Chorioamnionitis Research Articles

Identification of Microorganisms associated with intraamniotic infection among women with preterm birth at Ruhengeri Referral Hospital, Rwanda: A case control study

Background: Preterm birth is a global public health threat for maternal and child health. Each year, 15 million neonates are born preterm worldwide, with 40% resulting from intrauterine infections. Materials and Methods: This cross-sectional and case–control study was conducted from October to February 2019 at Ruhengeri Referral Hospital. A total of 120 swab samples were collected from 40 women, of which 20 were full-term delivery, while the other 20 were preterm delivery. The three samples, including the placental membranes, amniotic fluids, and fetal membranes, were collected immediately after birth. A sterile cotton swab was used to collect the samples and put into swab Stuart sterile plastic container to avoid sample contamination. Samples were transported in a tightly covered carrier to the clinical microbiology laboratory at INES Ruhengeri for microbiological investigation. Gram staining, culture, and biochemical tests were performed. The independent t-test was used to test for significant differences between the means of the two groups, while the Chi-square test (χ2) was used to test for significant association with microorganisms and intra-amniotic infections. Results: A half of the participants were in the age range of 24–29 years. Non-albicans candida (32.7%) and mold (27.9%) were the predominant microorganisms isolated. Non-albicans candida and mold were common to preterm and full-term samples. Staphylococcus species were observed in placental and fetal membrane samples. Escherichia coli, Klebsiella species, Streptococcus species, and Candida albicans were observed among women with preterm birth samples. There was a statistically significant difference between the two means in the amniotic fluid isolates (t = 4.023, P < 0.007), placental membrane isolates (t = 7.17, P < 0.0004), and fetal membrane isolates (t = 6.7, P < 0.0006). Association with microorganisms and intra-amniotic infection was statistically significant with E. coli (χ2 = 3.98, P < 0.05), Streptococcus species (χ2 = 5.53, P < 0.019), non-albicans candida (χ2 = 8.37, P < 0.004), and C. albicans (χ2 = 3.98, P < 0.05). Conclusions: Invasion of the amniotic fluid, placenta, and fetal membranes by pathogenic microorganisms may be associated with the incidence of preterm labor and birth. Early diagnosis is recommended to avoid both maternal and fetal complications.

Complement Activation Fragments in Cervicovaginal Fluid Are Associated with Intra-Amniotic Infection/Inflammation and Spontaneous Preterm Birth in Women with Preterm Premature Rupture of Membranes.

We sought to determine whether the levels of complement and other inflammatory and angiogenic mediators in cervicovaginal fluid (CVF) are independently associated with intra-amniotic infection and/or inflammation (IAI) and imminent spontaneous preterm birth (SPTB, £48 hours of sampling) in women with preterm premature rupture of membranes (PPROM). This was a retrospective study consisting of 85 singleton pregnant women with PPROM at 200/7 to 336/7 weeks. Amniotic fluid (AF) obtained via amniocentesis was cultured and assayed for interleukin-6. CVF samples collected at the time of amniocentesis were assayed for complement C3a, C4a, and C5a, HSP70 (heat shock protein 70), M-CSF (macrophage colony-stimulating factor), M-CSF-R (macrophage colony-stimulating factor-receptor), S100 A8, S100 A9, thrombospondin-2, VEGF (vascular endothelial growth factor-receptor), and VEGFR-1 (vascular endothelial growth factor-receptor 1) by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses revealed that elevated CVF concentrations of complement C3a, 4a, and 5a were significantly associated with an increased risk of IAI and imminent SPTB, whereas those of M-CSF were associated with IAI, but not imminent SPTB (p = 0.063), after adjustment for baseline covariates (e.g., gestational age at sampling). However, univariate, and multivariate analyses showed that the CVF concentrations of angiogenic (thrombospondin-2, VEGF, and VEGFR-1) and inflammatory (HSP70, M-CSF-R, S100 A8, and S100 A9) proteins were not associated with either IAI or imminent SPTB. In women with PPROM, elevated CVF concentrations of complement C3a, C4a, and C5a are independently related to an increased risk of IAI and imminent SPTB. These findings suggest that complement activation in CVF is significantly involved in mechanisms underlying preterm birth and in the host response to IAI in the context of PPROM. · Elevated CVF levels of C3a, 4a and 5a are associated with IAI and SPTB.. · CVF C3a, 4a and 5a have better predictability for SPTB, compared to AF WBC.. · Elevated CVF levels of M-CSF were associated with IAI, but not SPTB..

