Teresa Cobo

Clinical and inflammatory markers in amniotic fluid as predictors of adverse outcomes in preterm premature rupture of membranes.

OBJECTIVEnWe sought to evaluate gestational age, cervical length, amniotic fluid interleukin (IL)-6, and selected proteomic biomarkers as independent predictors of adverse outcome in preterm premature rupture of membranes (PPROM).nnnSTUDY DESIGNnThis was a prospective cohort study of 65 consecutive women with PPROM (20.0-34.6 weeks). Gestational age, cervical length, amniotic fluid IL-6, and proteomic biomarkers (calgranulins A and C, and neutrophil defensins 1 and 2) were evaluated at diagnosis. The predictive value for intraamniotic infection and neonatal composite morbidity was calculated by logistic regression.nnnRESULTSnProteomic biomarkers were independent predictors of intraamniotic infection (odds ratio, 22.1; P=.011) and neonatal composite morbidity (odds ratio, 17.6; P=.02). With the exception of a trend between gestational age and neonatal morbidity (P=.054), none of the other parameters were independent predictors of outcome measures.nnnCONCLUSIONnSelected proteomic biomarkers were the only independent predictors of adverse outcomes in PPROM. Contrary to what is reported in preterm labor with intact membranes, gestational age, cervical length, and IL-6 were not.

Amniotic fluid protein profiles of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria.

Objective This study aimed to evaluate the amniotic fluid protein profiles and the intensity of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria, using the multiplex xMAP technology. Methods A retrospective cohort study was undertaken in the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Czech Republic. A total of 145 pregnant women with preterm prelabor rupture of membranes between gestational age 24+0 and 36+6 weeks were included in the study. Amniocenteses were performed. The presence of Ureaplasma spp. and other bacteria was evaluated using 16S rRNA gene sequencing. The levels of specific proteins were determined using multiplex xMAP technology. Results The presence of Ureaplasma spp. and other bacteria in the amniotic fluid was associated with increased levels of interleukin (IL)-6, IL-8, IL-10, brain-derived neurotropic factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1, and matrix metalloproteinasis-9. Ureaplasma spp. were also associated with increased levels of neurotropin-3 and triggering receptor expressed on myeloid cells-1. Conclusions The presence of Ureaplasma spp. in the amniotic fluid is associated with a slightly different protein profile of inflammatory response, but the intensity of inflammatory response to Ureaplasma spp. is comparable with the inflammatory response to other bacteria.

Predictive value of combined amniotic fluid proteomic biomarkers and interleukin-6 in preterm labor with intact membranes

OBJECTIVEnTo assess proteomic biomarkers and interleukin-6 alone or in combination to predict intraamniotic infection, preterm birth, and neonatal morbidity in preterm labor with intact membranes.nnnSTUDY DESIGNnAmniotic fluid interleukin-6 and selected proteomic biomarkers were assayed from 86 patients with preterm labor and intact membranes (22-36 weeks). The predictive value of each marker alone or in combination was evaluated for intraamniotic infection, preterm birth, and neonatal composite morbidity.nnnRESULTSnBoth interleukin-6 (odds ratio, 19.5; P = .012) and proteomic biomarkers (odds ratio, 25.2; P = .001) were statistically independent predictors of intraamniotic infection with sensitivity, positive predictive value, and false-positive rates of 25%, 17.6%, and 20% when 1 marker was present and of 75%, 75%, and 4.3% when both were detected. Their combination did not improve prediction of preterm birth or neonatal morbidity.nnnCONCLUSIONnThe combined use of proteomic biomarkers and interleukin-6 to predict intraamniotic infection shows better accuracy than when used alone.

The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes.

Abstract Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the intensity of the fetal inflammatory response and the occurrence of fetal inflammatory response syndrome (FIRS) in preterm prelabor rupture of membranes (PPROM). Methods: One hundred and forty-nine women with singleton pregnancies complicated by PPROM between the gestational ages 24u2009+u20090 and 36u2009+u20096 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood interleukin (IL)-6 levels were evaluated using ELISA kits. The fetal inflammatory response was determined by IL-6 levels, and FIRS was defined as an umbilical cord blood IL-6 >11u2009pg/mL. Result: IL-6 levels and the occurrence of FIRS were higher in women complicated with both MIAC and HCA (median IL-6 35.5u2009pg/mL, FIRS in 68%) than in women with HCA alone (median IL-6 5.8u2009pg/mL, FIRS in 36%), MIAC alone (median IL-6 2.8u2009pg/mL, FIRS in 17%) or women without MIAC or HCA (median IL-6 4.3u2009pg/mL, FIRS in 29%). There were no differences in IL-6 levels or rates of FIRS among women with MIAC alone or HCA alone and women without both MIAC and HCA. Conclusion: A higher fetal inflammatory response mediated by umbilical cord blood IL-6 was identified when both MIAC and HCA were detected in pregnancies complicated by PPROM.

