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There has long been anecdotal evidence of early labor and delivery in severe weather events leading to preterm birth. In particular, significant barometric pressure changes are associated with hurricanes and bomb cyclones. Some authors have related these low pressure weather events to premature rupture of fetal membranes, hypothesizing that the membranes act as an inflated balloon and respond directly to pressure changes. In this article, the key literature including data supporting this hypothesis is reviewed. A simple numerical model, based on a competition between the driving and resisting forces for fetal membrane rupture, is presented. This model provides a quantitative mechanism for membrane failure in the context of storms with low atmospheric pressure. Other sequelae of severe storms that are unrelated to fetal membrane rupture are also discussed. Labor and delivery in the context of major weather events should be understood in a holistic framework that includes both exogenous and endogenous factors relevant to the pregnant patient.

There has long been anecdotal evidence of early labor and delivery in severe weather events leading to preterm birth. In particular, significant barometric pressure changes are associated with hurricanes and bomb cyclones. Some authors have related these low pressure weather events to premature rupture of fetal membranes, hypothesizing that the membranes act as an inflated balloon and respond directly to pressure changes. In this article, the key literature including data supporting this hypothesis is reviewed. A simple numerical model, based on a competition between the driving and resisting forces for fetal membrane rupture, is presented. This model provides a quantitative mechanism for membrane failure in the context of storms with low atmospheric pressure. Other sequelae of severe storms that are unrelated to fetal membrane rupture are also discussed. Labor and delivery in the context of major weather events should be understood in a holistic framework that includes both exogenous and endogenous factors relevant to the pregnant patient. [ABSTRACT FROM AUTHOR]

Purpose: Gal-3, which can regulate immune responses upon infection and inflammation, was not studied so far in intrauterine infection leading to preterm prelabor rupture of the membranes (PPROM), although gal-1 was reported to be implicated in the process. Gal-3 mRNA and protein expression in amnion and its changes during histological chorioamnionitis were studied here.Materials and Methods: Fetal membranes were obtained from women with PPROM with (n =15) and without histological chorioamnionitis (n =15) during second and third trimester. Immunohistochemical reactivity was evaluated semiquantitatively and analyzed using t-test. Galectin profile of amniotic epithelia was determined by polymerase chain reaction (PCR) and change assessed in gal-3 in PPROM with (n =5) or without histological chorioamnionitis (n =5) by real-time PCR.Results: Human amniotic epithelium was found to express gal-1, gal-3, gal-7 and gal-8 mRNA. Gal-3 mRNA and protein is increased in fetal membranes and in the amniotic epithelium in patients with chorionamnionitis.Conclusion: Histological chorioamnionitis is associated with increased gal-3 expression and strong immunoreactivity of the amnion. Gal-3 may participate in the regulation of the inflammatory responses to chorioamniotic infection and/or direct interaction with pathogens. [ABSTRACT FROM AUTHOR]

Chemical penetration enhancers (CPEs) have long been used for mass transport enhancement across membranes. Many CPEs are used in a solution or gel and could be a solvent. The use of CPEs is mainly limited due to their toxicity/irritation levels. This study presents the evaluation of encapsulated CPEs in nano-sized polymeric particles on the chorioamnion (CA) membrane mass transport. CPEs’ mass encapsulated in nanoparticles was decreased by 10,000-fold. Interestingly, this approach resulted in a 6-fold increase in mass transport across the CA. This approach may also be used with other CPEs' base applications necessitating lower CPE concentration. Applying Ultrasound (US) has shown to increase the release rate of and also the mass transport across the CA membrane. It is proposed that encapsulated CPEs penetrate into the CA membrane thus prolonging their exposure, possibly extending their penetration into the CA membrane, while insonation also deepens their penetration into the CA membrane. [ABSTRACT FROM AUTHOR]

Serotonin Reuptake Inhibitors (SRIs) are often used as first line therapy for depression and other psychiatric disorders. SRI use during pregnancy is associated with preterm premature rupture of membranes (PPROM) and subsequent preterm birth. The objective of this study was to investigate the mechanism(s) responsible for SRI-associated PPROM. Putative mechanisms underlying PPROM include fetal membrane (FM) inflammation, increased apoptosis, and/or accelerated senescence, the later which may be reversed by statins. Human FM explants from normal term deliveries without labor, infection, or antidepressant use were treated with or without the SRI, fluoxetine (FLX), either alone or in the presence of a p38 MAPK inhibitor or the statins, simvastatin or rosuvastatin. FMs were also collected from women either unexposed or exposed to FLX during pregnancy. FLX significantly increased FM p38 MAPK activity and secretion of inflammatory IL-6. Inhibition of p38 MAPK reduced FM IL-6 secretion in response to FLX. Statins did not reduce the SRI-induced FM IL-6 production. FMs from women exposed to FLX during pregnancy expressed elevated levels of p38 MAPK activity compared to matched unexposed women. FMs exposed to FLX did not exhibit signs of increased apoptosis and/or accelerated senescence. These results indicate that the SRI, FLX, may induce sterile FM inflammation during pregnancy through activation of the p38 MAPK pathway, and in the absence of apoptosis and senescence. These findings may better inform clinicians and patients as they weigh the risks and benefits of SRI antidepressant treatment during pregnancy. • The SRI, fluoxetine, increases fetal membrane p-38 MAPK activity and secretion of inflammatory IL-6. • Fetal membranes from women exposed to fluoxetine during pregnancy expressed elevated levels of p38 MAPK activity compared to matched unexposed women. • Inhibition of p-38 MAPK reduced fetal membrane IL-6 secretion in response to fluoxetine. • Statins did not reduce the fluoxetine-induced fetal membrane IL-6. [ABSTRACT FROM AUTHOR]

Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. Impact of PPROM is greatest in low- and middle-income countries where prematurity-related deaths are most common. Recent investigations identify cytokine and matrix metalloproteinase activation, oxidative stress, and apoptosis as primary pathways to PPROM. These biological processes are initiated by heterogeneous etiologies including infection/inflammation, placental bleeding, uterine overdistention, and genetic polymorphisms. We hypothesize that pathways to PPROM overlap and act synergistically to weaken membranes. We focus our discussion on membrane composition and strength, pathways linking risk factors to membrane weakening, and future research directions to reduce the global burden of PPROM. [ABSTRACT FROM AUTHOR]

Problem Preterm premature rupture of fetal membranes ( pPROM) occurs in 30-40% of spontaneous preterm births ( PTB) and is associated with intra-amniotic infection and inflammation. The membranes may sense and respond to microbes via Toll-like receptors ( TLRs); however, little is known about their expression and regulation in this tissue. The objective of this study was to evaluate the expression of TLRs 1-10 in fetal membranes after exposure to pathogens associated with intra-amniotic infection and PTB. Method of study Normal human term fetal membrane explants were exposed to various bacteria. After 24 hrs, RNA was extracted and quantitative RT- PCR performed for TLRs1-10. Results Treatment of fetal membranes with Mycoplasma hominis increased expression of TLR4, TLR6, and TLR8 mRNA. Ureaplasma parvum upregulated TLR8 mRNA, and Porphyromonas gingivalis significantly increased fetal membrane TLR7 expression. In contrast, treatment with Gram-negative Escherichia coli (and its cell wall component lipopolysaccharide) downregulated TLR10 mRNA. No effect was detected for Ureaplasma urealyticum, Gardnerella vaginalis, or Group B Streptococcus. Conclusion These findings demonstrate that different types of bacteria have distinct effects on fetal membrane TLR expression patterns. Moreover, these findings highlight the disparity of fetal membrane responses to infection and thus suggest heterogeneity in the mechanisms by which infection-associated pregnancy complications, such as pPROM and PTB, arise. [ABSTRACT FROM AUTHOR]

Abstract: Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size ∼400 Da) and fluorophore-tagged G4-PAMAM dendrimers (∼16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than <3%, whereas the transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10−7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10−8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5–4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother without affecting the fetus. [Copyright &y& Elsevier]

The normal mechanical functioning of an intact chorioamnion (CA) membrane is essential to successful human reproduction. The amnion and the chorion, separately and together as the bilayer chorioamnion, serve barrier and container functions throughout gestation, and these two important roles are required from conception to birth. The event associated with the “breaking of waters” is a landmark event in labor and delivery. Mechanical rupture of the CA membrane is part of the natural sequence of term delivery, but has serious implications when rupture occurs prior to term; preterm premature rupture of the CA membrane (PPROM) is associated with one-third of premature births. The current manuscript reviews PPROM from a clinical, anatomical, and mechanical perspective with a special focus on the clinically relevant fracture properties of these membranes. Emphasis is given to the link between membrane structure and properties at macroscopic and microscopic length scales. Because it has been demonstrated that the mechanical properties of prematurely failed membranes are not different from membranes of the same gestational age that have remained intact, membrane failure is a local process that must be explored in terms of local changes in structure and properties of isolated portions of the membrane. Future diagnostic techniques aimed at detection of changes in membrane structure (including thickness) and altered mechanical stiffness or strength may allow for prefailure diagnosis of membrane weak spots, thus opening the door for potential intervention and treatment techniques for preterm membrane rupture. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether intrapartum chlorhexidine vaginal irrigation reduces microbial colonization of the chorioamnion or placenta. Methods: Secondary analysis was made of a randomized trial. Cultures for aerobic and anaerobic bacteria, Mycoplasma species and Ureaplasma urealyticum were performed using standard isolation techniques. Results: The placentas of 83 trial participants allocated to chlorhexidine and 93 allocated to placebo underwent evaluation. These two groups were statistically balanced for risk factors for infection. Aerobic bacteria were isolated from 47% of the chlorhexidine placentas vs. 51% of the placebo placentas (relative risk 0.9, 95% confidence interval 0.7–1.3), anaerobic bacteria from 30% and 35%, respectively (0.8, 0.5–1.3), group B streptococcus from 12% and 15% (0.8, 0.4–1.7), U. urealyticum from 18% and 29% (0.6, 0.4–1.1), Mycoplasma species from 6% and 11% (0.6, 0.2–1.6), and any organism from 57% and 67%, respectively (0.8, 0.7–1.1). Conclusions: Intrapartum chlorhexidine vaginal irrigation was associated with non-significant reductions in the rates of placental microbial isolation. [Copyright &y& Elsevier]

