HCA [30% (12/40) versus 4% (1/28); p?=?0.01] than women without Ureaplasma species and Mycoplasma hominis DNA in the cervical fluid.

Conclusions: The presence of Ureaplasma species DNA with and without Mycoplasma hominis DNA in the cervical fluid is associated with a higher risk of MIAC or MIAC and HCA together in pregnancies complicated by PPROM.     

Neonatal outcomes in subgroups of women with preterm prelabor rupture of membranes before 34 weeks

Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on short-term neonatal outcome in women with preterm prelabor rupture of membranes before 34 weeks of gestation.

Methods: A prospective observational cohort study including 122 pregnant women with PPROM between 24+0 and 34+0. MIAC was defined as a positive PCR result for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive PCR result for the 16S rRNA gene in the amniotic fluid. HCA was defined according to the Salafia classification. Maternal and short-term neonatal outcomes were evaluated according to the presence or absence of MIAC and/or HCA.

Results: The presence of both MIAC and HCA was observed in 36% (45/122) of women, HCA alone in 34% (41/122) and MIAC in 5% (6/122). A significantly higher incidence of early onset sepsis was observed in newborns born from women with both MIAC and HCA [33% (15/45)] compared with women with HCA alone [12% (5/41)] or MIAC alone [0% (0/6)] or women without MIAC or HCA detected [0% (0/30); p?=?0.001].

Conclusions: The presence of both MIAC and HCA increases the risk of early onset sepsis in pregnancies complicated by preterm prelabor rupture of membranes before 34 weeks of gestation.     

Umbilical cord blood markers of oxidative stress in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine umbilical cord blood total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid-reacting substances (TBARS), advanced glycation end products (AGEs) and markers of oxidative stress in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and their associations with microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA), funisitis and selected aspects of short-term neonatal morbidity.

Materials and methods: One hundred and sixty-five women with singleton pregnancies complicated by PPROM were included in this study. Blood samples were obtained by venipuncture from the umbilical cord vein after the delivery of the newborn. The umbilical cord blood concentrations of TAC, FRAP, TBARS and AGEs were measured.

Results: The presence of MIAC, HCA and funisitis did not show differences in the umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations. Positive correlations were found between the gestational age at sampling and umbilical cord blood TAC and AGEs concentrations (TAC: rho?=?0.26; p?=?0.001; AGEs: rho?=?0.35; p?<?0.0001). There was no association between umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations and selected aspects of short-term neonatal morbidity.

Conclusions: Oxidative stress is associated with PPROM, as indicated by the presence of markers tested in the umbilical cord blood; however, the evaluated oxidative stress markers are not influenced by the presence of MIAC and/or HCA, and funisitis or subsequent development of selected aspects of short-term neonatal morbidity.     

Cervical fluid interleukin 6 and intra-amniotic complications of preterm prelabor rupture of membranes

Objective: To determine if cervical fluid interleukin (IL)-6 concentrations in women with preterm prelabor rupture of membranes (PPROM) allows identification of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: One hundred forty-four women with singleton pregnancies complicated by PPROM were included in this prospective cohort study. Cervical and amniotic fluids were collected at the time of admission and concentrations of IL-6 were measured using an ELISA and point-of-care test, respectively. Cervical fluid was obtained using a Dacron polyester swab and amniotic fluid was obtained by transabdominal amniocentesis. MIAC was diagnosed based on a positive PCR result for Ureaplasma species, M. hominis, and/or C. trachomatis and/or by positivity for the 16?S rRNA gene. IAI was defined as amniotic fluid point-of-care IL-6 concentrations ≥745?pg/mL. The women were assigned to four subgroups based on the presence of MIAC and/or IAI: microbial-associated IAI (both MIAC and IAI), sterile IAI (IAI alone), MIAC alone, and without either MIAC or IAI.

Results: (1) Women with microbial-associated IAI had higher cervical fluid IL-6 concentrations (median 560?pg/mL) than did women with sterile IAI (median 303?pg/mL; p?=?.001), women with MIAC alone (median 135?pg/mL; p?=?.0004), and women without MIAC and IAI (median 180?pg/mL; p?=?.0001). (2) No differences were found in cervical fluid IL-6 concentrations among women with sterile IAI, with MIAC alone, and without MIAC and IAI. (3) A positive correlation was observed between cervical fluid IL-6 concentrations and the amount of Ureaplasma species in amniotic fluid (copies DNA/mL; rho?=?0.57, p?p?Conclusions: The presence of microbial-associated IAI is associated with the highest cervical fluid IL-6 concentrations. Cervical IL-6 can be helpful in the identification of microbial-associated IAI.     

