No SARS-CoV-2 detected in amniotic fluid in mid-pregnancy.
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ABSTRACT:
SUBMITTER: Yu N
PROVIDER: S-EPMC7176395 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
No SARS-CoV-2 detected in amniotic fluid in mid-pregnancy.
Yu Nan N Li Wei W Kang Qingling Q Zeng Wanjiang W Feng Ling L Wu Jianli J
The Lancet. Infectious diseases 20200422 12
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Project description:We aimed to explore the proteomic profiles of mid-trimester amniotic fluid in pregnant women with systemic lupus erythematosus (SLE) according to the occurrence of adverse pregnancy outcome (APO). The study population included 35 pregnant women with SLE who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. Patients were divided into two groups according to pregnancy outcomes: SLE patients without APO (Group 1) and SLE patients with APO (Group 2). Stored samples of amniotic fluid were analyzed using mass spectrometry (MS)-based proteomics with two-step approach, consisting of discovery and verification phase. In the discovery phase, 44 proteins were differentially expressed between Group 1 and Group 2. In the verification phase, differentially expressed proteins (DEPs) were verified in independent samples using DIA method. Four proteins including filamin A (FLNA), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1), lecithin-cholesterol acyltransferase (LCAT), and transglutaminase 2 (TGM2) were differentially expressed both in discovery and verification phase. To select the best combination of proteins for discriminating two groups, three-fold cross validation (CV) with repetition of one hundred times was performed. The multi-marker model with three biomarkers (SVEP1, LCAT, TGM2) had a high discriminatory power to distinguish between the two groups (the area under the receiver operating characteristic, AUROC = 0.946, p <0.001). Our results indicate that the expression of FLNA, SVEP1, LCAT, and TGM2 in mid-trimester amniotic fluid was increased in SLE patients with APO (Group 2). A large-scale prospective study is warranted to verify this finding.
| S-EPMC7367458 | biostudies-literature
Project description:The prediction and monitoring of fetal growth restriction (FGR) fetuses has become with the use of ultrasound. However, these tools lack the fundamental evidence for the growth of fetus with FGR excluding pathogenic factors.Amniotic fluid samples were obtained from pregnant women for fetal karyotyping and genetic diagnosis at 16 to 19 weeks of gestation. For this study, 15 FGR and 9 control samples were selected, and cell-free fetal RNA was isolated from each supernatant of the amniotic fluid for microarray analysis.In this study, 411 genes were differentially expressed between the FGR and control group. Of these genes, 316 genes were up-regulated, while 95 genes were down-regulated. In terms of gene ontology, the up-regulated genes were highly related to metabolic process as well as protein synthesis, while the down-regulated genes were related to receptor activity and biological adhesion. In terms of tissue-specific expression, the up-regulated genes were involved in various organs while down-regulated genes were involved only in the brain. In terms of organ-specific expression, many genes were enriched for B-cell lymphoma, pancreas, eye, placenta, epithelium, skin, and muscle. In the functional significance of gene, low-density lipoprotein receptor-related protein 10 (LRP10) was significantly increased (6-fold) and insulin-like growth factor (IGF-2) was dramatically increased (17-fold) in the FGR cases.The results show that the important brain-related genes are predominantly down-regulated in the intrauterine growth restriction fetuses during the second trimester of pregnancy. This study also suggested possible genes related to fetal development such as B-cell lymphoma, LRP10, and IGF-2. To monitor the fetal development, further study may be needed to elucidate the role of the genes identified.
| S-EPMC5943846 | biostudies-literature
Project description: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.
| S-EPMC7205297 | biostudies-literature
Project description:BackgroundIn utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract.MethodsThis cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages.ResultsDespite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis.ConclusionsThese findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications.ImpactSARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.
| S-EPMC9388973 | biostudies-literature
Project description:Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2nd and 3rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at α = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies.
| S-EPMC4829258 | biostudies-literature
Project description:ImportanceAmniotic fluid embolism (AFE) is an uncommon pregnancy complication but is associated with high maternal mortality. Because of the rarity of AFE, associated risks factors and maternal outcomes have been relatively understudied.ObjectiveTo examine the clinical, pregnancy, and delivery characteristics and the maternal outcomes related to AFE in a recent period in the US.Design, setting, and participantsThis retrospective cohort study examined hospital deliveries from January 1, 2016, to December 31, 2019, from the Healthcare Cost and Utilization Project's National Inpatient Sample.Main outcomes and measuresThe primary outcome was clinical, pregnancy, and delivery characteristics of AFE, assessed with a multivariable binary logistic regression model. The coprimary outcome was failure to rescue, defined as maternal mortality after AFE. Associations with other severe maternal morbidity indicators and failure to rescue per clinical and pregnancy characteristics were also assessed.ResultsA total of 14 684 135 deliveries were examined, with AFE diagnosed in 880 women, corresponding to an incidence rate of 6.0 per 100 000 deliveries. The cohort-level median patient age was 29 years (IQR, 25-33 years). In a multivariable analysis, (1) patient factors of older age, Asian and Black race, Western US region, pregestational hypertension, asthma, illicit substance use, and grand multiparity; (2) pregnancy factors of placental accreta spectrum (PAS), placental abruption, uterine rupture, polyhydramnios, chorioamnionitis, preeclampsia, fetal growth restriction, and fetal demise; and (3) delivery factors of early gestational age, cervical ripening, cesarean delivery, operative delivery, and manual removal were associated with AFE. Among these characteristics, PAS had the largest association with AFE (adjusted odds ratio [aOR], 10.01; 95% CI, 7.03-14.24). When stratified by the PAS subtypes, more severe forms of PAS had a greater association with AFE (aOR for increta and percreta, 17.35; 95% CI, 10.21-28.48; and aOR for accreta, 7.62; 95% CI, 4.83-12.01). Patients who had AFE were more likely to have coagulopathy (aOR, 24.68; 95% CI, 19.38-31.44), cardiac arrest (aOR, 24.56; 95% CI, 17.84-33.81), and adult respiratory distress syndrome (aOR, 10.72; 95% CI, 8.09-14.20). The failure-to-rescue rate after AFE was 17.0% overall. However, the failure-to-rescue rate exceeded 30% when AFE co-occurred with other severe maternal morbidity indicators: 45.8% for AFE, cardiac arrest, and coagulopathy; 43.2% for AFE, shock, and cardiac rhythm conversion; and 38.6% for AFE, cardiac arrest, coagulopathy, and shock. The failure-to-rescue rate after AFE also exceeded 30% when AFE occurred in the setting of placental pathology: 42.9% for AFE and PAS and 31.3% for AFE and placental abruption.Conclusions and relevanceThis contemporaneous, national-level analysis validated previously known risk factors for AFE and confirmed the dismal outcomes of pregnancy complicated by AFE. The association between PAS and AFE, which was not previously reported, warrants further investigation.
