Inflammation In Chorionic Plate Research Articles

Acute chorioamnionitis and intra-amniotic inflammation are more severe according to outside-in neutrophil migration within the same chorio-decidua

ObjectiveNo information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue. Materials and methodsWe included 106 singleton preterm-births (gestational age at delivery: 20–34 weeks) due to either preterm-labor or preterm-PROM in the context of acute chorio-deciduitis. Study-population was divided into 3 groups according to outside-in neutrophil migration within chorio-decidua as follows: 1) group-1: ‘inflammation restricted to the decidua’ (n = 22); 2) group-2: ‘inflammation restricted to the MT of chorion and the decidua’ (n = 31); 3) group-3: ‘inflammation in the CT of chorion’ (n = 53). We examined the frequency of inflammation in each placental compartment beyond chorio-decidua (i.e., amnion, umbilical cord, and chorionic-plate), and total grade (1–8) of acute-HCA. Moreover, the frequency of intra-amniotic infection (defined as positive amniotic-fluid culture for aerobic and anaerobic bacteria and genital mycoplasmas) and intra-amniotic inflammation (defined as amniotic fluid WBC ≥ 19 cells/mm3), and an intra-amniotic inflammatory response gauged by amnioticfluid WBC count (cells/mm3) were examined in 50 amniotic fluid samples within 7 days of birth. ResultsAmnionitis, funisitis and chorionic plate inflammation were more frequent (each for P < 0.01) and median total grade of acute-HCA was increased (P < 0.001) according to outside-in neutrophil migration within chorio-decidua (group-1vs.group-2vs.group-3). Moreover, intra-amniotic infection and inflammation were more frequent (each-for P < 0.05) and median amniotic-fluid WBC count was increased (P < 0.01) according-to outside-in neutrophil-migration within chorio-decidua (group-1 vs. group-2 vs. group-3). ConclusionAcute-HCA is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. This finding suggests that what is now acute chorio-deciduitis should be subdivided.

The Relationship Among Intra-Amniotic Inflammatory Response, The Progression of Inflammation in Chorionic Plate and Early-Onset Neonatal Sepsis.

Background: The chorionic plate (CP) has been denigrated by the well-known route of the extraplacental membranes from the decidua parietalis through the chorion to the amnion in the progression of ascending intrauterine infection among preterm births (PTBs). However, considering previous studies reporting the relationship among intra-amniotic inflammatory response (IAIR), the progression of inflammation in extraplacental membranes and early-onset neonatal sepsis (EONS), and the anatomic connection between extraplacental membranes and CP, there is a good chance that IAIR would be more likely and severe according to the progression of inflammation in CP, and this progression of inflammation in CP would be associated with a significant increase in EONS in neonates delivered due to either PTL or preterm-PROM. Unfortunately, there is no information about the relationship among IAIR, the progression of inflammation in CP, and EONS among spontaneous PTBs. The objective of the current study is to examine this issue.Method: The study population included 309 singleton pregnant women-delivered preterm neonates with the following conditions: (1) gestational age (GA) at delivery: 20.0~36.9 weeks; (2) spontaneous PTBs: PTL (151 cases) or preterm-PROM (158 cases); (3) available results of placental histologic examination; (4) without congenital anomaly; and (5) delivery within 60 h of amniocentesis. We examined IAIR, and the frequency of intra-amniotic inflammation (IAI) and EONS according to the progression of inflammation in CP [i.e., stage-0, inflammation-free CP; stage-1, inflammation restricted to subchorionic fibrin (SCF); stage-2, inflammation in connective tissue (CT) of CP but without chorionic vasculitis; and stage-3, chorionic vasculitis]. IAIR was determined by amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) concentration (ng/ml), and IAI was defined as an elevated AF MMP-8 concentration (≥23 ng/ml). EONS included either suspected or proven EONS.Results: (1) Each stage (stage-0 to stage-3) was present in 69.3% (214/309), 15.9% (49/309), 11.0% (34/309), and 3.9% (12/309) of the study population. (2) AF MMP-8 concentrations continuously elevated according to the progression of inflammation in CP [stage-0 vs. stage-1 vs. stage-2 vs. stage-3; median (ng/ml), range (ng/ml); 6.0 (0.3–4202.7) vs. 153.9 (0.3–6142.6) vs. 464.9 (5.8–3929.0) vs. 1,780.4 (35.1–5019.5); Kruskal–Wallis test, P < 0.001 and Spearman's rank-correlation test, P < 0.000001, r = 0.553]. (3) Moreover, the frequency of IAI and EONS gradually increased with the progression of inflammation in CP [stage-0 vs. stage-1 vs. stage-2 vs. stage-3; IAI, 30.5% (64/210) vs. 70.2% (33/47) vs. 96.7% (29/30) vs. 100% (12/12); EONS, 3.5% (7/200) vs. 25.5% (12/47) vs. 32.3% (10/31) vs. 40.0% (4/10); each for Pearson's chi-square test, P < 0.000001 and linear-by-linear association, P < 0.000001]. (4) Of note, multiple logistic regression analysis demonstrated that a more advanced stage in the progression of inflammation within CP was associated with a higher odds ratio (OR) for EONS [stage-1 vs. stage-2 vs. stage-3; OR, 7.215, 95% confidence-interval (CI) (2.177–23.908) vs. OR, 10.705, 95% CI (2.613–43.849) vs. OR, 27.189, 95% CI (2.557–289.124)] compared with stage-0 even after the adjustment for potential confounding variables.Conclusion: IAIR is more likely and severe according to the progression of inflammation in CP, and this progression of inflammation in CP is an independent risk factor for EONS in spontaneous PTBs. This finding suggests that CP may be another playground for the progression of ascending intrauterine infection in addition to extraplacental membranes, and the progression of inflammation in CP may be used for the prediction of EONS in spontaneous PTBs.

