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Scientific Reports Sep 2023Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic...
Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and treatment response. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37-39 weeks) from women with normal pregnancies (n = 5) or carrying fetuses with CDH (n = 5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, in the MSP-RON signaling in macrophages pathway and in networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Differences in selected proteins, namely pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin-3 were validated by orthogonal testing using ELISA in larger cohorts and showed statistically significant differences aiding in the diagnosis and prediction of CDH. The findings provide potential tools for clinical management of CDH.
Topics: Pregnancy; Humans; Female; Hernias, Diaphragmatic, Congenital; Amniotic Fluid; Proteomics; Proteome; Biomarkers
PubMed: 37726509
DOI: 10.1038/s41598-023-42576-2 -
The Brazilian Journal of Infectious... 2023The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already...
The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of newborns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Toxoplasmosis, Congenital; Real-Time Polymerase Chain Reaction; Cohort Studies; Brazil; Toxoplasmosis; Toxoplasma; Prenatal Diagnosis
PubMed: 37743041
DOI: 10.1016/j.bjid.2023.102804 -
Journal of Obstetrics and Gynaecology :... Dec 2024The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth.
METHODS
On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software.
RESULTS
A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01).
CONCLUSIONS
The inflammatory biomarkers IL-1β, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.
Topics: Humans; Amniotic Fluid; Female; Pregnancy; Premature Birth; Biomarkers; Interleukin-6; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Inflammation; Matrix Metalloproteinase 9; Interleukin-10
PubMed: 38952221
DOI: 10.1080/01443615.2024.2368764 -
Radiology Case Reports Dec 2023Amniotic fluid embolism is a rare complication of peripartum. It is caused by the entry of fetal components into the maternal systemic circulation. There are 2 main...
Amniotic fluid embolism is a rare complication of peripartum. It is caused by the entry of fetal components into the maternal systemic circulation. There are 2 main types: typical; it presents with the triad of hemodynamic collapse, respiratory distress and disseminated intravascular coagulation type coagulopathy, while atypical; disseminated intravascular coagulation does not occur. SARS CoV-2 infection causes coagulopathy due to the alteration of Virchow's triad and coagulation factors. We present the case of a 21-year-old pregnant woman who consulted for premature rupture of membranes, with an indication for cesarean section, and during surgery presented bradycardia, hypotension, and desaturation until cardiorespiratory arrest. An angiotomography showed amniotic fluid embolism associated with pulmonary edema, ruling out differential diagnoses associated with the disease, leaving as the only cause of the infection confirmed by COVID-19, which, it was inferred, was closely related to the immunological disorder suffered by the patient.
PubMed: 37876891
DOI: 10.1016/j.radcr.2023.09.059 -
American Journal of Obstetrics &... Nov 2023Although most biological systems, including human tissues, contain rubidium, its biogeochemical functions and possible role in neonatal birthweight are largely unknown....
BACKGROUND
Although most biological systems, including human tissues, contain rubidium, its biogeochemical functions and possible role in neonatal birthweight are largely unknown. An animal study indicated a correlation between rubidium deficiency in the maternal diet and lower newborn birthweight.
OBJECTIVE
This pilot study measured rubidium concentrations in amniotic fluid during the second trimester of (low-risk) pregnancy and investigated potential correlations between rubidium levels and third-trimester newborn birthweight-small for gestational age, appropriate for gestational age, and large for gestational age-and between preterm birth and term birth in uncomplicated pregnancies.
STUDY DESIGN
This prospective, single-center study investigated a possible relationship between rubidium concentration in second-trimester amniotic fluid and third-trimester birthweight percentile. Amniotic fluid (at a median gestational age of 19 weeks) was sampled to determine rubidium concentration. Maternal and newborn characteristics were obtained from participant and delivery records.
RESULTS
After screening 173 pregnant women, 99 amniotic fluid samples were evaluated. Midpregnancy median rubidium concentrations were significantly lower among newborns that were classified as small for gestational age than among newborns that were classified as appropriate for gestational age (106 vs 136 μg/L; P<.01). Based on a logistic regression random forest model, amniotic fluid rubidium was identified as a significant contributing factor to appropriate-for-gestational-age birthweight with 54% of the total contribution.
CONCLUSION
Amniotic fluid rubidium concentration seems to be a strong predictor of appropriate-for-gestational-age birthweight and a potential marker for newborn birthweight classifications. In particular, low rubidium concentrations in amniotic fluid during midpregnancy are linked to third-trimester lower birthweight percentile. These findings could potentially serve as a valuable tool for early identification of pregnancy outcomes. Further investigation is necessary to fully explore the effect of rubidium on fetal development.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Infant; Birth Weight; Amniotic Fluid; Pilot Projects; Rubidium; Prospective Studies; Premature Birth
PubMed: 37660761
DOI: 10.1016/j.ajogmf.2023.101149 -
Biology Nov 2023Acrylamide, an organic compound, is, chemically speaking, a vinyl-substituted primary amide. It is produced industrially, principally as a precursor to polyacrylamides,...
