Role In Preterm Labor Research Articles

Evaluation of the Predictive Role of Neutrophil Lymphocyte Ratio and Mean Platelet Volume in Preterm Deliveries: A Cross-sectional Study

Introduction: Preterm birth is associated with high perinatal morbidity and mortality. Identifying women at risk for preterm labour early in pregnancy may improve pregnancy outcomes. Neutrophil-Lymphocyte Ratio (NLR) and Mean Platelet Volume (MPV) can be helpful in predicting preterm labour, as infection is an important factor in early preterm deliveries, with immunity playing a key role in preterm labour. Aim: To evaluate the predictive role of the NLR and MPV in preterm deliveries. Materials and Methods: This cross-sectional study was conducted in a tertiary care and research hospital from August 2022 to October 2023. Haematological and clinical data were retrieved for preterm deliveries (n=79, group I) and term deliveries (n=151, group II). The two groups were compared in terms of demographic characteristics, obstetric and laboratory findings, including maternal age, gravida, parity, birth weight, NLR, MPV, and haemoglobin levels. The data were analysed using Statistical Package for the Social Sciences (SPSS) version 29.0. One-way Analysis of Variance (ANOVA) was used to compare the mean values among different groups. Categorical values were evaluated with Pearson’s Chi-square test. Receiver Operating Characteristic (ROC) curve was used to assess the diagnostic properties of the tests. Results: The two groups showed no statistical difference in terms of demographic parameters such as the mother’s age (p-value=0.611), parity (p-value=0.798), and gravida (p-value=0.583). The NLR was higher in group I (5.8±5.01) compared to group II (4.3±1.75), and this difference was statistically significant with a p-value of <0.001. MPV was observed to be lower in group II (8.7±0.96) compared to group I (8.9±1.07); however, this difference was not statistically significant (p-value=0.128). The mean baby weight and mean maternal haemoglobin in group I were significantly lower compared to group II. Conclusion: In this study, the NLR value was significantly higher in patients with preterm deliveries compared to term deliveries. This study highlights the role of NLR as an emerging predictor of preterm deliveries and emphasises that NLR, obtained from an inexpensive and routinely conducted haemogram, has the potential to be used as an early indicator of preterm deliveries.

Low Maternal Serum Folic Acid as Risk Factor of Preterm Delivery

Introduction: Preterm delivery increases the risk of infant mortality and morbidity higher than that of term born babies, so it is still a big problem in the field of obstetrics. Preterm delivery is not only influenced by anatomical factors, but nutritional status can also be a risk factor. Various studies have reported the role of folic acid on the risk of preterm delivery. Folic acid is thought to play a role in preterm labor through inflammatory and infectious pathways, this pathway is triggered by low serum folic acid levels interfering with Hcy metabolism which causes an increase in Hcy levels. High levels of Hcy in serum induce oxidative stress processes in vascular tissue and placental endothelium. The occurrence of oxidative stress and cell apoptosis will release proinflammatory mediators that cause preterm labor. This study aims to prove the role of maternal serum folic acid levels in preterm delivery. Methods: This study used a case-control design that was carried out from January 2021 to June 2021. The target population of the case in this study was pregnant women in the process of preterm labor with control of preterm pregnant women. The sample in this study was taken by consecutive sampling (non random sampling). Examination of folic acid from venous blood samples was carried out using the ELISA method. Results: This study involved 27 cases (preterm delivery) and 27 controls (preterm pregnancy). In this study, serum folic acid levels were found to be lower in the case group compared to the control group (cases vs. controls: 9.86 ± 1.93 ng/mL vs. 13.59 ± 1.24 ng/mL), all samples the case and control groups received folic acid supplementation. In this study, the maternal serum folic acid threshold was found at a concentration of 12.2 ng/mL, the researchers also obtained a risk value (OR) of 5.71 which indicated that pregnant women with serum folate levels below the value of 12.2 ng/mL had a risk of preterm delivery. 6 times greater when compared to pregnant women with serum folate levels above this value. Folic acid plays a role in the developmental phase of EVT, angiogenesis, and secretion of MMP which is important in placental development. Low serum folic acid levels also increase the process of angiogenesis, expression of MMP2, MMP3, and MMP9 thereby increasing the risk of preterm labor. Conclusion: Low folic acid serum level in pregnancy is a risk factor for the occurrence of preterm labor by six times.