Fetal inflammatory response is positively correlated with the progress of inflammation in chorionic plate

IntroductionNo information exists about the relationship among the progress of inflammation in chorionic-plate, fetal inflammatory response (FIR), funisitis, amnionitis and early-onset neonatal sepsis (EONS) in patients with either preterm labor or preterm premature rupture of membranes (preterm-PROM). The objective of current study is to examine this issue. MethodsStudy population included 247 singleton preterm gestations (21.6 weeks ≤ gestational age at delivery≤36 weeks) who had either preterm-labor or preterm-PROM with acute placental inflammation. We examined the intensity of FIR, and the frequency of fetal inflammatory response syndrome (FIRS), funisitis, amnionitis and proven or suspected EONS according to the progress of inflammation in chorionic-plate. The intensity of FIR was measured with umbilical cord plasma (UCP)-CRP concentration (ng/ml) at birth, and FIRS was defined as an elevated UCP-CRP concentration (≥200 ng/ml). The progress of inflammation in chorionic-plate was divided with a slight modification from previously reported-criteria as follows: stage-0, inflammation-free chorionic-plate; stage-1, inflammation restricted to subchorionic fibrin (SCF); stage-2, inflammation in the connective tissue (CT) of chorionic-plate without chorionic vasculitis; stage-3, chorionic vasculitis. Results1) Stage-0, stage-1, stage-2 and stage-3 of inflammation in chorionic-plate were present in 36.8% (91/247), 29.6% (73/247), 25.5% (63/247), and 8.1% (20/247) of cases; 2) UCP-CRP concentration at birth was significantly and positively correlated with the progress of inflammation in chorionic-plate (Spearman's rank correlation test, P < .000001, γ = 0.391 and Kruskal-Wallis test, P < .001); 3) Moreover, FIRS, funisitis, amnionitis, and EONS were significantly more frequent as a function of the progress of inflammation in chorionic-plate. DiscussionThe intensity of FIR and the frequency of FIRS were positively correlated with the progress of inflammation in chorionic-plate in patients with either PTL or preterm-PROM. This suggests chorionic-plate may be an independent compartment for the analysis of inflammation.

664: Acute inflammation during ascending intra-uterine infection simultaneously progress in both extra-placental membranes and chorionic plate: evidence of anatomic connection between extra-placental membranes and chorionic plate

