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Scientific Reports Oct 2023Amniotic fluid is a complex biological medium that offers protection to the fetus and plays a key role in normal fetal nutrition, organogenesis, and potentially fetal...
Amniotic fluid is a complex biological medium that offers protection to the fetus and plays a key role in normal fetal nutrition, organogenesis, and potentially fetal programming. Amniotic fluid is also critically involved in longitudinally shaping the in utero milieu during pregnancy. Yet, the molecular mechanism(s) of action by which amniotic fluid regulates fetal development is ill-defined partly due to an incomplete understanding of the evolving composition of the amniotic fluid proteome. Prior research consisting of cross-sectional studies suggests that the amniotic fluid proteome changes as pregnancy advances, yet longitudinal alterations have not been confirmed because repeated sampling is prohibitive in humans. We therefore performed serial amniocenteses at early, mid, and late gestational time-points within the same pregnancies in a rhesus macaque model. Longitudinally-collected rhesus amniotic fluid samples were paired with gestational-age matched cross-sectional human samples. Utilizing LC-MS/MS isobaric labeling quantitative proteomics, we demonstrate considerable cross-species similarity between the amniotic fluid proteomes and large scale gestational-age associated changes in protein content throughout pregnancy. This is the first study to compare human and rhesus amniotic fluid proteomic profiles across gestation and establishes a reference amniotic fluid proteome. The non-human primate model holds promise as a translational platform for amniotic fluid studies.
Topics: Female; Animals; Humans; Pregnancy; Amniotic Fluid; Macaca mulatta; Proteome; Chromatography, Liquid; Proteomics; Cross-Sectional Studies; Tandem Mass Spectrometry; Gestational Age
PubMed: 37814009
DOI: 10.1038/s41598-023-44125-3 -
Canadian Medical Association Journal Jan 1958
Topics: Amniotic Fluid; Female; Humans; Polyhydramnios; Pregnancy
PubMed: 13489637
DOI: No ID Found -
Journal of Mother and Child Dec 2020Prolonged labour can lead to postpartum complications and adverse outcomes for both mother and baby. Measurable parameters can help in the active management of labour,... (Review)
Review
Prolonged labour can lead to postpartum complications and adverse outcomes for both mother and baby. Measurable parameters can help in the active management of labour, timely diagnosis of dystocia and in the choice of the method of delivery. Progressive uterine contractions are necessary to complete labour successfully. Myometrial fatigue during prolonged labour causes a change from aerobic to anaerobic metabolism, resulting in an accumulation of intramuscular lactic acid and probably a subsequent increase in amniotic fluid lactate concentration. High amniotic fluid lactate level has been associated with ineffective uterine contractions leading to labour arrest. A considerable number of studies conducted so far indicate that the level of lactate in amniotic fluid may be a new non-invasive diagnostic tool for early prediction of prolonged labour and the need for immediate obstetric intervention. Low amniotic fluid lactate level may facilitate a decision to continue vaginal labour by oxytocin augmentation. A high level of amniotic fluid lactate is associated with surgical obstetric procedures. Measuring amniotic fluid lactate level might simplify the patient's allocation to a group, which will benefit from the administration of oxytocin and to a group that will not benefit from further prolongation of labour. This study aimed to briefly review current knowledge on amniotic fluid lactate concentrations measured using standard biochemical methods during the first stage of labour following normal pregnancy, as a possible diagnostic tool for prolonged labour. For this purpose, PubMed, EMBASE, Medline (1990 to July 2020) trials register and reference lists of relevant articles were searched.
Topics: Amniotic Fluid; Female; Humans; Lactic Acid; Obstetric Labor Complications; Oxytocics; Pregnancy; Pregnancy Outcome; Time Factors
PubMed: 33470958
DOI: 10.34763/jmotherandchild.20202403.2027.d-20-00011 -
PloS One 2022Methylmalonic aciduria (MMA), a rare inherited disorder, is the most common organic aciduria in China, and prenatal diagnosis has contributed to its prevention. However,...
