Elective induction of labour and expectant management in late-term pregnancy : A prospective cohort study alongside the INDEX randomised controlled trial

Funding Information: BWM reports consultancy for ObsEva. BMW has received research funding from Ferring and Merck. The original RCT was funded by ZonMw: number NTR3431 , Netherlands Trial Registy . BWM is supported by a NHMRC Investigator grant (GNT1176437). Publisher Copyright: © 2022 The AuthorsPeer reviewedPublisher PD

Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model

Background: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO).Methods: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOBSPIR) or RIP flow (WOBRIP).Results: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOBSPIR to WOBRIP, a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences.Conclusion: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Impact: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates.There was a strong correlation between spirometry-based WOB versus RIP-based WOB.To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements.Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available.Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements.</p

Risk Factors for Necrotizing Enterocolitis:A Prospective Multicenter Case-Control Study

BACKGROUND: The identification of independent clinical risk factors for necrotizing enterocolitis (NEC) may contribute to early selection of infants at risk, allowing for the development of targeted strategies aimed at the prevention of NEC. OBJECTIVE: The objective of this study was to identify independent risk factors contributing to the development of NEC in a large multicenter cohort. METHODS: This prospective cohort study was performed in 9 neonatal intensive care units. Infants born at a gestational age &lt;/=30 weeks were included. Demographic and clinical data were collected daily until day 28 postnatally. Factors predictive of the development of NEC were identified using univariate and multivariable analyses in a 1: 5 matched case-control cohort. RESULTS: In total, 843 infants (56 NEC cases) were included in this study. In the case-control cohort, univariate analysis identified sepsis prior to the onset of NEC and formula feeding to be associated with an increased risk of developing NEC, whereas the administration of antibiotics directly postpartum was inversely associated with NEC. In a multivariable logistic regression model, enteral feeding type and the number of days parenterally fed remained statistically significantly associated with NEC, whereas the administration of antibiotics directly after birth was associated with a lower risk of developing NEC. CONCLUSIONS: Formula feeding and prolonged (duration of) parenteral feeding were associated with an increased risk of NEC. Contrary to expectations, the initiation of treatment with antibiotics within 24 h after birth was inversely associated with NEC

Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis

ObjectiveTo determine [1] expression levels of both DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) in human endometrium throughout the menstrual cycle and in eutopic and ectopic endometrium of patients with endometriosis and [2] hormone responsiveness of DNMT and MBD expression in explant cultures of proliferative phase endometrium.DesignIn vitro study.SettingAcademic medical center.Patient(s)Premenopausal women with and without endometriosis.Intervention(s)Explant cultures of proliferative phase endometrium were treated with vehicle, 17β-E2, or a combination of E2 and P (E2 + P) for 24 hours.Main Outcome Measure(s)Expression levels of DNMT1, DNMT2, and DNMT3B and MBD1, MBD2, and MeCP2 with use of real-time quantitative polymerase chain reaction.Result(s)Expression levels of DNMT1 and MBD2 were significantly higher in secretory-phase endometrium compared with proliferative endometrium and menstrual endometrium. In explant cultures, treatment with E2 + P resulted in significant up-regulation of DNMT1 and MBD2. Expression levels of several DNMTs and MBDs were significantly lower in endometriotic lesions compared with eutopic endometrium of women with endometriosis and disease-free controls.Conclusion(s)These findings suggest a role for DNMTs and MBDs in the growth and differentiation of the human endometrium and support the notion that endometriosis may be an epigenetic disease

Down-regulation of the histone methyltransferase EZH2 contributes to the epigenetic programming of decidualizing human endometrial stromal cells