| S-EPMC9675004 | biostudies-literature
Project description:Expression of OCT4A is one of the hallmarks of pluripotency, defined as a stem cell's ability to differentiate into all the lineages of the three germ layers. Despite being defined as non-tumorigenic cells with high translational potential, human mid-trimester amniotic fluid stem cells (hAFSCs) are often described as sharing features with embryonic stem cells, including the expression of OCT4A, which could hinder their clinical potential. To clarify the OCT4A status of hAFSCs, we first undertook a systematic review of the literature. We then performed extensive gene and protein expression analyses to discover that neither frozen, nor fresh hAFSCs cultivated in multipotent stem cell culture conditions expressed OCT4A, and that the OCT4A positive results from the literature are likely to be attributed to the expression of pseudogenes or other OCT4 variants. To address this issue, we provide a robust protocol for the assessment of OCT4A in other stem cells.
| S-EPMC6544653 | biostudies-literature
Project description:ObjectiveThe aim of this study was to identify early proteomic biomarkers of spontaneous preterm delivery (PTD) in mid-trimester amniotic fluid from asymptomatic women.MethodsThis is a case-cohort study. Amniotic fluid from mid-trimester genetic amniocentesis (14-19 weeks of gestation) was collected from 2008 to 2011. The analysis was conducted in 24 healthy women with subsequent spontaneous PTD (cases) and 40 randomly selected healthy women delivering at term (controls). An exploratory phase with proteomics analysis of pooled samples was followed by a verification phase with ELISA of individual case and control samples.ResultsThe median (interquartile range (IQR: 25th; 75th percentiles) gestational age at delivery was 35+5 (33+6-36+6) weeks in women with spontaneous PTD and 40+0 (39+1-40+5) weeks in women who delivered at term. In the exploratory phase, the most pronounced differences were found in C-reactive protein (CRP) levels, that were approximately two-fold higher in the pooled case samples than in the pooled control samples. However, we could not verify these differences with ELISA. The median (25th; 75th IQR) CRP level was 95.2 ng/mL (64.3; 163.5) in women with spontaneous PTD and 86.0 ng/mL (51.2; 145.8) in women delivering at term (p = 0.37; t-test).ConclusionsProteomic analysis with mass spectrometry of mid-trimester amniotic fluid suggests CRP as a potential marker of spontaneous preterm delivery, but this prognostic potential was not verified with ELISA.
| S-EPMC4876998 | biostudies-literature
Project description:IntroductionAt the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested.MethodsWomen near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth.ResultsIn bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R2 = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders.ConclusionGlucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The analysis of additional fetal growth factors and inflammation upon maternal stress in further biomaterials such as the placenta is warranted, to understand mechanistic alterations of how maternal stress links to fetal development and an increased vulnerability for psychopathology.
| S-EPMC11294724 | biostudies-literature
Project description:Infection and inflammation are well recognized causes of spontaneous preterm delivery (PTD) (<37 gestational weeks) and adverse infant outcomes. To date, there has been very little investigation into bacterial communities in amniotic fluid using next generation sequencing technology. In particular, it is important to characterize amniotic fluid bacterial profiles in complicated pregnancies as well as in asymptomatic women to identify predictive bacterial DNA signatures. Here, 1198 mid-trimester amniotic fluid samples from a cohort of Swedish women undergoing mid-trimester genetic amniocentesis were screened for bacterial DNA using qPCR protocols specifically designed to reduce the impacts of reagent contamination and human DNA mispriming. The majority of samples were devoid of detectable bacterial DNA; however, approximately a fifth of the cohort (19.9%) were 16S rRNA gene positive in duplicate screening. Among these, nine women had a spontaneous PTD. These nine women were matched with 18 healthy women with a delivery at term. We used PacBio SMRT technology, coupled with appropriate negative extraction and PCR controls, to sequence the full-length 16S rRNA gene in this subset of 27 women. The amniotic fluid samples contained low-abundance and low-diversity bacterial DNA profiles. Species typically associated with spontaneous PTD were absent. We were not able to identify any differences in the amniotic fluid bacterial DNA profiles of women with a subsequent spontaneous PTD compared to women who delivered at term. The findings suggest that, in a minor proportion of pregnancies, DNA from non-pathogenic bacteria may be present in the amniotic fluid far earlier than previously reported. Early detection of bacterial DNA in the amniotic fluid was, in this study, not associated with spontaneous PTD.
| S-EPMC7107015 | biostudies-literature