Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.

Background. It is widely assumed that the uterine cavity in non-pregnant women is physiologically sterile, also as a premise to the long-held view that human infants develop in a sterile uterine environment, though likely reflecting under-appraisal of the extent of the human bacterial metacommunity. In an exploratory study, we aimed to investigate the putative presence of a uterine microbiome in a selected series of non-pregnant women through deep sequencing of the V1-2 hypervariable region of the 16S ribosomal RNA (rRNA) gene.

Methods. Nineteen women with various reproductive conditions, including subfertility, scheduled for hysteroscopy and not showing uterine anomalies were recruited. Subjects were highly diverse with regard to demographic and medical history and included nulliparous and parous women. Endometrial tissue and mucus harvesting was performed by use of a transcervical device designed to obtain endometrial biopsy, while avoiding cervicovaginal contamination. Bacteria were targeted by use of a barcoded Illumina MiSeq paired-end sequencing method targeting the 16S rRNA gene V1-2 region, yielding an average of 41,194 reads per sample after quality filtering. Taxonomic annotation was pursued by comparison with sequences available through the Ribosomal Database Project and the NCBI database.

Results. Out of 183 unique 16S rRNA gene amplicon sequences, 15 phylotypes were present in all samples. In some 90% of the women included, community architecture was fairly similar inasmuch B. xylanisolvens, B. thetaiotaomicron, B. fragilis and an undetermined Pelomonas taxon constituted over one third of the endometrial bacterial community. On the singular phylotype level, six women showed predominance of L. crispatus or L. iners in the presence of the Bacteroides core. Two endometrial communities were highly dissimilar, largely lacking the Bacteroides core, one dominated by L. crispatus and another consisting of a highly diverse community, including Prevotella spp., Atopobium vaginae, and Mobiluncus curtisii.

Discussion. Our findings are, albeit not necessarily generalizable, consistent with the presence of a unique microbiota dominated by Bacteroides residing on the endometrium of the human non-pregnant uterus. The transcervical sampling approach may be influenced to an unknown extent by endocervical microbiota, which remain uncharacterised, and therefore warrants further validation. Nonetheless, consistent with our understanding of the human microbiome, the uterine microbiota are likely to have a previously unrecognized role in uterine physiology and human reproduction. Further study is therefore warranted to document community ecology and dynamics of the uterine microbiota, as well as the role of the uterine microbiome in health and disease.

Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene.

Uterine microbiota have been reported under various conditions and populations; however, it is uncertain the level to which these bacteria are residents that maintain homeostasis, tourists that are readily eliminated or invaders that contribute to human disease. This review provides a historical timeline and summarizes the current status of this topic with the aim of promoting research priorities and discussion on this controversial topic. Discrepancies exist in current reports of uterine microbiota and are critically reviewed and examined. Established and putative routes of bacterial seeding of the human uterus and interactions with distal mucosal sites are discussed. Based upon the current literature, we highlight the need for additional robust clinical and translational studies in this area. In addition, we discuss the necessity for investigating host-microbiota interactions and the physiologic and functional impact of these microbiota on the local endometrial microenvironment as these mechanisms may influence poor reproductive, obstetric, and gynecologic health outcomes and sequelae.

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Uterine Microbiota: Residents, Tourists, or Invaders?

Objective: To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix.Methods: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) ≤25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations.Results: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic in...

https://www.tandfonline.com/doi/pdf/10.3109/14767058.2014.954243

Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance.

Aim Chronic endometritis (CE) is a disease of continuous and subtle inflammation characterized by the infiltration of plasma cells in the endometrial stromal area. Although the clinical significance of CE has been thought in clinical practice for a long time because it is either asymptomatic or presents with subtle symptoms, recent studies have shown the potential adverse effects of CE on fertility. In the present review, we focus on the concept, diagnosis, etiology, pathophysiology, diagnosis, impact on reproduction and treatment for it to understand CE. Methods The published articles were reviewed. Results The prevalence of CE has been found to be 2.8-56.8% in infertile women, 14-67.5% in women with recurrent implantation failure (RIF), and 9.3-67.6% in women with recurrent pregnancy loss. Microorganisms are thought to be a main cause of CE, since antibiotic treatment has been reported to be an effective therapy for CE. Common bacteria are frequently detected in the uterine cavity of CE patients by microbial culture. In CE endometrium, the prevalence of immune cells and decidualization has been reported to be modified, and these modifications are thought to adversely affect fertility. The gold standard for the diagnosis of CE is the histological detection of plasma cells in the stromal area of the endometrium in endometrial specimens, although universally accepted criteria for the diagnosis of CE have not been determined. The treatment currently thought to be most effective for the recovery of fertility in CE is administration of oral antibiotics. Patients whose CE has been cured have been reported to have a higher ongoing pregnancy rate, clinical pregnancy rate, and implantation rate compared with patients with persistent CE. Conclusion CE greatly affects implantation and impairs fertility. Antibiotic administration is an effective therapeutic option. Pregnancy rate in in vitro fertilization is improved when CE is cured by antibiotic.

