Amniotic Fluid Embolism Coagulopathy Guided by the Point-of-Care Quantra QStat® Hemostasis System: A Case Report.

Amniotic fluid embolism (AFE) is a rare pregnancy complication associated with high maternal mortality that occurs during labor or in the early postpartum period. The diagnosis of AFE is challenging because signs and symptoms are common to other obstetric complications. Early identification and management of profound coagulopathy associated with AFE is essential to improve patient survival. We present a case of a 31-year-old woman with placenta previa and clinical suspicion of AFE after cesarean section. Immediately after delivery, the parturient presented hypotension, hypoxia, coagulopathy, and severe postpartum hemorrhage. We hereby discuss the role of the most recently developed point-of-care viscoelastic testing device, the Quantra QStat® system (Stago Group Company; HemoSonics LLC, Durham, NC), for early detection of acute obstetric coagulopathy and guided hemostatic treatment.

Meconium aspiration syndrome: from pathophysiology to treatment.

Meconium aspiration syndrome (MAS) is a clinical condition characterized by respiratory distress in neonates born through meconium-stained amniotic fluid (MSAF). Despite advances in obstetric practices and perinatal care, MAS remains an important cause of morbidity and mortality in term and post-term newborns. Since the 1960s, there have been significant changes in the perinatal and postnatal management of infants born through MSAF. Routine endotracheal suctioning is no longer recommended in both vigorous and non-vigorous neonates with MSAF. Supportive care along with new treatments such as surfactant, inhaled nitric oxide, and high-frequency ventilation has significantly improved the outcome of MAS patients. However, determining the most appropriate approach for this condition continues to be a topic of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management, and prognosis of infants with MAS.

Immersed in a reservoir of potential: amniotic fluid-derived extracellular vesicles.

This review aims to encapsulate the current knowledge in extracellular vesicles extracted from amniotic fluid and amniotic fluid derived stem/stromal cells. Amniotic fluid (AF) bathes the developing fetus, providing nutrients and protection from biological and mechanical dangers. In addition to containing a myriad of proteins, immunoglobulins and growth factors, AF is a rich source of extracellular vesicles (EVs). These vesicles originate from cells in the fetoplacental unit. They are biological messengers carrying an active cargo enveloped within the lipid bilayer. EVs in reproduction are known to play key roles in all stages of pregnancy, starting from fertilisation through to parturition. The intriguing biology of AF-derived EVs (AF-EVs) in pregnancy and their untapped potential as biomarkers is currently gaining attention. EV studies in numerous animal and human disease models have raised expectations of their utility as therapeutics. Amniotic fluid stem cell and mesenchymal stromal cell-derived EVs (AFSC-EVs) provide an established supply of laboratory-made EVs. This cell-free mode of therapy is popular as an alternative to stem cell therapy, revealing similar, if not better therapeutic outcomes. Research has demonstrated the successful application of AF-EVs and AFSC-EVs in therapy, harnessing their anti-inflammatory, angiogenic and regenerative properties. This review provides an overview of such studies and discusses concerns in this emerging field of research.

Is a Higher Amniotic Fluid Viral Load Associated with a Greater Risk of Fetal Injury in Congenital Cytomegalovirus Infection-A Systematic Review and Meta-Analysis.

Background: Numerous studies have aimed to predict prenatal and neonatal outcomes for pregnancies complicated by congenital cytomegalovirus (CMV). Presently, assessing CMV severity prenatally relies largely on fetal imaging. A controversy exists regarding CMV viral load (VL) and its association with fetal and neonatal sequelae. Objective: To perform a systematic review and meta-analysis investigating the association between CMV DNA VL in amniotic fluid and fetal and neonatal outcomes in pregnancies with congenital CMV. Results: All cohort, case-control and observational studies that compared outcomes of fetuses with congenital CMV and provided information on individual patient CMV VL quantified in copies per milliliter (c/mL) from inception to January 2023 were included, with no geographical or language restrictions. A total of 1251 citations were reviewed with eight studies meeting inclusion criteria and included in meta-analysis. Affected pregnancies had a higher VL in the amniotic fluid compared to those unaffected with a mean difference of 2.2e+7 (range 1.5e+7 to 2.8e+7). In subgroup analysis, the VL was significantly higher in the fetuses, with imaging findings related to CMV compared to asymptomatic fetuses with a mean difference of 4.1e+7 (95% CI 2.8e+7-5.4e+7). However, among babies with congenital CMV, the VL was not significantly different between symptomatic and asymptomatic babies. Conclusions: Amniotic fluid CMV VL is associated with fetal sequalae in congenital CMV, with a higher VL conferring a greater risk for prenatal injury.

