Leveraging bioengineering to assess cellular functions and communication within human fetal membranes

A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes

Elevated protease activities in human amnion and chorion correlate with preterm premature rupture of membranes

The management of preterm premature rupture of the membranes near the limit of fetal viability

Objective: Neutrophil elastase (NE), a multifunctional serine protease stored in azurophilic granules of mature neutrophils, is capable of intracellular degradation of proteins during phagocytosis and extracellular degradation of connective tissue during an inflammatory process. Secretory leukocyte protease inhibitor (SLPI) is a natural NE inhibitor present in amniotic fluid, fetal membranes and cervical mucus. An imbalance between NE and SLPI has been implicated as a mechanism of abnormal tissue destruction in chronic inflammatory diseases. The purpose of this study was to determine if parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of NE and SLPI. Study design: Amniotic fluid was retrieved by amniocentesis from 380 patients in the following groups: (1) preterm labor and intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 13) or prematurely (n = 26), and preterm labor with microbial invasion of the amniotic cavity (n = 9); (2) preterm PROM with (n = 34) and without (n = 51) microbial invasion of the amniotic cavity; and (3) term gestation without microbial invasion of the amniotic cavity with intact membranes not in labor n = 63), in labor (n = 158), and with rupture of membranes not in labor (n = 26). Microbial invasion of the amniotic cavity was determined by a positive amniotic fluid culture for micro-organisms including aerobic, anaerobic and Mycoplasma species. NE and SLPI amniotic fluid levels were determined by highly specific and sensitive immunoassays. Results: Preterm PROM was associated with a significant increase in the amniotic fluid concentration of NE. Microbial invasion of the amniotic cavity was associated with a significant increase in the amniotic fluid concentration of NE in women with preterm labor and intact membranes, as well as in women with preterm PROM. Term and preterm parturition was associated with a significant increase in the amniotic fluid concentration of NE. In the absence of microbial invasion of the amniotic cavity, preterm and term PROM were associated with a significant reduction in the amniotic fluid concentration of SLPI. Conclusion: Preterm PROM, microbial invasion of the amniotic cavity, and parturition at term and preterm are associated with a significant increase in the amniotic fluid concentration of NE. PROM is associated with a reduced amniotic fluid concentration of SLPI.

To investigate the role of transcription factor Ets-1 involved in premature rupture of membranes(PROM)by detecting its expression and location in human fetal membranes. Between Feb. and Nov. 2007, 100 pregnant women who delivered in the First Affiliated Hospital, Chongqing Medical University were enrolled in this study. According to gestational weeks, rupture of amniochorionic membranes and delivery mode, those women were classified into preterm labor group, preterm premature rupture of membranes (PPROM) group, term labor group and term premature rupture of membranes (TPROM) group, matched with elective term cesarean sections women as control group. There were 20 pregnant women in every group. The expression and distribution of Ets-1 protein in fetal membranes were detected by immunohistochemical streptravidin-biotin peroxidase (SP) method and histoscore. In the mean time, 6 cases were chosen from each group randomly and reverse transcription-PCR was used to measure the Ets-1 mRNA expression. (1) The expression of Ets-1 mRNA in fetal membranes were 0.342 ± 0.016 in preterm labor group, 0.603 ± 0.027 in PPROM group, 0.325 ± 0.013 in term labor group, 0.582 ± 0.075 in TPROM group, 0.139 ± 0.012 in control group, respectively. When compared with that in control group, Ets-1 mRNA expression were significantly increased in both PPROM and TPROM group (P < 0.05). However, it did not show remarkably difference between preterm group and term labor group, as well as between PPROM and TPROM group (P > 0.05). (2) Ets-1 was in stromal layers of amniochorionic membranes and in both cytoplasm and nuclei of trophoblast, which were shown with diffuse intracellular positive granularities (brown-yellow) clearly. No expression of Ets-1 was observed in amniotic epithelial cells. (3) The expression of Ets-1 protein was 0.552 ± 0.018 in preterm labor group, 2.853 ± 0.174 in PPROM group, 0.538 ± 0.042 in term labor group, 2.731 ± 0.090 in TPROM group and 0.214 ± 0.013 in control group, respectively. Ets-1 protein was significantly increased in the stroma of both PPROM and TPROM group than that in control group (P < 0.05). However, no remarkable different expression of Ets-1 was observed between preterm and term labor group, so was that between PPROM and TPROM group (P > 0.05). Transcription factor Ets-1 is expressed in human amniochorionic membranes and it could be up-regulated in PROM.

