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Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.

Amniotic fluid embolism (AFE) is a rare, yet life-threatening obstetric emergency characterised by sudden collapse of the mother due to circulatory and respiratory failure, often accompanied by coagulopathy. It accounts for a significant proportion of peripartum cardiac arrests and maternal deaths, with an incidence of 2-8 per 100,000 deliveries. The specific pathophysiology behind AFE remains unclear. However, one hypothesis states that amniotic fluid or fetal debris enters the maternal circulation, triggering a severe inflammatory and immunologic response. Diagnosis of AFE is primarily clinical as it relies on exclusion due to the unavailability of any definitive diagnostic test. Risk factors include caesarean delivery, multiple pregnancies, advanced maternal age, and pre-existing health conditions or comorbidities. Effective management centres on early recognition, aggressive, urgent supportive measures, and resuscitation. Advanced therapeutic options, such as veno-arterial extracorporeal membrane oxygenation (VA-ECMO), have shown potential in severe cases. Despite medical advancements in supportive care, which have led to reduced mortality rates, AFE remains highly unpredictable, carrying a significant risk of maternal and fetal mortality and morbidity. Survivors are often faced with long-term complications such as neurological deficits and cardiac problems. This comprehensive review aims to improve clinicians' awareness of AFE, summarize its risk factors, and provide an overview of the current strategies for early recognition and management, emphasizing recent advancements and the need for continued research in this critical area.

6-Nitrodopamine is an endogenous catecholamine responsible for numerous biological activities. Here, an improved method for the synthesis of both 6-nitrohomovanillic acid (6-NHVA) and its regioisomer 5-nitrohomovanillic acid (5-NHVA) is reported. The developed one-step synthetic procedures ensured the efficient preparation of the target compounds in good yields. Comprehensive structural characterization was achieved through one- and two-dimensional NMR studies and by high-resolution mass spectrometry (HR-MS/MS). The presence of both substances was identified in human amniotic fluid by LC-MS/MS.

Background Amniotic-fluid embolism (AFE) is a rare occurrence but life-threatening disease that can occur in process of delivery and postnatal women. The topic of cesarean section surgery and its associated risk factors has been neglected due to the infrequent occurrence of AFE. However, AFE significantly contribute to maternal morbidity and mortality. Purposes We aim to examine the correlation between clinical issues, prenatal complications, comorbidities, medical perioperative complications, and cesarean section surgery of AFE in the US, utilizing a Nationwide Inpatient Sample (NIS) database. Methods This study conducted a retrospective cohort analysis on cesarean deliveries in the United States using data from the NIS of the Healthcare Cost and Utilization Project (HCUP) to examine the incidence and risk factors of AFE during cesarean section surgery. The analysis included the period from January 1, 2010, to December 31, 2019. We employed a multivariable logistic regression to evaluate the main outcome, which encompassed the clinical, prenatal, comorbidity, and medical perioperative AFE undergoing cesarean deliveries. Results We identified AFE in 269 out of the 2,462,005 women whose cesarean deliveries we investigated, with an incidence rate of 0.0113%. In the AFE group, the median patient age at the cohort level was 32 years (IQR, 27–36 years). The in-hospital mortality rate for patients with AFE following cesarean delivery was significantly higher than for those without AFE (14.9% vs. 0.0%, P  < 0.001). In univariable analysis, P  < 0.05 served as the initial selection criterion. A multivariable analysis revealed that AFE at the time of cesarean deliveries was significantly correlated with chronic blood loss anemia, coagulopathy, congestive heart failure, other neurological disorders, fluid and electrolyte disorders, weight loss, pulmonary circulation disorders, abruptio placentae, and polyhydramnios. Conclusion This contemporaneous, nationwide investigation verified the incidence of cesarean deliveries by AFE and corroborated previously identified risk factors for AFE. Although the absolute risk of AFE is minimal, clinicians should be aware of the identified risk factors, such as chronic blood loss anemia, coagulopathy, and polyhydramnios, to enhance preparedness and optimize patient counseling, particularly in high-risk cases.

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.

Amniotic fluid embolism (AFE) remains one of the principal reported causes of direct maternal mortality in high-income countries. However, obtaining robust information about the condition is challenging because of its rarity and its difficulty to diagnose. This study aimed to pool data from multiple countries in order to describe risk factors, management, and outcomes of AFE and to explore the impact on the findings of considering United Kingdom, international, and United States AFE case definitions. A population-based cohort and nested case-control study was conducted using the International Network of Obstetric Survey Systems (INOSS). Secondary data on women with AFE (n = 99-218, depending on case definition) collected prospectively in population-based studies conducted in Australia, France, the Netherlands, Slovakia, and the UK were pooled along with secondary data on a sample of control women (n = 4,938) collected in Australia and the UK. Risk factors for AFE were investigated by comparing the women with AFE in Australia and the UK with the control women identified in these countries using logistic regression. Factors associated with poor maternal outcomes (fatality and composite of fatality or permanent neurological injury) amongst women with AFE from each of the countries were investigated using logistic regression or Wilcoxon rank-sum test. The estimated incidence of AFE ranged from 0.8-1.8 per 100,000 maternities, and the proportion of women with AFE who died or had permanent neurological injury ranged from 30%-41%, depending on the case definition. However, applying different case definitions did not materially alter findings regarding risk factors for AFE and factors associated with poor maternal outcomes amongst women with AFE. Using the most liberal case definition (UK) and adjusting for the severity of presentation when appropriate, women who died were more likely than those who survived to present with cardiac arrest (89% versus 40%, adjusted odds ratio [aOR] 10.58, 95% confidence interval [CI] 3.93-28.48, p < 0.001) and less likely to have a source of concentrated fibrinogen (40% versus 56%, aOR 0.44, 95% CI 0.21-0.92, p = 0.029) or platelets given (24% versus 49%, aOR 0.23, 95% CI 0.10-0.52, p < 0.001). They also had a lower dose of tranexamic acid (median dose 0.7 g versus 2 g, p = 0.035) and were less likely to have had an obstetrician and/or anaesthetist present at the time of the AFE (61% versus 75%, aOR 0.38, 95% CI 0.16-0.90, p = 0.027). Limitations of the study include limited statistical power to examine factors associated with poor maternal outcome and the potential for residual confounding or confounding by indication. The findings of our study suggest that when an AFE is suspected, initial supportive obstetric care is important, but having an obstetrician and/or anaesthetist present at the time of the AFE event and use of interventions to correct coagulopathy, including the administration of an adequate dose of tranexamic acid, may be important to improve maternal outcome. Future research should focus on early detection of the coagulation deficiencies seen in AFE alongside the role of tranexamic acid and other coagulopathy management strategies.