Streptococcus agalactiae or group B streptococci (GBS) are gram-positive diplococci and are the leading bacterial cause of pneumoniae, sepsis, and meningitis in neonates. Neonatal GBS infections may occur prior to or during birth. GBS have been cultured from the chorioamnionic membrane of pregnant women and have therefore been associated with chorioamnionitis and premature labor. A potential route for GBS to establish infection of a neonate would be to penetrate the placental membrane of colonized pregnant women. In our laboratory, we have constructed in vitro systems to emulate certain events during the colonization and invasion of host epithelial cell tissues by GBS. By utilizing techniques to grow primary cultures of both chorion cells and amnion cells isolated from human C-section placentas, we have established a relevant model to investigate certain aspects of GBS adherence and invasion into the placental membrane. To identify relevant molecules required for GBS to colonize the multiple tissues it encounters during an infection, we have applied a variety of biochemical approaches with host cell membrane preparations as well as purified extracellular matrix proteins. These techniques are enabling us to further characterize the pathogenic mechanisms utilized by GBS. [ABSTRACT FROM AUTHOR]

Abstract: The chorioamnion is the membrane that surrounds the fetus during gestation. Normally, it must remain intact for the duration of pregnancy, 37–42 weeks, and only rupture during or just before labour and delivery of the fetus. In a significant number (3%) of all births, this does not happen, and membranes rupture before term, resulting in preterm birth and significant perinatal morbidity. It is known that the material properties of chorioamnion may play a major role in mechanical rupture; a number of studies have been undertaken to characterise the physical nature of chorioamnion and examine factors that may predispose to rupture. However, the existing literature is inconsistent in its choice of both physical testing methods and data analysis techniques, motivating the current review. Experimental data from a large number of chorioamnion mechanical studies were collated, and data were converted to standard engineering quantities. The failure strength of the chorioamnion membrane was found consistently to value approximately 0.9MPa. It is hoped that past and future studies of membrane mechanics can provide insight into the role of chorioamnion in labour and delivery. In addition, biomechanical approaches can help elucidate the potential causes of early rupture, and suggest future protocols or treatments that could both diagnose and prevent its occurrence. [Copyright &y& Elsevier]

Ureaplasmas are the microorganisms most frequently isolated from the amniotic fluid of pregnant women and can cause chronic intrauterine infections. These tiny bacteria are thought to undergo rapid evolution and exhibit a hypermutatable phenotype; however, little is known about how ureaplasmas respond to selective pressures in utero. Using an ovine model of chronic intraamniotic infection, we investigated if exposure of ureaplasmas to subinhibitory concentrations of erythromycin could induce phenotypic or genetic indicators of macrolide resistance. At 55 days gestation, 12 pregnant ewes received an intraamniotic injection of a nonclonal, clinical Ureaplasma parvum strain followed by (i) erythromycin treatment (intramuscularly, 30 mg/kg/day, n = 6) or (ii) saline (intramuscularly, n = 6) at 100 days gestation. Fetuses were then delivered surgically at 125 days gestation. Despite injecting the same inoculum into all the ewes, significant differences between amniotic fluid and chorioamnion ureaplasmas were detected following chronic intraamniotic infection. Numerous polymorphisms were observed in domain V of the 23S rRNA gene of ureaplasmas isolated from the chorioamnion (but not the amniotic fluid), resulting in a mosaiclike sequence. Chorioamnion isolates also harbored the macrolide resistance genes erm(B) and msr(D) and were associated with variable roxithromycin minimum inhibitory concentrations. Remarkably, this variability occurred independently of exposure of ureaplasmas to erythromycin, suggesting that low-level erythromycin exposure does not induce ureaplasmal macrolide resistance in utero. Rather, the significant differences observed between amniotic fluid and chorioamnion ureaplasmas suggest that different anatomical sites may select for ureaplasma subtypes within nonclonal, clinical strains. This may have implications for the treatment of intrauterine ureaplasma infections.