Genital infection with Ureaplasma urealyticum and its effect on pregnancy

Chorioamnionitis or intra-amniotic infection is an infection that affects the intrauterine content during pregnancy. Numerous studies have reported vaginal colonization with various types of infectious agents as a risk factor for chorioamnionitis. Although this complication occurs due to the ascending polymicrobial bacterial infection at the time of membrane breakage, it may also occur in pregnant women with intact membranes, mainly due to Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis). The main aim of the present study was to identify a region-specific panel of infectious agents that can be used more accurately determine premature birth, as well as the premature rupture of membranes (PROM). Thus, a 10-year retrospective study was conducted. A total of 1,301 pregnant women with PROM and premature birth or spontaneous abortion were included in the study. It was observed that the main infectious agent varied in the five groups analyzed in total. The infectious agent distribution also varied depending on environmental parameters. Ureaplasma was found to be the most frequently detected germ amongst the infectious agents of the vaginal cultures from pregnant women enrolled in the present study, regardless of gestational age. On the whole, the findings of the present study suggest that additional studies are required, in order to confirm that diagnosis and treatment according to laboratory results of vaginal infections with U. urealyticum/M. hominis during the first trimester of pregnancy could prevent premature birth, abortion or chorioamnionitis.

Diagnostic accuracy of procalcitonin in maternal plasma to detect early intra-amniotic infection in preterm premature rupture of the membranes with respect of highvaginal swab as gold standard.

ABSTRACTObjective:To determine the diagnostic accuracy of procalcitonin in maternal plasma to detect early intra-amniotic infection in Preterm premature rupture of the membranes (PPROM) with respect of high vaginal swab as gold standardMethods:A cross-sectional study was conducted at Liaquat National Hospital, Karachi, from February to August 2017. The blood sample of women with PPROM were collected to measure procalcitonin level. PCT1 and PCT2 were run along with the sample for the accuracy of the results. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy of procalcitonin were calculated taking HVS C/S as gold standard.Results:Out of total 150 women, mean age was 28.78±4.79 years. Mean gestational age was 30.79±3.07 weeks. Mean procalcitonin level was 0.13±0.24 ng/ml. Intra-amniotic infection was diagnosed in 48.7% cases through procalcitonin levels and 51.3% through HVS culture and sensitivity. Sensitivity, Specificity, PPV (Positive predictive value), NPV (Negative predictive value) and accuracy were 87%, 91.8%, 91.78%, 87%, and 89.3% respectively. For females with gestational age ≤32 weeks, sensitivity, specificity, and diagnostic accuracy were 83.9%, 90.4%, and 87.03% respectively. For females with gestational age >32 weeks, sensitivity, specificity, and diagnostic accuracy were 95.2%, 92.5%, and 95.23% respectively.Conclusion:Diagnostic accuracy of maternal blood procalcitonin levels were found satisfactory in detection of early intra-amniotic infection in PPROM.

Identification of Escherichia coli strains in the vaginal cultures of healthy women and their patterns of antibiotic resistance.

