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A Peripheral Immune Signature of Labor Induction.

ABSTRACT: Approximately 1 in 4 pregnant women in the United States undergo labor induction. The onset and establishment of labor, particularly induced labor, is a complex and dynamic process influenced by multiple endocrine, inflammatory, and mechanical factors as well as obstetric and pharmacological interventions. The duration from labor induction to the onset of active labor remains unpredictable. Moreover, prolonged labor is associated with severe complications for the mother and her offspring, most importantly chorioamnionitis, uterine atony, and postpartum hemorrhage. While maternal immune system adaptations that are critical for the maintenance of a healthy pregnancy have been previously characterized, the role of the immune system during the establishment of labor is poorly understood. Understanding maternal immune adaptations during labor initiation can have important ramifications for predicting successful labor induction and labor complications in both induced and spontaneous types of labor. The aim of this study was to characterize labor-associated maternal immune system dynamics from labor induction to the start of active labor. Serial blood samples from fifteen participants were collected immediately prior to labor induction (baseline) and during the latent phase until the start of active labor. Using high-dimensional mass cytometry, a total of 1,059 single-cell immune features were extracted from each sample. A multivariate machine-learning method was employed to characterize the dynamic changes of the maternal immune system after labor induction until the establishment of active labor. A cross-validated linear sparse regression model (least absolute shrinkage and selection operator, LASSO) predicted the minutes since induction of labor with high accuracy (R = 0.86, p = 6.7e-15, RMSE = 277 min). Immune features most informative for the model included STAT5 signaling in central memory CD8⁺ T cells and pro-inflammatory STAT3 signaling responses across multiple adaptive and innate immune cell subsets. Our study reports a peripheral immune signature of labor induction, and provides important insights into biological mechanisms that may ultimately predict labor induction success as well as complications, thereby facilitating clinical decision-making to improve maternal and fetal well-being.

SUBMITTER: Ando K

PROVIDER: S-EPMC8458888 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough induction of labor of low-risk nulliparous women at 39 weeks reduces the risk of cesarean delivery compared with expectant management, concern regarding more frequent use of labor induction remains, given that this intervention historically has been thought to incur greater resource utilization.ObjectiveThe objective of the study was to determine whether planned elective labor induction at 39 weeks among low-risk nulliparous women, compared with expectant management, was associated with differences in health care resource utilization from the time of randomization through 8 weeks postpartum.Study designThis is a planned secondary analysis of a multicenter randomized trial in which low-risk nulliparous women were assigned to induction of labor at 39 weeks or expectant management. We assessed resource utilization after randomization in 3 time periods: antepartum, delivery admission, and discharge through 8 weeks postpartum.ResultsOf 6096 women with data available, those in the induction of labor group (n = 3059) were significantly less likely in the antepartum period after randomization to have at least 1 ambulatory visit for routine prenatal care (32.4% vs 68.4%), unanticipated care (0.5% vs 2.6%), or urgent care (16.2% vs 44.3%), or at least 1 antepartum hospitalization (0.8% vs 2.2%, P < .001 for all). They also had fewer tests (eg, sonograms, blood tests) and treatments (eg, antibiotics, intravenous hydration) prior to delivery. During the delivery admission, women in the induction of labor group spent a longer time in labor and delivery (median, 0.83 vs 0.57 days), but both women (P = .002) and their neonates (P < .001) had shorter postpartum stays. Women and neonates in both groups had similar frequencies of postpartum urgent care and hospital readmissions (P > .05 for all).ConclusionWomen randomized to induction of labor had longer durations in labor and delivery but significantly fewer antepartum visits, tests, and treatments and shorter maternal and neonatal hospital durations after delivery. These results demonstrate that the health outcome advantages associated with induction of labor are gained without incurring uniformly greater health care resource use.

Project description:Rationale: Pathogenesis of human coronary atherosclerosis is tightly associated with the imbalance of inflammation and resolution in the local immune microenvironment of AS plaques. However, how the peripheral immune system dynamically changes along with disease progression in humans remains unclear. As a result, the minimally-invasive clinical biomarkers that can sensitively distinguish different stages of human coronary atherosclerosis are still lacking. Methods: We performed single-cell Cytometry by Time-Of-Flight (CyTOF) analyses to comprehensively profile the compositions and phenotypes of CD45+ cells derived from 83 human peripheral blood samples with two independent antibody-staining panels (T cell panel and myeloid cell panel). Clinical associations between the frequencies of peripheral immune cell subsets with AS plaque burdens of coronary arteries (Gensini score) and serum lipids were also examined. By integrating immune and clinical features, we established novel CVD risk prediction models to stratify patients in different disease stages. Results: We revealed the disease stage-associated peripheral immune features for patients with coronary atherosclerosis (CAS) and atherosclerotic cardiovascular disease (ASCVD), and also identified the specific peripheral immune cell subsets that were tightly associated with the disease severity of coronary arteries (Gensini score). By integrating these peripheral immune signatures with clinical features, we have established a disease progression prediction (DPP) model that could precisely discriminate CAS patients from ASCVD patients with high prediction accuracy (ROC-AUC = 0.88). Conclusion: The progression of coronary atherosclerosis is accompanied by significant alterations of the peripheral immune system, including the changes in the distributions as well as phenotypic functions of specific immune cell subsets. The indicated stage-specific peripheral immune signatures thus become promising minimally-invasive liquid biomarkers that could help to potentially diagnose and monitor the CVD progression in humans.

Project description:Background/Objective: To evaluate adherence to labor arrest and failed induction of labor (IOL) criteria in nulliparous, term, singleton, and vertex (NTSV) cesarean deliveries at an academic medical center and to measure the impact of a quality-improvement educational initiative that focused on obstetric provider education of modern labor arrest and failed IOL criteria. Methods: This is a retrospective cohort study using electronic health record (EHR) data with a pre- (1 September 2018-30 September 2019) and post-intervention (1 October 2019-31 March 2020) study design of all NTSV cesarean deliveries for labor arrest or failed IOL performed at an academic medical center in the northeastern United States. The quality-improvement educational intervention consisted of the distribution of educational pocket cards outlining modern labor arrest and failed IOL criteria to obstetric providers. Outcomes included adherence to labor arrest and failed IOL criteria pre- and post-intervention with secondary outcomes evaluating adherence by provider type (Maternal-Fetal Medicine (MFM) or generalist obstetrician). Descriptive and bivariate statistics were used in the analysis. Results: Pre-intervention, 272 NTSV cesarean deliveries were performed for labor arrest or failed IOL versus 92 post-intervention. Adherence improved post-intervention amongst failed IOL (OR 6.5, CI 1.8-23.8), first-stage arrest (OR 4.5, CI 2.2-10.8) and second-stage arrest (OR 3.7, CI 1.5-9.4). When comparing provider type, MFM physicians were more likely to be adherent to labor arrest and failed IOL criteria compared to generalist obstetricians pre-intervention (OR 3.1, CI 1.7-5.5); however, post-intervention, there was no longer a difference in adherence (OR 3.3, CI 0.9-12.3). Conclusions: Adherence to labor arrest criteria was suboptimal in the pre-intervention period; however, a targeted quality-improvement educational intervention improved adherence rates to labor arrest and failed IOL criteria among obstetric providers.

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A Peripheral Immune Signature of Labor Induction.

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