BACKGROUND
Methylmalonic aciduria (MMA), a rare inherited disorder, is the most common organic aciduria in China, and prenatal diagnosis has contributed to its prevention. However, the prenatal diagnosis of MMA using cultured amniocytes or chorionic villi to detect gene mutations is exclusively applicable to families with a definite genetic diagnosis. To evaluate the reliability of mass spectrometry assays for the prenatal diagnosis of MMA, we conducted a retrospective study of our 10 years' experience.
MATERIALS AND METHODS
This retrospective compare study reviewed the medical records for maternal and fetuses data for 287 mothers with a family history of MMA from June 2010 to December 2020. Methylmalonate and propionylcarnitine in cell-free amniotic fluid were measured using a stable isotope dilution method (GC/MS) and MS/MS-based method (LC/MS/MS). Total homocysteine (tHcy) was measured by fluorescence polarization immunoassay. Depending on the presence of disease-causing gene mutations in probands, gene studies on amniocytes from 222 pregnant women were performed.
RESULTS
For 222 fetuses of the families with definite genetic diagnosis, gene analyses were performed using cultured amniocytes. 52 fetuses were affected by MMA, whereas 170 were "unaffected". For GC/MS and LC/MS/MS, the specificity was 96.5% and 95.9%, sensitivity was 71.2% and 84.6%, respectively. The positive and negative predictive values were 86.0% and 91.6% and 86.3% and 95.3%, respectively. Propionylcarnitine/butyrylcarnitine ratio showed the highest accuracy and could thus serve as a sensitive indicator to identify those at a risk for MMA. When GC/MS and LC/MS/MS were performed in parallel, the specificity was 92.5% and sensitivity was 95.6%. When evaluating tHcy, the positive and negative predictive values were 95.0% and 96.1%, respectively. In 65 fetuses without family genetic diagnosis, 11 were finally confirmed to have MMA and 54 were "unaffected" by amniotic fluid biochemical assays. The 54 children showed normal urine organic acids and healthy development after birth.
CONCLUSIONS
Amniotic fluid biochemical assays using GC/MS and LC/MS/MS in parallel increased the accuracy of prenatal diagnosis of MMA. Propionylcarnitine is a more reliable marker than methylmalonic acid in amniotic fluid. Further, tHcy is recommended for the prenatal diagnosis of combined MMA and homocysteinemia.
Topics: Amino Acid Metabolism, Inborn Errors; Amniotic Fluid; Child; Female; Humans; Methylmalonic Acid; Pregnancy; Prenatal Diagnosis; Reproducibility of Results; Retrospective Studies; Tandem Mass Spectrometry
PubMed: 35358224
DOI: 10.1371/journal.pone.0265766 -
PloS One 2020Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could...
BACKGROUND
Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery.
OBJECTIVE
The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort.
METHODS
Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls.
RESULTS
Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort.
CONCLUSIONS
Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.
Topics: Adult; Amniocentesis; Amniotic Fluid; Cohort Studies; Female; Gestational Age; Humans; Male; Pregnancy; Pregnancy Trimester, Second; Premature Birth; Proteome
PubMed: 32379834
DOI: 10.1371/journal.pone.0232553 -
Journal of Perinatal Medicine Sep 2023This study was conducted to determine whether bacteria, fungi, or archaea are detected in the amniotic fluid of patients who underwent midtrimester amniocentesis for...
OBJECTIVES
This study was conducted to determine whether bacteria, fungi, or archaea are detected in the amniotic fluid of patients who underwent midtrimester amniocentesis for clinical indications.
METHODS
Amniotic fluid samples from 692 pregnancies were tested by using a combination of culture and end-point polymerase chain reaction (PCR) techniques. Intra-amniotic inflammation was defined as an interleukin-6 concentration >2,935 pg/mL.
RESULTS
Microorganisms were detected in 0.3% (2/692) of cases based on cultivation, 1.73% (12/692) based on broad-range end-point PCR, and 2% (14/692) based on the combination of both methods. However, most (13/14) of these cases did not have evidence of intra-amniotic inflammation and delivered at term. Therefore, a positive culture or end-point PCR in most patients appears to have no apparent clinical significance.
