Comparison between Cervical Ureaplasma spp. Colonization and the Intensity of Inflammatory Mediators in the Amniotic Fluid Retrieved during Cesarean Delivery in Preterm Birth

We investigated whether cervical Ureaplasma spp. colonization affects the intensity of inflammatory mediators in amniotic fluid retrieved during cesarean delivery in singleton preterm birth. One hundred fifty-three cases in singleton preterm birth with 24–34 weeks’ gestation were enrolled. The intensities of seven inflammatory mediators (interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and matrix metalloproteins (MMP)-8, MMP-9) of amniotic fluid were measured. We tested cervical swab specimens using real-time polymerase chain reaction assays to detect Ureaplasma spp. colonization. Histologic chorioamnionitis (HCA) was diagnosed when acute inflammation was observed in any of the placental tissues. Mean gestational age at delivery and birth weight were 30.9 ± 2.4 weeks and 1567 ± 524 g, respectively. Cervical Ureaplasma spp. colonization was detected 78 cases. The incidence of HCA was 32.3% (43/133). Although the intensities of all inflammatory mediators were significantly different according to presence or absence of HCA, there were no significant differences according to cervical Ureaplasma spp. colonization. In all 43 cases with HCA and 90 cases without HCA, there were no significant differences between cervical Ureaplasma spp. colonization and the intensity of inflammatory mediators. Cervical Ureaplasma spp. colonization did not affect the intensity of inflammatory mediators in the amniotic fluid retrieved during cesarean delivery.

Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of the late preterm delivery regardless of the membrane status

Objectives To compare the immunohistochemical expression of IL-6 in placental membranes of late preterm delivery in women with histologically proven chorioamnionitis with and without preterm premature rupture of membranes (PPROM). Methods Fetal membranes were collected from 60 women who had late preterm delivery with histologic chorioamnionitis with and without PPROM (30 in each group). Immunohistochemistry for IL-6 was performed on formalin fixed and paraffin-embedded sections. The two groups were matched for age, body mass index and parity. SPSS Version 17.0 was used for statistical analysis. Results There was no difference in immunohistochemical expression of IL-6 in placental membranes of women with histologic chorioamnionitis regardless of the membrane status. Conclusions Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of women with late preterm delivery despite the clinical presentation.

To Identify Risk Factors Predicting Spontaneous Preterm Labor Less Than 28 Weeks After Emergency Cerclage in the Second Trimester of Pregnancy

Purpose To identify risk factors predicting spontaneous preterm labor (sPTB) less than 28 weeks after emergency cerclage in the second trimester of pregnancy.Methods 106 cases with Prolapsed membranes in the second trimester of pregnancy who underwent emergency cerclage were collected from July 2019-July 2021 .39 cases who happened sPTB less than 28 weeks were in case group. 67 cases were in control group.Univariate analysis and logistic regression analysis were used to identify the risk factors for sPTB less than 28 weeks after emergency cerclage.Results Among the 106 cases,37cases developed sPTB less than 28 weeks, and the incidence was 36.8%, Univariate analysis showed that positive cervical culture,cervical dilatation,the location of amniotic membranes and histologic chorioamnionitis were related with sPTB(P<0.05). Logistic regression analysis showed that histologic chorioamnionitis was the risk factors for sPTB after emergency cerclage in patients with Prolapsed membranes in the second trimester of pregnancy[relative risk14.603 ,95% confidence interval(CI)2.621-81.369,P<0.05].Amniotic membrane is an independent risk factor for less than 28 weeks of sPTB after emergency cerclage in middle pregnancy [relative risk11.993 ,95% confidence interval(CI)3.825-37.607,P<0.05].Conclusion The independent risk factors of sPTB less than 28 weeks after emergency cerclage with prolapsed membranes in the second trimester of pregnancy was histologic chorioamnionitis and Amniotic membrane.

Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis

IntroductionPreterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.PopulationFor objective one 59 term infants [mean gestational age (GA) 39+4 (37+3 to 42+0)] and 55 preterm infants [mean GA29+0(23+3 to 32+0)] with umbilical cord samples available were included; for objective two we studied 96 preterm infants [mean GA29+1(23+2 to 32+0)] for whom placental histology and postnatal blood samples were available.MethodsPlacental histopathology was used to identify reaction patterns indicative of HCA, and a customized immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.ResultsThe umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 8 immune proteins on postnatal day 5 (BDNF, C3, C5a, C9, IL-8, MCP-1, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.ConclusionPreterm birth is associated with a distinct immune profile in umbilical cord blood and preterm infants exposed to HCA with evidence of a fetal inflammatory response have specific alterations in immune function that are apparent on day 5 of postnatal life.

Cervical ureaplasma colonization affects intraamniotic inflammation in preterm labor with intact membrane: a cohort study

Background: A causative role between cervical ureaplasma colonization and adverse outcomes during pregnancy has remained controversial. We investigated whether cervical ureaplasma colonization affects the biochemically or histologically intraamniotic inflammation in preterm birth.Methods: Amniotic fluid was retrieved during delivery. Various chorioamnionitis-related cytokines (interleukin (IL)-1β, -6, -8, -10, and tumor necrosis factor-α) and regulators (matrix metalloproteins (MMP)-8 and MMP-9) were measured with Human Magnetic Luminex screening assay. We tested cervical swab specimens using real-time polymerase chain reaction assays for the detection of ureaplasma spp. colonization. Considering the clinical situation that causes intraamniotic infection, we arbitrarily divided into three categories of preterm labor with intact membrane, preterm premature rupture of membrane (PPROM), and control group with no exposure to preterm labor or preterm premature rupture of membrane.Results: The incidence of cervical ureaplasma colonization was 49.3% (136/276). The incidence of histologic chorioamnionitis was 27.5% (76/200). All differences in cytokines and regulators according to histologic chorioamnionitis were significant. Of the 153 cases that experienced preterm labor with intact membrane, IL-10, MMP-8, and MMP-9 levels in the ureaplasma positive group were significantly higher than those of the ureaplasma negative group. According to logistic regression analysis adjusted to preterm labor with intact membrane, PPROM, and gestational age at delivery, cervical ureaplasma colonization was an independent risk factor of histologic chorioamnionitis (odd ratio: 2.622, 95% confidence interval: 1.443-4.766).Conclusions: Cervical ureaplasma colonization augments biochemically intraamniotic inflammation in preterm labor with intact membrane, and was an independent risk factor of histologic chorioamnionitis.

Preterm birth is associated with immune dysregulation which persists in infants exposed to histologic chorioamnionitis

Objective. To characterise the umbilical cord blood immune profile in preterm infants compared to term-born controls and the postnatal immune response following exposure to histologic chorioamnionitis (HCA) in preterm infants. Design. Descriptive, observational cohort study. Setting. Edinburgh, UK. Population. 118 preterm infants (mean gestational age 29+0 weeks, range 23+2 to 32+0) and 59 term-born controls. Methods. Placental histopathology was used to identify reaction patterns indicative of HCA, and a customised immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group. Results. The umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 5 immune proteins on postnatal day 5 (BDNF, C3, IL-8, MIP-1β and MMP-9) when compared to preterm infants who were not exposed. Conclusion. Preterm birth is associated with a distinct immune profile in umbilical cord blood and infants exposed to HCA experience specific alterations in immune function that persist to day 5 of postnatal life.

Characterization of methylation signatures in spontaneous preterm birth

Preterm birth (PTB) is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous PTB (isPTB) and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology, and our transcriptomics studies suggest a role for placental maturity in isPTB. It is known that placental methylation changes over gestation and we hypothesized that if placental hypermaturity is present in our samples, we would observe unique isPTB methylation signature as well as identify loci where isPTB methylation is more similar to that of term birth (TB) than the gestational age matched controls. Our results indicate the isPTB DNA methylation pattern mimics the TB methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions (DMRs) fitting the isPTB specific hypomethylation (relative to the controls) pattern were identified, indicating unusually high similarity in DNA methylation between isPTB and TB samples. In contrast, 1,718 acute histologic chorioamnionitis(AHC) specific DMRs were identified with hypermethylated DMRs in WNT and cadherin pathways when compared to isPTB and TB samples. In these AHC DMRs, there were no significant differences between the isPTB and TB, which indicated again, a striking level of similarly between isPTB and TB sample sets. Taken together, these data reflect a more mature placenta than expected which may be impacting birth timing.