Predictive potential of various plasma inflammation-, angiogenesis-, and extracellular matrix remodeling-associated mediators for intra-amniotic inflammation and/or microbial invasion of the amniotic cavity in preterm labor.

PURPOSE: To determine whether various inflammatory-, angiogenic/anti-angiogenic-, and extracellular matrix remodeling-associated proteins in plasma, alone or in combination with conventional blood-based markers, can predict intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with spontaneous preterm labor (PTL). METHODS: A total of 193 singleton pregnant women with PTL (23-33 weeks) were included in this retrospective cohort study. Plasma samples were obtained at the time of amniocentesis. Amniotic fluid (AF) was cultured for microorganism detection and consequent MIAC diagnosis. IL-6 levels were determined in AF and used to identify IAI (AF IL-6 ≥ 2.6 ng/mL). Endostatin, haptoglobin, IGFBP-2/3, LBP, M-CSF, MMP-2/8, pentraxin 3, PlGF, S100A8/A9, and VEGFR-1 levels were assayed in plasma samples by ELISA. CRP levels and neutrophil-to-lymphocyte ratio (NLR) were measured. RESULTS: Plasma LBP, MMP-8, and S100A8/A9 levels, CRP levels, and NLR were significantly higher, and plasma IGFBP-2 and MMP-2 levels were significantly lower in women with IAI/MIAC than in those without this condition, whereas no baseline variables differed significantly between the two groups. Using a stepwise regression analysis, a noninvasive prediction model for IAI/MIAC was developed, which included plasma LBP, MMP-2, and MMP-8 levels (area under the curve [AUC], 0.785). The AUC for this prediction model was significantly or borderline greater than that of any single factor included in the model. CONCLUSIONS: IGFBP-2, LBP, MMP-2, MMP-8, and S100A8/A9 may represent valuable plasma biomarkers for predicting IAI/MIAC in women with PTL. Combination of LBP, MMP-2, and MMP-8 expression data can significantly improve the predictive potential for IAI/MIAC.

Vaginal microbiota in women with spontaneous preterm labor versus those with term labor in Kenya: a case control study.

BACKGROUND: Preterm birth is a global problem with about 12% of births in sub-Saharan Africa occurring before 37 weeks of gestation. Several studies have explored a potential association between vaginal microbiota and preterm birth, and some have found an association while others have not. We performed a study designed to determine whether there is an association with vaginal microbiota and/or placental microbiota and preterm birth in an African setting. METHODS: Women presenting to the study hospital in labor with a gestational age of 26 to 36 weeks plus six days were prospectively enrolled in a study of the microbiota in preterm labor along with controls matched for age and parity. A vaginal sample was collected at the time of presentation to the hospital in active labor. In addition, a placental sample was collected when available. Libraries were constructed using PCR primers to amplify the V6/V7/V8 variable regions of the 16S rRNA gene, followed by sequencing with an Illumina MiSeq machine and analysis using QIIME2 2022.2. RESULTS: Forty-nine women presenting with preterm labor and their controls were enrolled in the study of which 23 matched case-control pairs had sufficient sequence data for comparison. Lactobacillus was identified in all subjects, ranging in abundance from < 1% to > 99%, with Lactobacillus iners and Lactobacillus crispatus the most common species. Over half of the vaginal samples contained Gardnerella and/or Prevotella; both species were associated with preterm birth in previous studies. However, we found no significant difference in composition between mothers with preterm and those with full-term deliveries, with both groups showing roughly equal representation of different Lactobacillus species and dysbiosis-associated genera. Placental samples generally had poor DNA recovery, with a mix of probable sequencing artifacts, contamination, and bacteria acquired during passage through the birth canal. However, several placental samples showed strong evidence for the presence of Streptococcus species, which are known to infect the placenta. CONCLUSIONS: The current study showed no association of preterm birth with composition of the vaginal community. It does provide important information on the range of sequence types in African women and supports other data suggesting that women of African ancestry have an increased frequency of non-Lactobacillus types, but without evidence of associated adverse outcomes.

