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BACKGROUND: The aim of this study is to identify risk factors associated with histological chorioamnionitis (HCA) and develop a predictive model for antepartum assessment of the risk of PPROM with HCA. METHODS: This study retrospectively analyzed pregnant women who experienced PPROM between 25 + 0 and 35 + 0 weeks of gestational age. The women were divided into two groups based on the presence or absence of HCA. Univariate and multivariate logistic regression analyses were conducted to identify maternal risk factors and develop a clinical prediction model for HCA. The model's discrimination and consistency were evaluated using receiver operating characteristic (ROC) and calibration curves. RESULTS: Seventeen thousand one hundred forty-six (17,146) pregnant women were screened, and 726 (4.23 %) had PPROM. Out of the 286 subjects with PPROM, 160 developed HCA. The maternal age of these subjects ranged from 18 to 43 years (30.0 ± 5.4), while their gestational age (GA) ranged from 25 + 0 to 35 + 0 weeks (31.6 ± 2.0). The average GA at delivery was 32.2 ± 2.0 (weeks).Compared with the non-HCA group, the expectant time > 48 h, GA at delivery > 32 weeks, twin pregnancy, HGB (<110 g/Lg/L), degree of LGB (IIb-III), and WBC (>9.5 × 109 /L) were significantly more than in the PPROM with HCA group. The results show that the best model was obtained by leave-one-out logistic regression (AUC = 0.785, CA = 0.741, F1 = 0.739, Precision = 0.740, Recall = 0.741). In the validation set, logistic regression also achieved good results (AUC = 0.710, CA = 0.671, F1 = 0.654, Precision = 0.683, Recall = 0.671). Combining the previous analysis, we found that the prognostic model constructed using the core six features had the best predictive effect. CONCLUSIONS: Six features were associated with the occurrence of chorioamnionitis. These features were used to construct a diagnostic model that can accurately predict the probability of chorioamnionitis occurrence and provide a beneficial tool for the prevention and management of PPROM with HCA.

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BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common obstetric condition but outcomes can vary depending on gestation. Significant maternal and foetal complications occur including preterm birth, infection, abruption, cord prolapse, pulmonary hypoplasia and even death. Although the need for psychological support is recognised it is unclear how much is actually offered to women and their families. This study aimed to survey the views of women and their families who have undergone PPROM in order to understand the care and psychological burden these families face. METHODS: An online survey was conducted, recruiting women via social media with collaboration from the patient advocacy support group Little Heartbeats. Responses were collated where fields were binary or mean and standard deviations calculated. Framework analysis was used to identify and analyse themes in free text responses. RESULTS: 180PPROM pregnancies were described from 177 respondents. Although carewas variable and respondents were from across the world there werecommon themes. Five themes were highlighted which were: a lack ofbalanced information regarding the condition, support in decisionmaking and support with the process, specific psychological supportand ongoing psychological consequences of PPROM. CONCLUSION: This survey highlights areas in which care needs to be improved for women with PPROM. Previous studies have shown that providing good care during the antenatal period reduces long-term psychological morbidity for the whole family. The need for support, with regard both to information provided to women and their families and their psychological support needs to be addressed urgently.

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Preterm prelabour rupture of membranes (PPROMs) before viability carries significant perinatal mortality and morbidity. Clinical management and prenatal counselling are a challenge, especially in twin pregnancies, due to scarce evidence on how previable PPROM affects this population. The aim of this study was to describe pregnancy outcomes of twin pregnancies complicated with previable PPROM and evaluate potential prognostic factors that may predict perinatal mortality. A retrospective cohort including dichorionic and monochorionic diamniotic twin pregnancies complicated with PPROM before 24 + 0 weeks of pregnancy was evaluated. Perinatal outcomes of pregnancies managed expectantly were described. Factors predicting perinatal mortality or reaching periviability (defined from 23 + 0 weeks onwards) were evaluated. Of the 45 patients included, 7 (15.6%) spontaneously delivered within the first 24 h after diagnosis. Two patients (5.3%) requested selective termination of the affected twin. In the 36 ongoing pregnancies that opted for expectant management, the overall survival rate was 35/72 (48.6%). There were 25/36 (69.4%) patients who delivered after 23 + 0 weeks of pregnancy. When periviability was achieved, neonatal survival increased up to 35/44 (79.5%). Gestational age at delivery was the only independent risk factor of perinatal mortality. The overall survival rate of twin pregnancies complicated with previable PPROM is poor but similar to singletons. No prognostic factors, apart from achieving periviability, were identified as individual predictors of perinatal mortality.

