Objective To compare rates of vaginal delivery and adverse outcomes of instrumental delivery trials in obstetric theatre compared to primary emergency full dilation caesarean section. Design Retrospective cohort study. Setting University teaching hospital. Population Women with singleton, non‐anomalous, pregnancy undergoing instrumental delivery trial in obstetric theatre. Methods Data were collected from consecutive cases during 2014 until 2018 using clinical records. Multivariate regression analysis was used comparing outcomes per first delivery method. Main Outcome Measures Primary outcome was completion of vaginal delivery between all methods of instrumental delivery. Secondary outcome was a composite of immediate perinatal adverse outcomes for instrumental delivery modes and primary full dilation caesarean section. Results From 971 deliveries analysed: ventouse delivery was significantly less likely to achieve vaginal delivery compared with Keilland’s forceps delivery (odds ratio [OR] 0.42, 95% CI 0.22–0.79). Once confounding factors were adjusted for, adverse outcome rates were less frequent in the Keilland’s forceps group than with primary full dilation caesarean section (OR 0.37, 95% CI 0.16–0.81); however, the receiver operating characteristic curve produced from this model demonstrated a low predictive value (AUC 0.64). Conclusions Attempting instrumental delivery in delivery suite theatre, as an alternative to primary emergency full dilation caesarean section, is both reasonable and safe. In this study, ventouse delivery performed poorly in comparison with other modes of instrumental delivery. Further research in the form of randomised controlled trials to identify the optimal mode of second stage delivery is paramount. Tweetable abstract Instrumental delivery trials in theatre are safe but use of ventouse was associated with a higher rate of failure.
Complications arising from Preterm Birth are the leading causes of neonatal death globally. Current therapeutic strategies to prevent Preterm Birth are yet to demonstrate success in terms of reducing this neonatal disease burden. Upregulation of intracellular inflammatory pathways in uterine cells, including those involving nuclear factor kappa-B (NFκB), have been causally linked to both human term and preterm labor, but the barrier presented by the cell membrane presents an obstacle to interventions aimed at dampening these inflammatory responses. Cell penetrating peptides (CPPs) are novel vectors that can traverse cell membranes without the need for recognition by cell surface receptors and offer the ability to deliver therapeutic cargo internal to cell membranes. Using a human uterine cell culture inflammatory model, this study aimed to test the effectiveness of CPP-cargo delivery to inhibit inflammatory responses, comparing this effect with a small molecule inhibitor (Sc514) that has a similar intracellular target of action within the NFκB pathway (the IKK complex). The CPP Penetratin, conjugated to rhodamine, was able to enter uterine cells within a 60 min timeframe as assessed by live confocal microscopy, this phenomena was not observed with the use of a rhodamine-conjugated inert control peptide (GC(GS)4). Penetratin CPP conjugated to an IKK-inhibitory peptide (Pen-NBD) demonstrated ability to inhibit both the IL1β-induced expression of the inflammatory protein COX2 and dampen the expression of a bespoke array of inflammatory genes. Truncation of the CPP vector rendered the CPP-cargo conjugate much less effective, demonstrating the importance of careful vector selection. The small molecule inhibitor Sc514 also demonstrated ability to inhibit COX2 protein responses and a broad down-regulatory effect on uterine cell inflammatory gene expression. These results support the further exploration of either CPP-based or small molecular treatment strategies to dampen gestational cell inflammatory responses in the context of preterm birth. The work underlines both the importance of careful selection of CPP vector-cargo combinations and basic testing over a broad time and concentration range to ensure effective responses. Further work should demonstrate the effectiveness of CPP-linked cargos to dampen alternative pathways of inflammation linked to Preterm Birth such as MAP Kinase or AP1.