Comparison of vitamin D levels between mothers and infants with and without prolonged membrane rupture

Background. Premature membrane rupture is a known causes of preterm labor and accounts for approximately one-third of cases. Vitamin D deficiency may play a role in preterm labor as well. Objective. The present study aimed to compare vitamin D levels in mothers and infants with and without prolonged rupture of membranes (PROM). Materials and methods. This cross-sectional study was conducted with 241 babies, with and without a history of membrane rupture, in mothers in the neonatal ward of Ghaem Hospital, Mashhad, from 2019 to 2021 with available sampling methods. After confirmation of prolonged membrane rupture (more than 18 hours before birth) based on history and examination with a speculum, we completed a data collection tool, a checklist including laboratory evaluation and neonatal and maternal characteristics. The conditions of neonates with and without prolonged membrane rupture were compared. Data were analyzed by T-test and Chi-square. Results. We examined a total of 241 neonates including 148 (61.4%) without prolonged rupture of the membranes in mothers and 93 (38.6%) with PROM. There were statistically significant differences between the two groups regarding: maternal vitamin D level (p = 0.001); neonatal vitamin D level (p = 0.001); and fifth minute Apgar score (p = 0.003). These variables were lower in the group of neonates with PROM. Conclusion. Vitamin D deficiency in mothers was significantly associated with prolonged membrane rupture. With increasing severity of vitamin D deficiency, the probability of PROM increases and, therefore, the likelihood of preterm labor and its complications rises.

Secretory phospholipase A2 expression and activity in preterm clinical chorioamnionitis with fetal involvement.

Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma (P < 0.001) and amniotic fluid (P < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid (P = 0.045) or increased, although without statistical significance, in maternal plasma (P = 0.06) and amniotic fluid (P = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-α and IL-1β) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-α (P = 0.028), IL-1β (P < 0.001), and IL-8 (P = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth.

Myometrial-derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice.

Preterm birth is a major contributor to neonatal mortality and morbidity. Infection results in elevation of inflammation‐related cytokines followed by infiltration of immune cells into gestational tissue. CXCL12 levels are elevated in preterm birth indicating it may have a role in preterm labour (PTL); however, the pathophysiological correlations between CXCL12/CXCR4 signalling and premature labour are poorly understood. In this study, PTL was induced using lipopolysaccharide (LPS) in a murine model. LPS induced CXCL12 RNA and protein levels significantly and specifically in myometrium compared with controls (3‐fold and 3.5‐fold respectively). Highest levels were found just before the start of labour. LPS also enhanced the infiltration of neutrophils, macrophages and T cells, and induced macrophage M1 polarization. In vitro studies showed that condition medium from LPS‐treated primary smooth muscle cells (SMC) induced macrophage migration, M1 polarization and upregulated inflammation‐related cytokines such as interleukin (IL)‐1, IL‐6 and tumor necrosis factor alpha (TNF‐α). AMD3100 treatment in pregnant mice led to a significant decrease in the rate of PTL (70%), prolonged pregnancy duration and suppressed macrophage infiltration into gestation tissue by 2.5‐fold. Further, in‐vitro treatment of SMC by AMD3100 suppressed the macrophage migration, decreased polarization and downregulated IL‐1, IL‐6 and TNF‐α expression. LPS treatment in pregnant mice induced PTL by increasing myometrial CXCL12, which recruits immune cells that in turn produce inflammation‐related cytokines. These effects stimulated by LPS were completely reversed by AMD3100 through blocking of CXCL12/CXCR4 signalling. Thus, the CXCL12/CXCR4 axis presents an excellent target for preventing infection and inflammation‐related PTL.