Microbial invasion and histological chorioamnionitis upregulate neutrophil-gelatinase associated lipocalin in preterm prelabor rupture of membranes

Our recent exploratory proteomic study suggested increased levels of neutrophil-gelatinase associated lipocalin (P80188, NGAL_HUMAN) due to microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes. In this study, we verified the proteomics findings by assessing the amniotic fluid NGAL by ELISA in the original exploratory cohort. The NGAL level was significantly higher in women positive for both MIAC and HCA compared to women with both conditions ruled out (median 75.1?ng/ml versus 27.9?ng/ml; p?<?0.0001). For independent validation and to assess NGALs potential to stratify women positive for both MIAC and HCA from women in whom at least one of these conditions was absent, we subsequently designed a retrospective replication cohort. Significantly higher NGAL levels were found in women positive for both MIAC and HCA (median 65.9?ng/ml versus 34.2?ng/ml; p?=?0.0061). Significantly higher levels of NGAL were confirmed only in strata below 32 weeks of gestation. Based on the observed likelihood ratio, the best predictive cutoff level (47.1?ng/ml) was evaluated in both cohorts. Data from the verification cohort implied that NGAL is a valuable clinical marker for revealing MIAC leading to HCA; however, this potential was not replicated in the replication cohort.     

Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition,and intra-amniotic infection/inflammation

Objective.?Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI).

Study design.?This cross-sectional study included the following groups: (1) mid-trimester (n?=?55); (2) normal pregnancy at term with (n?=?50) and without (n?=?50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n?=?153); (b) PTL who delivered preterm without IAI (n?=?108); and (c) PTL with IAI (n?=?84); and (4) preterm PROM with (n?=?46) and without (n?=?44) IAI. sHLA-G concentrations were determined by ELISA. Non-parametric statistics were used for analysis.

Results.?(1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p?<?0.001 for both comparisons); (2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p?=?0.004); (3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p?<?0.001); and (4) The median AF sHLA-G concentration did not change with advancing gestational age.

Conclusions.?AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection.     

Cervical fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine the cervical fluid interleukin (IL)-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and the association of these interleukins with microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA).

Methods: Sixty women with singleton pregnancies were included in this study. Cervical fluid was sampled at the time of admission using Dacron polyester swabs, which were placed into the endocervical canal for 20?s. IL-6 and IL-8 levels were determined by ELISA. The management of PPROM was active management (except for in pregnancies <28 weeks of gestation) and occurs not later than 72?h after the rupture of membranes.

Result: The women with MIAC had higher IL-6 and IL-8 levels than did the women without MIAC (IL-6: p?=?0.01; IL-8: p?=?0.003). There was no difference in IL-6 levels between women with and without HCA (p?=?0.37). The women with HCA had higher IL-8 levels only in the crude analysis (p?=?0.01) but not after adjustment for gestational age (p?=?0.06). The women with both MIAC and HCA had higher levels of IL-6 and IL-8 than did the other women (IL-6: p?=?0.003; IL-8: p?=?0.001). IL-8 level of 2653?pg/mL was found to be the best cut-off point in the identification of PPROM pregnancies complicated by both MIAC and HCA with a likelihood ratio of 24.

Conclusions: The presence of MIAC is the most important factor impacting the local cervical inflammatory response, which is determined by IL-6 and IL-8 levels in the cervical fluid. IL-8 levels seem to be a promising non-invasive marker for the prediction of pregnancies complicated by the presence of both MIAC and HCA.     