Intra-Amniotic Inflammatory Response in Subgroups of Women with Preterm Prelabor Rupture of the Membranes

Background To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the magnitude of intra-amniotic inflammatory response in preterm prelabor rupture of membranes (PPROM). Methodology/Principal Finding A prospective cohort study was performed in 107 women with PPROM between 23.0 and 36.6 weeks of gestational age. Twenty-six proteins were assayed by multiple immunoassay in amniotic fluid. The policy for PPROM in Czech Republic is active, and 90% of the women were delivered within 96 hours of membrane rupture. Histopathological placental findings were evaluated based on the Salafia classification. Data were analyzed in four subgroups of population according to the presence of MIAC and/or HCA. Results were stratified by gestational age at PPROM (< or ≥34.0 weeks). The rates of MIAC and HCA were 44% and 57%, respectively. Regardless of gestational age at PPROM, intra-amniotic inflammatory response was higher when MIAC and HCA were both present. There were no differences in the intra-amniotic inflammatory response between women with MIAC or HCA alone and women without infection. Conclusion A higher intra-amniotic inflammatory response was identified when both HCA and MIAC were detected.

The association between histological chorioamnionitis, funisitis and neonatal outcome in women with preterm prelabor rupture of membranes

Abstract Objective: To determine the impact of histological chorioamnionitis (HCA) and funisitis on neonatal outcome in preterm prelabor rupture of membranes (PPROM) pregnancies. Methods: Women with PPROM between 24u2009+u20090 to 36u2009+u20096 weeks of gestation, admitted to the Department of Obstetrics and Gynecology at the University Hospital Hradec Kralove in the Czech Republic, between July 2008 and October 2010, were enrolled in the study (nu2009=u2009231). Results: The incidence of early-onset sepsis (EOS) differed significantly in neonates born to women with and without HCA, after adjustment for gestational age (11% versus 1%, pu2009=u20090.011). The incidence of EOS in neonates was also significantly different, after adjustment for gestational age, in cases with and without funisitis (18% versus 4%, pu2009=u20090.002). The same was also found for retinopathy of prematurity (ROP) cases with and without funisitis (23% versus 4%, pu2009=u20090.014), after adjustment for gestational age. Conclusions: HCA and funisitis increase the risk of adverse perinatal outcome in PPROM pregnancies.

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.

Systemic and local inflammatory response in women with preterm prelabor rupture of membranes.

Objective To evaluate the inflammatory pattern in maternal circulation, amniotic cavity, cervix and vagina from women with preterm prelabor rupture of membranes (PPROM) considering the occurrence of microbial invasion of the amniotic cavity (MIAC). Methodology A prospective study was performed in 58 women with PPROM before 34+0 weeks of gestational age. Twenty-six proteins were analyzed by a multiple immunoassay in samples of amniotic fluid, serum, cervix and vagina. Association of an inflammatory response in the invasive and non-invasive samples with MIAC was investigated. Results The rate of MIAC was 36.2% (21/58). Both amniotic fluid IL-6 and cervical C-reactive protein (CRP) showed to be independent predictors of MIAC. A cut-off level of cervical CRP≥1836 pg/mL showed a detection rate of 75%, false positive rate of 19% and positive and negative predictive values to predict MIAC of 67% and 87%, respectively. There were no independent biomarkers of MIAC either in the serum or vaginal compartment. Conclusion A cervical inflammatory response mediated by CRP was observed in PPROM women with MIAC. Evaluation of serum or vaginal samples did not add valuable information regarding the outcome evaluated.

Incidence and clinical implications of early inadvertent septostomy after laser therapy for twin–twin transfusion syndrome

To evaluate the incidence and clinical outcome of inadvertent septostomy after fetoscopic laser therapy for twin–twin transfusion syndrome (TTTS) and, particularly, to explore its association with the risk of developing pseudoamniotic band syndrome (PABS).

Maternal inflammatory response to microbial invasion of the amniotic cavity: analyses of multiple proteins in the maternal serum

Objective. To evaluate the maternal inflammatory response to microbial invasion of the amniotic cavity (MIAC) in women with preterm labor and preterm prelabor rupture of membranes using selected proteins in the maternal serum. Design. A prospective cohort study. Setting. Labor ward from Salgrenska University Hospital. The evaluation of the maternal inflammatory response in the presence of MIAC in preterm labor and preterm prelabor rupture of membranes. Population. One hundred and sixteen women with preterm labor and 73 women with preterm prelabor rupture of membranes between the gestational ages of 22+0 and 33+6 weeks. Methods. Twenty‐seven maternal serum proteins were assayed by a multiple immunoassay. Main outcome measures. The maternal serum inflammatory response was evaluated according to the presence of MIAC. Data were stratified by gestational age. Results. There were few differences in the maternal serum protein levels when MIAC was present in both preterm labor and preterm prelabor rupture of membranes. In preterm prelabor rupture of membranes, higher levels of interleukin‐18 (median 654 vs. 361 pg/mL, p= 0.003) and lower levels of interleukin‐1β (9.5 vs. 19.9 pg/mL, p= 0.008) and monocyte chemotactic protein‐1 (139.1 vs. 212.6 pg/mL, p= 0.039) were observed in women with MIAC. Interleukin‐6 (20.8 vs. 13.9 pg/mL, p= 0.019) was the only biomarker that increased significantly in preterm labor complicated with MIAC. All of the differences between preterm labor and preterm prelabor rupture of membranes were observed at less than 32+0 weeks of gestation. Conclusions. A weak maternal inflammatory response in the serum was observed in women with MIAC.