Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia.

Problem: Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.

Method Of Study: This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls.

The vaginal immunoproteome for the prediction of spontaneous preterm birth: A retrospective longitudinal study.

Background: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response.

COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative.

To investigate the relationship between preeclampsia and SARS-CoV-2 infection during pregnancy. This was a retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA formed the study population.

A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia.

Objective: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species.

Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death.

Objectives: Fetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined.

Perturbations in kinetics of the thrombin generation assay identify women at risk of preeclampsia in the first trimester and provide the rationale for a preventive approach.

Background: Activation of the coagulation system and increased thrombin generation have been implicated in the pathophysiology of preeclampsia, and this rationale supports the administration of low-molecular-weight heparin to prevent this syndrome in patients at risk. Yet, randomized trials of this prophylactic measure have yielded contradictory results. A possible explanation is that only a subset of patients with preeclampsia have excessive thrombin generation and would benefit from the administration of low-molecular-weight heparin.

Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology.

Background: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known.

Objective: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion.

Human Plasma Proteome During Normal Pregnancy.

The human plasma proteome is underexplored despite its potential value for monitoring health and disease. Herein, using a recently developed aptamer-based platform, we profiled 7288 proteins in 528 plasma samples from 91 normal pregnancies (Gene Expression Omnibus identifier GSE206454). The coefficient of variation was <20% for 93% of analytes (median 7%), and a cross-platform correlation for selected key angiogenic and anti-angiogenic proteins was significant.

The amniotic fluid proteome predicts imminent preterm delivery in asymptomatic women with a short cervix.

Preterm birth, the leading cause of perinatal morbidity and mortality, is associated with increased risk of short- and long-term adverse outcomes. For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid (AF) proteins that could predict imminent delivery in asymptomatic patients with a short cervix.

Bacteria in the amniotic fluid without inflammation: early colonization vs. contamination.

Objectives: Intra-amniotic infection, defined by the presence of microorganisms in the amniotic cavity, is often accompanied by intra-amniotic inflammation. Occasionally, laboratories report the growth of bacteria or the presence of microbial nucleic acids in amniotic fluid in the absence of intra-amniotic inflammation. This study was conducted to determine the clinical significance of the presence of bacteria in amniotic fluid samples in the absence of intra-amniotic inflammation.

Prostaglandin and prostamide concentrations in amniotic fluid of women with spontaneous labor at term with and without clinical chorioamnionitis.

Objective: Prostaglandins (PGs) are considered universal mediators for the process of physiological parturition. This is based on observations that amniotic fluid concentrations of PGs are elevated prior to and during the onset of labor (mostly utilizing immunoassays). Distinguishing PGs from similarly structured molecules (i.

Personalized assessment of cervical length improves prediction of spontaneous preterm birth: a standard and a percentile calculator.

Background: A sonographic short cervix (length <25 mm during midgestation) is the most powerful predictor of preterm birth. Current clinical practice assumes that the same cervical length cutoff value should apply to all women when screening for spontaneous preterm birth, yet this approach may be suboptimal.

Objective: This study aimed to (1) create a customized cervical length standard that considers relevant maternal characteristics and gestational age at sonographic examination and (2) assess whether the customization of cervical length evaluation improves the prediction of spontaneous preterm birth.

Nonovert disseminated intravascular coagulation (DIC) in pregnancy: a new scoring system for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion.

Background: Nonovert disseminated intravascular coagulation (DIC) is a subclinical hemostatic dysfunction that has not yet reached the decompensation stage. The detection of pregnant patients at this stage may assist in the identification of those who will develop severe obstetrical hemorrhage, as it is one of the leading causes for preventable maternal mortality. Currently, nonovert DIC is diagnosed by a scoring system based on nonpregnant patients, originally generated by the International Society on Thrombosis and Hemostasis (ISTH), which does not address the physiologic changes of the hemostatic system during pregnancy.

Maternal whole blood mRNA signatures identify women at risk of early preeclampsia: a longitudinal study.

Purpose: To determine whether previously established mRNA signatures are predictive of early preeclampsia when evaluated by maternal cellular transcriptome analysis in samples collected before clinical manifestation.