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BACKGROUND: Preterm prelabour rupture of the membranes (PPROM) complicates 3% of pregnancies and is associated with an increased risk of maternal and perinatal morbidity and mortality. In an attempt to better understand this diagnosis, patients routinely resort to the internet for medical information. The lack of governance online leaves patients at risk of relying on low-quality websites. OBJECTIVES: To assess systematically the accuracy, quality, readability and credibility of World Wide Web pages on PPROM. SEARCH STRATEGY: Five search engines (Google, AOL, Yahoo, Ask and Bing) were searched with location services and browser history disabled. Websites from the first page of all searches were included. SELECTION CRITERIA: Websites were included if they provided at least 300 words of health information aimed at patients relating to PPROM. DATA COLLECTION AND ANALYSIS: Validated assessments of health information readability, credibility and quality were undertaken, as was an accuracy assessment. Pertinent facts for accuracy assessment were based on feedback from healthcare professionals and patients through a survey. Characteristics were tabulated. MAIN RESULTS: In all, 39 websites were included, with 31 different texts. No pages were written with a reading age of 11 years or less, none were considered credible, and only three were high quality. An accuracy score of 50% or more was obtained by 45% of websites. Information that patients considered pertinent was not consistently reported. CONCLUSIONS: Search engines produce information on PPROM that is low quality, low accuracy and not credible. It is also difficult to read. This risks disempowerment. Healthcare professionals and researchers must consider how to ensure patients have access to information that they can recognise as high quality.

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OBJECTIVES: The aim of the presented work is to summarize the current knowledge about the pathophysiology of preterm birth in connection with premature amniotic fluid. METHODS: To analyze current knowledge and our own experiences regarding of preterm prelabour rupture of membranes. CONCLUSION: The most important factor influencing neonatal morbidity and mortality is gestational age. Early neonatal sepsis occurs with high risk after premature amniotic fluid outflow, associated with inflammatory complications.

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OBJECTIVES: To examine early pregnancy risk factors for preterm prelabour rupture of membranes (PPROM) and develop a predictive model. STUDY DESIGN: Retrospective analysis of a cohort of mixed-risk singleton pregnancies screened in the first and second trimesters in three Danish tertiary fetal medicine centres, including a cervical length measurement at 11-14 weeks, at 19-21 weeks and at 23-24 weeks of gestation. Univariable and multivariable logistic regression analyses were employed to identify predictive maternal characteristics, biochemical and sonographic factors. Receiver operating characteristic (ROC) curve analysis was used to determine predictors for the most accurate model. RESULTS: Of 3477 screened women, 77 (2.2%) had PPROM. Maternal factors predictive of PPROM in univariable analysis were nulliparity (OR 2.0 (95% CI 1.2-3.3)), PAPP-A < 0.5 MoM (OR 2.6 (1.1-6.2)), previous preterm birth (OR 4.2 (1.9-8.9)), previous cervical conization (OR 3.6 (2.0-6.4)) and cervical length ≤ 25 mm on transvaginal imaging (first-trimester OR 15.9 (4.3-59.3)). These factors all remained statistically significant in a multivariable adjusted model with an AUC of 0.72 in the most discriminatory first-trimester model. The detection rate using this model would be approximately 30% at a false-positive rate of 10%. Potential predictors such as bleeding in early pregnancy and pre-existing diabetes mellitus affected very few cases and could not be formally assessed. CONCLUSIONS: Several maternal characteristics, placental biochemical and sonographic features are predictive of PPROM with moderate discrimination. Larger numbers are required to validate this algorithm and additional biomarkers, not currently used for first-trimester screening, may improve model performance.