Extra-placental membranes (EPM) and fetal placental surface, that is, chorionic plate (CP), are continuous, and most processes are likely to be seen in both. However, there is no information about whether acute inflammatory processes simultaneously progress in both EPM and CP during ascending intra-uterine infection (AIUI). The objective of the study is to examine this issue. Study population included 179 singleton early preterm-births due to PTL and preterm-PROM. We examined the frequency of inflammation in sub-chorionic fibrin (SCF) and connective tissue (CT) within CP according to the progression of inflammation in EPM(i.e., inflammation-free chorio-decidua [CD] or inflammation restricted to decidua, inflammation restricted to membrane trophoblast (MT) of chorion, inflammation restricted to CT of chorion, and inflammation in amnion), and the frequency of inflammation in MT of chorion, CT of chorion, and amnion within EPM according to the progression of inflammation in CP(i.e., inflammation-free CP, inflammation restricted to SCF of CP, and inflammation in CT of CP). Acute inflammation in EPM and CP was defined according to the previously reported criteria. 1) Inflammation-free CD or inflammation restricted to decidua, inflammation restricted to MT of chorion, inflammation restricted to CT of chorion, and inflammation in amnion were present in 53%, 17%, 17% and 12% of cases; 2) Inflammation-free CP, inflammation restricted to SCF of CP, and inflammation in CT of CP were present in 75%, 10% and 16% of cases; 3) Inflammation in SCF (Fig.1.a) and CT (Fig.1.b) within CP was more frequent according to the progression of inflammation in EPM; 4) Inflammation in MT of chorion (Fig.2.a), CT of chorion (Fig.2.b) and amnion (Fig.2.c) within EPM more developed according to the progression of inflammation in CP. Inflammation in SCF and CT within CP is more frequent according to the progression of inflammation in EPM, and inflammation in MT of chorion, CT of chorion, and amnion within EPM more develops according to the progression of inflammation in CP. This finding suggests that acute inflammatory processes simultaneously progress in both EPM and CP during AIUI.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

667: Intra-amniotic inflammatory response elevates according to the increase in the grade of chorio-deciduitis in the context of inflammation restricted to chorio-decidua, but not inflammation in the compartments beyond chorio-decidua :‘relationship between the grade of chorio-deciduitis and intra-amniotic inflammatory response in spontaneous preterm birth’ revisited

No information exists about whether intra-amniotic inflammatory response(IAIR) elevates according to the increase in the grade of chorio-deciduitis in the context of the early stage(i.e., inflammation restricted to chorio-decidua[CD]) or advanced stage(i.e., inflammation in the compartments beyond CD[i.e., amnion, umbilical cord(UC) or chorionic plate(CP)]) of ascending intrauterine infection(AIUI) among spontaneous preterm gestations. The objective of the study is to examine this issue. Study population included 195singleton pregnant women who had acute histologic chorioamnionitis with CD involvement and delivered within 7days of amniocentesis before 35.7weeks due to PTL or preterm-PROM. We examined IAIR according to the grade of chorio-deciduitis in the context of inflammation-free amnion, UC and CP, and inflammation restricted to CD, and in the context of amnionitis, funisitis and CP inflammation, and inflammation in the compartments beyond CD. IAIR was measured by AF MMP-8 concentration(ng/ml). 1)Amnionitis, funsitis, CP inflammation and inflammation in the compartments beyond CD were present in 52%, 52%, 37% and 69% of cases;2) Median AF MMP-8 level was significantly elevated according to the increase in the grade of chorio-deciduitis in the context of inflammation-free amnion(Fig. 1.a), UC(Fig. 1.b) and CP(Fig. 1.c), and inflammation restricted to CD(Fig. 1.d);3) However, there was no significant difference in the median AF MMP-8 level between patients with grade 1 and grade 2 of chorio-deciduitis in the context of amnionitis(Fig. 2.a), funsitis(Fig. 2.b), CP inflammation(Fig. 2.c) and inflammation in the compartments beyond CD(Fig. 2.d). IAIR elevates according to the increase in the grade of chorio-deciduitis in the context of inflammation restricted to CD, but not inflammation in the compartments beyond CD. This finding suggests that the grade of chorio-deciduitis may have no effect on the intensification of IAIR in the context of inflammation in the compartments beyond CD among patients at risk for spontaneous preterm birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Effect of corticosteroid interval on markers of inflammation in spontaneous preterm birth

The objective of the study was to evaluate whether the time interval from corticosteroid administration to delivery is associated with variations in inflammatory/infectious markers in women with spontaneous preterm birth (SPTB). We conducted a secondary analysis of a prospectively collected cohort of women experiencing SPTB from 23(0/7) to 31(6/7) weeks. Patients were categorized by corticosteroid receipt and time interval until delivery. Prevalence of markers of inflammation and colonization/infection (cord blood interleukin [IL]-6 levels; Ureaplasma urealyticum [UU], Mycoplasma hominis [MH], and other anaerobic/aerobic cultures; histology of the placental disc, membranes and cord) were compared between groups using χ(2) and Mantel-Haenszel tests. Two hundred seventy-three patients had SPTB. Prevalence of elevated IL-6 (P= .028) and positive UU/MH cultures (P= .019) were highest in women not receiving corticosteroids and those delivering more than 7 days from receipt. The prevalence of both decreased in groups with delivery delayed at least 12 hours but increased as the interval lengthened to more than 48 hours. Overall positive placental cultures also nadired among those delivering at 12-24 hours after corticosteroids (P= .049). As the interval increased, prevalence of acute inflammation at the rupture site increased (P= .017). There were similar, but nonsignificant, increases in chorionic plate inflammation and funisitis. The relationship between time interval from corticosteroids and evidence of inflammation in women experiencing SPTB is U shaped, suggesting earlier stages of inflammation in women with delayed delivery or transient decreases of inflammation in response to corticosteroids. This warrants further investigation to elucidate the natural history of SPTB and its modulation by corticosteroids.