Objective To compare rates of vaginal delivery and adverse outcomes of instrumental delivery trials in obstetric theatre compared to primary emergency full dilatation Caesarean section Design Retrospective cohort study Setting University teaching hospital Population Women with singleton, non-anomalous, pregnancy undergoing instrumental delivery trial in obstetric theatre Methods Data was collected from consecutive cases during 2014 until 2018 using clinical records. Multivariate regression analysis was used comparing groups per first delivery attempt. Main Outcome Measures Primary outcome was completion of vaginal delivery between all methods of instrumental delivery. Secondary outcome was a composite of immediate perinatal adverse outcomes for instrumental delivery modes and primary full dilatation Caesarean section. Results From 971 deliveries analysed: ventouse delivery was significantly less likely to achieve vaginal delivery compared to Keilland's forceps delivery (OR 0.42, 95%CI 0.22-0.79). Once confounding factors were adjusted for, adverse outcome rates were less frequent in the Keilland's forceps group compared with primary full dilatation Caesarean section (OR 0.37, 95% CI: 0.16-0.81), however the receiver operating characteristic curve produced from this model demonstrated low predictive value (AUC 0.64). Conclusions Attempting instrumental delivery in delivery suite theatre, as an alternative to primary emergency full dilatation Caesarean section, is both reasonable and safe. Ventouse delivery in this situation may be associated with a higher chance of failure than other modes of instrumental delivery, thus making appropriate choice of delivery method of paramount importance according to each clinical situation. Funding None Keywords Caesarean section, Keilland's forceps, ventouse, trial of instrumental delivery
Fetal anaemia can be caused by alloimmune or infectious red cell destruction, disorders of fetal red cell production, fetal haemorrhage and as a complication of monochorionic multifetal pregnancy. A fetus at risk from maternal alloimmunisation can be detected by maternal serum screening for red cell antibodies and by fetal ultrasonography. Undiagnosed cases may present in routine obstetric practice, so awareness of the identification and initial management of fetal anaemia is important. Pregnancies must be triaged depending on clinical urgency, with input from fetal medicine specialists required. Developments in fetal ultrasound assessment and in fetal therapy have improved outcomes and contemporary research will focus on improving long term outcomes for neonatal survivors. Learning objectivesTo understand the varied aetiologies and pathophysiology of fetal anaemia and to adopt a system for reaching a diagnosis. To appreciate the different diagnostic tools available, comprising ultrasonography, microbiological testing, noninvasive and invasive tests in fetal medicine units and electronic fetal monitoring in the acute setting. Ethical issuesManagement involves balancing maternal and fetal risks. Research ethics should be considered in relation to experimental treatments and trials in fetal therapy.
Objective: An association between infections in pregnancy and increased risk of preterm birth (PTB) is described in the literature. We anticipated that differences may exist in screening and treatment approaches for infections associated with PTB, within and between European countries. The aim of this study was to examine and analyse these differences in clinical practice in greater detail. Study Design: We created a descriptive survey examining the screening and treatment of infections in pregnancy. The survey was sent to European representatives of the International Spontaneous Preterm Birth Young Investigators (I-SPY) group in Europe, who sent it to their network. Finally, we had 50 respondents from ten European countries. Results: We found substantial differences in screening for bacterial vaginosis and asymptomatic bacteriuria, administration of antibiotics to women with preterm prelabour rupture of membranes (PPROM), and timing of induction of labour after PPROM. These differences in clinical practice were present both within, and between countries. Conclusions: Approaches for screening and treatment of infections associated with PTB differ between European countries. There is a lack of robust evidence, which is reflected in a lack of uniformity in international guidelines. International collaboration is paramount to enlarge sample sizes in obstetric studies and to facilitate the process of developing, updating, and implementing consistent guidelines across Europe and beyond.
We report a case of maternally inherited autosomal dominant PLAG-1 related Silver Russell syndrome (SRS) in a fetus with IUGR and a mother who had growth and feeding problems in early life, dextrocardia and an atrio-ventricular septal defect.Amniocentesis was performed due to marked intra-uterine growth restriction (IUGR). The array was normal. Whole exome sequencing (WES) revealed a maternally inherited heterozygous likely pathogenic variant in PLAG1 (NM_002655.3): c.402delT p.(Gly135Aspfs*94). This variant has not been reported previously. PLAG1 pathogenic variants are associated with autosomal dominant Silver Russell syndrome, which fits with the clinical phenotypes of both fetus and mother. PLAG1 variants have previously been reported post-natally in Silver Russell syndrome, but the phenotype tends to be milder than in 11p15.5 methylation-related cases with fewer physical features. Although cardiac anomalies are uncommon in SRS, they have been previously reported. To our knowledge, dextrocardia has not been previously associated with SRS and there were no other potential causative genetic variants found. This report aims to highlight this rare type of SRS as a cause of IUGR.
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