Biofilm-Mediated Fragmentation and Degradation of Microcrystalline Cellulose by Cellulomonas flavigena KU (ATCC 53703).

Cellulomonas flavigena KU (ATCC 53703) produces an extracellular matrix involved in the degradation of microcrystalline cellulose. This extracellular material is primarily composed of the gel-forming, ß-1,3-glucan known as curdlan and associated, cellulose-degrading enzymes. In this study, the effects of various forms of nutrient limitation on cellulose attachment, cellular aggregation, curdlan production, and biofilm formation were investigated throughout a 7-day incubation period by using phase-contrast microscopy. Compared to cultures grown in non-limiting media, nitrogen-limitation promoted early attachment of C. flavigena KU cells to the cellulose surface, and cellulose attachment was congruent with cellular aggregation and curdlan production. Over the course of the experiment, microcolonies of attached cells grew into curdlan-producing biofilms on the cellulose. By contrast, bacterial cells grown on cellulose in non-limiting media remained unattached and unaggregated throughout most of the incubation period. By 7 days of incubation, bacterial aggregation was ninefold greater in N-limited cultures compared to nutritionally complete cultures. In a similar way, phosphorus- and vitamin-limitation (i.e., yeast extract-limitation) also resulted in early cellulose attachment and biofilm formation. Furthermore, nutrient limitation promoted more rapid and efficient fragmentation and degradation of cellulose, with cellulose fragments in low-N media averaging half the size of those in high-N media after 7 days. Two modes of cellulose degradation are proposed for C. flavigena KU, a "planktonic mode" and a "biofilm mode". Similar observations have been reported for other curdlan-producing cellulomonads, and these differing cellulose degradation strategies may ultimately prove to reflect sequential stages of a multifaceted biofilm cycle important in the bioconversion of this abundant and renewable natural resource.

A national population-based cohort study to investigate inequalities in maternal mortality in the United Kingdom, 2009-17.

BACKGROUND: Disparities have been documented in maternal mortality rates between women from different ethnic, age and socio-economic groups in the UK. It is unclear whether there are differential changes in these rates amongst women from different groups over time. The objectives of this analysis were to describe UK maternal mortality rates in different age, ethnic and socio-economic groups between 2009 and 2017, and to identify whether there were changes in the observed inequalities, or different trends amongst population subgroups. METHODS: Maternal mortality rates with 95% confidence intervals (CI) in specific age, deprivation and ethnic groups were calculated using numbers of maternal deaths as numerator and total maternities as denominator. Relative risks (RR) with 95% CI were calculated and compared using ratios of relative risk. Change over time was investigated using non-parametric tests for trend across ordered groups. RESULTS: Women from black and Asian groups had a higher mortality rate than white women in most time periods, as did women aged 35 and over and women from the most deprived quintile areas of residence. There was evidence of an increasing trend in maternal mortality amongst black women and a decrease in mortality amongst women from the least deprived areas, but no trends over time in any of the other ethnic, age or IMD groups were seen. There was a widening of the disparity between black and white women (RR 2.59 in 2009-11 compared with 5.27 in 2015-17, ratio of the relative risks 2.03, 95% CI 1.11, 3.72). CONCLUSIONS: The clear differences in the patterns of maternal mortality amongst different ethnic, age and socio-economic groups emphasise the importance of research and policies focussed specifically on women from black and minority ethnic groups, together with other disadvantaged groups, to begin to reduce maternal mortality in the UK.

'I didn't think you were allowed that, they didn't mention that.' A qualitative study exploring women's perceptions of home birth.

BACKGROUND: Evidence suggests that home birth is as safe as hospital birth for low risk multiparous women, and is associated with reduced intervention rates and increased rates of normal birth. However the home birth rate in the UK is low, and few women choose this option. The aims of this study were to identify what influences multiparous women's choice of birth place, and to explore their views of home birth. METHODS: Five focus groups were conducted with multiparous women (n = 28) attending mother and baby groups in a city in the UK with a diverse multi-ethnic population. Data were analysed thematically using the Framework Method, combining deductive and inductive approaches to the data. RESULTS: Several themes were developed from the data, these were: the expectation that birth would take place in an Obstetric Unit; perceptions of birth as a 'natural' event; lack of knowledge of what home birth looked like; and a lack of confidence in the reliability of the maternity service. Two themes emerged regarding the influences on women's choices: clear information provision, particularly for those from ethnic minority groups, and the role of health care professionals. A final theme concerned women's responses to the offer of choice. CONCLUSIONS: There are gaps in women's knowledge about the reality and practicalities of giving birth at home that have not been previously identified. Other findings are consistent with existing evidence, suggesting that many women still do not receive consistent, comprehensive information about home birth. The findings from this research can be used to develop approaches to meet women's information and support needs, and facilitate genuine choice of place of birth.

Midwives' experiences of performing maternal observations and escalating concerns: a focus group study.