Review: Chronic endometritis and its effect on reproduction.

Objective
To evaluate the microbial load and the inflammatory response in the distal and proximal parts of the cervical mucus plug.

Design
Experimental research.

Population
Twenty women with a normal, singleton pregnancy.

Sample
Vaginal swabs and specimens from the distal and proximal parts of the cervical mucus plug.

Methods
Immunohistochemistry, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and histology.

Results
The total bacterial load (16S rDNA) was significantly lower in the cervical mucus plug compared with the vagina (p = 0.001). Among women harboring Ureaplasma parvum, the median genome equivalents/g were 1574 (interquartile range 2526) in the proximal part, 657 (interquartile range 1620) in the distal part and 60 240 (interquartile range 96 386) in the vagina. Histological examinations and quantitative polymerase chain reaction revealed considerable amounts of lactobacilli and inflammatory cells in both parts of the cervical mucus plug. The matrix metalloproteinase-8 concentration was decreased in the proximal part of the plug compared with the distal part (p = 0.08).

Conclusion
The cervical mucus plug inhibits, but does not block, the passage of Ureaplasma parvum during its ascending route from the vagina through the cervical canal.

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The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy

British and American obstetric societies recommend that elective cesarean section (ECS) be scheduled after 39 weeks’ gestation to reduce the incidence of neonatal death or adverse events. This multicenter, open-label, randomized controlled trial was undertaken at 7 Danish hospitals to investigate the risk of neonatal intensive care unit (NICU) admission associated with ECS scheduled before versus after 39 weeks’ gestation. Participants with a singleton pregnancy were randomly assigned to an ECS scheduled 11 days before the estimated due date (38 weeks; 38-week group) or to an ECS scheduled 4 days before the estimated due date (39 weeks; 39-week group). Neonatal outcomes were assessed 30 days after delivery or at final discharge. Maternal outcomes were assessed 30 days postpartum. The primary outcome was admission to the NICU, regardless of cause, within 48 hours of birth. Secondary short-term neonatal outcomes were admission to the NICU within 7 days of birth, NICU length of stay, type and duration of treatment, Apgar score, and umbilical artery pH and standard base excess values. A composite maternal outcome included at least 1 of these adverse outcomes: maternal death, hysterectomy, pulmonary embolism or deep venous thrombosis, uterine incision lateral tear, injury to bowel or bladder, procedural or anesthesia complications, rupture or dehiscence, bleeding requiring treatment, additional operations, or antibiotic treatment within 30 days of delivery. The Fisher exact, Wilcoxon rank sum, and Student t tests were used for statistical analyses. All analyses were performed using the statistical software program STATA version 11. A total of 1274 pregnant women were enrolled, with 119 to 329 participants at each site. At trial entry, the 2 intervention groups were similar in baseline characteristics. A total of 571 women in the 38-week group and 526 in the 39-week group had an ECS, and 59 and 97, respectively, had an unscheduled CS. Five women in the 38-week and 16 in the 39-week group delivered vaginally. The median difference in gestational age at delivery was 6 days (38; IQR 38 to 38 vs 39; IQR 38 to 39). Eighty-eight (13.9%) of 635 neonates in the 38-week group were admitted to the NICU compared with 76 of 637 neonates (11.9%) in the 39-week group. The relative risk (RR) of NICU admission was 0.86 (95% CI, 0.65Y1.15) for ECS at 39 weeks compared with 38 weeks, and the risk difference was j1.9% (95% CI, j5.6 to 1.8). Treatment with continuous oxygen for more than 1 day was significantly less frequent in the 39-week group, with an RR of 0.31 (95% CI, 0.10Y0.94) and a risk difference of j1.4% (95% CI, j2.7 to j0.2). No significant differences were seen in the frequency of NICU admission within 7 days of birth, respiratory morbidity, or treatment with intravenous antibiotics. The 2 groups were similar for NICU length of stay of 2 or more days. No cases of maternal death, hysterectomy, or serious thromboembolic events occurred. The risk of maternal bleeding greater than 500 mL was 17.1% in the 39-week group and 21.7% in the 38-week group (RR, 0.79; 95% CI, 0.63Y0.99). The risk of the composite maternal outcome was 10.3% and 9.4% in the 39and 38-week groups, respectively (RR, 1.1; 95% CI, 0.79Y1.53). 