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OBJECTIVE: To investigate reliable biomarkers for predicting histological chorioamnionitis (HCA) in women with preterm prelabour rupture of membranes (PPROM). DESIGN: A retrospective study. SETTING: A maternity care hospital in Shanghai. POPULATION: Women with PPROM before 34+0/7  weeks of gestation. METHODS: Mean values of biomarkers were compared by two-way analysis of variance (ANOVA). Log-binomial regression models were used to assess the association between biomarkers and risk of HCA. A stepwise logistic regression model was used to develop a multi-biomarker prediction model and identify the independent predictors. The area under the receiver operating characteristic curve (AUC) was used to assess prediction performance. MAIN OUTCOME MEASURES: The ability of the individual biomarker and the combination of multiple biomarkers to predict HCA. RESULTS: In 157 mothers with PPROM, 98 (62.42%) women had HCA and 59 (37.58%) women did not have HCA. No significant differences were observed between the two groups in white blood cell, neutrophil or lymphocyte counts, whereas both high-sensitivity C-reactive protein (hsCRP) and procalcitonin (PCT) were significantly higher in the HCA group. HsCRP and PCT were found to be independently associated with the risk of HCA, and PCT had a larger AUC value than hsCRP (p < 0.05). The optimal multi-biomarker prediction model for HCA (AUC = 93.61%) included hsCRP at 72 hours and PCT at 48 and 72 hours, and PCT had a stronger prediction capacity than hsCRP. CONCLUSIONS: PCT could be a reliable biomarker for the early prediction of HCA in women with PPROM within 72 hours of dexamethasone treatment.

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PROBLEM: This study aimed to evaluate and compare the predictive accuracy of serum markers for histological chorioamnionitis (HCA) among women with preterm prelabour rupture of membranes (PPROM), and to develop a nomogram prediction model to minimize the damage of the disease. METHOD OF STUDY: This case-control study included 153 pregnant women with PPROM with a gestational age of 20+0 ∼36+6 weeks. The subjects were assigned into two groups: PPROM with and without HCA. According to the results of logistic regression analysis, the predictive equation and nomogram were generated using key parameters, and the discrimination and consistency of the model were evaluated by receiver operating characteristic (ROC) curves and calibration curves. RESULTS: From 153 subjects with PPROM, 77 developed HCA. Compared with the PPROM without HCA group, the CRP, PCT and NLR were significantly higher in HCA group (P < 0.001), and the CRP had the highest predictive value. The area under the curve (AUC) of the prediction model was 0.873, and the sensitivity and specificity of predicting HCA were 68.8% and 92.1%, respectively. And the calibration curves fitted well with the realistic situation. CONCLUSION: Maternal serum CRP and NLR could be used as predictive biomarkers for HCA in women with PPROM, while PCT needs to be further explored due to its slightly lower predictive value. Our serum markers and gestational age at PPROM could be used as a non-invasive and convenient method to predict HCA in women with PPROM.

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Preterm prelabour rupture of membranes (PPROM) complicates up to 3% of pregnancy and is responsible for one third of preterm deliveries. PPROM at extremely preterm gestations (<24 weeks) affects 0.4% of pregnancies and is associated with low neonatal survival rates, high rate of neonatal complications in survivors, and carries major risk of maternal morbidity and mortality. We present a rare case of pregnancy complicated by PPROM at 14 weeks which resulted in a term delivery and a good neonatal outcome.