Whole-genome sequencing-based phylogeny, antibiotic resistance, and invasive phenotype of Escherichia coli strains colonizing the cervix of women in preterm labor.

BACKGROUND: Escherichia coli is a major neonatal pathogen and the leading cause of early-onset sepsis in preterm newborns. Maternal E. coli strains are transmitted to the newborn causing invasive neonatal disease. However, there is a lack of data regarding the phenotypic and genotypic characterization of E. coli strains colonizing pregnant women during labor. METHODS: This prospective study performed at the University of Oklahoma Medical Center (OUHSC) from March 2014 to December 2015, aimed to investigate the colonization rate, and the phylogeny, antibiotic resistance traits, and invasive properties of E. coli strains colonizing the cervix of fifty pregnant women diagnosed with preterm labor (PTL). Molecular analyses including bacterial whole-genome sequencing (WGS), were performed to examine phylogenetic relationships among the colonizing strains and compare them with WGS data of representative invasive neonatal E. coli isolates. Phenotypic and genotypic antibiotic resistance traits were investigated. The bacteria's ability to invade epithelial cells in vitro was determined. RESULTS: We recruited fifty women in PTL. Cervical samples yielded E. coli in 12 % (n=6). The mean gestational age was 32.5 (SD±3.19) weeks. None delivered an infant with E. coli disease. Phenotypic and genotypic antibiotic resistance testing did not overall demonstrate extensive drug resistance traits among the cervical E. coli isolates, however, one isolate was multi-drug resistant. The isolates belonged to five different phylogroups, and WGS analyses assigned each to individual multi-locus sequence types. Single nucleotide polymorphism-based comparisons of cervical E. coli strains with six representative neonatal E. coli bacteremia isolates demonstrated that only half of the cervical E. coli isolates were phylogenetically related to these neonatal invasive strains. Moreover, WGS comparisons showed that each cervical E. coli isolate had distinct genomic regions that were not shared with neonatal E. coli isolates. Cervical and neonatal E. coli isolates that were most closely related at the phylogenetic level had similar invasion capacity into intestinal epithelial cells. In contrast, phylogenetically dissimilar cervical E. coli strains were the least invasive among all isolates. CONCLUSIONS: This pilot study showed that a minority of women in PTL were colonized in the cervix with E. coli, and colonizing strains were not phylogenetically uniformly representative of E. coli strains that commonly cause invasive disease in newborns. Larger studies are needed to determine the molecular characteristics of E. coli strains colonizing pregnant women associated with an increased risk of neonatal septicemia.

Relationship between histologic chorioamnionitis and genital tract cultures in pre term labour.

The objective was to determine the relationship of histological chorioamnionitis (HCA) with genital tract cultures in preterm birth. Among two hundred women recruited for the study, 100 were taken as cases with gestational age between ≥28 and <37 weeks and 100 women with gestational age >37 weeks were taken as controls. Vaginal swabs were taken for culture sensitivity and vaginal smears were made for performing whiff test and heat dry gram stained smear was examined for growth of microorganisms. Histopathologic examination of the placenta was done after delivery. 49 cases and 26 controls had evidence of histological chorioamnionitis. A significant difference was observed in relation to the presence of E. coli, presence of clue cells, positive whiff test and occurrence of bacterial vaginosis in subjects with and without histological chorioamnionitis. Thus, we conclude that the presence of histological chorioamnionitis is closely related to the presence of pathogenic microorganisms in the cervicovaginal region.IMPACT STATEMENTWhat is already known on the subject? Histologic chorioamnionitis has been regarded to reflect amniotic fluid infection and there are studies showing an association between histologic chorioamnionitis, amniotic fluid, and subchorionic plate cultures. Nevertheless, studies of the correlation of the cervical swab cultures with intrauterine infection in preterm birth remain inconclusive.What do the results of this study add? Histologic chorioamnionitis is closely related to the presence of pathogenic microorganisms in the cervicovaginal region.What are the implications of these findings for clinical practice and/or further research? High vaginal swab cultures and gram staining of vaginal smear is useful in detecting antenatal patients who are at a higher risk for preterm labour. After detection, early intervention may be done to avoid preterm deliveries in these high-risk pregnancies.