Maternal and fetal Toll-like receptor 4 genotype and chorionic plate inflammatory lesions

The objective of the study was to explore the relation between maternal and fetal genetic variation in Toll-like receptor 4 (TLR4) and chorionic plate inflammation In this prospective observational cohort of 109 women with singleton gestations, 13 tag single nucleotide polymorphisms (SNPs) were genotyped in the TLR4 gene. The diagnosis of chorionic plate inflammation was made by a single blinded perinatal pathologist. After adjustment for multiple comparisons, 1 maternal SNP (rs10759932) and 1 fetal SNP (rs1554973) in the TLR4 gene demonstrated highly significant association with chorionic plate inflammation. After adjustment for race, smoking, and bacterial vaginosis, carriage of these alleles was associated with chorionic plate inflammation (maternal rs1554973: odds ratio [OR] 5.2, 95% confidence interval, 3.2-6.4, P = .006; fetal rs10759932: OR 4.95, 95% confidence interval, 3.0-5.6, P = .005). There was no evidence of interaction between these 2 SNPs. Maternal and fetal genetic variation in TLR4 is strongly associated with chorionic plate inflammation. This maternal and fetal genotypic effect are independent of each other as well as other environmental covariates.

Characterization of Chorioamnionitis in 2nd-Trimester C-Section Placentas and Correlation with Microorganism Recovery from Subamniotic Tissues

Prolonged exposure to infection appears to influence fetal/neonatal development. We characterize the relationship between histologic patterns of inflammation and microorganism recovery from the placentas of live born infants delivered before the 28th postmenstrual week. The subamniotic parenchyma of 835 placentas delivered by cesarean section were cultured and evaluated for specific histologic patterns of inflammation in a blinded fashion. Cases with prolonged membrane rupture were excluded. Microorganisms were recovered from 41% of placentas. Microorganisms found more frequently in placentas with high-grade chorionic plate inflammation include Actinomyces, Prevotella bivia, Corynebacterium sp., Escherichia coli, Peptostreptococcus magnus, multiple species of Streptococci, and Mycoplasma sp., including Ureaplasma urealyticum. These microorganisms were also associated with fetal vasculitis (neutrophilic infiltration of chorionic plate stem vessels or umbilical cord). Recovery of microorganisms from placental parenchyma is associated with histologic inflammation. The same microorganisms responsible for inciting high-grade chorionic plate inflammation are also most likely to promote fetal inflammation.

Subclinical chorioamnionitis as an etiologic factor in preterm deliveries

Objective: This study was performed to determine the possible relationship between histologic chorioamnionitis and genital tract cultures and their contribution to preterm delivery. Methods: The study group consisted of 45 preterm and 37 term pregnancies. Cervico-vaginal cultures were obtained from all patients at admission and placentas were histopathologically evaluated and graded for inflammation of the chorial plate, amniochorionic membrane, umbilical cord and villi. Inflammation scores and presence of pathogenic bacteria were compared between the preterm and term patients. Results: Severe chorionic plate inflammation was present in 35.5% of 45 preterm deliveries as compared to 5.4% of 37 term deliveries. Amniochorionic-decidual inflammation was not present in 14 of the term deliveries (38%), mild (Grade 1–2) in 20 (54%) and severe (Grade 3–4) in 3 (8%) as compared to 14 (31%), 17 (38%), and 14 (31%) in the preterm group, respectively ( P<0.05). Pathogenic bacteria were isolated from the lower genital tracts of all patients who had severe chorionic plate (CP) and/or chorioamnionic (CA) inflammation while this was true only in 37.5% of the patients with no or only mild chorionic plate inflammation ( P<0.001 for CP, P<0.01 for CA). Conclusion: Our results show that pathogenic bacterial colonisation of the cervicovaginal region is closely associated with placental inflammation, preterm labor and cervico-vaginal cultures which may be useful in determining the pregnancies at risk for preterm labor.

Lack of relationship between histologic chorioamnionitis and duration of the latency period in preterm rupture of membranes.