Revolutionising Understanding of the Myometrium to Prevent Preterm Birth

Great advances in the field of science and medicine have seen treatments and cures developed for some of the worst diseases ever known. Despite this, the potentially devastating, but sadly common occurrence of preterm birth is not yet preventable. Dr Iain Buxton at the University of Nevada, USA, has been studying the role of the smooth muscle of the uterus to elucidate its role in preterm labour and birth. His research is paving the way for the development of much-needed interventions to prevent early birth.

Maternal and fetal T cells in term pregnancy and preterm labor

Pregnancy is a state of immunological balance during which the mother and the developing fetus must tolerate each other while maintaining sufficient immunocompetence to ward off potential threats. The site of closest contact between the mother and fetus is the decidua, which represents the maternal-fetal interface. Many of the immune cell subsets present at the maternal-fetal interface have been well described; however, the importance of the maternal T cells in this compartment during late gestation and its complications, such as preterm labor and birth, has only recently been established. Moreover, pioneer and recent studies have indicated that fetal T cells are activated in different subsets of preterm labor and may elicit distinct inflammatory responses in the amniotic cavity, leading to preterm birth. In this review, we describe the established and proposed roles for maternal T cells at the maternal-fetal interface in normal term parturition, as well as the demonstrated contributions of such cells to the pathological process of preterm labor and birth. We also summarize the current knowledge of and proposed roles for fetal T cells in the pathophysiology of the preterm labor syndrome. It is our hope that this review provides a solid conceptual framework highlighting the importance of maternal and fetal T cells in late gestation and catalyzes new research questions that can further scientific understanding of these cells and their role in preterm labor and birth, the leading cause of neonatal mortality and morbidity worldwide.

The interplay between immune system and microbiota in gynecological diseases: a narrative review.

The vaginal microbiome is a dynamic environment, depending on the results of a complex interplay between microbiota and the host. In physiological conditions, Lactobacillus species are the most represented, regulating glycogen metabolism in order to maintain normal pH. Vaginal flora has been divided into five subtypes. Pattern recognition receptors are present on both squamous epithelial cells lining the vagina and columnar cells lining the upper female genital tract. They respond directly to bacterial product expressed by vaginal microbiome. The vagina contains different immune related cells and receptors which can recognize and react with the microbial environment. Altered microbiota and altered interplay between microbiota and immune system underlie several gynecologic diseases. In this review, literature data related to vaginal microbiota, vaginal inflammation, immune system and menopause, preterm labor and miscarriage, were summarized. Relevant publications were retrieved from: PubMed, Medline, Scopus and Web of Science. The vaginal microbiome and the relationship with immune system has been analyzed in different gynecologic conditions. Menopause is associated to estrogen loss which causes vaginal atrophy, reduced abundance of Lactobacilli and increased amount of other bacterial species. Estrogens influence vaginal immunity through known and unknown mechanisms. In bacterial vaginosis (BV), due to many bacterial species, there has been found an inhibition of the chemotaxis and cytokine secretion. A decreased concentration of Lactobacilli seems to be playing a role in preterm labor as well as the increased levels of pro-inflammatory cytokines. Finally, the disequilibrium in the Th1/Th2 immune adaptive response, with a shift from Th2 to Th1, appears to be playing a role in miscarriage. The interplay between microbiota and the host closely involves the immune system. In particular, the vaginal microbiota is classically characterized by Lactobacilli even if vaginal microbiome of asymptomatic woman of reproductive age includes multiple aerobic and facultative or obligate anaerobic species. The role of microbiota and immune system in determining gynecological and obstetric events has been studied throughout recent years reaching new advancements. Therefore, additional studies are needed to better comprehend the complexity of the issue.