3 Preconception and Prenatal Care Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Scheduling ECS at 39 weeks compared with 38 weeks did not significantly decrease neonatal NICU admissions within 2 days of birth, and no secondary neonatal or maternal outcomes improved significantly with late scheduling. Any long-term consequences to the neonate or mother of ECS timing at term are uncertain and require additional investigations. EDITORIAL COMMENT (Over the past 5 years, increasing attention has been focused on the timing of elective deliveries at term. Although data have been published for more than a decade suggesting differentiation between weeks of gestation from 37 to 41 weeks in neonatal morbidity, an article looking at the cesarean delivery registry within the Maternal-Fetal Medicine Units network gained national attention (N Engl J Med. 2009;360:111Y120). This study, which examined outcomes in neonates born via cesarean at 37, 38, 39, 40, and 41 weeks’ gestation, found that NICU admissions and respiratory complications declined from 37 to 38 weeks’ gestation and from 38 to 39 weeks’ gestation. These and other findings have led to a national March of Dimes campaign to reduce elective delivery before 39 weeks’ gestation. However, one concern of an aggressive push toward waiting for 39 weeks’ gestation is that women who are not at the lowest risk will also get delayed. This point was emphasized in the Eunice Kennedy Shriver National Institute of Child Health and Human Development/Society for Maternal-Fetal Medicine/American Congress of Obstetricians and Gynecologists document (Obstet Gynecol. 2011;118:323Y333) regarding indications for early term delivery (deliveries at 37 or 38 weeks’ gestation) and reemphasized in the recent American Congress of Obstetricians and Gynecologists Committee Opinion No. 460 (Obstet Gynecol. 2013;121:908Y910). Delaying such moderate risk patients as those with chronic hypertension, twins, or poorly controlled diabetes may contribute to increased neonatal morbidity and, in particular, stillbirths. In a study of a program designed to delay unindicated deliveries to 39 weeks or beyond, there was a statistically significant increase in stillbirths (Obstet Gynecol. 2011;118:1047Y1055). However, in other studies, a similar increase in stillbirths has not been demonstrated (Obstet Gynecol. 2013;121:1025Y1031). When one considers that the absolute risk of stillbirth is 2 to 3 per 10,000 at 37 and 38 weeks’ gestation (Obstet Gynecol. 2012;120:76Y82), adequately powering such studies is challenging. Now, much of the data on timing of delivery come from cohort studies, most of them retrospective. Thus, I was delighted to see the prospective, randomized controlled study abstracted above published in BJOG. Considering the background discussed previously, Glavind et al conducted a study in Denmark randomizing 1274 women who were scheduled to have a repeat cesarean to delivery at 38 3/7 vs 39 3/7 weeks’ gestation. Not surprisingly, more women in the 39-week group ended up with an unscheduled cesarean (97 vs 59), which was largely due to spontaneous labor (82 [12.9%] in the 39-week group vs 49 [7.7%] in the 38-week group). Furthermore, 16 of these laboring women experienced a vaginal delivery in the 39-week group versus 5 in the 38-week groupVwhich, for some, might be considered a good outcome. Unfortunately, 1 woman in each group experienced a stillbirth. As noted in the abstract above, the only statistically significant difference in the nineteen neonatal outcomes examined was the rate of neonates who received continuous oxygen supplementation for more than 1 day. Clearly, the authors are to be congratulated for conducting such an ambitious study, and this certainly underscores the minimal differences achieved by waiting the additional week from 38 to 39 weeks’ gestation. I think the study also helps to frame another issue that patients and providers are concerned about which is the unscheduled delivery, particularly in the middle of the night. There certainly were more in the 39-week group, although the difference was modest, approximately 5%. The study was simply too underpowered to examine the risk of stillbirth or neonatal mortality. Larger studies have found that at 38 weeks the tradeoff between stillbirth and neonatal death is essentially equivalent (Obstet Gynecol. 2012;120:76Y82). Thus, the increased neonatal respiratory morbidity seen in 4 Obstetrical and Gynecological Survey Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. the current study does underscore the need to continue to wait until 39 weeks’ gestation for scheduled cesarean deliveries. The 1 caveat about such scheduled cesareans is that if the practice environment is such that performing a scheduled cesarean in the middle of the night is challenging because of a lack of in-hospital resources as is commonly seen in smaller hospitals, a patient might wish to decrease that probability by undergoing a 38-week cesarean. The current standard allows for that, as long as an amniocentesis, which documents lung maturity, is performed. Without such documentation, the standard of care for scheduled repeat cesareans remains 39 weeks’ gestation.VABC) Use of Oral Fluconazole During Pregnancy and the Risk of Birth Defects Ditte Mo/ lgaard-Nielsen, Björn Pasternak, and Anders Hviid Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark N Engl J Med 2013;369:830Y839

Julie Glavind

Papers

The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy

Elective Caesarean Section at 38 Weeks Versus 39 Weeks: Neonatal and Maternal Outcomes in a Randomised Controlled Trial

Elective Cesarean Section at 38 Weeks Versus 39 Weeks: Neonatal and Maternal Outcomes in a Randomized Controlled Trial

O277 timing of elective cesarean section and neonatal morbidity: a randomized controlled trial

Childbirth Experience Questionnaire (CEQ)- validation of its use in a Danish population