A Case of Consumptive Coagulopathy Before Cardiopulmonary Failure in Amniotic Fluid Embolism and Review of Literature: A Perspective of the Latent Onset and Progression of Coagulopathy.

Amniotic fluid embolism (AFE) induces cardiopulmonary insufficiency with consumptive coagulopathy. Previous studies reported that refractory coagulopathy has already advanced at the onset of maternal cardiovascular and/or respiratory symptoms. However, when the consumption of coagulation factors starts during the clinical course, AFE remains to be elucidated. We report an intrapartum AFE case of consumptive coagulopathy before dyspnea with hypotension developing during urgent cesarean delivery that was revealed by non-reassuring fetal heart rate tracing. The patient, a 42-year-old multiparous parturient, underwent induced labor after a premature rupture of membranes in week 39 of pregnancy. Coagulation screening was initially within the normal range. Fetal heart rate monitoring demonstrated bradycardia coincided with uterine tachysystole after three hours, which required urgent cesarean section with preoperative blood screening. The hemoglobin level was maintained at 129 g/L; however, the fibrinogen value reduced to 1.79 g/L with D-dimer elevation over 60 µg/mL. Ninety minutes later, she developed dyspnea with hypotension at suturing hysterotomy. At the end of surgery, her fibrinogen further decreased to below 0.3 g/L with prolonged prothrombin time. After vigorous intensive care, she was discharged without sequelae. Consumptive coagulopathy may initiate and progress before apparent cardiopulmonary symptoms in some AFE cases. Non-reassuring fetal heart rate tracing concomitant with abrupt uterine tachysystole and/or hypertonus may be an earlier time point for the detection and intervention of AFE-related coagulopathy.

Possible germline mosaicism in a pedigree with Treacher Collins syndrome: A case report and brief review.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder, typically inherited as an autosomal dominant condition. Here, we report on a family in which germline mosaicism for TCS was likely present. The proband was diagnosed with TCS based on the typical clinical features and a pathogenic variant TCOF1 (c.4369_4373delAAGAA, p.K1457Efs*12). The mutation was not detected in his parents' peripheral blood DNA samples, suggesting a de novo mutation had occurred in the proband. However, a year later, the proband's mother became pregnant, and the amniotic fluid puncture revealed that the fetus carried the same mutation as the proband. Prenatal ultrasound also indicated a maxillofacial dysplasia with unilateral microtia. The mother then disclosed a previous birth history in which a baby had died of respiratory distress shortly after birth, displaying a TCS-like phenotype. Around the same time, the proband's father was diagnosed with mild bilateral conductive hearing loss. Based on array data, we concluded that the father may have had germline mosaicism for TCOF1 mutation. Our findings highlight the importance of considering germline mosaicism in sporadic de novo TCOF1 mutations when providing genetic consulting, and prenatal diagnosis is important when the proband's parents become pregnant again.

Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation.

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, versus 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.

Evaluation of Congenital Cytomegalovirus Infection in Pregnant Women Admitted to a University Hospital in Istanbul.

Cytomegalovirus (CMV) can cause serious complications in immunocompromised individuals and fetuses with congenital infections. These can include neurodevelopmental impairments and congenital abnormalities in newborns. This paper emphasizes the importance of concurrently evaluating ultrasonography findings and laboratory parameters in diagnosing congenital CMV infection. To examine the prenatal characteristics of CMV DNA-positive patients, we assessed serum and amniotic fluid from 141 pregnant women aged 19-45 years, each with fetal anomalies. ELISA and PCR tests, conducted in response to these amniocentesis findings, were performed at an average gestational age of 25 weeks. Serological tests revealed that all 141 women were CMV IgG-positive, and 2 (1.41%) had low-avidity CMV IgG, suggesting a recent infection. CMV DNA was detected in 17 (12.05%) amniotic fluid samples using quantitative PCR. Of these, 82% exhibited central nervous system abnormalities. Given that most infections in pregnant women are undetectable and indicators non-specific, diagnosing primary CMV in pregnant women using clinical findings alone is challenging. We contend that serological tests should not be the sole means of diagnosing congenital CMV infection during pregnancy.

Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic-ischemic encephalopathy and biomarkers of brain damage.

BACKGROUND: Amniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed. METHODS: This single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis. RESULTS: (1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°-III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001). CONCLUSION: Among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.

