OBJECTIVES: To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes. METHODS: From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0 weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients. RESULTS: We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33. CONCLUSIONS: External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes.

• Keywords
• intra-amniotic inflammation, point-of-care, prediction models, preterm labor and intact membranes, vaginal alpha-fetoprotein, vaginal interleukin-6,
• MeSH
• alpha-Fetoproteins * analysis   MeSH
• Amniocentesis MeSH
• Biomarkers analysis   MeSH
• Chorioamnionitis * diagnosis   metabolism   MeSH
• Adult MeSH
• Risk Assessment methods   MeSH
• Interleukin-6 analysis   metabolism   MeSH
• Humans MeSH
• Amniotic Fluid chemistry   MeSH
• Obstetric Labor, Premature * diagnosis   metabolism   MeSH
• Prospective Studies MeSH
• Pregnancy MeSH
• Vagina metabolism   chemistry   MeSH
• Point-of-Care Systems MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH
• Names of Substances
• alpha-Fetoproteins * MeSH
• Biomarkers MeSH
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH

BACKGROUND: This study aimed to assess variations in the absolute counts of various leukocyte subsets in the peripheral blood of women with pregnancies affected by preterm prelabour rupture of membranes (PPROM), in relation to the presence of intra-amniotic inflammation (IAI). METHODS: The study included fifty-two women with singleton pregnancies experiencing PPROM. Absolute counts of different leukocyte subpopulations, such as granulocytes, monocytes, lymphocytes, T cells and their subsets, B cells and their subsets, and NK cells and their subsets, were measured in maternal peripheral blood samples using multicolour flow cytometry. IAI was identified by elevated concentrations of interleukin 6 (IL-6) in the amniotic fluid, which was collected through transabdominal amniocentesis. RESULTS: Women with IAI exhibited higher absolute counts of leukocytes (p = 0.003), granulocytes (p = 0.008), and monocytes (p = 0.009). However, the presence of IAI did not significantly affect the absolute counts of lymphocytes or their subpopulations. CONCLUSIONS: The study found that IAI is associated with changes in the absolute counts of leukocytes from the innate immunity compartment in the peripheral blood of women with pregnancies complicated by PPROM. Conversely, it does not significantly alter the counts of cells from the adaptive immune system. The changes observed may reflect the natural, temporal, and localised characteristics of IAI.

Preterm birth is the most serious complication in contemporary perinatal medicine. Preterm birth, which is defined as a labour before the completion of 37 weeks of pregnancy, is often accompanied by premature rupture of the amniotic membranes and drainage of amniotic fluid. Such a situation is often complicated by inflammation, which adversely affects the health of the foetus. A number of procedures and markers have been developed for the diagnosis of inflammation, but they are determined from hard-to-reach amniotic fluid. It is therefore appropriate to try to find reliable markers of inflammation in the much more accessible maternal peripheral blood. Such a marker can be increased numbers of leukocytes, which have been repeatedly investigated in this context. However, little attention is directed to other leukocyte populations and especially to various lymphocyte subpopulations. This study aimed to test changes in absolute counts of different types of leukocytes and lymphocyte subpopulations in women with premature rupture of membranes with respect to ongoing inflammation. The results of the study showed that inflammation is accompanied by increased numbers of leukocytes, granulocytes and monocytes, however, the results did not show significant changes in the number of lymphocytes and their subpopulations.

• Keywords
• Intra-amniotic inflammation, PPROM, flow cytometry, preterm birth, subpopulations of leukocytes,
• MeSH
• Amniocentesis MeSH
• Chorioamnionitis * blood   MeSH
• Adult MeSH
• Interleukin-6 blood   analysis   MeSH
• Leukocytes MeSH
• Humans MeSH
• Amniotic Fluid cytology   MeSH
• Leukocyte Count MeSH
• Fetal Membranes, Premature Rupture * blood   MeSH
• Immunity, Innate MeSH
• Flow Cytometry MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Interleukin-6 MeSH

INTRODUCTION: This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations. MATERIAL AND METHODS: This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra-amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra-amniotic inflammation (by amniotic fluid interleukin-6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt-1 and PlGF were assessed using the Elecsys® sFlt-1 and Elecsys® PlGF immunoassays and converted into multiples of medians. RESULTS: Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt-1 and sFlt-1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt-1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt-1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt-1 and sFlt-1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion. CONCLUSIONS: Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra-amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.