Extensive subclinical venous sinus thrombosis in the dehydrated infant

Objective: To determine amniotic fluid myeloperoxidase concentration in women with preterm prelabor rupture of the membranes with microbial invasion of the amniotic cavity and histological chorioamnionitis. Methods: One hundred eighty-one women with singleton pregnancies with a gestational age between 24+0 and 36+6 weeks were included in this study. Amniocenteses were performed, and myeloperoxidase concentration in the amniotic fluid was determined using ELISA. Result: Women with microbial invasion of the amniotic cavity had higher median myeloperoxidase concentration than women without this condition (149.2?ng/mL vs. 54.6?ng/mL; p = 0.0006). Women with the presence of histological chorioamnionitis had higher median myeloperoxidase concentration than women without histological chorioamnionitis (103.7?ng/mL vs. 50.0?ng/mL; p = 0.0001). The presence of both microbial invasion of the amniotic cavity and histological chorioamnionitis was associated with higher median myeloperoxidase concentration (456.0?ng/mL vs. 52.9?ng/mL; p < 0.0001). The results remained significant after adjusting for gestational age. Conclusions: Increased amniotic fluid myeloperoxidase in microbial invasion of the amniotic cavity and histological chorioamnionitis confirm a role of myeloperoxidase in preterm prelabor rupture of the membranes pathophysiology.     

Amniotic fluid CD200 levels in pregnancies complicated by preterm prelabor rupture of the membranes

Abstract

Objective: To determine the amniotic fluid CD200 levels in uncomplicated pregnancies and in preterm prelabor rupture of the membranes (PPROM) according to microbial invasion of the amniotic cavity and histological chorioamnionitis and its association with neonatal outcomes.

Methods: One hundred and fifty-nine women with singleton pregnancies were included in this study. Amniotic fluid was collected, and CD200 levels were determined using ELISA.

Results: No difference was found in CD200 levels between women in the second trimester and women at term without labor. Women at term with labor had higher CD200 levels than women in the second trimester and women at term without labor. The presence of funisitis in PPROM pregnancies was associated with higher CD200 levels independent of gestational age (with funisitis: median 197.5?pg/mL versus without funisitis: median 61.0?pg/mL; p?=?0.003). The need for tracheal intubation and the development of bronchopulmonary dysplasia were associated with higher CD200 levels.

Conclusions: Amniotic fluid CD200 levels remained stable in advanced pregnancy and they were increased during parturition. Elevated CD200 levels in the presence of funisitis suggest the involvement of negative regulatory mechanisms of innate immunity. CD200 may play a role in the development of pulmonary aspects of neonatal morbidity.     

Amniotic fluid calreticulin in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: This study aimed to determine the amniotic fluid calreticulin concentrations in women with the preterm prelabor rupture of membranes (PPROM) based on the microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred sixty-eight women with singleton pregnancies were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis and were assayed for calreticulin concentrations by ELISA. IAI was defined as an amniotic fluid interleukin-6 concentration?>?745?pg/ml. Microbial-associated IAI was defined as the presence of both MIAC and IAI.

Result: Women with MIAC (with MIAC: median 54.4?ng/ml, versus without MIAC: median 32.6?ng/ml; p?<?0.0001), IAI (with IAI: median 66.8?ng/ml, versus without IAI: median 33.0?ng/ml; p?<?0.0001) and microbial-associated IAI (with microbial-associated IAI: median 82.5?ng/ml, versus without microbial-associated IAI: median 33.7?ng/ml; p?<?0.0001) had higher concentrations of calreticulin than women without these complications. An amniotic fluid calreticulin concentration of 81.4?ng/ml was found to be the best cutoff point for identifying women with microbial-associated IAI.

Conclusions: The presence of microbial-associated IAI is associated with increased amniotic fluid calreticulin concentrations. Calreticulin seems to be a promising marker for the early identification of PPROM complicated by microbial-associated IAI.     

A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection

Objective: Preterm prelabor rupture of membranes (preterm PROM) accounts for 30–40% of spontaneous preterm deliveries and thus is a major contributor to perinatal morbidity and mortality. An amniotic fluid (AF) interleukin-6 (IL-6) concentration is a key cytokine for the identification of intra-amniotic inflammation, patients at risk of impending preterm delivery and adverse pregnancy complications. The conventional method to determine IL-6 concentrations in AF is an enzyme-linked immunosorbent assay (ELISA). However, this technique is not available in clinical settings, and the results may take several days. A lateral flow-based immunoassay, or point of care (POC) test, has been developed to address this issue. The objective of this study was to compare the performance of AF IL-6 determined by the POC test to that determined by ELISA for the identification of intra-amniotic inflammation in patients with preterm PROM.

Materials and methods: This retrospective cohort study includes 56 women with singleton pregnancies who presented with preterm PROM. Amniocentesis was performed at the time of diagnosis, and AF was analyzed using cultivation techniques for aerobic and anaerobic bacteria as well as genital mycoplasmas. AF Gram stain and AF white blood cell counts were determined. AF IL-6 concentrations were measured using both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation defined as AF ELISA IL-6?≥?2600?pg/ml. A previously determined cut-off of 745?pg/ml was used to define a positive POC test.