Lactobacillus crispatus dominant vaginal microbita in pregnancy.

OBJECTIVE: To summarize current knowledge regarding Lactobacillus crispatus-dominated vaginal microbiota in pregnancy, as well as an association between the presence of Lactobacillus crispatus-dominated vaginal microbiota and pregnancy complications. DESIGN: Review. SETTING: Department of Obstetrics and Gynecology, University Hospital Hradec Kralove. MATERIAL AND METHODOLOGY: In this review, the results from literature available about the presence of L. crispatus-dominated microbiota in pregnancy are summarized. RESULTS: Pregnant women with Lactobacillus crispatus-dominated vaginal microbiota is very common in pregnancy and it is associated with a lower risk of preterm delivery. CONCLUSION: Lactobacillus crispatus-dominated vaginal microbiota represents an optimal vaginal microbiota in pregnancy.

Lactobacillus iners-dominated vaginal microbiota in pregnancy.

OBJECTIVE: To summarize current knowledge regarding Lactobacillus iners-dominated vaginal microbiota in pregnancy, as well as an association between the presence of Lactobacillus iners and pregnancy complications Type of study: Review. SETTING: Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove. METHODS AND RESULTS: In this review, the results from literature available about the presence of L. iners-dominated microbiota in pregnancy and the association between the presence of L. iners-dominated microbiota and abortion, spontaneous preterm delivery with intact membranes, and preterm prelabor rupture of membranes are summarized. CONCLUSION: L. iners-dominated vaginal microbiota appears to be associated with an increased risk of the development of specific pregnancies pathologies.

Detection of urinary Chlamydia trachomatis, Mycoplasma genitalium and human papilloma virus in the first trimester of pregnancy by PCR method.

BACKGROUND: Miscarriage and preterm delivery are the most important challenges of pregnancy. Different bacterial and viral infection may cause miscarriage and preterm delivery. Among bacterial factors, Mycoplasma genitalium and Chlamydia trachomatis have the most important role and human papilloma virus (HPV) is the leading viral factor in this regard. METHODS: First void urine samples were collected from 119 pregnant women who visited health centers for routine first-trimester screening (12-14 weeks gestation). About 10 ml of the sample was centrifuged at 3000×g for 20 min and 1-2 ml of the sediment was transferred to sterile microfuges and stored at - 20 °C until analysis. DNA extraction was conducted using A101211 kits imported by Pars Tous Biotechnology Company. The following commercial kits, imported by Pars Tous Biotechnology, were used for PCR. RESULTS: There is no significant association between urinary isolation of C. trachomatis and miscarriage (P = 0.93) and there is no significant association between urinary isolation of M. genitalium and miscarriage (P = 0.80). Regarding HPV, since all urine samples were PCR-negative, comparison was not possible. C. trachomatis was isolated from the urine samples of 6.72% of the pregnant women who underwent first-trimester screening in health centers using PCR. Previous studies reported a mean chlamydia isolation rate of 3% from urine specimens collected from pregnant women in general. T test showed no significant difference between the two groups (P = 0.10). Based on present study the mycoplasma isolation rate was 17.65% using PCR. Previous studies reported a mean mycoplasma isolation rate of 10% from urine specimens collected from pregnant women in general. T-test showed a significant difference between the two groups (P = 0.03). DISCUSSION: First void urine samples in pregnant women may be an appropriate sample for detection of C. trachomatis and M. genitalium; however, it is not a good method for HPV isolation therefore vaginal or cervical discharge specimens should be used instead for detection of HPV.

Plasma inflammatory and immune proteins as predictors of intra-amniotic infection and spontaneous preterm delivery in women with preterm labor: a retrospective study.