• Keywords
• amniotic fluid, angiogenic factors, inflammation, microorganism, preterm delivery,
• MeSH
• Amniocentesis MeSH
• Biomarkers blood   MeSH
• Chorioamnionitis blood   MeSH
• Adult MeSH
• Gestational Age MeSH
• Humans MeSH
• Placenta Growth Factor * blood   MeSH
• Amniotic Fluid * microbiology   metabolism   MeSH
• Fetal Membranes, Premature Rupture * blood   MeSH
• Vascular Endothelial Growth Factor Receptor-1 * blood   MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• FLT1 protein, human MeSH Browser
• PGF protein, human MeSH Browser

BACKGROUND: Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intraamniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intraamniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear. OBJECTIVE: This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma species DNA in amniotic fluid. STUDY DESIGN: This retrospective cohort study included singleton-gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission. Follow-up amniocentesis was performed in a subset of patients unless abortion or delivery occurred earlier. Concentrations of interleukin-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intraamniotic inflammation was defined as an interleukin-6 concentration ≥3000 pg/mL in the amniotic fluid samples. RESULTS: A total of 36 patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intraamniotic inflammation (n=25) were treated using a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. The patients without intraamniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intraamniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the interleukin-6 concentration in the amniotic fluid at follow-up amniocentesis compared with that at the initial amniocentesis in patients with intraamniotic inflammation (median [interquartile range]: 3457 pg/mL [2493-13,203] vs 19,812 pg/mL [11,973-34,518]; P=.0001). Amniotic fluid samples with Ureaplasma species DNA had a lower microbial load at the time of follow-up amniocentesis compared with the initial amniocentesis (median [interquartile range]: 1.5×105 copies DNA/mL [1.3×105-1.7×105] vs 8.0×107 copies DNA/mL [6.7×106-1.6×108]; P=.02). CONCLUSION: Antibiotic therapy was associated with reduced intraamniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intraamniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma species DNA in the amniotic fluid.

• Keywords
• 16S ribosomal RNA, Ureaplasma, abortion, amniocentesis, amniotic fluid, bacteria, biomarker, ceftriaxone, chorioamnionitis, clarithromycin, funisitis, genital mycoplasma, inflammation, interleukin 6, intraamniotic infection, microbial invasion of the amniotic cavity, neonatal outcome, nucleic acid, polymerase chain reaction, pregnancy, prematurity, preterm birth, rapid point-of-care test, sterile intraamniotic inflammation,
• MeSH
• Amniocentesis adverse effects   MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Chorioamnionitis * microbiology   MeSH
• Uterine Hemorrhage MeSH
• DNA MeSH
• Pregnancy Trimester, Second MeSH
• Interleukin-6 MeSH
• Humans MeSH
• Amniotic Fluid microbiology   MeSH
• Fetal Membranes, Premature Rupture * drug therapy   MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Ureaplasma MeSH
• Inflammation complications   MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• DNA MeSH
• Interleukin-6 MeSH

INTRODUCTION: Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery. OBJECTIVE: The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women. METHOD: A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14-19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery. RESULTS: Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated. CONCLUSIONS: Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.

• Keywords
• Amniotic fluid, gestational duration, metabolomics, mid-trimester, spontaneous preterm delivery,
• MeSH
• Amniocentesis MeSH
• Biomarkers metabolism   MeSH
• Pregnancy Trimester, Second MeSH
• Gestational Age MeSH
• Cohort Studies MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Amniotic Fluid * metabolism   MeSH
• Premature Birth * diagnosis   metabolism   MeSH
• Case-Control Studies MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH

OBJECTIVE: CD11b is an integrin molecule located on the surface of leukocytes. CD11b is involved in the processes of cell adhesion and migration. Expression of CD11b increases during inflammation. Therefore, this study was aimed at the evaluation of concentrations of CD11b in the amniotic fluid from pregnancies complicated by preterm prelabor rupture of the membranes (PPROM), with respect to the presence of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI (the presence of both MIAC and IAI). METHODS: Eighty women with singleton pregnancies complicated by PPROM were included. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid CD11b concentrations were determined by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined by a bedside amniotic fluid interleukin-6 concentration ≥745 pg/mL. RESULT: Women with MIAC or microbial-associated IAI had higher CD11b concentrations in the amniotic fluid than women without these complications (with MIAC: median 0.31 ng/mL versus without MIAC: median 0.17 ng/mL, p = .001; with microbial associated-IAI: median 0.35 ng/mL versus without microbial-associated IAI: median 0.16 ng/mL; p =.02). The presence of IAI was not associated with elevated CD11b concentrations. A weak negative correlation was found between amniotic fluid CD11b concentrations and interleukin-6 concentrations (rho = 0.26; p = .02). CONCLUSIONS: MIAC and microbial-associated IAI are characterized by higher amniotic fluid CD11b concentrations in pregnancies complicated by PPROM.

• Keywords
• Amniotic fluid, inflammation, intergrin, preterm delivery,
• MeSH
• Amniocentesis MeSH
• Chorioamnionitis * metabolism   MeSH
• Gestational Age MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Amniotic Fluid metabolism   MeSH
• Fetal Membranes, Premature Rupture * metabolism   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

AIMS: The aim of this study was to evaluate the role of IL-6 point-of-care test in amniotic fluid obtained from serial amniocentesis in expectantly managed women with PPROM between 24 and 34 weeks of gestation. METHODS: We conducted a prospective observational cohort study which included 62 pregnant women with PPROM in gestational weeks between 22+0 and 34+0. Women aged >18 years were eligible if they presented with PPROM and a singleton pregnancy. Only women who delivered at >24.0 weeks were included in the study. In all women, the maternal blood sampling and a transabdominal amniocentesis were performed at the time of admission prior to the administration of corticosteroids, antibiotics, or tocolytics, to rule out signs of chorioamnionitis. Maternal temperature, maternal serum C-reactive protein (CRP) and white blood cell (WBC) counts were assayed every subsequent day until delivery. Amniotic fluid was used for the clinical assessment (IL-6 point-of-care test, identification of microorganisms in the amniotic fluid. After one week of expectant management of PPROM, second amniocentesis with amniotic fluid sampling was performed in patients who did not deliver. For all newborns, medical records regarding neonatal morbidity and mortality were reviewed. RESULTS: In total, 62 women aged 19 to 41 years were recruited in the study. The mean gestational age at the time of PPROM was 31+0, the mean gestational age at labor was 32+1, and the median time from PPROM to childbirth was 112 h. IL-6 point-of-care test values above 1,000 pg/mL (positive Il-6 AMC) were found in 12 women (19.4%) with median interval from PPROM to childbirth 56 h (min-max: 6.4-288). IL-6 point-of-care test values below 1,000 pg/mL (negative Il-6 AMC) were found in 51 women (81.0%). The neonatal mortality rate was 1.9% and was associated with prematurity. CONCLUSION: The major clinical finding of our study is that serial transabdominal amniocentesis with Il-6 point-of-care test helps to identify a high inflammatory status in amniotic fluid in women with PPROM. Subsequent expectant management of women with PPROM does not lead to worsening of short-term neonatal outcomes.

• Keywords
• Il-6, PPROM, amniocentesis, poin-of-care test,
• MeSH
• Amniocentesis * MeSH
• Interleukin-6 * MeSH
• Humans MeSH
• Watchful Waiting MeSH
• Fetal Membranes, Premature Rupture MeSH
• Prospective Studies MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Interleukin-6 * MeSH

The development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008-2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259 days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this.

• Keywords
• Amniotic fluid, Gestational duration, Inflammation, Mid-trimester, Proteins,
• MeSH
• Amniocentesis MeSH
• Chemokine CCL4 analysis   MeSH
• Adult MeSH
• Gestational Age MeSH
• Calgranulin A analysis   MeSH
• Humans MeSH
• Labor Onset MeSH
• Amniotic Fluid chemistry   MeSH
• Prospective Studies MeSH
• Pregnancy metabolism   MeSH
• Thrombospondin 1 analysis   MeSH
• Pregnancy Trimesters * MeSH
• Pregnancy Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy metabolism   MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chemokine CCL4 MeSH
• Calgranulin A MeSH
• S100A8 protein, human MeSH Browser
• Thrombospondin 1 MeSH