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Prelabour rupture of membranes (PROM) refers to the disruption of foetal membranes before the onset of labour, resulting in the leakage of amniotic fluid. PROM complicates 3% and 8% of preterm and term pregnancies, respectively. Accurate and timely diagnosis is crucial for effective management to prevent adverse maternal- and foetal-outcomes. The diagnosis of equivocal PROM cases with traditional methods often becomes challenging in current obstetrics practice; therefore, various novel biochemical markers have emerged as promising diagnostic tools. This narrative review is sought to review the published data to understand the current and emerging trends in diagnostic modalities in term and preterm pregnancies complicated with PROM and the potential role of various markers for predicting preterm PROM (pPROM) and chorioamnionitis in women with pPROM.

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Sneathia is an emerging pathogen implicated in adverse reproductive and perinatal outcomes. Although scarce, recent data suggest that vaginally residing Sneathia becomes pathogenic following its ascension into the upper urogenital tract, amniotic fluid, placenta, and foetal membranes. The role of Sneathia in women's health and disease is generally underappreciated because the cultivation of these bacteria is limited by their complex nutritional requirements, slow growth patterns, and anaerobic nature. For this reason, molecular methods are typically required for the detection and differential diagnosis of Sneathia infections. Here, we review the laboratory methods used for the diagnosis of Sneathia infections, the molecular mechanisms underlying its virulence, and its sensitivity to antibiotics. We further review the evidence of Sneathia's contributions to the pathogenesis of bacterial vaginosis, chorioamnionitis, preterm prelabour rupture of membranes, spontaneous preterm labour, stillbirth, maternal and neonatal sepsis, HIV infection, and cervical cancer. Collectively, growing evidence indicates that Sneathia represents an important yet underappreciated pathogen affecting the development and progression of several adverse clinical conditions diagnosed in pregnant women and their neonates, as well as in non-pregnant women.

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OBJECTIVE: Preterm prelabour rupture of membranes occurs in over one third of pregnant women with a cervical cerclage in situ. In the setting of preterm prelabour rupture of membranes, clinicians are faced with the difficult decision of the optimal timing for removing the cerclage. We compared the maternal and neonatal outcomes following immediate removal or retention of the cervical cerclage. STUDY DESIGN: Women were retrospectively identified from St Thomas's Hospital Preterm Surveillance clinic database. Asymptomatic women with preterm prelabour rupture of membranes were identified and separated into those that had the cerclage removed and those that had the cerclage retained within 24 h of presentation. Women who were symptomatic at presentation and who delivered within 24 h of presentation were excluded from the analysis. Maternal outcomes measured were latency between preterm prelabour rupture of membranes and delivery, gestation at delivery and maternal chorioamnionitis and infection markers. Neonatal outcomes including birthweight and Apgar scores were also measured. RESULTS: 43 women with cerclage retained for over 24 h following preterm prelabour rupture of membranes were compared to 25 women in whom the cerclage was removed. The latency between preterm prelabour rupture of membranes and delivery was on average 70.4 h longer in women who had their cerclage retained compared to the removed group (p = 0.009). Rates of chorioamnionitis, maternal blood results, neonatal birthweight and Apgar scores did not differ significantly between the two groups, however a trend towards higher rates of chorioamnionitis (60 % vs 45 %) were seen in the retained group. CONCLUSION: Cervical cerclage retention in women following preterm prelabour rupture of membranes was associated with a longer latency period to delivery and was not significantly associated with any adverse obstetric, maternal or neonatal outcomes. Therefore, in women at risk of spontaneous preterm birth, cerclage retention may be beneficial, however these women and their babies should be monitored closely for any signs of infection. Further prospective randomised controlled studies assessing these outcomes as well as longer-term outcomes in these women and their children are needed.