Human Myometrial Interstitial Cajal Like Cell (Telocyte) in Preterm and Full Term Labour : Histological and Immunohistochemical Studies

Introduction: Preterm labour is a common obstetric problem. The human myometrium is formed of two types of cells namely smooth muscles and interstitial Cajal like cells or telocytes which express both estrogen and progesterone receptors. Aim of the work: This study aimed to know how many telocytes are present in the pregnant uteri at time of labour in the different gestational ages and the possible role of telocytes in preterm labour. Patients and methods: 10 pregnant women were included in the study planned to do cesarean section. They were divided into two groups: Group I: included 5 cases whose gestational age was less than 37 weeks (preterm). Group II: included 5 cases whose gestational age was more than 37 weeks (full term). Specimens were obtained from the myometrium at the time of the operation and processed for histological and immunohistochemical study. Results: H&E stained sections revealed hypertrophied smooth muscle fibers with different orientations. Methylene blue stain revealed telocytes between the smooth muscle fibers as a branched cell with small cell body and thin long processes. CD 117 (ckit) immunostaining revealed an apparent increase in the number of telocytes in preterm cases (Group I) compared to full term cases (Group II). Morphometric study revealed a significant increase in the number of ckit positive telocytes in preterm cases compared to the full term one. Conclusion: telocytes are present in the pregnant uteri at different gestational ages with a significant increase in their number in the preterm cases; they may have a possible role in preterm labour.

Lower Serum Catalase Level is Associated with Preterm Labor among Pregnant Women at Sanglah Hospital Denpasar, Bali-Indonesia

Background: Preterm labor is still become a serious health problem in Obstetric and Perinatology with no sensitive biomarker currently approved. Several studies show that decrease antioxidant activity may play significant role in preterm labor. However, only few studies had been conducted to evaluate blood catalase level in preterm labor and assess its role in preterm labor. Objective: The aim this study was to identify the differences of maternal serum catalase level in preterm labor compared with preterm pregnancy. Methods: An observational analytic cross sectional study was conducted from February to December 2014 using pregnant women with 28-36 weeks’ gestational age. Blood catalase level was evaluated by colorimetric method and the data was analyzed by SPPS for Windows 17.0 program. Results: 12 subjects were enrolled and divided into preterm and control group. No significant differences between mean age, gestational age, and parity between preterm and control group. However, blood catalase level was significantly lower in preterm group compared with control group (81.82 ± 20.38 vs 159.38 ± 35.79; p=0.001). Conclusion: Serum maternal catalase level were significantly lower in preterm labor compared with preterm normal pregnancy.

Novel Noncompetitive IL-1 Receptor-Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth.

Preterm birth (PTB) is firmly linked to inflammation regardless of the presence of infection. Proinflammatory cytokines, including IL-1β, are produced in gestational tissues and can locally upregulate uterine activation proteins. Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has been identified as a key inducer of this condition. However, all currently available IL-1 inhibitors are large molecules that exhibit competitive antagonism properties by inhibiting all IL-1R signaling, including transcription factor NF-κB, which conveys important physiological roles. We hereby demonstrate the efficacy of a small noncompetitive (all-d peptide) IL-1R-biased ligand, termed rytvela (labeled 101.10) in delaying IL-1β-, TLR2-, and TLR4-induced PTB in mice. The 101.10 acts without significant inhibition of NF-κB, and instead selectively inhibits IL-1R downstream stress-associated protein kinases/transcription factor c-jun and Rho GTPase/Rho-associated coiled-coil-containing protein kinase signaling pathways. The 101.10 is effective at decreasing proinflammatory and/or prolabor genes in myometrium tissue and circulating leukocytes in all PTB models independently of NF-κB, undermining NF-κB role in preterm labor. In this work, biased signaling modulation of IL-1R by 101.10 uncovers a novel strategy to prevent PTB without inhibiting NF-κB.

Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor.

