Does vaginal bacterial colonization contribute to preterm birth in women with asymptomatic shortened cervix?

PURPOSE: The aim of this study is to describe the typical microbial spectrum and the influence of distinct vaginal infections on preterm birth in pregnancies affected by cervical incompetence. METHODS: 327 patients were admitted because of asymptomatic shortening of the cervix in the second and third trimester of pregnancy. Clinical data such as age, cervical length, gestational age at admission and at delivery and vaginal microbiologic findings were collected and analyzed. RESULTS: The spectrum of germs in the vagina revealed seven different distinct species; the most common bacteria were Ureaplasma spp. and E. coli. In 327 included patients, 217 revealed a bacterial colonization, 110 did not. Most common bacteria in women with preterm birth before 34 weeks were Ureaplasma spp., while E. coli was most common in women undergoing preterm birth after 34 weeks. Nevertheless, the rates of occurrence of these bacterial taxa were not significantly different between who underwent preterm birth to those who did not. CONCLUSIONS: This study gives an overview over the vaginal bacterial colonization in pregnant women with cervical incompetence. The clinical relevance of vaginal bacterial colonization remains unclear.

Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.

BACKGROUND: Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome. OBJECTIVE: To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation. STUDY DESIGN: The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm3) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation. RESULTS: Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases. CONCLUSION: In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.

Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage.

OBJECTIVE: To investigate the relation between vaginal microbiota composition and outcome of rescue cervical cerclage. DESIGN: Prospective observational study. SETTING: Queen Charlotte's and Chelsea Hospital, London. POPULATION: Twenty singleton pregnancies undergoing a rescue cervical cerclage. METHODS: Vaginal microbiota composition was analysed in women presenting with a dilated cervix and exposed fetal membranes before and 10 days following rescue cervical cerclage and was correlated with clinical outcomes. MAIN OUTCOME MEASURES: Composition of vaginal bacteria was characterised by culture-independent next generation sequencing. Successful cerclage was defined as that resulting in the birth of a neonate discharged from hospital without morbidity. Unsuccessful cerclage was defined as procedures culminating in miscarriage, intrauterine death, neonatal death or significant neonatal morbidity. RESULTS: Reduced Lactobacillus spp. relative abundance was observed in 40% of cases prior to rescue cerclage compared with 10% of gestation age-matched controls (8/20, 40% versus 3/30, 10%, P = 0.017). Gardnerella vaginalis was over-represented in women presenting with symptoms (3/7, 43% versus 0/13, 0%, P = 0.03, linear discriminant analysis, LDA (log 10) and cases culminating in miscarriage (3/6, 50% versus 0/14, 0%, P = 0.017). In the majority of cases (10/14, 71%) bacterial composition was unchanged following cerclage insertion and perioperative interventions. CONCLUSIONS: Reduced relative abundance of Lactobacillus spp. is associated with premature cervical dilation, whereas high levels of G. vaginalis are associated with unsuccessful rescue cerclage cases. The insertion of a rescue cerclage does not affect the underlying bacterial composition in the majority of cases. TWEETABLE ABSTRACT: Preterm cervical dilatation associates with reduced Lactobacillus spp. Presence of Gardnerella vaginalis predicts rescue cerclage failure.

Amniotic fluid sludge as a marker of intra-amniotic infection and histological chorioamnionitis in cervical insufficiency: a report of four cases and literature review.

Amniotic fluid sludge (AFS) is defined as the presence of particulate matter in the amniotic fluid in close proximity to the cervix. Although its prevalence is known to correlate with the risk of preterm delivery, initial reports describe a strong association between AFS and microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis. However, AFS is also present in uncomplicated pregnancies, and its prevalence appears to increase with gestational age. Recent evidence debates the usefulness of AFS as a marker of early preterm delivery risk. We present four cases with AFS diagnosed by transvaginal ultrasound at admission for cervical insufficiency between 20 and 24 weeks of gestation, with confirmed lower genital tract and intra-amniotic infections by amniocentesis and histological chorioamnionitis and funisitis. Our findings reinforce the presence of AFS as a useful marker of MIAC, chorioamnionitis and funisitis that increase the likelihood of preterm delivery at an extreme gestational age.