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BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common preterm birth antecedent. Preterm infants experience increased adverse newborn outcome risks. Infection is a risk factor for early birth in PPROM. Current management is antibiotic therapy, antenatal corticosteroids and to plan delivery at 37 weeks gestation. The microbiota and probiotics are potentially protective and may improve outcomes. AIMS: The primary aim is to evaluate whether oral probiotic therapy (Lactobacillus fermentum CECT5716) administered during PPROM between 24 and 34 weeks gestation prolongs pregnancy duration. The secondary aim is to evaluate maternal and neonatal outcomes. MATERIALS AND METHODS: This is a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial in Australia. The population will be women with a singleton pregnancy and PPROM less than 34 weeks gestation. The intervention will be an oral probiotic therapy compared with a placebo control. The primary outcome will be the proportion of women still pregnant at seven days following PPROM. One-to-one randomisation will occur within 24 h of PPROM. The trial is powered (80%, alpha = 0.05) to detect an absolute percentage increase in the primary outcome of 30%, (from expected rate of 20% up to 50%). DISCUSSION: This trial will provide evidence for the effectiveness of the probiotic in prolonging pregnancy duration. Findings will inform the feasibility of a larger trial to examine the effect of oral probiotics on clinically important maternal and neonatal outcomes in PPROM.

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BACKGROUND: Preterm prelabour rupture of membranes (PPRoM) is commonly associated with preterm delivery and affects up to 3% of all pregnancies. It is associated with high rates of morbidity and mortality for the mother and the newborn. OBJECTIVES: To identify risk factors for PPRoM and develop a model for first-trimester prediction of risk of PPRoM. METHODS: A retrospective analysis of a series of women who had first-trimester (11-13+6 weeks) screening for aneuploidy and pre-eclampsia and delivered in the same institution was performed. Univariate and multivariate logistic regression analyses were used to identify maternal and pregnancy factors and then develop a clinical prediction model for PPRoM. RESULTS: 10,280 women were screened between April 2010 and October 2016. 144 (1.4%) had PPRoM. Maternal factors predictive of PPRoM included nulliparity (parous women, OR 0.53; 95% CI 0.4-0.8), pre-existing diabetes mellitus (DM) (Type 1 DM, OR 6.7; 95% CI 2.3-19.4, Type 2 DM, OR 5.3; 95% CI 1.6-18.3), maternal age group (p = 0.004), and BMI category (p = 0.012). Uterine artery pulsatility index (UAPI) and biochemical parameters (PAPP-A, free ßHCG) did not reach statistical significance. The predictive model had moderate efficacy with an area under the ROC curve of 0.67. CONCLUSIONS: Several maternal characteristics collected during first-trimester screening predict PPRoM. Biomarkers currently measured during first-trimester screening (PAPP-A, ßHCG, and UAPI) do not predict PPRoM. Whilst a predictive model can be generated with information currently collected at 11-13+6 weeks, this has only modest screening performance. First-trimester screening provides a structured framework where other predictors could improve model performance, and future studies should focus on the addition of other risk factors and biomarkers that may improve screening efficacy.

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Spontaneous Preterm birth (SPTB) is a common obstetric complication affecting 12.9 million births worldwide and is the leading cause of neonatal morbidity and mortality. Disruption in the vaginal microbiota has an impact on the maternal immunological profile leading to SPTBs. Scientists have struggled to link maternal infectious agents with the dysregulation of the maternal immune response in cases of SPTBs. Throughout the last decade, important findings regarding the role of microbiota and its genome, the so-called microbiome, have linked alterations within the population of the microorganisms in our bodies with changes in nutrition, immunity, behaviour and diseases. In this review, evidence regarding the female genital tract microbiota and microbiome has been examined to help further our understanding of its role in disrupting the maternal immune system resulting in spontaneous preterm birth.

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The placenta accreta spectrum (PAS) describes invasion and adherence of the placenta onto or beyond the myometrium. Prenatal imaging improves management outcomes. In low- and middle-income countries (LMIC), however, the unavailability of ultrasonography in some health facilities delays the diagnosis, particularly if the prenatal period is asymptomatic. Following vaginal delivery, it often manifests as failure to remove a retained placenta manually. In the absence of haemorrhage, expectant management involving leaving the placenta in situ, is an option. In the presence of haemorrhage and/or sepsis, hysterectomy is usually recommended. We present a case of an expectantly managed PAS following a spontaneous preterm vaginal birth. The patient developed puerperal uterine prolapse with the placenta in situ, a previously unreported complication, but this was successfully reduced manually.