BACKGROUND: We investigated whether various inflammatory and immune proteins in plasma predict intra-amniotic infection and imminent preterm delivery in women with preterm labor and compared their predictive ability with that of amniotic fluid (AF) interleukin (IL)-6 and serum C-reactive protein (CRP). METHODS: This retrospective cohort study included 173 consecutive women with preterm labor who underwent amniocentesis for diagnosis of infection and/or inflammation in the AF. The AF was cultured, and assayed for IL-6. CRP levels and cervical length by transvaginal ultrasound were measured at the time of amniocentesis. The stored maternal plasma was assayed for IL-6, matrix metalloproteinase (MMP)-9, and complements C3a and C5a using ELISA kits. The primary and secondary outcome criteria were positive AF cultures and spontaneous preterm delivery (SPTD) within 48 h, respectively. Univariate, multivariate, and receiver operating characteristic analysis were used for the statistical analysis. RESULTS: In bivariate analyses, elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery, whereas elevated plasma levels of MMP-9, C3a, and C5a were not associated with these two outcomes. On multivariate analyses, an elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery after adjusting for confounders, including high serum CRP levels and short cervical length. In predicting intra-amniotic infection, the area under the curve (AUC) was significantly lower for plasma IL-6 than for AF IL-6 but was similar to that for serum CRP. Differences in the AUCs between plasma IL-6, AF IL-6, and serum CRP were not statistically significant in predicting imminent preterm delivery. CONCLUSIONS: Maternal plasma IL-6 independently predicts intra-amniotic infection in women with preterm labor; however, it has worse diagnostic performance than that of AF IL-6 and similar performance to that of serum CRP. To predict imminent preterm delivery, plasma IL-6 had an overall diagnostic performance similar to that of AF IL-6 and serum CRP. Plasma MMP-9, C3a, and C5a levels could not predict intra-amniotic infection or imminent preterm delivery.

Microbial invasion of the amniotic cavity in midtrimester pregnancies using molecular microbiology.

OBJECTIVE: The objective of the study was to determine the frequency of microbial invasion of the amniotic cavity in the midtrimester of pregnancy in patients undergoing amniocentesis for clinical indications. STUDY DESIGN: This was a prospective investigation of the amniotic fluid of 344 asymptomatic women recruited in midpregnancy for the presence of microbial DNA. Amniotic samples obtained at the time of amniocentesis for genetic testing on women between 15 and 22 weeks of gestation were tested specifically for the presence of Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, and Mycoplasma genitalium as well as for other bacteria and fungi using broad-range polymerase chain reaction only. Pregnancy outcomes were reviewed independent of all molecular test results. RESULTS: Using broad-range polymerase chain reaction, the prevalence of microbial invasion of the amniotic cavity in women between 15 and 22 weeks of gestation was 0% (0 vs 344). Early preterm delivery occurred in only 4 women (1%); 1 delivered electively and 3 spontaneously. None were associated with Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, or Mycoplasma genitalium. In addition, broad range polymerase chain reaction did not reveal the presence of other bacterial or fungal microbes. CONCLUSION: Microbial invasion of the amniotic cavity in midtrimester gestations of low-risk pregnant women was not detected using molecular methods in 344 patients.

Candida Chorioamnionitis Leads to Preterm Birth and Adverse Fetal-Neonatal Outcome.

Candida chorioamnionitis is rare but can lead to neonatal infection, high mortality, and neurodevelopmental impairment. We aimed to investigate maternal clinical features and perinatal outcomes and discuss future management strategies. We reviewed the medical records of women with Candida chorioamnionitis at our hospital over a 10-year period (n = 9) and previous published case reports and case series. The most prevalent Candida species was C. albicans (71.3% of the all cases). The most prevalent predisposing condition was preterm premature rupture of membranes (31/123, 25.2%), followed by pregnancy with a retained intrauterine contraceptive device (26/123, 21.1%) and pregnancy after in vitro fertilization (25/123, 20.3%). Preterm labor was the most common symptom (52/123, 42.3%), and only 13% of cases involved fever. Of the infants, 27% of the singletons and 23.8% of the twins were born before 22 gestational weeks, while 60% of the singletons and 76.2% of the twins were born at 22-36 weeks. The median birth weight of the babies born after 22 weeks was 1230 g. The mortality rates of the singletons and twins born after 22 weeks of gestation in the year 2000 or later were 28.6% and 52.4%, respectively. Antenatal treatment for Candida chorioamnionitis has not been established.