Results: (1) The POC test for AF IL-6 concentrations had 97% sensitivity and 96% specificity for the identification of intra-amniotic inflammation, as defined using ELISA among patients with preterm PROM and (2) the diagnostic performance of the POC test for IL-6 was strongly correlated to that of an ELISA test for the identification of intra-amniotic inflammation and was equivalent for the identification of acute inflammatory placental lesions and microbial invasion of the amniotic cavity (MIAC).

Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in patients with preterm PROM. Results can be available within 20?min – this makes it possible to implement interventions designed to treat intra-amniotic inflammation and improve pregnancy outcomes.     

Amniotic fluid markers of oxidative stress in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine amniotic fluid total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substances (TBARS), markers of oxidative stress, in pregnancies complicated by preterm prelabor rupture of membranes (pPROM) and their correlation to microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA).

Methods: One-hundred thirty-eight women with singleton pregnancies complicated by pPROM were included in this study. Amniotic fluid was collected by transabdominal amniocentesis at the time of admission and amniotic fluid concentrations of TAC, FRAP and TBARS were measured.

Result: The presence of MIAC and/or HCA did not show any significant differences in the amniotic fluid TAC, FRAP and TBARS concentrations. Positive correlations between gestational age at sampling and amniotic fluid TAC and FRAP concentrations were found (TAC: rho?=?0.32; p?=?0.0002; FRAP: rho?=?0.36; p?<?0.0001). A negative correlation between gestation age at sampling and amniotic fluid TBARS concentrations was identified (rho?=?–0.25; p?=?0.004).

Conclusions: Oxidative stress is associated with pPROM as indicated by the presence of markers tested in the amniotic fluid; however, oxidative stress markers tested are not influenced by the presence of MIAC or HCA.     

Cervical fluid calreticulin and cathepsin-G in pregnancies complicated by preterm prelabor rupture of membranes

Objective: The study aimed to determine the cervical calreticulin and cathepsin-G concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI).

Methods: Eighty women with singleton pregnancies complicated by PPROM were included in this study. Cervical and amniotic fluids were obtained at the time of admission, and concentrations of calreticulin and cathepsin-G in cervical fluid were determined using ELISA. The MIAC was defined as a positive PCR analysis for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and/or by positivity for the 16S rRNA gene. IAI was defined as amniotic fluid bedside IL-6 concentrations ≥745?pg/mL

Result: Neither women with MIAC nor with IAI had different cervical fluid concentrations of calreticulin (with MIAC: median 18.9?pg/mL vs. without MIAC: median 14.7?pg/mL, p?=?0.28; with IAI: median 14.3?pg/mL vs. without IAI: median 15.6?pg/mL, p?=?0.57;) or of cathepsin-G (with MIAC: median 30.7?pg/mL vs. without MIAC: median 24.7?pg/mL, p?=?0.28; with IAI: median 27.3?pg/mL vs. without IAI: median 25.1?pg/mL, p?=?0.80) than women without those complications. No associations between amniotic fluid IL-6 concentrations, gestational age at sampling, and cervical fluid calreticulin and cathepsin-G concentrations were found.

Conclusions: Cervical fluid calreticulin and cathepsin-G concentrations did not reflect the presence of MIAC or IAI in women with PPROM.     

Amniotic fluid cathepsin-G in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate the amniotic fluid cathepsin-G concentrations in women with preterm prelabor rupture of membranes (PPROM) based on the presence of the microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: A total of 154 women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid cathepsin-G concentrations were assessed by ELISA. MIAC was determined using a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥?745?pg/mL.

Results: Women with MIAC had higher amniotic fluid cathepsin-G concentrations than women without MIAC (with MIAC: median 82.7?ng/mL, versus without MIAC: median 64.7?ng/mL; p?=?0.0003). Women with IAI had higher amniotic fluid cathepsin-G concentrations than women without this complication (with IAI: median 103.0?ng/mL, versus without IAI: median 66.2?ng/mL; p?p?Conclusions: The presence of either microbial-associated or sterile IAI was associated with increased amniotic fluid cathepsin-G concentrations in pregnancies complicated by PPROM. Amniotic fluid cathepsin-G appears to be a potential marker of IAI.     

