Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial invasion of the amniotic fluid,intra-amniotic inflammation and preterm delivery

Objective To evaluate the relationship between interleukin (IL)-18 in cervical mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm delivery and intra-amniotic inflammation in women in preterm labour, with preterm prelabour rupture of membranes and at term.
Design A prospective follow up study.
Setting Sahlgrenska University Hospital, Göteborg, Sweden.
Sample Women with singleton pregnancies (  <34 weeks  ) presenting with preterm labour (   n = 87  ) or preterm prelabour rupture of membranes (   n = 47  ) and women, not in labour, at term (   n = 28  ).
Methods Amniotic fluid was retrieved transabdominally. Cervical mucus was taken from the uterine cervix of women in preterm labour and at term. IL-18 was analysed with enzyme-linked immunosorbent assay.
Main outcome measures IL-18 in relation to microbial invasion of the amniotic fluid, delivery within seven days or  <34 weeks  of gestation and intra-amniotic inflammation.
Results The levels of IL-18 in cervical mucus and amniotic fluid were higher in women with preterm labour than in those not in labour at term. In the preterm labour group, significant associations were found between elevated IL-18 in amniotic fluid and microbial invasion of the amniotic fluid, as well as between delivery within seven days or  <34 weeks  of gestation and intra-amniotic inflammation. Delivery was delayed longer in the preterm prelabour rupture of membranes subgroup with  IL-18 ≥1.0 ng/mL than in that with IL-18 <1.0 ng/mL  .
Conclusions In the preterm labour group, high IL-18 in amniotic fluid (but not in the cervix) was associated with microbial invasion of the amniotic fluid, intra-amniotic inflammation and prompt delivery. On the other hand, elevated IL-18 in preterm prelabour rupture of the membranes group correlated with a longer interval to delivery.     

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes

BACKGROUND: Previous studies have shown an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines [interleukin (IL)-6 and IL-8] in a Swedish population, with low incidence of preterm birth, of women with preterm prelabor rupture of membranes and their correlation to preterm birth. METHODS: Amniotic fluid was retrieved transabdominally from 58 patients with preterm prelabor rupture of membranes before 34 weeks of gestation. Polymerase chain reaction (PCR) analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. IL-6 and IL-8 were analyzed with enzyme-linked immunosorbent assay (ELISA). RESULTS: Microorganisms in amniotic fluid were detected in 13 patients (25%). Patients with bacteria detected in the amniotic fluid had significantly higher levels of IL-6 and IL-8. An amniotic fluid concentration of IL-6 >/= 0.80 ng/ml [relative risk 1.93, 95% confidence interval (CI) 1.13-3.29, sensitivity 63%, specificity 75%] was associated with an increased risk of delivery within 7 days. There was also an association between IL-8 and preterm birth (< 34 weeks). CONCLUSIONS: Intra-amniotic microbial invasion and inflammation in this population of Swedish women with preterm prelabor rupture of membranes were similar to data reported from populations with a higher incidence of preterm delivery. Amniotic IL-6 correlated to the presence of microorganisms and delivery within 7 days and IL-8 to delivery before 34 weeks.     

Lung and brain damage in preterm newborns, and their association with gestational age, prematurity subgroup, infection/inflammation and long term outcome

Compared with those born at term, preterm newborns are at an increased risk of short term disorders of the lung (bronchopulmonary dysplasia; BPD) and the brain (white matter damage; WMD), and of long term developmental and pulmonary dysfunctions. Although all of these adverse outcomes are associated with low gestational age, brain, but not lung, damage appears to be associated with the prematurity subgroup [spontaneous preterm labour and/or preterm prelabour rupture of membranes (PPROM) vs pregnancy-induced hypertension (PIH)]. Part of the association between brain damage and prematurity subgroup might be due to a differential exposure of members of these subgroups to perinatal infection/inflammation. There is a lack of studies evaluating the association of antenatal and perinatal risk factors with late childhood pulmonary dysfunction among those born during the second trimester. In this paper we discuss the complexities that paediatricians, perinatologists and perinatal epidemiologists face as they try to understand the contributions of factors associated with preterm birth to neonatal and childhood disorders.     