The prevalence of abnormal vaginal flora and predictive factors for intrauterine infection in pregnant Korean women with preterm labor.

OBJECTIVE: To investigate the prevalence of abnormal vaginal flora (AVF) and predictive factors for intrauterine infection in pregnant Korean women with preterm labor. MATERIALS AND METHODS: The authors reviewed the medical records of 106 pregnant Korean women with preterm labor admitted to Eulji Medical Center between January 2006 and August 2011. The results of vaginal discharge tests and maternal serum C-reactive protein (CRP) level at admission, placental biopsy, and perinatal outcomes were searched. The prevalence of abnormal vaginal flora was calculated. The perinatal outcomes and predictive factors for intrauterine infections were analyzed based on placental pathology and early-onset neonatal sepsis. RESULTS: The prevalence of abnormal vaginal flora was 75.4%. Ureaplasma urealyticunz (UU), intermediate flora, Candidiasis, bacterial vaginosis, and aerobic bacterial colonization were detected in 40.6%, 38.7%, 17%, 14.2%, and 11.3% of the women, respectively. The frequency of early-onset neonatal sepsis was significantly different between women with aerobic bacterial colonization and those with normal flora (p = 0.008). An elevated maternal serum CRP level was an independent intrauterine infection predictor (odds ratio, 1.918; 95% confidence interval, 1.102-3.338; p = 0.048). CONCLUSION: Aerobic bacterial colonization may predict early-onset neonatal sepsis. An elevated maternal serum CRP level was an independent intrauterine infection predictor based on placental infections and early-onset neonatal sepsis.

The state of immunity in pregnancies complicated by intrauterine infection of the fetus.

OBJECTIVES: To study the state of immunity in pregnancies associated with urogenital infection and complicated by intrauterine infection. MATERIAL AND METHODS: The comparative study involved the examination of 250 pregnant women with urogenital infection and ultrasonographic signs of intrauterine infection and their newborns in order to assess the state of cellular and humoral immunity components and nonspecific resistance. A direct prospective examination of pregnant women was carried out in the 2nd and 3rd trimesters of gestation. Depending on the outcome of each pregnancy on the basis of the follow-up of newborns, performed on the first day after birth, the patients were retrospectively divided into two groups. The study group included 93 (37.2%) pregnant women who developed intrauterine infection. The comparison group (n=157 (62.8%)) comprised pregnant-carriers of perinatally significant infection who gave birth to conditionally healthy children. The control group consisted of 50 healthy women with a physiological pregnancy. RESULTS: In the gestation period under investigation, the development of intrauterine infection in pregnant women with urogenital infections was found to be associated with a deficiency of T-helpers / inducers, an increase in thymus-dependent lymphocyte killer activity, a high content of IL-1ß, TNF-α in the systemic circulation, and a decrease in the level of IL-10 secondary to the oppression of the effector link of phagocytic neutrophils of peripheral blood. CONCLUSIONS: An increased concentration of systemic proinflammatory cytokines IL-1ß, IL-6 and TNFα with a simultaneous decrease in the IL-10 content and suppression of the killing activity of peripheral blood phagocytes reflects the presence of an active inflammatory process in the mother-placenta-fetus system and can be one of the factors affecting the development of intrauterine infection in pregnancy, complicated by urogenital infection.

Maternal and fetal roles in bacterially induced preterm labor in the mouse.