Cellular organelles and proteins are degraded and recycled through autophagy, a process during which vesicles known as autophagosomes fuse with lysosomes. Altered autophagy occurs in various diseases, but its role in preterm labor (PTL) is unknown. We investigated the role of autophagic flux in two mouse models of PTL compared to controls: 1) inflammation-induced PTL (IPTL), induced by toll-like receptor agonists; and 2) non-inflammation (hormonally)-induced PTL (NIPTL). We demonstrate that the autophagy related genes Atg4c and Atg7 (involved in the lipidation of microtubule-associated protein 1 light chain 3 (LC3) B-I to the autophagosome-associated form, LC3B-II) decrease significantly in uterus and placenta during IPTL but not NIPTL. Autophagic flux is altered in IPTL, as shown by the accumulation of LC3B paralogues and diminishment of lysosome associated membrane protein (LAMP)-1, LAMP-2 and the a2 isoform of V-ATPase (a2V, an enzyme involved in lysosome acidification). These alterations in autophagy are associated with increased activation of NF-κB and proinflammatory cytokines/chemokines in both uterus and placenta. Similar changes are seen in macrophages exposed to TLR ligands and are enhanced with blockade of a2V. These novel findings represent the first evidence of an association between altered autophagic flux and hyper-inflammation and labor in IPTL.

Effects of 4-Hydroxy-2-Nonenal, a Major Lipid Peroxidation-Derived Aldehyde, and N-Acetylcysteine on the Cyclooxygenase-2 Expression in Human Uterine Myometrium

Background: Chorioamnionitis is one of the important causes of preterm labor. Preterm labor with chorioamnionitis is associated with oxidative stress. We reported that 4-hydroxy-2-nonenal (4-HNE), a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with chorioamnionitis. The aim of this study was to confirm the effect of 4-HNE on cyclooxygenase-2 (COX-2) and prostaglandin (PG) induction in the uterine myometrial tissues. We also examined the effect of N-acetylcysteine (NAC) on 4-HNE-induced COX-2 expression. Methods: Uterine myometrial tissues were obtained from 5 patients. One of them underwent elective cesarean section without labor, and 4 of them underwent hysterectomy because of placental previa or atonic bleeding. We stimulated the uterine myometrial tissues with 4-HNE. In addition, the tissues were pretreated with NAC before 4-HNE treatment. The expression of COX-2 mRNA was observed by real-time PCR. PGE2 and prostacyclin release into the supernatants of the tissue cultures was measured by ELISA. Results: 4-HNE induced the COX-2 mRNA expression and PGE2 production in the uterine myometrial tissue culture in a dose-dependent and time-dependent manner. NAC inhibited 4-HNE-induced COX-2 expression. Conclusion: 4-HNE may play an important role in preterm labor. NAC might be protective against preterm labor under oxidative stress.

Contemporary Usage of Obstetric Magnesium Sulfate

Obstetric Anesthesia Digest: December 2010 - Volume 30 - Issue 4 - p 203-204 doi: 10.1097/01.aoa.0000389573.25461.00

Contemporary Usage of Obstetric Magnesium Sulfate

Magnesium sulfate, a biologically potent compound, given sometimes in extraordinarily high doses, is among the most commonly used pharmaceuticals in American obstetric practice. Although most clinicians are in accord regarding its value for seizure prophylaxis in the setting of preeclampsia, such unanimity is not the case regarding its role in preterm labor. Credible scientific data indicate not only a lack of efficacy, but also toxicity to susceptible fetuses when magnesium sulfate is used in the high dosages found in tocolysis. In apparent contrast, three recent clinical trials, although individually inconclusive, provide data from which a very recent meta-analysis affirms a potential role for magnesium sulfate in prophylaxis against fetal neurologic injury. Comparing outcomes from these trials, with attention to dosage, relationships are revealed that unify observations previously regarded as conflicting: Magnesium sulfate indeed may have both neuroprotective and fetal toxic effects. The better, and safer, neuroprotection seems to occur at comparatively low antenatal doses (perhaps in a range between 4 g and 10.5 g), whereas increasing dosages exceed a "therapeutic window" whereby, as with most drugs, toxic sequelae begin to accrue.