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Objective: Ureaplasma urealyticum and Mycoplasma hominis are the most common microorganisms found in the amniotic fluid of patients at risk for preterm delivery. However, culture techniques for genital mycoplasms require special conditions, are barely considered as part of the evaluation of suspected intra-amniotic infection (IAI) and the results are available within 2 and 7 days. The objectives of this study are to validate the use of two commercially available kits (Mycoplasma IES y MYCOFAST® RevolutioN) for the identification of Ureaplasma spp. and Mycoplasma hominis in amniotic fluid, to compare the results of these kits with those obtained by culture and real-time polymerase chain reaction (qPCR) and to report the antibiotic sensitivity profile of the genital mycoplasms identified.Methods: This is a prospective cohort study including women with singleton and twin gestations between 16 and 36 weeks. Patients were admitted to perform an amniocentesis due to pregnancy complications considered at high risk for IAI (e.g. preterm labor with intact membranes, preterm prelabour rupture of membranes, short cervix, etc.), treatment of polyhydramnios, and for the assessment of fetal death and fever without a focus.Results: Overall, 93 patients underwent amniocentesis and 63 had results available for all tests. The prevalence of a positive culture was 6% (4/63). There were four cases of Ureaplasma spp. and none of Mycoplasma hominis. The qPCR identified one case as Ureaplasma spp., one case as Ureaplasma parvum and two cases as Ureaplasma urealyticum. For all tests, the diagnostic performance was as follows: sensitivity 100% [95% CI (39.8-100%)], specificity 100% [95% CI (93.9-100%)], positive predictive value 100% [95% CI (39.8-100%)] and negative predictive value 100% [95% CI (93.9-100%)]. In this cohort, Ureaplasma spp. showed low resistance to erythromycin, but a high resistance to clindamycin and clarithromycin that may change according to the antibiotic concentration.Conclusions: To our knowledge, this is the first study that validates the use of the Mycoplasma IES and MYCOFAST® RevolutioN kits for the identification of genital mycoplasmas in amniotic fluid. The results of these kits are mostly available within 24 hours, have an excellent correlation with those from broth cultures and qPCR and characterize the antibiotic sensitivity profile of the genital mycoplasms identified, providing an opportunity for specific treatment in cases of IAI. Further validation studies in other populations are needed.

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OBJECTIVE: To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population-based cohort. DESIGN: Retrospective cohort study. SETTING: California, USA. POPULATION: All live singleton births in California between 2007 and 2011 were analysed. Patients with autoimmune disease at delivery were identified by International Classification of Diseases, Ninth Revision , Clinical Modification (ICD-9-CM), codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA). METHODS: Maternally linked hospital and birth certificate records of 2 481 516 deliveries were assessed (SLE n = 2272, RA n = 1501, SSc n = 88, JIA n = 187, DM/PM n = 38). Multivariable Poisson regression models estimated the risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared with the general obstetric population, adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care. MAIN OUTCOME MEASURES: Preterm birth (PTB) was assessed overall (20-36 weeks of gestation) and by subphenotype: preterm prelabour rupture of membranes (PPROM), spontaneous birth, or medically indicated PTB. The risk of PTB overall and for each phenotype was partitioned by gestational age: early (20-31 weeks of gestation) and late (32-36 weeks of gestation). RESULTS: Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27, 95% CI 3.01-3.56), RA (RR 2.04, 95% CI 1.79-2.33), SSc (RR 3.74, 95% CI 2.51-5.58), JIA (RR 2.23, 95% CI 1.54-3.23), and DM/PM (RR 5.26, 95% CI 3.12-8.89). These elevated risks were observed for the majority of PTB phenotypes as well. CONCLUSIONS: Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counselling and close monitoring during pregnancy is crucial. TWEETABLE ABSTRACT: This study found that women with systemic autoimmune diseases have an elevated risk of preterm birth phenotypes.

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OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP-9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes.

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BACKGROUND: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. METHODS: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. RESULTS: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. CONCLUSIONS: Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

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