BACKGROUND: The relative roles of the mother and fetus in signaling for labor remain poorly understood. OBJECTIVE: We previously demonstrated using gene knockout (KO) mice that Escherichia coli-induced preterm delivery is completely dependent on MyD88, a toll-like receptor adaptor protein. Here we leveraged this finding to conduct a genetic experiment testing whether the mother, the fetus, or both signal for parturition in bacterially induced labor. STUDY DESIGN: Six different maternal/fetal genotype combinations for MyD88 were studied: wild-type (WT) dams carrying one of the following: (1) WT or (2) MyD88 heterozygous (het) fetuses (generated by mating WT females with WT or MyD88-knockout [KO] males, respectively); (3) WT dams carrying MyD88-KO fetuses (generated by replacing the ovaries of WT females with MyD88-KO ovaries, followed by mating with MyD88-KO males); a similar strategy was used to generate MyD88-KO dams carrying (4) MyD88-KO, (5) MyD88 het, or (6) WT fetuses. On day 14.5 of gestation, mice received intrauterine injections of either 1 × 10(9) killed E coli or sterile medium. Delivery of ≥ 1 fetus within 48 hours was considered preterm. A separate group of similarly treated pregnant mice was euthanized 5 hours after surgery for gene expression and tissue analysis. RESULTS: E coli-induced preterm delivery is dependent on maternal and not fetal genotype: > 95% of WT and < 5% of MyD88-KO dams deliver prematurely, regardless of fetal genotype (P = .0001). In contrast, fetal survival in utero is influenced by fetal genotype: in MyD88-KO dams, in which premature birth rarely occurs, only 81% of WT and 86% of MyD88-heterozygous fetuses were alive 48 hours after surgery compared with 100% of MyD88-KO fetuses (P < .01). Messenger ribonucleic acids for the inflammatory mediators interleukin-1ß, tumor necrosis factor, interleukin-6, and cyclooxygenase-2 were elevated in uterine tissues only in WT mothers treated with E coli and were low or undetectable in the uteri of KO mothers or in animals treated with saline. Serum progesterone levels were lower in KO mothers with WT ovaries than in WT mothers with KO ovaries, but bacterial exposure did not have an impact on these levels. CONCLUSION: In the murine E coli-induced labor model, preterm delivery and uterine expression of inflammatory mediators is determined by the mother and not the fetus and is not attributable to a decline in serum progesterone.

Benefits and harms of screening for and treatment of asymptomatic bacteriuria in pregnancy: a systematic review.

BACKGROUND: Most European and North American clinical practice guidelines recommend screening for asymptomatic bacteriuria (ASB) as a routine pregnancy test. Antibiotic treatment of ASB in pregnant women is supposed to reduce maternal upper urinary tract infections (upper UTIs) and preterm labour. However, most studies supporting the treatment of ASB were conducted in the 1950s to 1980s. Because of subsequent changes in treatment options for ASB and UTI, the applicability of findings from these studies has come into question. Our systematic review had three objectives: firstly, to assess the patient-relevant benefits and harms of screening for ASB versus no screening; secondly, to compare the benefits and harms of different screening strategies; and thirdly, in case no reliable evidence on the overarching screening question was identified, to determine the benefits and harms of treatment of ASB. METHODS: We systematically searched several bibliographic databases, trial registries, and other sources (up to 02/2016) for randomised controlled trials (RCTs) and prospective non-randomised trials. Two authors independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. As meta-analyses were not possible, we summarised the results qualitatively. RESULTS: We did not identify any eligible studies that investigated the benefits and harms of screening for ASB versus no screening or that compared different screening strategies. We identified four RCTs comparing antibiotics with no treatment or placebo in 454 pregnant women with ASB. The results of 2 studies published in the 1960s showed a statistically significant reduction in rates of pyelonephritis (odds ratio [OR] = 0.21, 95 % confidence interval [CI] 0.07-0.59) and lower UTI (OR = 0.10, 95 % CI 0.03-0.35) in women treated with antibiotics. By contrast, event rates reported by a recent study were not statistically significantly different, neither regarding pyelonephritis (0 % vs. 2.2 %; OR = 0.37, CI 0.01-9.25, p = 0.515) nor regarding lower UTI during pregnancy (10 % vs. 18 %; Peto odds ratio [POR] = 0.53, CI 0.16-1.79, p = 0.357). Data were insufficient to determine the risk of harms. As three of the four studies were conducted several decades ago and have serious methodological shortcomings, the applicability of their findings to current health care settings is likely to be low. The recent high-quality RCT was stopped early due to a very low number of primary outcome events, a composite of preterm delivery and pyelonephritis. Therefore, the results did not show a benefit of treating ASB. CONCLUSIONS: To date, no reliable evidence supports routine screening for ASB in pregnant women.