The preterm cervix reveals a transcriptomic signature in the presence of premature prelabor rupture of membranes

Objective To explore the method of rapid diagnosis preterm premature rupture of membrane (PPROM)and prognosis factors of residual amniotic fluid in mother and infant through monitoring nonphosphorylated insulin-like growth factor binding protein-1(IGFBP-1)and the residual amniotic fluid index(AFI)of the cervi-covaginal secretions from PPROM women. Methods 96 cases of PPROM were tested IGFBP-1 of cervicovaginal secretions, AFI were tested by abdominal ultrasound through fast chromatography methods, and the cause was ana-lyzed. The pregnancy outcome and neonatal prognosis were compared. Results 92 cases positive of IGFBP-1 were diagnosed with PPROM. The risk factors of PPROM were mainly reproductive tract infections, abortion, induced labor history and unknown causes(including no evidence of infection, fetal membrane dysplasia unclear or other factors), the twins, multiplets, macrosomia, breech or cephalopelvic disproportion, gestational hypertension disease, uterine fibroids or deformity, malnutrition and polyhydramnios. In the 92 patients with PPROM pregnant women, the duration from premature rupture of membrane to delivery was(105.7±13.9)h, cesarean section rate was 51.1%, fever rate of pregnant women was 7.6%, the rate of placental abruption was 4.3%,the rate of fetal distress was14.1%, perinatal infection rate was 21.7%, and neonatal asphyxia rate was 7.6%, the neonatal mortality was 7.6%. To compare the AFI≤40mm group with AFI＞40 mm group, the duration from premature rupture of membrane to delivery was short-ened remarkably(t＝10.904,P＜0.05), the neonatal mortality rate was significantly increased(χ2＝4.359,P＜0.05). Conclusion Measurement of IGFBP-1 and AFI in cervicovaginal secretions can rapid diagnosis PPROM and evaluate the results of pregnancy and neonatal prognosis, and can guide clinical improvement of pregnancy safety and reduce neonatal mortality. Key words: Premature rupture of membranes; Insulin-like growth factor binding protein-1; Amniotic fluid index; Diagnose

Association of polymorphism within the promoter of the tumor necrosis factor α gene with increased risk of preterm premature rupture of the fetal membranes

Uterine activity after preterm premature rupture of the membranes

Cervicovaginal microflora and pregnancy outcome: Results of a double-blind, placebo-controlled trial of erythromycin treatment

Residual amniotic fluid volume predicts the sealing of preterm prelabor rupture of fetal membranes in the pre- and periviable period

The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant women with (A) threatened premature labor (n = 41), (B) preterm premature rupture of membranes (n = 49), and (C) preterm rupture of membranes at term (n = 48). The relationship between these and classic intrauterine infection markers and the latent time from symptoms up to delivery depending on RAGE's concentration were investigated. In groups A and B, a positive correlation was found between plasma sRAGE and latent time (r = 0,422; p = 0,001; r = 0,413, p = 0,004, resp.). High prognostic values were found in both groups for plasma sRAGE concentration and the latent time from symptoms up to delivery. Groups B and C presented higher levels of esRAGE than group A (526,315 ± 129,453 pg/mL and 576,212 ± 136,237 pg/mL versus 485,918 ± 133,127 pg/mL, p< 0,05). The conclusion is that sRAGE concentration can be a favorable prognostic factor in the presence of symptoms of threatened premature labor. Higher esRAGE plasma level in case of the rupture of membranes in mature and premature pregnancy suggests its participation in fetal membranes destruction.

Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection

Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection

Objective To discuss detect cervical length and funnel-like change for preterm premature rupture of the membranes(PPROM) high-risk pregnant women by transvaginal ultrasonography(TVS)to predict the occurrence of PPROM. Methods A total of 68 cases of PPROM high-risk pregnant women hospitalized in Tianjin Central Hospital of Gynecology Obstetrics from June 2009 to December 2013 were selected as study subjects, according to whether PPROM occurred or not after admission, they were divided into PPROM group(n=28) and non PPROM group(n=40). All subjects were given TVS to detect cervical length and the occurrence of cervical funnel-like changes, statistically analyzed the differences of cervical length and cervical funnel-like change rate of pregnant women between two groups, and the accuracy of different cervical length and funnel-like change to predict occurrence of PPROM and the relationship with PPROM occurrence. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Tianjin Central Hospital of Gynecology Obstetrics.Informed consent was obtained from each participant.There were no significant differences between two groups in general clinical data such as maternal age, pre-pregnant body weight and gestational age(P>0.05). Results ①Cervical length of pregnant women of PPROM group was significantly shorter than that of non PPROM group, the cervical funnel-like change rate was significantly higher than that of non PPROM group, and the differences were statistically(t=2.273, 5.909; P<0.05). ②With the length of cervical getting shorter and cervical funnel-like change rate getting higher, the prediction specificity and positive predictive value of PPROM increased gradually, and cervical length<5 mm or 75%<funnel-like change rate≤100% had highest prediction specificity of PPROM (97.2% and 96.3%) and positive predictive value(79.6% and 76.3%), they had the closest relationship with PPROM occurrence(OR=6.47, 95%CI: 1.33-38.21, P<0.05; OR=5.80, 95%CI: 1.11-30.22, P<0.05). Conclusion TVS detecting cervical length and cervical funnel-like change can effectively predict the occurrence of PPROM of high risk PPROM pregnant women; Cervical length 75% have the highest prediction value of PPROM occurrence. Key words: Transvaginal ultrasonography; Preterm premature rupture of the membranes; Cervix uteri; Forecasting