Relaxin Stimulates Interleukin-6 and Interleukin-8 Secretion from the Extraplacental Chorionic Cytotrophoblast

In the absence of infection, decidual relaxin (RLN) expression is increased in patients with preterm premature rupture of the membranes (PPROM) resulting in preterm birth, but it is not known whether inflammation stimulates RLN expression or vice versa. This study examined the effect of lipopolysaccharide (LPS) on the expression of RLN mRNA and secreted protein and whether RLN treatment influences secretion of proinflammatory cytokines from the fetal membranes. Explants of human fetal membranes in vitro and rhesus monkey fetal membranes in vivo were treated with LPS, which increased expression of IL-6 but had no effect on RLN. RLN treatment stimulated IL-6 and IL-8 secretion from choriodecidual explants in a subset of patients, as well as from isolated chorionic cytotrophoblast cells but not decidual cells. In vivo results obtained in rhesus monkeys after intra-amniotic infusion of RLN demonstrated increased IL-6 and IL-8 concentrations in amniotic fluid. Our results indicate that increased decidual RLN expression is independent of LPS but may induce a local sterile inflammatory process which potentially contributes to extracellular matrix degradation and weakening of the fetal membranes.     

Role of matrix metalloproteinases in preterm labour

Extracellular matrix homeostasis is a key process in the maintenance of the tensile strength of the amniochorion. This tensile strength guarantees the role of the membranes as a physical and functional boundary for the fetus during human pregnancy. Pathological rupture of these structures before 37 completed weeks of gestation is known as preterm prelabour rupture of the membranes (PPROM) and it is a major cause of spontaneous preterm labour and preterm birth. A mechanism involving the activation of matrix metalloproteinases (MMP)-9, a 92-kDa type IV collagenase, as an essential mediator of tissue damage is under investigation. The proposed mechanism involves the abnormal expression and activity of MMP-9 with subsequent connective tissue degradation taking place at a time that does not synchronise with other events of labour. The local physiological signal by amniochorion cells to induce MMP-9 expression is not known, but bacterial products and/or the proinflammatory cytokines, IL-1β and TNF-α, as paracrine or autocrine signals may trigger these processes in pregnancies complicated with intra-amniotic infection. These signalling pathways indicate complex cooperative and bidirectional communications between amnion and choriodecidua in response to bacterial products, which include intermembranous cytokine traffic and signalling between tissues. Products secreted in culture by amniochorion and choriodecidual leucocytes, obtained from women who delivered following normal labour in the absence of infection, condition a specific microenvironment that induces collagen degradation in fetal membranes. Further characterisation of the role of choriodecidual leucocytes in the control of extracellular matrix degradation in amniochorion is currently under way.     

An evidence-based approach to the evaluation and treatment of premature rupture of membranes: Part I

Preterm premature rupture of membranes (PPROM) occurs in 3% of pregnancies and is responsible for one third of all preterm births. PPROM will affect 120,000 women in the United States each year. It is associated with significant maternal, fetal, and neonatal morbidity and mortality resulting from infection, umbilical cord compression, abruptio placentae, and prematurity. The etiology is multifactorial, but the most significant risk factors are previous preterm birth and previous preterm premature rupture of membranes. Accurate diagnosis is extremely important to assure proper treatment. Evaluation is based on patient history and clinical examination. This review presents the available evidence and grades it according to the U.S. Preventative Task Force recommendations. In part I of this review, the definition, pathophysiology, and methods of PPROM diagnosis are presented. In part II, the management, treatment, neonatal outcome, and the maternal and fetal evaluation of women with PPROM in the presence of cerclage and medical complications is reviewed. LEARNING OBJECTIVES: After completion of this article, the reader should be able to define the term: preterm premature rupture of membranes, to list the factors associated with premature rupture of membranes, and to outline the tests available for the diagnosis of intra-amniotic infection.     

Levels of multiple proteins in gingival crevicular fluid and intra-amniotic complications in women with preterm prelabor rupture of membranes

Objective: The primary aim of this study was to identify the association between the local inflammatory response in gingival crevicular fluid measured by the levels of multiple proteins and maternal and intra-amniotic inflammatory responses measured by maternal serum C-reactive protein (CRP) and amniotic fluid interleukin (IL)-6 concentrations, respectively, in women with preterm prelabor rupture of membranes (PPROM).