Preterm labor and neonatal sepsis caused by intrauterine Helicobacter cinaedi infection.

Helicobacter cinaedi is a rare pathogen but known to cause bacteremia, cellulitis and enterocolitis. Recently, cases of involving various organs are increasingly reported such as endocarditis, meningitis, and kidney cyst infection. We report a case of intrauterine H. cinaedi infection leading preterm birth and neonatal sepsis. A 29-year-old pregnant women who was no underlying disease hospitalized due to threatened preterm labor at 22 weeks of gestation. Clinical findings showed uterine tenderness, fever, leukocytosis and elevated C-reactive protein. H. cinaedi was isolated from amniotic fluid obtained by transabdominal amniocentesis. We diagnosed as intrauterine H. cinaedi infection and administered intravenous ampicillin followed by oxytocin to terminate pregnancy. A live 446 g male infant was delivered. The patient was no signs of infection throughout postpartum course and discharged on post-delivery day 5. The neonate was admitted in neonatal intensive care unit and administered ampicillin and amikacin. H. cinaedi was isolated from umbilical cord blood culture. He has no signs of infection on day 5 but died from uncontrollable hyperglycemia and ketoacidosis on 15 days of age. H. cinaedi can cause intrauterine infection during pregnancy and lead preterm labor and neonatal sepsis.

[The relationship between group B streptococcus genital infection and premature rupture of membrane].

OBJECTIVE: To investigate the relationship between the group B streptococcal (GBS) genital infection of the pregnant women and premature rupture of membrane (PROM). METHODS: Five hundred and eighty seven cases in our hospital maternity clinic or hospital delivery of pregnant women were enrolled from October 2014 to December 2014, including 189 cases of pregnant women with PROM as the observation group and 398 cases of pregnant women without PROM as a control group.GBS in their rectum and vagina secretion was separated and tested by using Group B Streptococcus Chromogenic Agar. RESULTS: Fifty eight cases were detected GBS positive in all 587 pregnant women.The positive rate was 9.9%.In 189 cases of PROM, 37 cases were GBS positive and the positive rate was 19.6%.While in 398 cases of normal pregnant women, 21 cases were positive and the positive rate was 5.3%.The difference has statistically significant (P<0.01). CONCLUSION: GBS infection may be a risk factor for the occurrence of PROM.Psychological counseling, health education and antibiotics should be applied to the GBS positive pregnant women as a preventive strategy.

Depletion of polymorphonuclear leukocytes has no effect on preterm delivery in a mouse model of Escherichia coli-induced labor.