Anaphylaxis-induced premature uterine contractions: a case report and literature review.

BACKGROUND: Preterm labor is caused by multiple etiologies, including intra-amniotic infection and/or intra-amniotic inflammation, vascular disorders, cervical disease, decidual senescence, and breakdown of maternal-fetal tolerance. Accumulating evidence in vivo and in vitro has shown that an allergic reaction, including anaphylaxis, can induce preterm uterine contractions. This report describes a case of a pregnant woman who developed anaphylaxis and regular uterine contractions after the ingestion of a strawberry-coated biscuit. We also review the mechanism of allergic reaction (hypersensitivity)-induced preterm labor. Case presentation A 31-year-old woman (gravida 1, para 0) at 30+2 weeks of gestation was admitted to the labor and delivery unit with regular uterine contractions and anaphylactic symptoms after she ingested a strawberry-coated biscuit as a snack. The uterine contractions resolved after the treatment of anaphylaxis by administering antihistamines and epinephrine. The patient subsequently delivered at 39+3 weeks of gestation. The amniotic fluid profile showed no infection or inflammation. A postpartum skin-prick test confirmed a positive type 1 hypersensitivity reaction to the strawberry-coated biscuit. CONCLUSIONS: We report a case of anaphylaxis-induced uterine contractility in which uterine contractions subsided after the treatment of anaphylaxis. The absence of intra-amniotic infection and/or intra-amniotic inflammation and the cause of the anaphylaxis were confirmed. Our findings indicate that maternal allergic reactions may be one of the mechanisms of preterm labor.

A multicenter study of maternal conditions and amniotic fluid volume in Ethiopia in 2023.

The amniotic fluid is a protective liquid found in amniotic found in the amniotic sac and mainly containing water and some solid substances including epitheloid and fibroblastic type cells. Most of the studies conducted about amniotic fluid volume (AFV) reported fetal and placental factors as a determinant of AFV. The aim of this study is to examine maternal and obstetric conditions in relation to AFV among women with term pregnancies. A multicenter institutional based cross-sectional study was conducted among clients attending selected public hospitals of South Gondar Zone, Ethiopia from January 01, 2023 to May 30, 2023. The sample size was calculated by using the assumption of single population proportion formula considering the prevalence value of 50%, 95% confidence interval, and margin of error 5% and 10% non respondent rate. In our study rural residency AOR = 3.21 (1.19-5.37), chronic illness AOR = 2.12 (1.33-4.61), short inter pregnancy interval AOR = 3.03 (2.18-6.28), Hypermesis gravidarum AOR = 1.19 (1.02-4.41), and maternal diabetics AOR = 2.16 (1.32-4.75) had significant association with the outcome variable. These maternal conditions may be correlated with an abnormal volume of amniotic fluid.

Duration of biophysical profile in periviable and very preterm low-risk pregnancies.

BACKGROUND: In recent years, perinatal viability has shifted from 24 to 22 weeks of gestation at many institutions after improvements in survival in neonates delivered at the limit of viability. Monitoring these fetuses is essential because antenatal interventions with resuscitation efforts are available for patients at risk of delivery at the limit of viability. However, fetal monitoring using biophysical profiles has not been extensively studied in very preterm pregnancies, particularly in the periviable period (20 weeks 0 days to 23 weeks 6 days). OBJECTIVE: This study aimed to (1) investigate whether the completion of biophysical profiles within 30 minutes is feasible in very preterm pregnancies, and (2) determine the average observation time required to achieve a score of 8 out of 8 in very preterm pregnancies from 20 weeks 0 days to 31 weeks 6 days. STUDY DESIGN: This study prospectively evaluated biophysical scores in singleton pregnancies undergoing routine ultrasonography at or near viability from 20 weeks 0 days to 23 weeks 6 days (periviable or group I), 24 weeks 0 days to 27 weeks 6 days (group II), and 28 weeks 0 days to 31 weeks 6 days (group III). The results and duration of biophysical profiles were compared with those of a control group (32 weeks 0 days to 35 weeks 6 days) undergoing indicated fetal surveillance. Biophysical profiles were performed for all studied pregnancies until a score of 8 out of 8 was obtained. When >1 biophysical profile was obtained during pregnancy, each was analyzed individually. Pregnancies with fetal anomalies or obstetrical/medical indications for fetal well-being surveillance were excluded. Analysis of variance and post hoc Tukey tests were used for comparisons. RESULTS: Data were collected for 123 participants, yielding 79, 75, and 72 studies for groups I, II, and III, respectively. The control group included 42 patients, yielding 140 studies. At 30 minutes, 80% (63/79) of the studies in the periviable group had a score of 8 out of 8, as opposed to 100% (140/140) in the control group (P<.001). The mean±standard deviation time in minutes to achieve a biophysical score of 8 out of 8 was 23.3±10.1 in the periviable group, as opposed to 9.4±6.5 in controls (P<.001). Extending the study to +2 standard deviations (43.6 minutes) in the periviable group resulted in 97% (77/79) of the scans scoring 8 out of 8 in the absence of adverse outcomes. In the other groups, a biophysical score of 8 out of 8 within 30 minutes was obtained in 97% (73/75) and 100% (72/72) in groups II and III, respectively; the mean±standard deviation times were 17.1±8.4 minutes (group II) and 13.1±7.3 minutes (group III). No adverse outcomes developed during the study participation in groups I to III. CONCLUSION: Biophysical scores of 8 out of 8 can be successfully achieved in low-risk periviable pregnancies (20 weeks 0 days to 23 weeks 6 days) within an observation time longer than the standard 30-minute duration. The time required to reach a score of 8 out of 8 decreases as gestation progresses. We suggest adjusting the observation time for biophysical profile completion according to the gestational age.