Detection and Quantification of Acrylamide in Second Trimester Amniotic Fluid Using a Novel LC-MS/MS Technique to Determine Whether High Acrylamide Content during Pregnancy Is Associated with Fetal Growth.
INTRODUCTION
Acrylamide, an organic compound, is, chemically speaking, a vinyl-substituted primary amide. It is produced industrially, principally as a precursor to polyacrylamides, for use in such products as plastics and cosmetics. This same compound, however, forms naturally in certain foods, both home-cooked and packaged, especially when prepared at high temperatures. We developed and validated a novel reliable technique for the determination of acrylamide in amniotic fluid. Multiple reaction monitoring (MRM) is a targeted mass spectrometry (MS) technique which enables the detection and quantification of particular molecules in a complex mixture. Thanks to its throughput, selectivity, and sensitivity, MRM-MS has been identified as offering an alternative to antibody-based studies for the purpose of biomarker verification. Our aim was to investigate the presence of acrylamide in amniotic fluid and, via the MRM-MS technique, to determine whether there is any correlation between maternal exposure to acrylamide, through a woman's diet, and fetal growth.
METHODS
Our amniotic fluid bank included 40 samples from various fetal growth rates, as objectively denoted by the neonatal weight centile at delivery, while our analytical detection method was based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acrylamide was determined with reversed phase chromatography and monitoring of two multiple reaction monitoring (MRM) transitions. Quantification was performed using the matrix-matched calibration curve.
RESULTS
Acrylamide was detected at concentrations between 7.1 and 1468 ng/mL in six out of the total of 40 amniotic fluid samples that were used. Our method limit of detection and quantification was 1.4 ng/mL and 4.6 ng/mL, respectively. The repeatability of our method ranged between 11 and 14%, expressed as relative standard deviation levels between 5 and 100 ng/mL.
CONCLUSIONS
Detection of acrylamide in early second trimester amniotic fluid, for the first time in the literature to our knowledge, raises concerns about fetal health, given that published data on animal studies have attributed a number of birth defects to acrylamide. Our novel LC-MS/MS method for the determination of acrylamide in amniotic fluid proved to be effective and its performance in practice was very accurate, simple, and fast. Validation of the method revealed that the use of a matrix-matched curve is necessary for the quantification.
PubMed: 37998024
DOI: 10.3390/biology12111425 -
Acta Obstetricia Et Gynecologica... Aug 2023Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool for detecting a broad range of...
INTRODUCTION
Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool for detecting a broad range of chromosomal aberrations in a single assay, but relevant clinical feasibility studies of optical genome mapping in prenatal diagnosis are limited.
MATERIAL AND METHODS
We retrospectively performed optical genome mapping analysis of amniotic fluid samples from 34 fetuses with various clinical indications and chromosomal aberrations detected through standard-of-care technologies, including karyotyping, fluorescence in situ hybridization, and/or chromosomal microarray analysis.
RESULTS
In total, we analyzed 46 chromosomal aberrations from 34 amniotic fluid samples, including 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, and 1 region of homozygosity. Overall, 45 chromosomal aberrations could be confirmed by our customized analysis strategy. Optical genome mapping reached 97.8% concordant clinical diagnosis with standard-of-care methods for all chromosomal aberrations in a blinded fashion. Compared with the widely used chromosomal microarray analysis, optical genome mapping additionally determined the relative orientation and position of repetitive segments for seven cases with duplications or triplications. The additional information provided by optical genome mapping will be conducive to characterizing complex chromosomal rearrangements and allowing us to propose mechanisms to explain rearrangements and predict the genetic recurrence risk.
CONCLUSIONS
Our study highlights that optical genome mapping can provide comprehensive and accurate information on chromosomal aberrations in a single test, suggesting that optical genome mapping has the potential to become a promising cytogenetic tool for prenatal diagnosis.
Topics: Pregnancy; Female; Humans; Chromosome Disorders; In Situ Hybridization, Fluorescence; DNA Copy Number Variations; Retrospective Studies; Chromosome Aberrations; Prenatal Diagnosis; Chromosome Mapping
PubMed: 37366235
DOI: 10.1111/aogs.14613 -
EBioMedicine Dec 2023Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks...
BACKGROUND
Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.
METHODS
Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α. The blockade of IL-6R by using an aIL-6R was tested as prenatal treatment for preterm birth and adverse neonatal outcomes. QUEST-MRI evaluated brain oxidative stress in utero. Targeted transcriptomic profiling assessed maternal, foetal, and neonatal inflammation. Neonatal biometrics and neurodevelopment were tested. The neonatal gut immune-microbiome was evaluated using metagenomic sequencing and immunophenotyping.