OBJECTIVE: The objective of the study was to investigate the role of polymorphonuclear leukocytes (PMNs) in a mouse model of Escherichia coli-induced labor. STUDY DESIGN: Intraperitoneal injection of rabbit antimouse PMN antiserum or control was performed in CD-1 mice 29 hours and 5 hours prior to laparotomy and intrauterine injection of either killed E coli or phosphate-buffered saline on day 14.5 of pregnancy. Preterm delivery was defined as delivery of at least 1 pup within 48 hours. Circulating leukocyte counts were determined manually or by flow cytometry at the time of surgery and 8, 24, and 48 hours afterward. Maternal and fetal tissues were analyzed in a separate group of animals 8 hours after surgery. RESULTS: Pretreatment with anti-PMN antiserum significantly decreased the numbers of circulating leukocytes and the proportion of neutrophils among all leukocytes by 70-80% at surgery and at least 8 hours thereafter. Neutrophil depletion significantly reduced 2 markers of neutrophil activation in the uterus and placenta (neutrophil elastase and myeloperoxidase activity) and neutrophil infiltration into gestational tissues in bacterially treated animals to baseline (control) levels but did not affect preterm birth rates. The large E coli-induced increases in uterine inflammatory markers (interleukin-1ß, tumor necrosis factor, chemokine ligand-5, cyclooxygenase-2) were not affected or were only minimally affected by neutrophil depletion. CONCLUSION: Although PMN antiserum reduces both neutrophil number and activity, it does not diminish sensitivity to bacterially induced delivery or meaningfully alter the expression of inflammatory markers in the mouse model. Preterm birth and inflammation in this model are not likely to depend on neutrophil function.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Regulation of apoptosis and innate immune stimuli in inflammation-induced preterm labor.

An innate immune response is required for successful implantation and placentation. This is regulated, in part, by the a2 isoform of V-ATPase (a2V) and the concurrent infiltration of M1 (inflammatory) and M2 (anti-inflammatory) macrophages to the uterus and placenta. The objective of the present study was to identify the role of a2V during inflammation-induced preterm labor in mice and its relationship to the regulation of apoptosis and innate immune responses. Using a mouse model of infection-induced preterm delivery, gestational tissues were collected 8 h after intrauterine inoculation on day 14.5 of pregnancy with either saline or peptidoglycan (PGN; a TLR 2 agonist) and polyinosinic-polycytidylic acid [poly(I:C); a TLR3 agonist], modeling Gram-positive bacterial and viral infections, respectively. Expression of a2V decreased significantly in the placenta, uterus, and fetal membranes during PGN+poly(I:C)-induced preterm labor. Expression of inducible NO synthase was significantly upregulated in PGN+poly(I:C)-treated placenta and uterus. PGN+poly(I:C) treatment disturbed adherens junction proteins and increased apoptotic cell death via an extrinsic pathway of apoptosis among uterine decidual cells and spongiotrophoblasts. F4/80(+) macrophages were increased and polarization was skewed in PGN+poly(I:C)-treated uterus toward double-positive CD11c(+) (M1) and CD206(+) (M2) cells, which are critical for the clearance of dying cells and rapid resolution of inflammation. Expression of Nlrp3 and activation of caspase-1 were increased in PGN+poly(I:C)-treated uterus, which could induce pyroptosis. These results suggest that the double hit of PGN+poly(I:C) induces preterm labor via reduction of a2V expression and simultaneous activation of apoptosis and inflammatory processes.

Screening for Chlamydia and Gonorrhea Cervicitis and Implications for Pregnancy Outcome. Are We Testing and Treating at the Right Time?

OBJECTIVE: To evaluate the effect of gonorrheal and chlamydial cervicitis (GCC) on the risk of preterm labor (PTL) and preterm premature rupture of membranes (PPROM). STUDY DESIGN: A large cross-sectional sample of patients (N = 1,120) was studied. Data on samples for GCC and pregnancy outcome were entered into a database from a retrospective chart review. RESULTS: There were 1,120 pregnancies with adequate data for analysis. Of those pregnancies 933 were unaffected by GCC, and 187 were affected. The rates of preterm delivery were 17.79% and 16.58% for GCC-negative and GCC-positive pregnancies, respectively. PPROM occurred in 3.97% and 2.67% of GCC-negative and GCC-positive pregnancies, respectively. PTL occurred in 8.25% and 8.02% of GCC-negative and GCC-positive pregnancies, respectively. No outcomes met statistical significance. When pregnancy outcomes were analyzed by trimester of infection, there was a higher risk of preterm delivery but not preterm labor with earlier infection. This did meet statistical significance. There was a trend towards lower rate of cesarean section in the infected group of patients, which did not meet statistical significance. CONCLUSION: Maternal infection with gonorrhea and/or chlamydia is not associated with PPROM or PTL.