Methods: A prospective study was performed in which 78 women with singleton pregnancies complicated by PPROM between 24?+?0 and 36?+?6 weeks of gestation were included. Transabdominal amniocenteses were performed at the time of admission. A bedside assessment of amniotic fluid IL-6 was performed. Maternal serum CRP concentration was also measured at the time of admission. Gingival crevicular fluid was collected from the pocket of the selected tooth (the tooth with the deepest pocket) using standard sterile paper strips within 72?h after admission. Twenty-six proteins in the gingival crevicular fluid were assessed by multiplex the Meso-Scale technology.

Results: No correlations between the levels of proteins in the gingival crevicular fluid and maternal serum CRP and amniotic fluid IL-6 concentrations were found, except for a weak positive correlation between granulocyte macrophage colony-stimulating factor and CRP.

Conclusions: The local inflammatory response in the gingival crevicular fluid is not related to the maternal and intra-amniotic inflammatory responses in women with PPROM.     

The relationship between sonographic fetal thymus size and the components of the systemic fetal inflammatory response syndrome in women with preterm prelabour rupture of membranes

Objective  To assess the relation between sonographic fetal thymus size and the components of fetal inflammatory response syndrome (FIRS) in women with preterm prelabour rupture of membranes (PPROM).
Design  Prospective cohort study.
Setting  University hospital from January through October 2006.
Population  Fifty-six women with PPROM.
Methods  In these women, fetal thymus perimeter was measured sonographically. At birth, cord venous plasma interleukin-6 (IL-6) level estimation and histopathological examination of the placentas and umbilical cords were performed.
Main outcome measures  Small thymus size (<5th percentile for gestational age) and its association with FIRS.
Results  From the 56 women with PPROM, 54% had chorioamnionitis (CA), 23% had funisitis. IL-6 level was >11 pg/ml in 52% of women and >18 pg/ml in 41%. A small thymus was more associated with male fetuses, shorter preterm prelabour rupture of membranes delivery interval, higher IL-6 level, higher frequency of funisitis and CA. When data were regressed for confounding, only IL-6 level and funisitis remained significant independent factors that influence the thymus size. In the subset of women ( n = 19) who delivered within 1 week of first measurements, a small thymus had sensitivity and positive predictive value of 93%, specificity and negative predictive value of 75% and accuracy of 89% in the identification of FIRS (IL-6 >18 pg/ml and/or funisitis).
Conclusions  An association exists between fetal thymic involution and components of FIRS in women with PPROM. Small fetal thymus size may be considered a reliable sonographic marker of fetal involvement in the inflammatory response.     

A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes

Objective: Preterm birth is associated with 5–18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated AF IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow-based immunoassay for measurement of AF IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection and those destined to deliver spontaneously before term among women with preterm labor and intact membranes.

Methods: One-hundred thirty-six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6?≥?2600?pg/ml.

Results: (1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%) and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745?pg/ml; (2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta and patients at risk of impending spontaneous preterm delivery.

Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20?min – this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.     

孕产妇血清中MMP-3、TNF-α、IL-10的表达与早产和早产胎膜早破的关系

目的探讨基质金属蛋白酶-3（MMP-3）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（lL-10）在孕产妇血清中的表达与早产、胎膜早破的关系。方法选择单胎头位初产妇80例作为研究对象,按孕周、胎膜是否破裂和产妇是否临产分为早产临产组（sPTD）、早产胎膜早破组（PPROM）、先兆早产组（TPL）和妊娠28～36＋6周无产兆组（对照组）,每组各20例。用ELISA法检测孕妇血清中MMP-3及TNF-α、lL-10的水平。结果①早产临产组、早产胎膜早破组、先兆早产组和对照组血清中MMP-3的浓度分别为（242.25±72.40）ng/ml、（225.95±85.43）ng/ml、（197.85±57.08）ng/ml、（186.80±54.33）ng/ml;TNF-α的浓度分别为（1332.35±346.65）pg/ml、（1365.00±211.80）pg/ml、（1188.15±269.43）pg/ml、（1061.85±210.02）pg/ml;IL-10的浓度分别为（563.65±116.50）pg/ml、（566.80±123.03）pg/ml、（521.00±105.14）pg/ml、（483.50±119.17）pg/ml;②早产组血清中MMP-3,TNF-α浓度高于对照组,以TNF-α升高更明显（P〈0.01）;而IL-10在前两组中有增高趋势,但与后两组相比差异无统计学意义（P〉0.05）;③血清中MMP-3、TNF-α、IL-10浓度呈两两正相关。结论①孕产妇血清中MMP-3及TNF-α浓度与早产、胎膜早破密切相关;②孕产妇血清中MMP-3、TNF-α及IL-10在临产、胎膜早破中可能起协同作用。     