BACKGROUND: For the past decade, Maternal Mortality Reports, published in the United Kingdom every three years, have consistently raised concerns about maternal observations in maternity care. The reports identify that observations are not being done, not being completed fully, are not recorded on Early Warning Score systems, and/or are not escalated appropriately. This has resulted in delays in referral, intervention and increases the risk of maternal morbidity or mortality. However there has been little exploration of the possible reasons for non-completion of maternal observations. METHODS: The aim of this study was to explore midwives' experiences of performing maternal observations and escalating concerns in rural and urban maternity settings in the West Midlands of England. A qualitative design involving a series of six focus groups with midwives and Supervisors of Midwives was employed to investigate the facilitators of, and barriers to the completion of maternal observations. RESULTS: Eighteen Midwives and 8 Supervisors of Midwives participated in a total of 6 focus groups. Three key themes emerged from the data: (1) Organisation of Maternal Observations (including delegation of tasks to Midwifery Support Workers, variation in their training, the care model used e.g. one to one care, and staffing issues); (2) Prioritisation of Maternal Observations (including the role of professional judgement and concerns expressed by midwives that they did not feel equipped to care for women with complex clinical needs; and (3) Negotiated Escalation (including the inappropriate response from senior staff to use of Modified Early Warning Score systems, and the emotional impact of escalation). CONCLUSIONS: A number of organisational and cultural barriers exist to the completion of maternal observations and the escalation of concerns. In order to address these the following actions are recommended: standardised training for Midwifery Support Workers, review of training of midwives to ensure it addresses the increasing complexity of the maternal population, identification and agreement regarding the organisation of maternal observations among staff, an emphasis on increasing the priority placed on maternal observations in all clinical settings, and clarification and reinforcement of escalation procedures for both midwives and senior clinicians.

The design and implementation of an obstetric triage system for unscheduled pregnancy related attendances: a mixed methods evaluation.

BACKGROUND: No standardised system of triage exists in Maternity Care and local audit identified this to be problematic. We designed, implemented and evaluated an Obstetric Triage System in a large UK maternity unit. This includes a standard clinical triage assessment by a midwife, within 15 min of attendance, leading to assignment to a category of clinical urgency (on a 4-category scale). This guides timing of subsequent standardised immediate care for the eight most common reasons for attendance. A training programme was integral to the introduction. METHODS: A mixed methods evaluation was conducted. A structured audit of 994 sets of maternity notes before and after implementation identified the number of women seen within 15 min of attendance. Secondary measures reviewed included time to subsequent care and attendance. An inter-operator reliability study using scenarios was completed by midwives. A focus group and two questionnaire studies were undertaken to explore midwives' views of the system and to evaluate the training. In addition a national postal survey of practice in UK maternity units was undertaken in 2015. RESULTS: The structured audit of 974/992 (98%) of notes demonstrated an increase in the number of women seen within 15 min of attendance from 39% before implementation to 54% afterwards (RR (95% CI) 1.4 (1.2, 1.7) p = <0.0001). Excellent inter-operator reliability (ICC 0.961 (95% CI 0.91-0.99)) was demonstrated with breakdown showing consistently good rates. Thematic analysis of focus group data (n = 12) informed the development of the questionnaire which was sent to all appropriate midwives. The response rate was 53/79 (67%) and the midwives reported that the new system helped them manage the department and improved safety. The National Survey (response rate 85/135 [63%]) demonstrated wide variation in where women are seen and staffing models in place. The majority of units 69/85 (81%) did not use a triage system based on clinical assessment to prioritise care. CONCLUSIONS: This obstetric triage system has excellent inter- operator reliability and appears to be a reliable way of assessing the clinical priority of women as well as improving organisation of the department. Our survey has demonstrated the widespread need for implementation of such a system.

A systematic review to examine the evidence regarding discussions by midwives, with women, around their options for where to give birth.

BACKGROUND: Discussion of place of birth is important for women and maternity services, yet the detail, content and delivery of these discussions are unclear. The Birthplace Study found that for low risk, multiparous women, there was no significant difference in neonatal safety outcomes between women giving birth in obstetric units, midwifery-led units, or home. For low risk, nulliparous women giving birth in a midwifery-led unit was as safe as in hospital, whilst birth at home was associated with a small, increased risk of adverse perinatal outcomes. Intervention rates were reduced in all settings outside hospital. NICE guidelines recommend all women are supported in their choice of birth setting. Midwives have the opportunity to provide information to women about where they choose to give birth. However, research suggests women are sometimes unaware of all the options available. This systematic review will establish what is known about midwives' perspectives of discussions with women about their options for where to give birth and whether any interventions have been implemented to support these discussions. METHODS: The systematic review was PROSPERO registered (registration number: CRD42015017334). The PRISMA statement was followed. Medline, Cochrane, CINAHL, PsycINFO, Popline and EMBASE databases were searched between 2000-March 2015 and grey literature was searched. All identified studies were screened for inclusion. Qualitative data was thematically analysed, whilst quantitative data was summarised. RESULTS: The themes identified relating to influences on midwives' place of birth discussions with women were organisational pressures and professional norms, inadequate knowledge and confidence of midwives, variation in what midwives told women and the influence of colleagues. None of the interventions identified provided sufficient evidence of effectiveness and were of poor quality. CONCLUSIONS: The review has suggested the need for a pragmatic, understandable place of birth dialogue containing standard content to ensure midwives provide low risk women with adequate information about their place of birth options and the need to improve midwives knowledge about place of birth. A more robust, systematic evaluation of any interventions designed is required to improve the quality of place of birth discussions. By engaging with co-produced research, more effective interventions can be designed, implemented and sustained.