Differentiation of human endometrial stromal cells (HESC) into decidual cells represents a highly coordinated process essential for embryo implantation. We show that decidualizing HESC down-regulate the histone methyltransferase enhancer of Zeste homolog 2 (EZH2), resulting in declining levels of trimethylation of histone 3 on lysine 27 (H3K27me3) at the proximal promoters of key decidual marker genes PRL and IGFBP1. Loss of H3K27me3 was associated with a reciprocal enrichment in acetylation of the same lysine residue, indicating active remodeling from repressive to transcriptionally permissive chromatin. Chromatin immunoprecipitation coupled with DNA microarray analysis demonstrated that decidualization triggers genome-wide changes in H3K27me3 distribution that only partly overlap those observed upon EZH2 knockdown in undifferentiated HESC. Gene ontology revealed that gain of the repressive H3K27me3 mark in response to decidualization and upon EZH2 knockdown in undifferentiated cells was enriched at the promoter regions of genes involved in transcriptional regulation and growth/cell proliferation, respectively. However, loss of the H3K27me3 mark (indicating increased chromatin accessibility) in decidualizing cells and upon EZH2 knockdown occurred at selective loci enriched for genes functionally implicated in responses to stimulus. In agreement, EZH2 knockdown in undifferentiated HESC was sufficient to augment the induction of decidual marker genes in response to cyclic AMP and progesterone signaling. Thus, loss of EZH2-dependent methyltransferase activity in the endometrium is integral to the process of chromatin remodeling that enables the transition from a proliferative to a decidual phenotype in response to differentiation cues

Estudo do atendimento ao público em bancos o método das projeções cotadas

Objective To compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk women. Design Open label, randomised controlled non-inferiority trial. Setting 123 primary care midwifery practices and 45 hospitals (secondary care) in the Netherlands, 2012-16. Participants 1801 low risk women with an uncomplicated singleton pregnancy: randomised to induction (n=900) or to expectant management until 42 weeks (n=901). Interventions Induction at 41 weeks or expectant management until 42 weeks with induction if necessary. Primary outcome measures Primary outcome was a composite of perinatal mortality and neonatal morbidity (Apgar score <7 at five minutes, arterial pH <7.05, meconium aspiration syndrome, plexus brachialis injury, intracranial haemorrhage, and admission to a neonatal intensive care unit (NICU). Secondary outcomes included maternal outcomes and mode of delivery. The null hypothesis that expectant management is inferior to induction was tested with a non-inferiority margin of 2%. Results Median gestational age at delivery was 41 weeks+0 days (interquartile range 41 weeks+0 days-41 weeks+1 day) for the induction group and 41 weeks+2 days (41 weeks+0 days-41 weeks+5 days) for the expectant management group. The primary outcome was analysed for both the intention-to-treat population and the per protocol population. In the induction group, 15/900 (1.7%) women had an adverse perinatal outcome versus 28/901 (3.1%) in the expectant management group (absolute risk difference a '1.4%, 95% confidence interval a '2.9% to 0.0%, P=0.22 for non-inferiority). 11 (1.2%) infants in the induction group and 23 (2.6%) in the expectant management group had an Apgar score <7 at five minutes (relative risk (RR) 0.48, 95% CI 0.23 to 0.98). No infants in the induction group and three (0.3%) in the expectant management group had an Apgar score <4 at five minutes. One fetal death (0.1%) occurred in the induction group and two (0.2%) in the expectant management group. No neonatal deaths occurred. 3 (0.3%) neonates in the induction group versus 8 (0.9%) in the expectant management group were admitted to an NICU (RR 0.38, 95% CI 0.10 to 1.41). No significant difference was found in composite adverse maternal outcomes (induction n=122 (13.6%) v expectant management n=102 (11.3%)) or in caesarean section rate (both groups n=97 (10.8%)). Conclusions This study could not show non-inferiority of expectant management compared with induction of labour in women with uncomplicated pregnancies at 41 weeks; instead a significant difference of 1.4% was found for risk of adverse perinatal outcomes in favour of induction, although the chances of a good perinatal outcome were high with both strategies and the incidence of perinatal mortality, Apgar score <4 at five minutes, and NICU admission low. Trial registration Netherlands Trial Register NTR3431