The calcium binding protein, S100B, is increased in the amniotic fluid of women with intra-amniotic infection/inflammation and preterm labor with intact or ruptured membranes

OBJECTIVE: S100B is produced by glia of the central and peripheral nervous systems and is considered a marker of neurologic injury in the perinatal period. Indeed, increased neonatal urine S100B concentration is associated with adverse neurological outcomes including intraventricular hemorrhage and hypoxic-ischemic encephalopathy, while elevated adult serum concentrations are associated with infectious diseases/sepsis. The objective of this study was to determine whether amniotic fluid (AF) S100B concentrations change with advancing gestational age and intra-amniotic infection (IAI). STUDY DESIGN: S100B concentration was measured in the AF of women in midtrimester, at term, and in pregnancies with preterm labor and intact membranes (PTL) or preterm premature rupture of membranes (PPROM), with and without IAI. Placental pathology was performed and neonatal outcomes were analyzed. RESULTS: (1) AF S100B concentration did not change during gestation; (2) patients with IAI had significantly higher AF S100B concentration than those without IAI following an episode of PTL or PPROM and; (3) neonates who had morbidity/mortality had had an elevated AF S100B concentration; however, this could be explained by the association with intra-amniotic infection/inflammation. Thus, AF S100B concentration was not an independent predictor of neonatal morbidity or fetal/neonatal death. CONCLUSIONS: An elevated concentration of AF S100B may reflect intra-amniotic infection/inflammation and not necessarily fetal neurologic damage.     

Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery

OBJECTIVE: The purpose of this study was to evaluate the role of monocyte chemotactic protein-1 in cervical and amniotic fluid in women in preterm labor and with preterm premature rupture of membranes. STUDY DESIGN: Women with singleton pregnancies (相似文献   

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.     

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.     

Estimated time to emergence of secondary intra-amniotic infection or inflammation since the onset of the preterm premature rupture of membranes

ObjectivePrematurity is the most important prognostic factor for infants born following preterm premature rupture of membranes (PPROM). Therefore, when PPROM occurs between 22 and 33 weeks of gestation, prolonging pregnancy is recommended. Determination of management strategies requires screening for the presence of intra-amniotic infection or inflammation at the time of PPROM diagnosis. If intra-amniotic infection/inflammation is not detected, it is important to monitor the patient to diagnose any new infection/inflammation. We examined the period from PPROM to secondary intra-amniotic infection/inflammation and associated factors.Materials and methodsThis retrospective study was conducted at a single facility. We examined 26 patients who experienced PPROM between 26 and 33 weeks of gestation and were negative for intra-amniotic infection/inflammation at the time of diagnosis and underwent serial amniocentesis. Antibiotic therapy comprising ampicillin, amoxicillin, and clarithromycin for 7 days was started after the first amniocentesis. The period from PPROM to secondary intra-amniotic infection/inflammation was analyzed using a Kaplan–Meier survival curve. The onset of intra-amniotic infection/inflammation was considered as the time at which amniotic fluid bacterial culture results became positive, the time when amniotic fluid Interleukin (IL)-6 increased beyond 2.6 ng/mL, or the day of delivery if histological chorioamnionitis was observed in the delivered placenta. Patients were treated as censored if no intra-amniotic infection/inflammation could be confirmed in the amniotic fluid and delivered placenta.ResultsThe median time from PPROM to secondary intra-amniotic infection/inflammation was 18 days. Six patients developed intra-amniotic infection/inflammation, while 13 patients without intra-amniotic infections/inflammation delivered fewer than 7 days after PPROM. No confounding factors at the time of PPROM diagnosis were associated with the time from PPROM until secondary intra-amniotic infection/inflammation.ConclusionsThe time between PPROM and onset of secondary intra-amniotic infection/inflammation appears prolonged. Treatments other than antimicrobial agents may need to be added to prolong pregnancy.     

Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes

Objective: The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM.

Methods: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes.

Results: (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p?=?0.001].

Conclusions: (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.     