Purpose Amniotic fluid embolism (AFE) is a leading cause of obstetrical cardiac arrest and maternal morbidity. The pathogenesis of hemodynamic collapse is thought to be from right ventricular (RV) failure; however, there is a paucity of data documenting echocardiography findings in this population. We undertook a systematic review of the literature to evaluate the echocardiography findings in patients with AFE. Sources We retrieved all case reports and case series reporting AFE in Embase and MEDLINE from inception to 20 November 2021. Studies reporting AFE diagnosed by fulfilling at least one of three different proposed AFE criteria and echocardiography findings during hospitalization were included. Patient and echocardiographic data were retrieved, and univariate logistic regression analysis was performed for outcomes of interest. Bias was assessed using the Joanna Briggs Institute clinical appraisal tool for case series. Principal findings Eighty publications reporting on 84 patients were included in the final review. Fifty-five out of 82 patients with data (67%) showed RV dysfunction, including 11/82 (13%) with biventricular dysfunction; 14/82 (17%) had normal systolic function. No data on RV or left ventricular function were reported for two patients. The presence of RV dysfunction on echocardiography was associated with cardiac arrest (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.39 to 9.67; P = 0.009), and a composite risk of cardiac arrest, maternal death or use of extracorporeal membrane oxygenation (OR, 3.86; 95% CI, 1.43 to 10.4; P = 0.007). A low risk of bias was observed in 15/84 (18%) cases. Conclusions Right ventricular dysfunction on echocardiography is a common finding in AFE and is associated with a high risk of cardiac arrest. The finding of RV dysfunction on echocardiography may help diagnose AFE and help triage the highest risk patients with AFE. Study registration PROSPERO (CRD42021271323); registered 1 September 2021.

Interaction with intestinal microbes in infancy has a profound impact on health and disease in later life through programming of immune and metabolic pathways. We collected maternal faeces, placenta, amniotic fluid, colostrum, meconium and infant faeces samples from 15 mother-infant pairs in an effort to rigorously investigate prenatal and neonatal microbial transfer and gut colonisation. To ensure sterile sampling, only deliveries at full term by elective caesarean section were studied. Microbiota composition and activity assessment by conventional bacterial culture, 16S rRNA gene pyrosequencing, quantitative PCR, and denaturing gradient gel electrophoresis revealed that the placenta and amniotic fluid harbour a distinct microbiota characterised by low richness, low diversity and the predominance of Proteobacteria. Shared features between the microbiota detected in the placenta and amniotic fluid and in infant meconium suggest microbial transfer at the foeto-maternal interface. At the age of 3–4 days, the infant gut microbiota composition begins to resemble that detected in colostrum. Based on these data, we propose that the stepwise microbial gut colonisation process may be initiated already prenatally by a distinct microbiota in the placenta and amniotic fluid. The link between the mother and the offspring is continued after birth by microbes present in breast milk.

Myelomeningocele (MMC) and myeloschisis (MS) are considered as the most severe forms of spina bifida aperta characterized by incomplete closure of the neural tube during the first trimester of pregnancy. Open maternal-fetal surgery has been identified as a promising alternative for the repair of MMC/MS. The main goal of this study was the isolation and characterization of stem cells derived from MMC/MS amniotic fluid samples. Human amniotic fluid samples were obtained from pregnant women who underwent surgery for fetal spina bifida repair. We applied fluorescence activated-cell sorting (FACS) to immunoselect stem cells from heterogeneous populations of amniocytes based on cKIT (CD117) expression. The cKIT + amniocytes were then contrasted with cKIT − and unselected amniocytes in order to characterize the phenotype of these cells. cKIT-expressing amniocytes exhibited spindle-shape morphology, while amniocytes negative for cKIT were round-shaped. qRT-PCR analysis revealed significant upregulation of mean mRNA levels of KIT and CD90 genes and downregulation of CK8 gene in cKIT-expressing amniocytes, compared to the negative and unsorted cells. The expression of pluripotency antigens was comparable in sorted cKIT + and cKIT − amniocytes and in unselected cells. Our results are of pivotal importance for the future application of amniotic fluid derived stem cells in spina bidfida repair.

Recent studies have conflicting data regarding the presence of intra-amniotic microbiota. Viral communities are increasingly recognized as important although overlooked components of the human microbiota. It is unknown if the developing fetus is exposed to a community of viruses (virome). Given the debate over the existence of an intra-amniotic microbial community and the importance of understanding how the infant gut is populated, we characterized the virome and bacterial microbiota of amniotic fluid from 24 uncomplicated term pregnancies using next-generation sequencing methods. Contrary to expectations, the bacterial microbiota of amniotic fluid was indistinguishable from contamination controls. Viral reads were sparse in the amniotic fluid, and we found no evidence of a core viral community across samples.