Background: Bacterial vaginosis is the most common cause of vaginitis in women of childbearing age, and it predominantly affects young sexually active women. Escherichia coli is one of the most common bacteria found in the genital tract of non-pregnant (9–28%) and pregnant women (24–31%). E. coli strains can colonize the vaginal and endocervical regions in pregnant women, and may lead to the development of urinary tract, intra-amniotic or puerperal infections. Aim of the study: Isolation and identification of the antibiotic resistance patterns of extended spectrum beta-lactamase (ESBL)-producing and non-producing E. coli in the vaginal cultures of healthy women. Material and methods: Vaginal samples were taken from 55 healthy women. For the bacterial identification and resistance patterns, automated equipment from Beckman Coulter was used. Phenotypic techniques were used to confirm the presence or absence of ESBL. Results: Fifty-five cultures developed E. coli, with the rest of the strains corresponding to different bacteria. Of the 55 E. coli cultures, 35 (63.63%) were ESBL-producing and 20 (36.36%) did not produce ESBL. There was an 80% resistance to penicillin, and a 76.4% and 65.5% resistance to the first and fourth generation cephalosporins, respectively. A 45.5% resistance was observed for the fluoroquinolones, 52.7% for trimethoprim/ sulfamethoxazole, and 100% sensitivity to carbapenemics and amikacin. Conclusions: A large presence of vaginal ESBL-producing E. coli was observed in healthy women, which increases the risk of therapeutic failure due to high levels of antibiotic resistance.

The Role of Innate Immune System in the Human Amniotic Membrane and Human Amniotic Fluid in Protection Against Intra-Amniotic Infections and Inflammation

Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often lead to adverse neonatal outcomes. Human amniotic membrane (hAM), the inner part of the amnio-chorionic membrane, protects the embryo/fetus from environmental dangers, including microbial infection. However, weakened amnio-chorionic membrane may be breached or pathogens may enter through a different route, leading to IAI. The hAM and human amniotic fluid (hAF) respond by activation of all components of the innate immune system. This includes changes in 1) hAM structure, 2) presence of immune cells, 3) pattern recognition receptors, 4) cytokines, 5) antimicrobial peptides, 6) lipid derivatives, and 7) complement system. Herein we provide a comprehensive and integrative review of the current understanding of the innate immune response in the hAM and hAF, which will aid in design of novel studies that may lead to breakthroughs in how we perceive the IAI.

About the absence of the need to prescribe antibacterial therapy to newborns from mothers with clinical chorioamnionitis

Background. The diagnosis of a woman in labor chorioamnionitis (CA) implies a high risk of infectious complications for the mother and fetus, which determines the need for additional examination of infants and the decision on the appointment of antibacterial therapy. The purpouse of this study was determine the need to administration antibiotic therapy to full-term newborns from mothers diagnosed with chorioamnionitis. Materials and methods. 113 full-term newborns were examined, of which the main group consisted of children whose mothers were diagnosed with chorioamnionitis (n = 77), the comparison group children born to healthy mothers (n = 36). All children performed clinical and laboratory monitoring, including a clinical analysis of capillary blood in the first 24 hours of life; determination of the level of C-reactive protein (CRP) in venous blood on the 3rd day of life. Bacteriological examination of newborns included sampling of material from the ear fold, buccal mucosa, umbilical cord blood, as well as the contents of the tracheobronchial tree (TBD) during respiratory therapy with mechanical ventilation. Special research methods included studies of the proinflammatory cytokines (IL-1, IL-6) in umbilical cord blood. Histological CA was diagnosed in the presence of morphological and functional signs of inflammation in the placenta. Results. Newborns of the main group more often developed respiratory disorders requiring respiratory and oxygen therapy (p = 0,045). The production of IL-1, IL-6 in umbilical cord blood in the examined newborns of the main group was higher than in the comparison group [Odds Ratio (OR) 8.4; 95% Confidence Interval (CI): 1.067.9; OR 7.4; 95% CI: 2.521.7 respectively]. The study of blood samples revealed leukocytosis (34109) 6.5% vs 0%, p 0.05) and a shift in the leukocyte count to young forms of neutrophils (45.4% vs 16.7%, p 0.05) in the peripheral blood of infants of the main group. Infants exposed to maternal clinical chorioamnionitis had increased level of CRP 10.3 times more frequent (95% CI: 2.837.1) than in newborns in the comparison group. With dynamic clinical and laboratory monitoring, 72 children of the main group (93.5%) had no data for the course of the infection, as a result of which they did not receive antibiotic therapy. Conclusion: Administration antibiotic therapy to clinically healthy full-term newborns from mothers diagnosed with chorioamnionitis is unjustified. Infants of this group require clinical laboratory, dynamic observation with laboratory control, including a clinical blood test and determination of the CRP level, which is a preferred alternative to the appointment of antibiotic therapy.

