Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study

Background: Caesarean section (CS) rates are increasing worldwide and as a result repeat CS is common. The optimal mode of delivery in women with one previous CS is widely debated and the risks to the infant are understudied. The aim of the current study was to evaluate if women with a trial of labour after caesarean (TOLAC) had an increased odds of neonatal and infant death compared to women with an elective repeat CS (ERCS). Methods: A population register-based cohort study was conducted in Denmark between 1982 and 2010. All women with two deliveries [in which the first was a CS, and the second was an uncomplicated, term delivery (n = 61,626)] were included in the study. Logistic regression models were used to report adjusted odds ratios (AOR) and 95% confidence intervals (CI) of the odds of death according to mode of delivery. The main outcome measures were neonatal death (early and late) and infant death. Results: Women with a TOLAC had an increased odds of neonatal death (AOR 1 · 87, 95% CI 1 · 12 to 3 · 12) due to an increased risk of early neonatal death (AOR 2 · 06, 95% CI 1 · 19 to 3 · 56) and no effect on late neonatal death (AOR 0 · 97, 95% CI 0 · 22 to 4 · 32), or infant death (AOR 1 · 12, 95% CI 0 · 79 to 1 · 59) when compared to the reference group of women with an ERCS. There was evidence of a cohort effect as the increased odds of neonatal death (AOR 3 · 89, 95% CI 1 · 33 to 11 · 39) was most significant in the earlier years (1982–1991) and gradually disappeared (AOR 1 · 01, 95% CI 0 · 44 to 2 · 31) in the later years (2002–2010). Conclusions: Although an increased risk of neonatal death was found in women with a TOLAC, there was evidence of a cohort effect, which showed this increased odds disappearing over time. Advances in modern healthcare including improved monitoring and earlier detection of underlying pregnancy complications may explain the findings

Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study

Background: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. Conclusions: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery

Event-triggered logical flow control for comprehensive process integration of multi-step assays on centrifugal microfluidic platforms

Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.The centrifugal "lab-on-a-disc" concept has proven to have great potential for process integration of bioanalytical assays, in particular where ease-of-use, ruggedness, portability, fast turn-around time and cost efficiency are of paramount importance. Yet, as all liquids residing on the disc are exposed to the same centrifugal field, an inherent challenge of these systems remains the automation of multi-step, multi-liquid sample processing and subsequent detection. In order to orchestrate the underlying bioanalytical protocols, an ample palette of rotationally and externally actuated valving schemes has been developed. While excelling with the level of flow control, externally actuated valves require interaction with peripheral instrumentation, thus compromising the conceptual simplicity of the centrifugal platform. In turn, for rotationally controlled schemes, such as common capillary burst valves, typical manufacturing tolerances tend to limit the number of consecutive laboratory unit operations (LUOs) that can be automated on a single disc. In this paper, a major advancement on recently established dissolvable film (DF) valving is presented; for the very first time, a liquid handling sequence can be controlled in response to completion of preceding liquid transfer event, i.e. completely independent of external stimulus or changes in speed of disc rotation. The basic, event-triggered valve configuration is further adapted to leverage conditional, large-scale process integration. First, we demonstrate a fluidic network on a disc encompassing 10 discrete valving steps including logical relationships such as an AND-conditional as well as serial and parallel flow control. Then we present a disc which is capable of implementing common laboratory unit operations such as metering and selective routing of flows. Finally, as a pilot study, these functions are integrated on a single disc to automate a common, multi-step lab protocol for the extraction of total RNA from mammalian cell homogenate.Peer reviewe

Caesarean delivery and subsequent stillbirth or miscarriage: systematic review and meta-analysis

Contains fulltext : 118096.pdf (publisher's version ) (Open Access)OBJECTIVE: To compare the risk of stillbirth and miscarriage in a subsequent pregnancy in women with a previous caesarean or vaginal delivery. DESIGN: Systematic review of the published literature including seven databases: CINAHL; the Cochrane library; Embase; Medline; PubMed; SCOPUS and Web of Knowledge from 1945 until November 11(th) 2011, using a detailed search-strategy and cross-checking of reference lists. STUDY SELECTION: Cohort, case-control and cross-sectional studies examining the association between previous caesarean section and subsequent stillbirth or miscarriage risk. Two assessors screened titles to identify eligible studies, using a standardised data abstraction form and assessed study quality. DATA SYNTHESIS: 11 articles were included for stillbirth, totalling 1,961,829 pregnancies and 7,308 events. Eight eligible articles were included for miscarriage, totalling 147,017 pregnancies and 12,682 events. Pooled estimates across the stillbirth studies were obtained using random-effect models. Among women with a previous caesarean an increase in odds of 1.23 [95% CI 1.08, 1.40] for stillbirth was yielded. Subgroup analyses including unexplained stillbirths yielded an OR of 1.47 [95% CI 1.20, 1.80], an OR of 2.11 [95% CI 1.16, 3.84] for explained stillbirths and an OR of 1.27 [95% CI 0.95, 1.70] for antepartum stillbirths. Only one study reported adjusted estimates in the miscarriage review, therefore results are presented individually. CONCLUSIONS: Given the recent revision of the National Institute for Health and Clinical Excellence guidelines (NICE), providing women the right to request a caesarean, it is essential to establish whether mode of delivery has an association with subsequent risk of stillbirth or miscarriage. Overall, compared to vaginal delivery, the pooled estimates suggest that caesarean delivery may increase the risk of stillbirth by 23%. Results for the miscarriage review were inconsistent and lack of adjustment for confounding was a major limitation. Higher methodological quality research is required to reliably assess the risk of miscarriage in subsequent pregnancies

Comparison of Hydrostatic, Dynamic and Hybrid centrifugo-pneumatic siphon valves (CPSVs).