Nanopore-based metagenomics analysis reveals microbial presence in amniotic fluid: A prospective study.

Background: Current research on amniotic fluid (AF) microbiota yields contradictory data, necessitating an accurate, comprehensive, and scientifically rigorous evaluation. Objective: This study aimed to characterise the microbial features of AF and explore the correlation between microbial information and clinical parameters. Methods: 76 AF samples were collected in this prospective cohort study. Fourteen samples were utilised to establish the nanopore metagenomic sequencing methodology, whereas the remaining 62 samples underwent a final statistical analysis along with clinical information. Negative controls included the operating room environment (OE), surgical instruments (SI), and laboratory experimental processes (EP) to elucidate the background contamination at each step. Simultaneously, levels of five cytokines (IL-1ß, IL-6, IL-8, TNF-α, MMP-8) in AF were assessed. Results: Among the 62 AF samples, microbial analysis identified seven without microbes and 55 with low microbial diversity and abundance. No significant clinical differences were observed between AF samples with and without microbes. The correlation between microbes and clinical parameters in AF with normal chromosomal structure revealed noteworthy findings. In particular, the third trimester exhibited richer microbial diversity. Pseudomonas demonstrated higher detection rates and relative abundance in the second trimester and Preterm Birth (PTB) groups. S. yanoikuyae in the PTB group exhibited elevated detection frequencies and relative abundance. Notably, Pseudomonas negatively correlated with activated partial thromboplastin time (APTT) (r = -0.329, P = 0.016), while Staphylococcus showed positive correlations with APTT (r = 0.395, P = 0.003). Furthermore, Staphylococcus negatively correlated with birth weight (r = -0.297, P = 0.034). Conclusion: Most AF samples exhibited low microbial diversity and abundance. Certain microbes in AF may correlate with clinical parameters such as gestational age and PTB. However, these associations require further investigation. It is essential to expand the sample size and undertake more comprehensive research to elucidate the clinical implications of microbial presence in AF.

Proteomic Analysis of Preeclampsia Amniotic Fluid Based on a Novel Solid-State Preservation Method.

Objective: Amniotic fluid (AF) plays a crucial role in diagnosing and predicting perinatal diseases, specifically preeclampsia (PE). Adequate preservation of AF samples is essential for advancing the development of PE-related biomarkers and understanding the disease's mechanisms. Materials and Methods: This study presents a method for preserving proteins in AF on a solid medium, specifically a nitrocellulose membrane, which is referred to as an AF membrane. Samples were collected from normotensive subjects and PE patients and treated with direct freezing and the AF membrane methods, respectively. Protein quality was assessed through sodium dodecyl sulfate-page and capillary electrophoresis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) with data-independent acquisition was employed for proteomic analysis. Bioinformatics analysis identified differentially expressed proteins and pathways distinguishing normotensive subjects from PE patients. Results: Comparison of the AF membrane method to the direct freezing method showed no significant impact on the protein content in the AF. The preservation methods employed did not result in evident protein differences or degradation in the AF obtained from both normotensive subjects and PE patients. Analysis based on Gene Ontology and HALLMARK gene sets revealed the upregulation of pathways associated with angiotensin, reactive oxygen species, and coagulation in PE patients. Furthermore, several biomarkers previously reported to be increased in PE serum, namely ENG, ERN1, FLT1, GDF15, HSPA5, LGALS3, PAPPA, PTX3, and SERPINE1, were significantly elevated in the AF. Conclusion: The AF membrane method proved to be highly effective, reliable, and durable for preserving proteins in AF samples. Preserving AF samples in a solid state holds significant value in discovering novel protein biomarkers and investigating the underlying mechanisms of PE.