Detection of ureaplasmas by the polymerase chain reaction in the amniotic fluid of patients with cervical insufficiency.

AIMS: The purpose of this study was to determine the clinical significance of detecting microbial footprints of ureaplasmas in amniotic fluid (AF) using specific primers for the polymerase chain reaction (PCR) in patients presenting with cervical insufficiency. METHODS: Amniocentesis was performed in 58 patients with acute cervical insufficiency (cervical dilatation, > or =1.5 cm) and intact membranes, and without regular contractions (gestational age, 16-29 weeks). AF was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) were detected by PCR using specific primers. Patients were divided into three groups according to the results of AF culture and PCR for ureaplasmas: those with a negative AF culture and a negative PCR (n=44), those with a negative AF culture and a positive PCR (n=10), and those with a positive AF culture regardless of PCR result (n=4). RESULTS: 1) Ureaplasmas were detected by PCR in 19.0% (11/58) of patients, by culture in 5.2% (3/58), and by culture and/or PCR in 22.4% (13/58); 2) Among the 11 patients with a positive PCR for ureaplasmas, the AF culture was negative in 91% (10/11); 3) Patients with a negative AF culture and a positive PCR for ureaplasmas had a significantly higher median AF matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count than those with a negative AF culture and a negative PCR (P<0.001 and P<0.05, respectively); 4) Patients with a positive PCR for ureaplasmas but a negative AF culture had a higher rate of spontaneous preterm birth within two weeks of amniocentesis than those with a negative AF culture and a negative PCR (P<0.05 after adjusting for gestational age at amnio-centesis); 5) Of the patients who delivered within two weeks of amniocentesis, those with a positive PCR for ureaplasmas and a negative AF culture had higher rates of histologic amnionitis and funisitis than those with a negative AF culture and a negative PCR (P<0.05 after adjusting for gestational age at amniocentesis, for each); 6) However, no significant differences in the intensity of the intra-amniotic inflammatory response and perinatal outcome were found between patients with a positive AF culture and those with a negative AF culture and a positive PCR. CONCLUSIONS: 1) Cultivation techniques for ureaplasmas did not detect most cases of intra-amniotic infection caused by these microorganisms (91% of cases with cervical insufficiency and microbial footprints for ureaplasmas in the amniotic cavity had a negative AF culture); 2) Patients with a negative AF culture and a positive PCR assay were at risk for intra-amniotic and fetal inflammation as well as spontaneous preterm birth.

The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency.

OBJECTIVE: The purpose of this study was to determine the frequency and clinical significance of intraamniotic inflammation in patients with acute cervical insufficiency. STUDY DESIGN: Amniocentesis was performed in 52 patients with acute cervical insufficiency (cervical dilation, > or =1.5 cm) and intact membranes and without regular uterine contractions (gestational age, 17-29 weeks). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8. Intraamniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 concentration (>23 ng/mL). Nonparametric statistics and survival techniques were used for analysis. RESULTS: The prevalence of intraamniotic inflammation was 81% (42/52); the prevalence of a positive AF culture was 8% (4/52). Intraamniotic inflammation was present in all cases with a positive AF culture. Preterm delivery within 7 days occurred in 50% of cases (19/38), and delivery before 34 weeks of gestation occurred in 84% of cases (32/38) with intraamniotic inflammation but without AF infection. Fifty-five percent of newborn infants (21/38) who were born to mothers with intraamniotic inflammation but without AF infection died immediately after birth (<1 day). The amniocentesis-to-delivery interval was shorter in patients with intraamniotic inflammation than in those without inflammation (P < .05). There were no differences in the interval-to-delivery or the rate of adverse outcome between patients with intraamniotic inflammation and a negative culture and patients with proven AF infection. CONCLUSION: Intraamniotic inflammation, regardless of AF culture result, is present in approximately 80% of patients with acute cervical insufficiency and is a risk factor for impending preterm delivery and adverse outcomes.

Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance.

OBJECTIVE: The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity in patients presenting with cervical dilatation in the midtrimester of pregnancy. STUDY DESIGN: Amniocentesis for microbial studies was performed in women admitted with cervical dilatation > or = 2 cm, intact membranes, and without active labor between 14 and 24 weeks of gestation. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Gram stain was performed on all samples. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 51.5% (17/33). The most common microbial isolates were Ureaplasma urealyticum, Gardnerella vaginalis, Candida albicans, and Fusobacterium sp. All patients with microbial invasion of the amniotic cavity had complications. Patients who underwent cervical cerclage in the presence of a positive amniotic fluid culture had rupture of membranes, clinical chorioamnionitis, or pregnancy loss. On the other hand, the prognosis of patients with a negative amniotic fluid culture was better than that of patients with a positive culture. Of 16 patients with a negative amniotic culture, nine were delivered at > 34 weeks. CONCLUSIONS: (1) Microbial invasion of the amniotic cavity occurs frequently in women presenting with cervical dilatation in the midtrimester; (2) the microbiologic state of the amniotic cavity is an important prognostic factor for pregnancy outcome; (3) amniocentesis to determine the microbiologic characteristics of the amniotic cavity should be considered before a cerclage is placed in women presenting with cervical dilatation in the midtrimester.

[Bacteriological analysis of the cervical canal in uterine cervix insufficiency]. / Bakterioloska analiza cervikalnog kanala kod insuficijencije grla maternice.

A bacteriological analysis was made of pyogenic agents from the cervical canal of 260 pregnant women with cervical incompetency, in whom the cerclage of the cervix was performed. Pyogenic agents were found in 139 (53.5%) pregnancies. The most frequently isolated pathogenic agent was Enterococcus--in 19.2% of all pregnant women and in 36.0% in those with a pathologic swab. E. coli was isolated in 16.5% of all pregnant women and in 30.9% of those with the pathologic swab. A significantly higher number of pathologic swabs were found in women with colpitis and the cleanliness 3 degree of the vaginal discharge and without colpitis (6.4%). In pregnant women with a pathologic swab, in spite of the cervical cerclage, spontaneous abortions and premature deliveries were significantly more frequent (8.2% and 16.4% respectively) than in pregnant women with a sterile swab (1.8% and 6.1% respectively).

[Effect of atypical pathogen colonization on cervical priming in cervix insufficiency]. / Einfluss auf das cervikale Priming durch atypische Keimbesiedlung bei der Cervixinsuffizienz.

In a prospective study the cervical bacterial flora of pregnant women with insufficiency of the cervix is compared with the flora of asymptomatic pregnant women. It could be demonstrated, that in case of insufficiency of the cervix a different bacterial flora is found: in addition to the incidence of pathological bacterial groups, a shift of the physiological flora with Doederlein's bacilli to a mixed flora is observed. New findings in the cervical priming lead to the idea, that an atypical cervical flora could influence the cervical priming. The changing of the cervical environment is able to induce an increased production of prostaglandins with cervical dilatation of its structure. Regarding the different cervical flora in case of cervical insufficiency, the importance of the circular suture in the prophylactic management of premature delivery will be discussed. The results lead to the necessity of precise vaginal check-up and therapy of genital infections during pregnancy.

[Changes in the vaginal flora caused by supporting pessary treatment in pregnancy]. / Untersuchungen über Veränderungen der Vaginalflora bei Stützpessarbehandlung in der Schwangerschaft.

200 pregnant women with supporting pessary treatment because of cervical insufficiency were compared with one of normal pregnancies concerning microbiological findings and puerperal morbidity. -- 5,5% of the women in the supporting pessary group had pathogenic organisms in their cervix before first amnioscopy, compared to 2% in the control group. The different results of cultural microbiologic examinations in both groups depend on type and duration of birth as well as time of amnion rupture. Women with premature rupture of the membranes (31,0%) had more pathogenic organisms than women with rupture (2,5%) in time. There was no higher infection morbidity compared to the control group.