Clinical chorioamnionitis and histologic placental inflammation: association with early-neonatal sepsis

Objective Chorioamnionitis and fetal inflammatory response syndrome (FIRS) are significant risk factors for early onset sepsis (EOS). Recently, the use “Intrauterine Inflammation or Infection or both” or triple I has been proposed, classifying cases into an isolated maternal fever, suspected triple I, or confirmed chorioamnionitis. Evidence suggests that the association between suspected chorioamnionitis and confirmed histological chorioamnionitis (HCA) is not consistent, as well as the impact of HCA on the development of EOS. We aimed to evaluate the association between suspected chorioamnionitis and HCA, the impact of HCA on EOS, and the effect of antepartum antibiotic prophylaxis on EOS. Methods We retrospectively reviewed the medical records of all infants admitted to our institution, between 2017 and 2018, with a diagnosis of chorioamnionitis. We recorded the clinical evidence of chorioamnionitis, the histologic report of the placenta, the maternal and neonatal data, the neonatal inflammatory markers including C-reactive protein (CRP), and the incidence of EOS. The impact of antepartum antibiotic prophylaxis on the infants’ CRP and EOS was calculated, and the logistic regression model was performed to estimate the association of confirmed HCA with EOS, while controlling for FIRS stage, gestation age, birth weight, maternal fever, foul-smelling amniotic fluid, and prolonged rupture of membranes. Results During the study period, a total of 266 infants were identified; 81 (30%) infants had a confirmed HCA (HCA-present cases), and 185 (70%) infants were diagnosed with suspected triple I (HCA-absent cases). Antepartum antibiotics had been commenced in a significantly higher proportion in HCA-present cases (46%) in comparison to 14% of HCA-absent cases (p < .001). HCA-present infants were of significantly lower gestation (31.6 ± 4weeks versus 33.3 ± 4weeks, p = .004), and birth weight (1826 ± 840 g versus 2092 ± 849 g, p = .019), they had a significantly higher rate of clinical symptoms (31% versus 6%, p < .001), and a higher CRP at birth and 24 h (1.4 ± 1.5 mg/dL versus 0.3 ± 0.2 mg/dL, p < .001, and 2.1 ± 2.3 mg/dL versus 0.4 ± 0.6 mg/dL, p < .001, respectively). All HCA-present cases had evidence of FIRS; 43% were stage I, 25% stage II, and 32% were FIRS stage III. A significantly higher proportion of HCA-present infants were diagnosed with EOS (46% as compared to 6%, p < .001). The antepartum antibiotic administration was related to a significantly lower CRP at birth and 24 h only in HCA-present cases, albeit not with any reduction ιn EOS incidence. HCA was significantly associated with EOS (RR 3.18, 95% CI 2.81–5.18, p < .001). After adjusting for perinatal factors, the presence of HCA (OR 7.89, 95% CI 1.19-23.34, p = .032) and an advanced FIRS stage (OR 10.35, 95% CI 4.23–25.32, p < .001) were significantly associated with EOS. Conclusions Amongst infants with suspected chorioamnionitis, the diagnosis is partially supported by histological confirmation, and that is more prominent in pregnancies of a lower gestation. The presence of HCA and an advanced FIRS stage predispose to an increased risk of EOS after adjusting for other perinatal and neonatal factors. The antepartum prophylaxis against intra-amniotic infection was related to a significantly lower CRP in HCA-present cases.