FINDINGS
IL-6 plays a critical role in the human intra-amniotic inflammatory response, which is associated with elevated concentrations of the alarmin IL-1α. Intra-amniotic injection of IL-1α resembles SIAI, inducing preterm birth (7% vs. 50%, p = 0.03, Fisher's exact test) and neonatal mortality (18% vs. 56%, p = 0.02, Mann-Whitney U-test). QUEST-MRI revealed no foetal brain oxidative stress upon in utero IL-1α exposure (p > 0.05, mixed linear model). Prenatal treatment with aIL-6R abrogated IL-1α-induced preterm birth (50% vs. 7%, p = 0.03, Fisher's exact test) by dampening inflammatory processes associated with the common pathway of labour. Importantly, aIL-6R reduces neonatal mortality (56% vs. 22%, p = 0.03, Mann-Whitney U-test) by crossing from the mother to the amniotic cavity, dampening foetal organ inflammation and improving growth. Beneficial effects of prenatal IL-6R blockade carried over to neonatal life, improving survival, growth, neurodevelopment, and gut immune homeostasis.
INTERPRETATION
IL-6R blockade can serve as a strategy to treat SIAI, preventing preterm birth and adverse neonatal outcomes.
FUNDING
NICHD/NIH/DHHS, Contract HHSN275201300006C. WSU Perinatal Initiative in Maternal, Perinatal and Child Health.
Topics: Animals; Child; Female; Humans; Infant, Newborn; Mice; Pregnancy; Amniotic Fluid; Inflammation; Interleukin-6; Premature Birth; Proteomics; Receptors, Interleukin-6; Antibodies, Monoclonal
PubMed: 37944273
DOI: 10.1016/j.ebiom.2023.104865 -
World Journal of Cardiology Oct 2023Persistent left superior vena cava (PLSVC) is the most common venous system variant. The clinical characteristics and amniotic fluid cytogenetics of fetuses with PLSVC...
BACKGROUND
Persistent left superior vena cava (PLSVC) is the most common venous system variant. The clinical characteristics and amniotic fluid cytogenetics of fetuses with PLSVC remain to be further explored.
AIM
To develop reliable prenatal diagnostic recommendations through integrated analysis of the clinical characteristics of fetuses with PLSVC.
METHODS
Cases of PLSVC diagnosed using prenatal ultrasonography between September 2019 and November 2022 were retrospectively studied. The clinical characteristics of the pregnant women, ultrasonic imaging information, gestational age at diagnosis, pregnancy outcomes, and amniocentesis results were summarized and analyzed using categorical statistics and the chi-square test or Fisher's exact test.
RESULTS
Of the 97 cases diagnosed by prenatal ultrasound, 49 (50.5%) had isolated PLSVC and 48 (49.5%) had other structural abnormalities. The differences in pregnancy outcomes and amniocentesis conditions between the two groups were statistically significant ( < 0.05). No significant differences were identified between the two groups in terms of advanced maternal age and gestational age ( > 0.05). According to the results of the classification statistics, the most common intracardiac abnormality was a ventricular septal defect and the most common extracardiac abnormality was a single umbilical artery. In the subgroup analysis, the concurrent combination of intra- and extracardiac structural abnormalities was a risk factor for adverse pregnancy outcomes (odds ratio > 1, < 0.05). Additionally, all abnormal cytogenetic findings on amniocentesis were observed in the comorbidity group. One case was diagnosed with 21-trisomy and six cases was diagnosed with chromosome segment duplication.
CONCLUSION
Examination for other structural abnormalities is strongly recommended when PLSVC is diagnosed. Poorer pregnancy outcomes and increased amniocentesis were observed in PLSVC cases with other structural abnormalities. Amniotic fluid cytogenetics of fetuses is recommended for PLSVC with other structural abnormalities.
PubMed: 37900905
DOI: 10.4330/wjc.v15.i10.500 -
Journal of Perinatal Medicine Jul 2023Early diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We...
OBJECTIVES
Early diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We determined whether the 16S amplicon sequencing performed by a nanopore sequencing technique make possible rapid bacterial identification at the species level in intra-amniotic infection.
METHODS
Five cases of confirmed intra-amniotic infection, determined by either cultivation or 16S rDNA polymerase chain reaction (PCR) Sanger sequencing, and 10 cases of women who underwent mid-trimester genetic amniocentesis were included. DNA was extracted from amniotic fluid and PCR was performed on the full-length 16S rDNA. Nanopore sequencing was performed. The results derived from nanopore sequencing were compared with those derived from cultivation and Sanger sequencing methods.
RESULTS
Bacteria were successfully detected from amniotic fluid using nanopore sequencing in all cases of intra-amniotic infection. Nanopore sequencing identified additional bacterial species and polymicrobial infections. All patients who underwent a mid-trimester amniocentesis had negative cultures, negative 16S PCR Sanger sequencing and nanopore sequencing. Identification of the microorganisms using nanopore sequencing technique at the bacterial species level was achieved within 5-9 h from DNA extraction.
CONCLUSIONS
This is the first study demonstrating that the nanopore sequencing technique is capable of rapid diagnosis of intra-amniotic infection using fresh amniotic fluid samples.
Topics: Pregnancy; Humans; Female; Chorioamnionitis; Nanopore Sequencing; Nanopores; Amniotic Fluid; Amniocentesis; Bacteria
PubMed: 36503654
DOI: 10.1515/jpm-2022-0504