INTRODUCTION: The impact of bleeding for women with bleeding disorders (WBD) is of increasing focus and importance. Despite this, optimal management strategies are unclear and knowledge gaps persist. AIM: To examine practices and define research priorities on diagnosis and management of WBD in Europe. METHODS: An electronic survey on clinical management of WBD was sent to 136 European haemophilia treatment centres (HTCs), including open questions on knowledge gaps and research priorities. RESULTS: Fifty-nine HTCs from 12 Western (WE) and 13 Central/Eastern European (CEE) countries completed the survey. Less than half runs a joint clinic (24 HTCs, 42%). Most centres without a joint clinic have a named obstetrician (81%) and/or gynaecologist (75%) available for collaboration. Overall 18/54 (33%) European HTCs do not offer preimplantation genetic diagnosis. Third trimester amniocentesis to guide obstetric management is available 28/54 HTCs (52%), less frequent in CEE compared to WE countries (5/17 vs 23/37, P = .03). 53% of HTCs (28/53) reported that only 0%-25% of WBD seek medical advice for heavy menstrual bleeding (HMB). An algorithm managing acute HMB in WBD is lacking in 22/53 (42%) HTCs. The main reported knowledge and research gaps are lack of awareness & education on WBD among patients and caregivers, optimal diagnostic strategies and effective multidisciplinary management of pregnancy & HMB. CONCLUSION: Joint clinics, prenatal diagnostics and algorithms for managing acute HMB are lacking in many European HTCs. HMB may be an underestimated issue. This survey highlights the need to prioritize improvement of knowledge and patient care for WBD across Europe.

• Keywords
• bleeding disorder, haemophilia, heavy menstrual bleeding, postpartum haemorrhage and reproduction, survey, von Willebrand disease,
• MeSH
• Algorithms MeSH
• Amniocentesis statistics & numerical data   MeSH
• Pregnancy Complications, Hematologic epidemiology   MeSH
• Hemophilia A * complications   diagnosis   drug therapy   MeSH
• Blood Coagulation Disorders * complications   diagnosis   drug therapy   epidemiology   MeSH
• Humans MeSH
• Postpartum Hemorrhage epidemiology   etiology   MeSH
• Counseling MeSH
• Preimplantation Diagnosis statistics & numerical data   MeSH
• Prenatal Diagnosis standards   MeSH
• Surveys and Questionnaires MeSH
• Menorrhagia * diagnosis   etiology   therapy   MeSH
• Pregnancy MeSH
• Pregnancy Trimester, Third MeSH
• von Willebrand Diseases * complications   diagnosis   drug therapy   MeSH
• Health Knowledge, Attitudes, Practice MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe epidemiology   MeSH

BACKGROUND: Iatrogenic pneumothorax is a common complication of various diagnostic and therapeutic procedures such as transbronchial lung biopsies. The classical mode of treatment is chest tube insertion. Pneumothorax devices are now available on the market but there is a dearth of data on their efficacy to treat iatrogenic pneumothorax. It is important to provide such data as the pathophysiology of iatrogenic pneumothorax is different in comparison with spontaneous pneumothorax for which some data is available. METHODS: This is a randomized, non-blinded, actively controlled trial of effectivity of iatrogenic pneumothorax treatment using the Pleuralvent™ device and chest tube insertion (16F). The secondary aim is to compare the overall pain level and the need for analgesic treatment in both treatment arms. We are planning to enrol 126 patients (63 in each treatment arm). DISCUSSION: Preliminary results showed similar effectivity of the Pleuralvent™ system compared to large bore chest tube insertion. This randomized clinical trial should confirm these results and prove that the Pleuralvent™ system is an effective way of treatment of patients with iatrogenic pneumothorax. If Pleuralvent™ proves to have the same level of efficacy, it may become the standard of care of patients with iatrogenic pneumothorax. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03700554.

• Keywords
• Pleuralvent™, chest tube, iatrogenic pneumothorax,
• MeSH
• Analgesics therapeutic use   MeSH
• Chest Pain drug therapy   etiology   MeSH
• Chest Tubes * MeSH
• Iatrogenic Disease * MeSH
• Humans MeSH
• Pneumothorax therapy   MeSH
• Randomized Controlled Trials as Topic MeSH
• Thoracentesis adverse effects   instrumentation   methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH
• Names of Substances
• Analgesics MeSH