Matrix metalloproteinse-9 expression in fetal membranes and maternal serum in cases of premature rupture of membranes: Impact of subclinical chorioamnionitis

Background: Matrix metalloproteinase-9 (MMP-9) is the most active MMPs in the fetomaternal membranes. It plays an important role in the breakdown and remodeling of these membranes. Thus, increased knowledge of its expression in cases of premature rupture of membranes (PROM) with and without chorioamnionitis (CA) is essential for developing effective treatment strategies. Patients and Methods: expression of MMP-9 in fetomaternal membranes and maternal serum were performed in 70 full-term pregnant women; 20 cases were with intact membranes (group I), 35 with PROM (group IIA) and 15 with PROM and CA (group IIB). Results: A significant difference in MMMP-9 expression was detected between the studied groups. The highest MMP-9 expression was reached in women with PROM accompanied by histological (subclinical) CA followed by women with PROM without CA, compared to the control group (with intact membranes) at the time of delivery. Immunohistochemical expression was associated with a concomitant increase in serum MMP-9. Conclusion: MMP-9 could predict women liable for premature rupture of membranes, and the determination of its serum level may be an effective tool for PROM detection.

Vaginal microbiome as a tool for prediction of chorioamnionitis in preterm labor: a pilot study

Intra-amniotic infection (IAI) is a major cause of preterm birth with a poor perinatal prognosis. We aimed to determine whether analyzing vaginal microbiota can evaluate the risk of chorioamnionitis (CAM) in preterm labor cases. Vaginal discharge samples were collected from 83 pregnant women admitted for preterm labor. Based on Blanc’s classification, the participants were divided into CAM (stage ≥ II; n = 46) and non-CAM (stage ≤ I; n = 37) groups. The 16S rDNA amplicons (V1–V2) from vaginal samples were sequenced and analyzed. Using a random forest algorithm, the bacterial species associated with CAM were identified, and a predictive CAM (PCAM) scoring method was developed. The α diversity was significantly higher in the CAM than in the non-CAM group (P < 0.001). The area under the curve was 0.849 (95% confidence interval 0.765–0.934) using the PCAM score. Among patients at < 35 weeks of gestation, the PCAM group (n = 22) had a significantly shorter extended gestational period than the non-PCAM group (n = 25; P = 0.022). Multivariate analysis revealed a significant difference in the frequency of developmental disorders in 3-year-old infants (PCAM, 28%, non-PCAM, 4%; P = 0.022). Analyzing vaginal microbiota can evaluate the risk of IAI. Future studies should establish appropriate interventions for IAI high-risk patients to improve perinatal prognosis.

Initiative to Reduce Antibiotic Exposure of Asymptomatic Infants Born to Mothers with Intraamniotic Infection.

Introduction:Infants born to mothers with intraamniotic infection (IAI) received antibiotic treatment per the Centers for Disease Control and Prevention and American Academy of Pediatrics guidelines in our neonatal intensive care unit (NICU) for early-onset bacterial sepsis evaluation. We conducted a quality improvement project to decrease antibiotic use and NICU admission in infants born to mothers with IAI.Methods:We aimed to decrease the antibiotic exposure for asymptomatic infants born to mothers with IAI from 100% to 20% in 6 months. We obtained baseline data on these infants from January 2018 to January 2019, with the intervention starting in February 2019. A new standardized guideline to clinically monitor and follow laboratories on asymptomatic infants in couplet care was created with a multidisciplinary team’s help and implemented after provider education. The team reviewed data monthly and used PDSA cycles to make necessary changes, including updating order sets, more educational handouts, and real-time coaching to both nurses and physicians.Results:There was a dramatic decline (93%–0%) in antibiotic exposure and NICU admission after implementing this guideline. There was also a decrease in IAI diagnosis. There were no readmissions of infants for infection within 30 days of discharge, and there were no positive blood cultures.Conclusions:Implementing best antibiotic stewardship practices through a standardized guideline, testing, implementation of processes, and education by a multidisciplinary team limited the antibiotic exposure and NICU admissions for infants born to mothers with IAI with no known increase in readmissions.

The Role of Antimicrobial Peptides in Preterm Birth.

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.

High Mobility Group Box 1 in Pig Amniotic Membrane Experimentally Infected with E. coli O55.