Preterm and infection-driven preterm labor: the role of peroxisome proliferator-activated receptors and retinoid X receptor

Approximately 8% of births are complicated by preterm delivery. To improve neonatal outcomes, a greater understanding of the mechanisms surrounding preterm parturition is required. Peroxisome proliferator-activated receptors (PPARs) have been implicated in the regulation of labor at term where they exhibit anti-inflammatory properties. Thus, we hypothesize that dysregulation of PPAR expression and activity may be associated with preterm labor and infection-associated preterm labor. The aim of this study was to compare the expression and activity of PPARs and the expression of retinoid X-receptor alpha (RXRA) in gestational tissues from term and preterm deliveries, and from infection-associated preterm deliveries. Quantitative RT-PCR, western blotting and activity ELISA were used to study expression and DNA binding profiles. Compared with term, preterm parturition was associated with an increased expression of PPAR delta (PPARD; mRNA and protein), PPAR gamma (PPARG; protein) and RXRA (protein) in the placenta and PPARD (mRNA and protein) and RXRA (mRNA) in the choriodecidua. There was, however, no change in preterm PPAR DNA binding activity compared with term. Preterm chorioamnionitis (CAM) demonstrated protein degradation in the choriodecidua and was associated with a decline in the mRNA expression of PPAR alpha (PPARA) and RXRA compared with uninfected preterm cases. PPAR DNA binding activity increased in the placenta (PPARD and PPARG) and decreased in the amnion (PPARA and PPARG) in association with preterm CAM. In conclusion, idiopathic preterm deliveries were associated with an increase in PPAR:RXR expression and preterm CAM was associated with a decrease in PPAR:RXR expression and tissue-specific alterations in transcriptional activity. The reasons for such dysregulation remain to be determined; however, the data are consistent with the hypothesis that PPARs may play a role in preterm labor and infection-complicated preterm deliveries.

The Prevalence of Chronic Deciduitis in Cases of Preterm Labor without Clinical Chorioamnionitis

Preterm labor is a major cause of perinatal mortality and morbidity, and in approximately 30% of cases a clinical cause is not identified. Acute chorioamnionitis is found histologically in a significant percentage of placentas from preterm deliveries, and the mother is often asymptomatic. Although such subclinical acute chorioamnionitis is known to play a role in preterm labor, this study explores the hypothesis that chronic deciduitis with plasma cells is seen more frequently in cases of preterm labor than in control placentas. Thirty-nine singleton placentas from patients with idiopathic preterm labor were examined microscopically and compared in a blinded fashion with 39 gestational age-matched control placentas. Cases of clinical acute chorioamnionitis and known chronic maternal diseases were excluded. Thirty-nine control singleton placentas were obtained from patients undergoing induction of labor for fetal structural abnormalities, excluding aneuploidy. The presence or absence of acute chorioamnionitis, acute fetal inflammatory response, chronic deciduitis, chronic villitis, infarction, and decidual vasculopathy was noted. Immunohistochemical staining was undertaken to further define leukocyte subtypes. Forty-one percent of cases and 15% of controls showed chronic deciduitis (P = 0.022). Forty-six percent of cases and 18% of controls showed histologic acute chorioamnionitis (P = 0.015). There were 8 cases demonstrating acute fetal inflammatory response but only 1 control (P = 0.029). Little difference was seen in the distribution of lymphocyte subsets between cases and control placentas. Our findings suggest that chronic deciduitis plays a role in the etiology of some cases of preterm labor.

The Human Fetal Adrenal Gland, Corticotropin-Releasing Hormone, and Parturition

Labor initiation is a complex process that remains to be fully elucidated. An area of active research involves the study of the different mechanisms that may lead to successful signaling for parturition. This review focuses on the fetal-derived signals that lead to the initiation of labor. These signals may also play a role in preterm labor when activated prematurely. Studying these signals may prove important in the prediction, diagnosis, and possible intervention in preterm labor.

Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection

Objective. Pro-inflammatory chemokines have been associated with preterm parturition. Monocyte chemotactic protein-1 (MCP-1) is a chemokine capable of recruiting monocytes/macrophages into sites of inflammation, as well as stimulating the respiratory burst required for macrophage activation. MCP-1 transcripts and immuno-reactivity are expressed by uterine tissues (i.e., decidual cells and myometrium) and, thus, may participate in the process of labor. This study was conducted to determine if preterm labor leading to preterm delivery and intra-amniotic infection (IAI) are associated with changes in the amniotic fluid concentrations of MCP-1.Study design. A cross-sectional study was designed to examine the amniotic fluid concentrations of MCP-1 in women in two groups: 1) those presenting with preterm labor with intact membranes; and 2) those with preterm prelabor rupture of membranes (PROM). Amniotic fluid was obtained by transabdominal amniocentesis from 131 women in preterm labor with intact membranes and 105 women with preterm PROM. IAI was defined by a positive amniotic fluid culture for microorganisms. Group 1 included women with preterm labor and intact membranes (n = 131), and was subdivided into the following groups: a) delivery at term in the absence of IAI (n = 42); b) preterm delivery ( < 37 weeks) in the absence of IAI (n = 58); and c) preterm delivery in the presence of IAI (n = 31). Group 2 consisted of women with PROM (n = 105), and was subdivided into women with (n = 51) and without (n = 54) IAI. Non-parametric statistics were used for data analysis.Results. 1) Immuno-reactive MCP-1 was detected in all amniotic fluid samples; 2) IAI, regardless of the membrane status, was associated with a significantly higher median amniotic fluid concentration of immuno-reactive MCP-1 than those without IAI (p < 0.001 for both comparisons); 3) women in preterm labor who delivered preterm without IAI had a significantly higher median amniotic fluid concentration of immuno-reactive MCP-1 than those who delivered at term (p < 0.001); 4) histological chorioamnionitis was associated with increased amniotic fluid concentrations of immuno-reactive MCP-1; and 5) a significant relationship existed between the amniotic fluid concentrations of immuno-reactive MCP-1 and the interval from amniocentesis to delivery.Conclusions. Amniotic fluid concentrations of immuno-reactive MCP-1 were increased in women in preterm labor with IAI, those without IAI who delivered preterm, and those who displayed acute inflammatory lesions in the extra-placental membranes. These findings suggest that MCP-1 may play a role in preterm labor regardless of the presence of IAI.

Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on the cyclooxygenase-2 of human placenta in chorioamnionitis.

Chorioamnionitis (CAM) is one of the causes of preterm labour. A recent study has indicated that NADPH oxidase, a reactive oxygen species (ROS)-producing enzyme, is activated in CAM. CAM is thought to be closely associated with oxidative stress. We have hypothesized that oxidative stress in CAM may induce preterm labour. The purpose of this study is to examine the effect of 4-hydroxy-2-nonenal (HNE), which is a marker of oxidative stress, on human placenta during preterm labour. We initially examined the HNE-modified proteins in human placentas by immunoblotting and immunohistochemistry using anti-HNE antibody. To examine the effect of HNE on human placenta, we stimulated human placental tissue with HNE. The expressions of cyclooxygenase-2 (COX-2) mRNA and protein were observed by RT-PCR and western blot analysis respectively. Furthermore, we measured the peroxidase activity of COX-2 by COX activity assay kit. Prostaglandin E(2) (PGE(2)) in the supernatants of placental tissue was also determined by enzyme-linked immunosorbent assay. Immunoblotting and immunohistochemistry showed that the levels of HNE-modified proteins were increased in the placentas with CAM, compared to the normal placenta. HNE induced the expression of COX-2 mRNA, protein and activity in the placental tissue culture stimulated with HNE. In addition, PGE(2) was also released into the medium in a time-dependent fashion. These findings suggest that HNE-modified proteins, which were increased in the placenta with CAM, play an important role in preterm labour.