CONCLUSIONS
Amniotic fluid in the midtrimester of pregnancy generally does not contain bacteria, fungi, or archaea. Interpretation of amniotic fluid culture and molecular microbiologic results is aided by the assessment of the inflammatory state of the amniotic cavity. The presence of microorganisms, as determined by culture or a microbial signal in the absence of intra-amniotic inflammation, appears to be a benign condition.
Topics: Pregnancy; Female; Humans; Amniotic Fluid; Pregnancy Trimester, Second; Chorioamnionitis; Archaea; Retrospective Studies; Bacteria; Inflammation; Fungi
PubMed: 37194083
DOI: 10.1515/jpm-2022-0604 -
Environment International Jan 2022To examine whether selected endocrine disrupting chemicals were present in pregnant women and passed through the placental barrier to amniotic fluid, potentially...
OBJECTIVE
To examine whether selected endocrine disrupting chemicals were present in pregnant women and passed through the placental barrier to amniotic fluid, potentially exposing the developing fetus.
METHODS
Paired samples of maternal serum, urine and amniotic fluid were concurrently collected (<1 h) from 200 pregnant women (age >18 years) with a singleton pregnancy and undergoing amniocentesis between gestational weeks 12 - 36. The concentration of six different parabens, seven phenols, 31 metabolites from 15 phthalate diesters and the polychlorinated substance triclocarban were analyzed by isotope diluted TurboFlow-liquid chromatography-tandem mass spectrometry.
RESULTS
Concentrations of all included compounds were highest in maternal urine followed by serum, and lowest in amniotic fluid. Of the six parabens measured in amniotic fluid, methylparaben (MeP) and ethylparaben (EtP) were detectable most often (87% and 33% of the samples, respectively). Of the seven phenols measured, three (2,4-dichlorphenol, 2,5-dichlorphenol, 2-propylphenol) were detectable in the range of 14-21% of the amniotic fluid samples, at low concentrations (<0.12 ng/ml). Two secondary phthalates metabolites, mono-(2-carboxymethyl-hexyl) phthalate and mono-carboxy-iso-octyl phthalate were each present in ≤15% of the amniotic fluid samples at concentrations 2-5 times lower than in maternal serum and 20-100 times lower than in maternal urine. A modest statistically significant correlation between the levels of MeP and EtP was detected in paired maternal urine-amniotic fluid samples was detected (Spearman r: 0.246; r: 0.364). Likewise, the concentration of mono-ethyl phthalate (MEP) in paired maternal urine and amniotic fluid samples indicated a modest statistically significant correlation (Spearman r: 0.264), driven by detectable levels of MEP in only 3% of the amniotic fluid samples.
CONCLUSIONS
In general, the included parabens, phenols and phthalates were effectively metabolized and excreted via the urine, which was the matrix that reflected the highest detectable levels. The detectable levels of several included parabens and phthalates in human amniotic fluid calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of individual and multiple endocrine disruptors in order to better assess the risk to the developing fetus.
Topics: Amniotic Fluid; Female; Humans; Infant; Maternal Exposure; Parabens; Phenols; Phthalic Acids; Placenta; Pregnancy
PubMed: 34991249
DOI: 10.1016/j.envint.2021.106987 -
Microbiome Nov 2023Reports regarding the presence of bacteria in the fetal environment remain limited and controversial. Recently, extracellular vesicles secreted by the human gut...
BACKGROUND
Reports regarding the presence of bacteria in the fetal environment remain limited and controversial. Recently, extracellular vesicles secreted by the human gut microbiota have emerged as a novel mechanism for host-microbiota interaction. We aimed to investigate the presence of bacterial extracellular vesicles in the fetal environment during healthy pregnancies and determine whether extracellular vesicles derived from the gut microbiota can cross biological barriers to reach the fetus.
RESULTS
Bacterial extracellular vesicles were detectable in the amniotic fluid of healthy pregnant women, exhibiting similarities to extracellular vesicles found in the maternal gut microbiota. In pregnant mice, extracellular vesicles derived from human maternal gut microbiota were found to reach the intra-amniotic space.
CONCLUSIONS
Our findings reveal maternal microbiota-derived extracellular vesicles as an interaction mechanism between the maternal microbiota and fetus, potentially playing a pivotal role in priming the prenatal immune system for gut colonization after birth. Video Abstract.