Erythrocyte aggregation is increased in preterm premature rupture of the membranes

OBJECTIVE: To asses the degree of erythrocyte aggregation in the peripheral blood of women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: This was a prospective case control study. Twenty patients with preterm premature rupture of the membranes and matched controls were recruited at the Lis Maternity Hospital. A slide test and image analysis were used to quantitate the degree of erythrocyte aggregation. Hematological indices and markers of inflammation such as the erythrocyte sedimentation rate and C-reactive protein were also compared. RESULTS: The vacuum radius (VR) of the study group was significantly higher than in the control group at 14.8+/-1.6 microm versus 10.0+/-1.0 microm, respectively (P=0.03). Other hematological indices were not changed significantly between the groups. CONCLUSIONS: We found an increase in erythrocyte aggregation in the peripheral blood of patients with preterm premature rupture of the membranes. We used this sensitive marker of inflammation to further support the theory that PPROM is an inflammatory state.     

Decreased expression of progesterone receptor membrane component 1 in fetal membranes with chorioamnionitis among women with preterm birth

Progesterone receptor membrane component 1 (PGRMC1) have anti-inflammatory and anti-apoptotic properties. This study aimed to determine the expression of PGRMC1 in fetal membranes among women with preterm labor (PTL), preterm premature rupture of membranes (PPROM), and acute histologic chorioamnionitis (HCA) during preterm birth. Full thickness fetal membranes were obtained from women with gestational age-matched (32–34 weeks of gestational age), and categorized as PTL without HCA (PTL, n = 10), PPROM without HCA (PPROM, n = 10), PPROM with HCA (HCA, n = 10), and term without labor and HCA (term birth (TB), n = 9). The expression of PGRMC1 was assessed using western blot and Immunohistochemistry (IHC). As CD14 is a component of the innate immune system during inflammation, CD14 was used as inflammatory indicator. Nonparametric statistics were used for analysis. PGRMC1 expression for all of preterm birth was lower than in TB (P = 0.01). In HCA, PGRMC1 expression was significantly decreased compared to that in PTL and PPROM (P = 0.006. P = 0.001, respectively). PGRMC1 expression in PPROM was higher than that in PTL (P = 0.002). There was a negative correlation between PGRMC1 and CD 14/β-actin ratio (r = − 0.518; P = 0.002). IHC showed that PGRMC1 was predominant in the cytoplasm of cells, these results were consistent with those of the western blot analysis. Preterm birth with PTL, PPROM, and especially HCA is associated with a decreased PGRMC1 in fetal membranes and inversely associated with increased CD 14.     

Maternal serum concentrations of s-Endoglin and IL-6 in pregnancy complicated by preterm premature membrane rupture

Objective: This study aimed to investigate maternal serum concentrations of s-Endoglin and compare s-Endoglin with other inflammatory markers in prediction of time to delivery, in pregnancies complicated by preterm premature rupture of membranes (PPROM).

Materials and methods: Fifty five patients complicated by PPROM whose gestational age were between 2433 weeks and 44 matched healthy pregnant women were included in present study. Maternal concentrations of s-Endoglin concentrations were measured by an enzyme-linked immunosorbent assay (ELISA) and compared with maternal inflammatory markers including interleukin-6 (IL-6), white blood cell (WBC) count and serum C-reactive protein (CRP). The best variable for prediction of preterm birth was computed.

Results: Mean s-Endoglin levels in PPROM were lower than control groups (0.24?±?0.12?pg/ml and 0.69?±?0.25?pg/ml, respectively, p?<?0.01). Besides IL-6 (p?<?0.01), WBC (p?=?0.016) and CRP (p?=?0.010) levels were higher in PPROM group. In PPROM group, ROC analysis results of s-Endoglin for prediction of preterm delivery <48 h, <7 days, <32 weeks were not different (p?>?0.05). For predicting preterm birth before 48 h and 7 days, only IL-6 at cut off value >0.70 (pg/ml) and >0.55 (pg/ml) had area under curve (AUC); 0.871 (0.7750.965), p?<?0.01, AUC; 0.925 (0.8560.993), p?<?0.001, respectively.

Conclusion: s-Endoglin as an anti-angiogenic marker seemed to have a role in pathogenesis but results of present study showed that, unlike IL-6, it was unsatisfactory for estimating time to delivery in PPROM.