It is often believed that the frequency of clinical chorioamnionitis in preterm premature rupture of membranes (PROM) increases with the duration of the interval between membrane rupture and delivery. We tested the hypothesis that the prevalence of histologic evidence of intrauterine infection increases proportionally to the duration of the latency period. A total of 191 consecutive placentas of singleton, nonanomalous, liveborn infants delivered at <32 weeks' gestation with PROM were examined prospectively. Demographic, obstetric, histopathologic, and neonatal information was obtained. Histopathologic evidence of acute inflammation in choriodecidua, amnion, umbilical cord, and chorionic plate was recorded and scored. The prevalence and severity of pathological evidence of intrauterine infection was correlated with the interval between membrane rupture and delivery. Maternal and neonatal outcomes were assessed in six groups defined by different intervals between membrane rupture and delivery. Statistical analysis utilized regression, Fisher's exact test, Chi-square, and one-way analysis of variance after log transformation where applicable. P < 0.05 was considered significant. No correlation was observed between total score of placental acute inflammation and the interval membrane rupture-to-delivery (r = 0.068, 95% confidence interval -0.075, 0.211; P = 0.35). There was no evidence that the rate of maternal (P = 0.4) or neonatal (P = 0.15) infectious morbidity, or the total score of acute placental inflammation (P = 0.13), acute amnionitis (P = 0.35), choriodeciduitis (P = 0.46), chorionic plate inflammation (P = 0.38), or umbilical and chorionic vasculitis (P = 0.06) increase with the prolongation of the PROM-to-delivery interval. This study had an 85% power to detect the lack of association that was actually observed. The rate of histologic evidence of chorioamnionitis in preterm PROM does not increase with the duration of the PROM-to-delivery interval.

Lack of relationship between histologic chorioamnionitis and duration of the latency period in preterm rupture of membranes

It is often believed that the frequency of clinical chorioamnionitis in preterm premature rupture of membranes (PROM) increases with the duration of the interval between membrane rupture and delivery. We tested the hypothesis that the prevalence of histologic evidence of intrauterine infection increases proportionally to the duration of the latency period. A total of 191 consecutive placentas of singleton, nonanomalous, liveborn infants delivered at > 32 weeks' gestation with PROM were examined prospectively. Demographic, obstetric, histopathologic, and neonatal information was obtained. Histopathologic evidence of acute inflammation in choriodecidua, amnion, umbilical cord, and chorionic plate was recorded and scored. The prevalence and severity of pathological evidence of intrauterine infection was correlated with the interval between membrane rupture and delivery. Maternal and neonatal outcomes were assessed in six groups defined by different intervals between membrane rupture and delivery. Statistical analysis utilized regression, Fisher's exact test, Chi-square, and one-way analysis of variance after log transformation where applicable. P > 0.05 was considered significant. No correlation was observed between total score of placental acute inflammation and the interval membrane rupture-to-delivery (r = 0.068, 95% confidence interval –0.075, 0.211; P = 0.35). There was no evidence that the rate of maternal (P = 0.4) or neonatal (P = 0.15) infectious morbidity, or the total score of acute placental inflammation (P = 0.13), acute amnionitis (P = 0.35), choriodeciduitis (P = 0.46), chorionic plate inflammation (P = 0.38), or umbilical and chorionic vasculitis (P = 0.06) increase with the prolongation of the PROM-to-delivery interval. This study had an 85% power to detect the lack of association that was actually observed. The rate of histologic evidence of chorioamnionitis in preterm PROM does not increase with the duration of the PROM-to-delivery interval.

Abnormal fetal heart rate patterns and placental inflammation

Can acute inflammation in the placental membranes, amniotic fluid, or both, predispose to the development of abnormal fetal heart rate patterns? One hundred cases in which bradycardia was noted were compared with 48 cases in which abnormal fetal heart rate patterns did not occur. Case and control subjects were matched to provide an equivalent risk of developing ascending infection in the two groups. Fetoplacental weight ratio and the presence of other placental diseases were also considered. The presence of acute inflammation in the umbilical cord (p = 0.03), amnion (p = 0.01), and choriodecidua (p = 0.03), and higher grades of inflammation in chorionic plate (p = 0.03) were linked to the presence of abnormal fetal heart rate patterns. No other placental factors were associated with increased risk of fetal bradycardia. The association of abnormal fetal heart rate patterns with acute inflammation suggests that intra-amniotic inflammation is important in the genesis of fetal bradycardias. The inflamed amniotic fluid could alter fetal metabolism via effects on the pulmonary or gastrointestinal systems or effects on umbilical and chorionic vessels.