Intra-amniotic infections (IAI) are one of the reasons for preterm birth. High mobility group box 1 (HMGB1) is a nuclear protein with various physiological functions, including tissue healing. Its excessive extracellular release potentiates inflammatory reaction and can revert its action from beneficial to detrimental. We infected the amniotic fluid of a pig on the 80th day of gestation with 1 × 104 colony forming units (CFUs) of E. coli O55 for 10 h, and evaluated the appearance of HMGB1, receptor for glycation endproducts (RAGE), and Toll-like receptor (TLR) 4 in the amniotic membrane and fluid. Sham-infected amniotic fluid served as a control. The expression and release of HMGB1 were evaluated by Real-Time PCR, immunofluorescence, immunohistochemistry, and ELISA. The infection downregulated HMGB1 mRNA expression in the amniotic membrane, changed the distribution of HMGB1 protein in the amniotic membrane, and increased its level in amniotic fluid. All RAGE mRNA, protein expression in the amniotic membrane, and soluble RAGE level in the amniotic fluid were downregulated. TLR4 mRNA and protein expression and soluble TLR4 were all upregulated. HMGB1 is a potential target for therapy to suppress the exaggerated inflammatory response. This controlled expression and release can, in some cases, prevent the preterm birth of vulnerable infants. Studies on suitable animal models can contribute to the development of appropriate therapy.

Birth weight and intra-amniotic inflammatory and infection-related complications in pregnancies with preterm prelabor rupture of membranes: a retrospective cohort study

Objective To assess the association between the birth weight of newborns and microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation in pregnancies with preterm prelabor rupture of membranes. Methods A total of 528 pregnancies with preterm prelabor rupture of membranes were included in this retrospective cohort study. Transabdominal amniocentesis to determine the presence of MIAC (through culturing and molecular biology methods) and intra-amniotic inflammation (according to amniotic fluid interleukin-6 level) was performed as part of standard clinical management. Based on the presence of MIAC and/or intra-amniotic inflammation, the participants were divided into four subgroups: with intra-amniotic infection (presence of both), with sterile IAI (intra-amniotic inflammation alone), with colonization (MIAC alone), and with negative amniotic fluid (absence of both). Birth weights of newborns are expressed as percentiles derived from INTERGROWTH-21st standards for (i) newborn birth weight and (ii) estimated fetal weight. Results No differences in birth weights, expressed as percentiles derived from newborn weight standards (infection: median 52; sterile: median 54; colonization: median 50; negative amniotic fluid: median 51; p = .93) and estimated fetal weight standards (infection: median 47; sterile: median 51; colonization: median 47; negative amniotic fluid: median 53; p = .48) were found among the four subgroups. No differences in percentiles (derived from both standards) were found in the subset of participants who delivered within 72 h after rupture of membranes (newborn weight standard, p = .99; estimated fetal weight standard, p = .81). Conclusions No association was identified between the birth weight of newborns and the presence of intra-amniotic inflammatory and infection-related complications in pregnancies with preterm prelabor rupture of membranes.

Advanced Abdominal Pregnancy (AAP) after 20 Weeks of Gestation in Japan: A Retrospective Review.