Materials And Methods: We profiled gene expression at exon-level resolution in whole blood samples collected longitudinally from 49 women with normal pregnancy (controls) and 13 with early preeclampsia (delivery <34 weeks of gestation). After preprocessing and removal of gestational age-related trends in gene expression, data were converted into Z-scores based on the mean and standard deviation among controls for six gestational-age intervals.

Preterm labor is characterized by a high abundance of amniotic fluid prostaglandins in patients with intra-amniotic infection or sterile intra-amniotic inflammation.

Objective: To distinguish between prostaglandin and prostamide concentrations in the amniotic fluid of women who had an episode of preterm labor with intact membranes through the utilisation of liquid chromatography-tandem mass spectrometry.

Study Design: Liquid chromatography-tandem mass spectrometry analysis of amniotic fluid of women with preterm labor and (1) subsequent delivery at term (2) preterm delivery without intra-amniotic inflammation; (3) preterm delivery with sterile intra-amniotic inflammation (interleukin (IL)-6>2.6 ng/mL without detectable microorganisms); and (4) preterm delivery with intra-amniotic infection [IL-6>2.

Gasdermin D: Evidence of pyroptosis in spontaneous preterm labor with sterile intra-amniotic inflammation or intra-amniotic infection.

Problem: Pyroptosis, inflammatory programmed cell death, is initiated through the inflammasome and relies on the pore-forming actions of the effector molecule gasdermin D. Herein, we investigated whether gasdermin D is detectable in women with spontaneous preterm labor and sterile intra-amniotic inflammation or intra-amniotic infection.

Method Of Study: Amniotic fluid samples (n = 124) from women with spontaneous preterm labor were subdivided into the following groups: (a) those who delivered at term (n = 32); and those who delivered preterm (b) without intra-amniotic inflammation (n = 41), (c) with sterile intra-amniotic inflammation (n = 32), or (d) with intra-amniotic infection (n = 19), based on amniotic fluid IL-6 concentrations and the microbiological status of amniotic fluid (culture and PCR/ESI-MS).

The prediction of early preeclampsia: Results from a longitudinal proteomics study.

Objectives: To identify maternal plasma protein markers for early preeclampsia (delivery <34 weeks of gestation) and to determine whether the prediction performance is affected by disease severity and presence of placental lesions consistent with maternal vascular malperfusion (MVM) among cases.

Study Design: This longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman.

Gasdermin D: evidence of pyroptosis in spontaneous labor at term.

Pyroptosis is an inflammatory form of programmed cell death that is mediated by the activation of the inflammasome and depends on the pore-forming function of gasdermin D. Therefore, the detection of gasdermin D represents evidence of pyroptosis. We recently showed that there is intra-amniotic inflammasome activation in spontaneous labor at term; however, evidence of pyroptosis is lacking.

A new customized fetal growth standard for African American women: the PRB/NICHD Detroit study.

Background: The assessment of fetal growth disorders requires a standard. Current nomograms for the assessment of fetal growth in African American women have been derived either from neonatal (rather than fetal) biometry data or have not been customized for maternal ethnicity, weight, height, and parity and fetal sex.

Objective: We sought to (1) develop a new customized fetal growth standard for African American mothers; and (2) compare such a standard to 3 existing standards for the classification of fetuses as small (SGA) or large (LGA) for gestational age.

Statistical power of likelihood ratio and Wald tests in latent class models with covariates.

This paper discusses power and sample-size computation for likelihood ratio and Wald testing of the significance of covariate effects in latent class models. For both tests, asymptotic distributions can be used; that is, the test statistic can be assumed to follow a central Chi-square under the null hypothesis and a non-central Chi-square under the alternative hypothesis. Power or sample-size computation using these asymptotic distributions requires specification of the non-centrality parameter, which in practice is rarely known.

Power Analysis for the Likelihood-Ratio Test in Latent Markov Models: Shortcutting the Bootstrap p-Value-Based Method.

The latent Markov (LM) model is a popular method for identifying distinct unobserved states and transitions between these states over time in longitudinally observed responses. The bootstrap likelihood-ratio (BLR) test yields the most rigorous test for determining the number of latent states, yet little is known about power analysis for this test. Power could be computed as the proportion of the bootstrap p values (PBP) for which the null hypothesis is rejected.