<p>Gas pressure is indicated in subfigures through the intensity of colour. (a) Liquid is loaded to the disc. (b) Upon spinning, the liquid advances into the central chamber while seeking hydrostatic equilibrium. However, the centrifugal compression of the gas volumes in the compartments enclosed by the liquid creates a counter pressure. (c, d) In the hydrostatic mechanism, the air in the closed side chamber expands upon reduction of the spin rate, so the liquid level in the open central chamber rises above the crest point of the siphon to forward the liquid into the open receiving chamber. In the hybrid CPSV, air is compressed in the closed central chamber during fast spinning. After lowering the angular frequency, the resulting decompression of air and the reduction of the centrifugal field jointly lift the liquid levels in the side arms above the crest point to empty the liquid into the open outer chamber. The operation of the dynamic CPSV follows a similar mechanism. However, the crest point of the siphon is now located above the level of the hydrostatic equilibrium; the siphon valve thus only opens upon rapid change of the spin rate so inertia propels the flow until the meniscus in the outlet channel has protruded past the liquid level in the central chamber.</p

Density-Gradient Mediated Band Extraction of Leukocytes from Whole Blood Using Centrifugo-Pneumatic Siphon Valving on Centrifugal Microfluidic Discs - Fig 7

<p><b>Phase Switching Data and Quantitative Results</b> (a-b) highlight ‘phase-switching’. This trait occurs where the system switches from drawing one phase, the DGM, to the other phase, plasma, while leaving a significant number of PBMCs within the main sedimentation chamber (c) and image from the haemocytometer showing mononuclear leukocytes enumeration (d) comparison of mononuclear leukocytes extracted from the single pneumatic chamber (Disc A) to a whole blood count (hospital laboratory) and using a HemoCue™.</p

Schematic of Multi-layer discs Multi-layer discs are assembled from of 1.5-mm PMMA layers interspersed by 86-μm thin PSA films.

<p>Schematic of Multi-layer discs Multi-layer discs are assembled from of 1.5-mm PMMA layers interspersed by 86-μm thin PSA films.</p

WBC Isolation using a dual siphon, split pneumatic chamber CPSV (Disc C).

<p>(a) The disc is loaded with DGM as the whole blood is introduced during disc acceleration. (b) RBCs sediment. Note that the siphons have a number of capillary burst valves. The upper capillary valve on the lower siphon prevents the DGM pre-priming siphon while the disc is stopped for blood loading. (c) Stratified blood in the chamber. Note that the plasma remains below the siphon crest points. (d) The disc is decelerated and the bulk liquid is displaced radially inwards and the siphon prime. The siphon priming is halted by the capillary burst valves. The siphons must be primed at a lower frequency (~2.5 Hz) than the nominal frequency (~15 Hz) to prevent the capillary valves from bursting early or out of sequence. However, due to the low hydrostatic priming pressure at this spin rate, the crest of the lower siphon required treatment using a surfactant to achieve reliable priming. The upper siphon was not treated. (e) The spin rate is increased and the burst valve of the upper siphon capillary is opened, thus removing the plasma to the collection chamber. (f) The spin rate is increased further and the lower siphon valve opens for removing the WBCs (with some plasma and DGM) to the WBC collection chamber. See ESI <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155545#pone.0155545.s001" target="_blank">S1 Movie</a> showing blood processing in Disc C.</p

Digital process control of multi-step assays on centrifugal platforms using high-low-high rotational-pulse triggered valving.

Due to their capability for comprehensive sample-to-answer automation, the interest in centrifugal microfluidic systems has greatly increased in industry and academia over the last quarter century. The main applications of these "Lab-on-a-Disc" (LoaD) platforms are in decentralised bioanalytical point-of-use / point-of-care testing. Due to the unidirectional and omnipresent nature of the centrifugal force, advanced flow control is key to coordinate multi-step / multi-reagent assay formats on the LoaD. Formerly, flow control was often achieved by capillary burst valves which require gradual increments of the spin speed of the system-innate spindle motor. Recent advanced introduced a flow control scheme called 'rotational pulse actuated valves'. In these valves the sequence of valve actuation is determined by the architecture of the disc while actuation is triggered by freely programmable upward spike (i.e. Low-High-Low (LHL)) in the rotational frequency. This paradigm shift from conventional 'analogue' burst valves to 'digital' pulsing significantly increases the number of sequential while also improving the overall robustness of flow control. In this work, we expand on these LHL valves by introducing High-Low-High (HLH) pulse-actuated (PA) valving which are actuated by 'downward' spike in the disc spin-rate. These HLH valves are particularly useful for high spin-rate operations such as centrifugation of blood. We introduce two different HLH architectures and then combine the most promising with LHL valves to implement the time-dependent liquid handling protocol underlying a common liver function test panel

WBC isolation using a dynamically CPSV (Disc D).

<p>(a) The disc loaded with DGM while the whole blood is introduced during disc acceleration. (b) RBCs sediment to the bottom. Note that the pneumatic chamber is extended by channel (lower level) indicated in a blue dash. This large pneumatic chamber is required to ensure that the valves function at the volumes processed. (c) Stratified blood in the chamber. (d) The spin rate is decreased and both siphons are simultaneously primed. Note that the siphon crests are located radially inwards of the bulk liquid and the liquid displaced radially inwards along the loading channel. (e) The spin rate is increased and both siphons empty. See ESI <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155545#pone.0155545.s001" target="_blank">S1 Movie</a> showing blood processing in Disc D.</p