Background An advanced abdominal pregnancy (AAP) rarely continues to a live birth, but sometimes, a live birth may occur. In developed countries, women with AAP who have not been diagnosed preoperatively are expected to be diagnosed quickly, and the pregnant woman and the fetus will be saved. After careful examination of the past cases, we sought to derive what is the best diagnosis and treatment choice in the current medical environment. Materials and Methods We retrospectively studied AAP cases in Japan. We examined diagnosis of AAP before fetal delivery and placental treatment at the time of delivery. AAP was well documented in 10 cases. We contacted the AAP authors, who reported 10 AAP cases in Japan, directly to confirm any unclear points. Results Two cases were diagnosed with AAP before laparotomy, one was diagnosed after IUFD, and seven were diagnosed at the time of laparotomy. The two most recent cases were diagnosed with AAP preoperatively by ultrasound and MRI. Six cases were described for preoperative diagnosis. There were two cases of placenta previa, one of a bicornuate uterus, one of breech presentation, one of a combination of uterine cervical fibroids and placenta previa, and one of a combination of presentation and placental abnormality with uterine fibroids. In five cases, the placenta was removed at the time of laparotomy. Simultaneous removal of the placenta during laparotomy could not be performed because of intra-amniotic infection with a macerated fetus in an IUFD case. Among eight cases, excluding 20-week and 21-week gestation with no expectation of viable newborns, there were one male and seven female fetuses. The birth weight ranged from 1765 to 3520 g, with a median birth weight of 2241 g. Combined malformations were described in six of the seven live births. Clubfoot, torticollis, joint contracture, and bone deformity were transient because intrauterine compression quickly improved. Conclusion In recent cases, AAP has been diagnosed by MRI and ultrasound. MRI should be performed if abdominal pregnancy is suspected. Postoperative infections may occur if the placenta is not removed at the time of delivery. We recommend placental resection with the help of an anesthesiologist, a gynecologist, a urologist, and a surgeon in the current medical environment.

Microbial profile of placentas from Tanzanian mothers with adverse pregnancy outcomes and periodontitis.

To investigate microbial profiles in placentas from a population of East African mothers with and without adverse pregnancy outcomes and with regard to their periodontal status. Thirty-six placentas from pregnant women from Tanzania were classified into three groups according to both pregnancy outcome and the mother's periodontal health. The microbial composition in each group was then compared using 16S rRNA metagenomics. Additionally, placenta specimens were analyzed histologically for chorioamnionitis by a single pathologist blinded to the clinical data. The greatest differences were observed in the group of mothers with periodontitis. The microbial load was low in all three groups of mothers. Periodontitis had a notable influence on the structure of the placental microbiota. Three phyla and 44genera were associated with periodontitis, whereas only the Tenericutes phylum was associated with the adverse pregnancy variable. Streptococcaceae and Mycoplasmataceae families were associated with both periodontitis and adverse pregnancy outcomes. Finally, although the differences for chorioamnionitis were not significant, this intra-amniotic infection was more frequent in the placentas from mothers with periodontitis. Our findings suggest that bacteria from the oral cavity may involve the feto-placental unit, and that periodontitis may be a modulating factor of the microbial community present in this niche.

Intra-amniotic infection and sterile intra-amniotic inflammation in women with preterm labor with intact membranes are associated with a higher rate of Ureaplasma species DNA presence in the cervical fluid

Objective To determine the prevalence of Ureaplasma spp. DNA and its load in the cervical fluid in women with preterm labor with intact membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation) or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone). Methods Overall, 115 women with singleton pregnancies complicated by PTL between gestational ages of 22 + 0 and 34 + 6 weeks were included in this study. Paired amniotic and cervical fluid samples were collected at the time of admission via transabdominal amniocentesis using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on a combination of culture and molecular biology methods. Intra-amniotic inflammation was determined based on the concentration of interleukin-6 in the amniotic fluid. Bacterial and Ureaplasma spp. DNA loads were assessed in the cervical fluid using PCR. Results Intra-amniotic infection and sterile inflammation were identified in 14% (16/115) and 25% (29/115) of the women, respectively. Ureaplasma spp. DNA in the cervical fluid was identified in 51% (59/115) of women. The presence of Ureaplasma spp. DNA in the cervical fluid was higher in women with intra-amniotic infection (75% (12/16)) and sterile intra-amniotic inflammation (76% (22/29)) than in women without intra-amniotic inflammation (36% (25/70); p = .0002). Concurrent presence of Ureaplasma spp. and Mycoplasma hominis DNA was higher in women with intra-amniotic infection (42% (5/12)) than women with sterile intra-amniotic inflammation (7% (2/29)) and women without intra-amniotic inflammation (7% (5/70); p = .001). There were no differences in the load of Ureaplasma spp. DNA in the cervical fluid among women with intra-amniotic infection, sterile intra-amniotic inflammation, and those without intra-amniotic inflammation (median values; infection: 1.2 × 104 copies DNA/mL; sterile: 5.0 × 105 copies DNA/mL; without: 8.4 × 104 copies DNA/mL; p = .18). Conclusions In PTL , both forms of intra-amniotic inflammation were associated with a higher prevalence of Ureaplasma spp. DNA in the cervical fluid. The presence of intra-amniotic infection was related to a higher rate of concurrent Ureaplasma spp. and M. hominis DNA in the cervical fluid.

ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth.

COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (n = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women (n = 6). Second trimester placental explants (16–20 weeks, n = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased ACE2 and CCL2 mRNA expression (p < 0.05). LPS increased cytokine and ACE2 mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta (p < 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.

Acute chorioamnionitis and intra-amniotic inflammation are more severe according to outside-in neutrophil migration within the same chorio-decidua

ObjectiveNo information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue. Materials and methodsWe included 106 singleton preterm-births (gestational age at delivery: 20–34 weeks) due to either preterm-labor or preterm-PROM in the context of acute chorio-deciduitis. Study-population was divided into 3 groups according to outside-in neutrophil migration within chorio-decidua as follows: 1) group-1: ‘inflammation restricted to the decidua’ (n = 22); 2) group-2: ‘inflammation restricted to the MT of chorion and the decidua’ (n = 31); 3) group-3: ‘inflammation in the CT of chorion’ (n = 53). We examined the frequency of inflammation in each placental compartment beyond chorio-decidua (i.e., amnion, umbilical cord, and chorionic-plate), and total grade (1–8) of acute-HCA. Moreover, the frequency of intra-amniotic infection (defined as positive amniotic-fluid culture for aerobic and anaerobic bacteria and genital mycoplasmas) and intra-amniotic inflammation (defined as amniotic fluid WBC ≥ 19 cells/mm3), and an intra-amniotic inflammatory response gauged by amnioticfluid WBC count (cells/mm3) were examined in 50 amniotic fluid samples within 7 days of birth. ResultsAmnionitis, funisitis and chorionic plate inflammation were more frequent (each for P < 0.01) and median total grade of acute-HCA was increased (P < 0.001) according to outside-in neutrophil migration within chorio-decidua (group-1vs.group-2vs.group-3). Moreover, intra-amniotic infection and inflammation were more frequent (each-for P < 0.05) and median amniotic-fluid WBC count was increased (P < 0.01) according-to outside-in neutrophil-migration within chorio-decidua (group-1 vs. group-2 vs. group-3). ConclusionAcute-HCA is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. This finding suggests that what is now acute chorio-deciduitis should be subdivided.

Bacterial endotoxin-induced maternal inflammation leads to fetal intestinal injury and affects microbial colonization in the neonatal period

Background Intraamniotic infection is associated with an increased risk of multiple adverse outcomes in offspring, especially neonatal necrotizing enterocolitis (NEC), which is one of the serious gastrointestinal diseases in neonates. However, the underlying mechanism remains undefined. We hypothesize that bacterial endotoxin-induced maternal inflammation causes intestinal injury in offspring, thereby affecting the composition of the intestinal microbiome. Methods Pregnant Sprague Dawley rats were received intraperitoneal injections with 700 μg/kg lipopolysaccharide (LPS, which was the same as bacterial endotoxin) or saline at 15 days of gestation. Pups were allowed to deliver naturally and euthanized at days 0, 3 and 7 after birth. Intestinal tissue and feces samples from offspring were collected to evaluate the effects of maternal inflammation on intestinal flora colonization and intestinal mucosal development. Results Significant intestinal injury of the offspring induced by prenatal LPS exposure was observed on day 0 and 3 after birth. In addition, prenatal LPS exposure also induced significant changes in the intestinal microbiome of the offspring with a significant increase in Proteobacteria (Escherichia-Shigella) and a decrease in Firmicutes at 7 days after birth. Conclusions Thus, our findings suggest that LPS-induced maternal inflammation induces intestinal injury in offspring and subsequently leads to NEC-like changes in the composition of the intestinal microbiome.