A central question is why some women develop an ascending intra-amniotic infection, while whereas most do not. The relationship between the mucosa of the lower genital tract (vagina and cervix) and the microbial ecosystem appears to be a key factor predisposing to ascending infection. Bacterial vaginosis a change in the microbial ecosystem in which there is proliferation of anaerobic bacteria confers risk for intra-amniotic infection and spontaneous preterm delivery. Similarly, trichomonas vaginalis infection is a risk factor for preterm delivery. However, antibiotic treatment of asymptomatic women with bacterial vaginosis or trichomonas vaginalis has not reduced the rate of preterm delivery. A comprehensive understanding of microbial ecology, genetic factors that control susceptibility to infection and the inflammatory response is required, particularly in light of evidence that gene-environment interactions may predispose to preterm labor (2). Characterization of the microbial composition of ecological niches in the human body, including the vagina, using culture-independent techniques, is now possible. This year, we reported a study which showed that the composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. This included non-pregnant women (N=32) and pregnant women who delivered at term (38-42 weeks) without complications (n = 22). Serial samples of vaginal fluid were collected from both non-pregnant and pregnant patients. A 16S rRNA gene sequence-based survey was conducted using pyrosequencing to characterize the structure and stability of the vaginal microbiota. Linear mixed effects models and generalized estimating equations were used to identify the phylotypes whose relative abundance was different between the two study groups. The vaginal microbiota of normal pregnant women was different from that of non-pregnant women (higher abundance of Lactobacillus vaginalis, L. crispatus, L. gasseri and L. jensenii and lower abundance of 22 other phylotypes in pregnant women). Bacterial community state type (CST) IV-B or CST IV-A characterized by high relative abundance of species of genus Atopobium as well as the presence of Prevotella, Sneathia, Gardnerella, Ruminococcaceae, Parvimonas, Mobiluncus and other taxa previously shown to be associated with bacterial vaginosis were less frequent in normal pregnancy. The stability of the vaginal microbiota of pregnant women was higher than that of non-pregnant women;however, during normal pregnancy, bacterial communities shift almost exclusively from one CST dominated by Lactobacillus spp. to another CST dominated by Lactobacillus spp.(3). We then conducted a study to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery. We included a control group of pregnant women who had a term delivery and those who had a spontaneous preterm delivery before 34 weeks of gestation (cases). Samples of vaginal fluid were collected longitudinally and stored at −70C until assayed. A microbial survey using pyrosequencing of V1-V3 regions of 16S rRNA genes was performed, and we tested the hypothesis of whether the relative abundance of individual microbial species (phylotypes) was different between women who had a term versus preterm delivery. The findings were that: the composition of the vaginal microbiota during normal pregnancy changed as a function of gestational age, with an increase in the relative abundance of four Lactobacillus spp., and decreased in anaerobe or strict-anaerobe microbial species as pregnancy progressed;however, no change in the relative abundance of bacterial taxa was observed between women who had a spontaneous preterm delivery and those who delivered at term. The same was the case for the frequency of the vaginal community state types (CST I, III, IV-B). These early findings suggest that changes in the vaginal microbiota are not easily detected in women who subsequently have a spontaneous preterm delivery. Future studies need to take into consideration the indices of the maternal immune response and functional aspects of the vaginal microbiota (4). Meconium-stained amniotic fluid (MSAF) affects 5-20% of all pregnancies (400,000-600,000 deliveries per year in the United States alone), and is a risk factor for meconium aspiration syndrome (MAS);however, only 5% of infants with MSAF develop MAS. A critical question is why some neonates exposed to meconium develop this syndrome, and others do not. Attempts to prevent MAS with mechanical methods such as oropharyngeal, nasopharyngeal and tracheal suctioning and amnioinfusion have been attempted, but none have proven effective. Patients with MSAF are at increased risk for clinical chorioamnionitis, puerperal endometritis, neonatal sepsis, and intra-amniotic infection. Therefore, we conducted a series of studies to determine if MSAF was associated with the presence of bacteria in the amniotic fluid or bacterial products such as endotoxin. We found that 19% of patients with MSAF have microorganisms detected by culture, and there were frequently gram-negative bacteria. Endotoxin was detected in 46% of patients with MSAF, and these patients were also more likely to have intra-amniotic inflammation (an elevation in AF IL-6). In a separate study, we found that MSAF containing bacterial endotoxin also had a higher concentration of secreted phospholipase A2, an enzyme implicated in the pathogenesis of MAS. Studies are now in progress to determine if fetal systemic inflammation may be a predisposing factor for the development of MAS (5). The mainstay for the treatment of preterm labor remains arresting uterine contractility (tocolysis). We previously reported systematic reviews and meta-analyses of calcium-channel blockers for this indication. This year, we reported a systematic review and meta-analysis of transdermal nitroglycerin for the treatment of preterm labor. We found that, although transdermal nitroglycerin appears to be more effective than beta adrenergic receptor agonists, the current evidence does not support its routine use as a tocolytic agent for the treatment of preterm labor (6).
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