Amniotic fluid prostaglandin E2 in pregnancies complicated by preterm prelabor rupture of the membranes

Objective: To determine amniotic fluid prostaglandin E2 concentrations in women preterm prelabor rupture of the membranes (PPROM) with respect to microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation (IAI), microbial-associated IAI, histological chorioamnionitis, and short-term neonatal morbidity.

Methods: One hundred forty-five women with singleton pregnancies were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis and were assayed for prostaglandin E2 concentrations by ELISA. IAI was defined as amniotic fluid interleukin-6 >745?pg/mL. Microbial-associated IAI was defined as the presence of both MIAC and IAI.

Result: No differences in prostaglandin E2 concentrations were found between women with and without MIAC (p?=?0.27). Women with IAI (p?=?0.0008) and microbial-associated IAI (p?=?0.01) had higher prostaglandin E2 concentrations than women without these complications. Women with histological chorioamnionitis had higher prostaglandin E2 concentrations only in crude analysis (p?=?0.02), but not after adjustment for gestational age at sampling (p?=?0.10). No associations between amniotic fluid prostaglandin E2 concentrations and the selected conditions of severe neonatal morbidity were found.

Conclusions: The intraamniotic inflammatory response either to infectious or to non-infectious stimulus, but not MIAC per se, seems to be a main factor associated with the elevation of the amniotic fluid PGE2 concentrations in women with PPROM.     

Cervical and vaginal fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine the cervical and vaginal fluid soluble Toll-like receptor-2 (sTLR2) levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and their correlation to microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA).

Methods: Sixty-eight women with singleton pregnancies complicated by PPROM were included in this study. Cervical and vaginal fluid was collected at the time of admission, and levels of sTLR2 in the cervical and vaginal fluid were determined using enzyme-linked immunosorbent assay.

Result: Women with MIAC and both MIAC and HCA did not have different cervical and vaginal fluid sTLR2 levels compared to those without MIAC and without both MIAC and HCA. Women with HCA had higher cervical fluid sTLR2 levels in crude analysis (with HCA: median 11.6?pg/mL versus without HCA: median 5.5?pg/mL; p?=?0.04) but not after adjustment for gestational age at sampling (p?=?0.19). No difference in vaginal fluid sTLR2 levels between women with and without HCA was found. A positive correlation between cervical and vaginal fluid sTLR2 levels was identified (rho?=?0.54; p?Conclusions: Cervical and vaginal fluid sTLR2 levels did not reflect the presence of MIAC and/or HCA.     

Periodontal disease and intra-amniotic complications in women with preterm prelabor rupture of membranes

Objective: Periodontal disease is frequently suggested as a possible causal factor for preterm delivery. The link between periodontal disease and preterm delivery is a possible translocation of periopathogenic bacteria to the placenta and amniotic fluid as well as a systemic response to this chronic inflammatory disease. However, there is a lack of information on whether there is an association between clinical periodontal status in women with preterm prelabor rupture of membranes (PPROM) and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI). Therefore, the main aim of this study was to evaluate the incidence and severity of periodontal disease in women with PPROM. The secondary aim was to characterize an association between periodontal status and the presence of intra-amniotic PPROM complications (MIAC and/or IAI).

Materials and methods: Seventy-eight women with PPROM at gestational ages between 24?+?0 and 36?+?6 weeks were included in this study. The samples of amniotic fluid were obtained at admission via transabdominal amniocentesis, and amniotic fluid interleukin (IL)-6 concentrations were determined using a point-of-care test. All women had a full-mouth recording to determine the periodontal and oral hygiene status. Probing pocket depth and clinical attachment loss were measured at four sites on each fully erupted tooth.

Results: In total, 45% (35/78) of women with PPROM had periodontal disease. Mild, moderate, and severe periodontal disease was present in 19% (15/78), 19% (15/78), and 6% (5/78) of women, respectively. The presence of MIAC and IAI was found in 28% (22/78) and 26% (20/78) of women, respectively. Periopathogenic bacteria (2?×?Streptococcus intermedius and 1?×?Fusobacterium nucleatum) was found in the amniotic fluid of 4% (3/78) of women. There were no differences in periodontal status between women with MIAC and/or IAI and women without these intra-amniotic complications.

Conclusions: The presence of MIAC and IAI was not related to the periodontal status of women with PPROM.