Second Trimester Amniotic Fluid Angiotensinogen Levels Linked to Increased Fetal Birth Weight and Shorter Gestational Age in Term Pregnancies.

BACKGROUND: Despite the considerable progress made in recent years in fetal assessment, the etiology of fetal growth disturbances is not as yet well understood. In an effort to enhance our knowledge in this area, we investigated the associations of the amniotic fluid angiotensinogen of the renin-angiotensin system with fetal growth abnormalities. METHODS: We collected amniotic fluid samples from 70 pregnant women who underwent amniocentesis during their early second trimester. Birth weight was documented upon delivery, after which the embryos corresponding to the respective amniotic fluid samples were categorized into three groups as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Amniotic fluid angiotensinogen levels were determined by using ELISA kits. RESULTS: Mean angiotensinogen values were 3885 ng/mL (range: 1625-5375 ng/mL), 4885 ng/mL (range: 1580-8460 ng/mL), and 4670 ng/mL (range: 1995-7250 ng/mL) in the SGA, LGA, and AGA fetuses, respectively. The concentrations in the three groups were not statistically significantly different. Although there were wide discrepancies between the mean values of the subgroups, the large confidence intervals in the three groups negatively affected the statistical analysis. However, multiple regression analysis revealed a statistically significant negative correlation between the angiotensinogen levels and gestational age and a statistically significant positive correlation between the birth weight and angiotensinogen levels. DISCUSSION: Our findings suggest that fetal growth abnormalities did not correlate with differences in the amniotic fluid levels of angiotensinogen in early second trimester pregnancies. However, increased angiotensinogen levels were found to be consistent with a smaller gestational age at birth and increased BMI of neonates.

[Maternal mortality due to Amniotic Fluid Embolism in France 2016-2018]. / Mortalité maternelle par embolie amniotique en France 2016­2018.

Amniotic embolism remains the 3rd leading cause of maternal death in France, with 21 maternal deaths over the 2016-2018 triennium. The women who died were more likely to be obese (25%), to benefit from induction of labor (71%) and be cared in a maternity hospital <1500 deliveries/year (45%), compared with the reference population (ENP 2016). The symptom occurred mainly during labor (95%) and the course was rapid, with a symptom-to-fatality interval of 4hours 45minutes (min: 25minutes - max: 8 days). Preventability was proposed for 35% of the deaths assessed, with areas for improvement identified in terms of technical skills (haemostasis procedures, management of polytransfusion), non-technical skills (communication) and health care organization (human resources, vital emergency plan, wide access to PSL). An autopsy was performed in 38% of deaths.

Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021-2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415-6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887-13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400-9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51-15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02-16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05-15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Evaluation of stability and safety of equine mesenchymal stem cells derived from amniotic fluid for clinical application.

Amniotic fluid mesenchymal stem cells (AF-MSCs), which can be obtained from fetal tissue, reportedly have self-renewal capacity and multi-lineage differentiation potential. The aim of this study was to identify the biological characteristics of AF-MSCs and evaluate their stability and safety in long-term culture. To confirm the biological characteristics of AF-MSCs, morphology, proliferation capacity, karyotype, differentiation capacity, gene expression level, and immunophenotype were analyzed after isolating AF-MSCs from equine amniotic fluid. AF-MSCs were differentiated into adipocytes, chondrocytes, and osteocytes. Immunophenotype analyses revealed expression levels of ≥95% and ≤ 2% of cells for a positive and negative marker, respectively. Analysis of the MSCs relative gene expression levels of AF-MSCs was approximately at least twice that of the control. The endotoxin level was measured to verify the safety of AF-MSCs and was found to be less than the standard value of 0.5 EU/ml. AF-MSCs were cultured for a long time without any evidence of abnormalities in morphology, proliferation ability, and karyotype. These results suggest that amniotic fluid is a competent source for acquiring equine MSCs and that it is valuable as a cell therapy due to its high stability.