Topics: Pregnancy; Female; Humans; Mice; Animals; Fetus; Microbiota; Amniotic Fluid; Gastrointestinal Microbiome; Bacteria; Extracellular Vesicles
PubMed: 37953319
DOI: 10.1186/s40168-023-01694-9 -
Annals of Medicine 2023Interleukin (IL)-6 is a pro-inflammatory cytokine that plays an important role in preterm birth (PTB), Several meta-analyses investigated the association between IL-6... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Interleukin (IL)-6 is a pro-inflammatory cytokine that plays an important role in preterm birth (PTB), Several meta-analyses investigated the association between IL-6 and PTB, but definitive conclusion has not yet been achieved. This updated meta-analysis aimed to ascertain the association between IL-6 and PTB by examining IL-6 levels in both normal birth and PTB groups.
MATERIAL AND METHODS
Prospective cohort studies were retrieved in PubMed, Embase, and the Cochrane library from their inception until 18 February 2020. The primary outcome was the association between IL-6 and PTB, and secondary outcomes were the association between IL-6 and spontaneous PTB.
RESULTS
Nine studies involving 1904 patients were included. Overall, IL-6 from different sample types (maternal blood, amniotic fluid and cervicovaginal fluid) was associated with PTB (standard mean difference [SMD]: 0.86, 95% confidence interval [CI]: 0.32 to 1.39, < 0.001). Furthermore, the association was significant for IL-6 only in amniotic fluid (SMD: 1.87, 95%CI: 0.82 to 2.93, < 0.001) and cervicovaginal fluid (SMD: 0.46, 95%CI: 0.09 to 0.84, = 0.022), but not significant in maternal blood (SMD: -0.11, 95%CI: -0.57 to 0.34, = 0.623). In addition, IL-6 was also associated with spontaneous PTB (SMD: 1.57, 95% CI: 0.18 to 2.95, < 0.001).
CONCLUSIONS
Based on the available evidence, IL-6 in amniotic fluid and cervicovaginal fluid might be useful for predicting preterm birth.
Topics: Female; Humans; Infant, Newborn; Premature Birth; Interleukin-6; Prospective Studies; Cytokines; Amniotic Fluid
PubMed: 38010798
DOI: 10.1080/07853890.2023.2284384 -
Human Reproduction Update 2011Research into cell-free fetal (cff) nucleic acids has primarily focused on maternal plasma; however, cff DNA and RNA are also detectable in other body fluids such as... (Review)
Review
BACKGROUND
Research into cell-free fetal (cff) nucleic acids has primarily focused on maternal plasma; however, cff DNA and RNA are also detectable in other body fluids such as amniotic fluid (AF). In AF, cff DNA is present in much greater concentrations than in maternal plasma and represents a pure fetal sample uncontaminated by maternal- and trophoblast-derived nucleic acids. The aim of this review was to summarize the current knowledge on cff nucleic acids in AF and to outline future research directions.
METHODS
MEDLINE and PREMEDLINE were searched up to August 2010 for original investigations of cell-free RNA or DNA in AF. Sixteen studies were included in the review.
RESULTS
AF cff DNA represents a physiologically separate pool from cff DNA in maternal plasma. The placenta is not a major source of nucleic acids in AF. It is feasible to isolate cff nucleic acids from small volumes of discarded AF supernatant in sufficient quality and quantity to perform microarray studies and downstream applications such as pathway analysis. This 'discovery-driven approach' has resulted in new information on the pathogenesis of Down syndrome and polyhydramnios. There is otherwise a paucity of information relating to the basic biology and clinical applications of cff nucleic acids in AF.
CONCLUSIONS
AF supernatant is a valuable and widely available but under-utilized biological resource. Further studies of cff nucleic acids in AF may lead to new insights into human fetal development and ultimately new approaches to antenatal treatment of human disease.
Topics: Amniotic Fluid; DNA; Female; Fetus; Humans; Maternal-Fetal Exchange; Pregnancy; Prenatal Diagnosis; Proteome; RNA
PubMed: 20923874
DOI: 10.1093/humupd/dmq049