Improving the care pathway for women who request Caesarean section: an experience-based co-design study.

BACKGROUND: Maternal request for Caesarean section is controversial and yet the NICE Caesarean section Guideline recommends that that if this is requested, following discussion of the risks and benefits, women should be supported in their choice. There was a desire to improve the pathway at Birmingham Women's NHS Foundation Trust. METHODS: Experience-based co-design methodology uses service user and clinicians experiences collected using qualitative methods to jointly re-design services. Firstly semi-structured interviews were conducted to elicit the views and experiences of health care professionals and women who requested Caesarean section (with and without medical indication). Analysis identified key themes arising from the health care professionals' interviews and 'touch points' (key moments or events related to the experience of care) arising from the interviews with women.. Separate workshops were then held with each group to ensure these resonated and to identify key areas for service improvement. At the first joint workshop a pathway using 'audio clips' demonstrating women's agreed 'touch points' prompted discussion and joint working began to change the pathway. A final second workshop was held to agree changes to the pathway. RESULTS: Interviews were conducted with health care professionals (n = 22, 10 consultant obstetricians and 12 midwives) and women (n = 15). The women's 'touch points' included repetition of request, delay in the decision for Caesarean section to be made, feeling judged, and that information was poor with similar findings identified from the health care professionals. Joint working resulted in a revised pathway for women who request Caesarean section. Changes to the pathway for women as a result of the work include written information about 'The way your baby may be born' which is given to the woman followed by a discussion about mode of birth around the 16 week appointment. If the woman wishes to have a Caesarean section, referral is made to appropriate health care professionals (e.g., Consultant Midwife, counsellor) only if support and information would be useful. If Caesarean section is requested, woman is referred to a consultant obstetrician for an appointment at 20/40, with a decision by 28/40. Recording this in the notes minimises repeated challenge described by women. Final consent and timing of Caesarean section remain as recommended. CONCLUSION: This has resulted in changes to the pathway agreed by a co-design process and which are acceptable to both health care professionals and women. Use of such methodologies should be considered more frequently when implementing service change.

Examining the impact of introducing ICD-MM on observed trends in maternal mortality rates in the UK 2003-13.

BACKGROUND: The causes of maternal death are now classified internationally according to ICD-MM. One significant change with the introduction of ICD-MM in 2012 was the reclassification of maternal suicide from the indirect group to the direct group. This has led to concerns about the impact of this reclassification on calculated mortality rates. The aim of this analysis was to examine the trends in maternal deaths in the UK over the past 10 years, and to investigate the impact of reclassification using ICD-MM on the observed rates. METHODS: Data about all maternal deaths between 2003-13 in the UK were included in this analysis. Data about maternal deaths occurring prior to 2009 were obtained from previously published reports. The deaths of women from 2009-13 during or after pregnancy were identified through the MBRRACE-UK Confidential Enquiry into Maternal Deaths. The underlying causes of maternal death were reclassified from a disease-based system to ICD-MM. Maternal mortality rates with 95 % confidence intervals were calculated using national data on the number of maternities as the denominator. Rate ratios with 95 % CI were calculated to compare the change in rates of maternal death as per ICD-MM relative to the old classification system. RESULTS: There was a decrease in the maternal death rate between 2003-05 and 2011-13 (rate ratio (RR) 0.65; 95 % CI 0.54-0.77 comparing 2003-5 with 2011-13; p = 0.005 for trend over time). The direct maternal death rate calculated using the old classification decreased with a RR of 0.47 (95 % CI 0.34-0.63) when comparing 2011-13 with 2003-05; p = 0.005 for trend over time. Reclassification using ICD-MM made little material difference to the observed trend in direct maternal death rates, RR = 0.51 (95 % CI 0.39-0.68) when comparing 2003-5 with 2011-13; p = 0.005 for trend over time. CONCLUSIONS: The impact of reclassifying maternal deaths according to ICD-MM in the UK was minimal. However, such reclassification raises awareness of maternal suicides and hence is the first step to actions to prevent women dying by suicide in the future. Recognising and acknowledging these women's deaths is more important than concerns over the impact reclassification using ICD-MM might have on reported maternal death rates.

Consent revisited: the impact of return of results on participants' views and expectations about trial participation.

BACKGROUND: Increasingly, the sharing of study results with participants is advocated as an element of good research practice. Yet little is known about how receiving the results of trials may impact on participants' perceptions of their original decision to consent. OBJECTIVE: We explored participants' views of their decision to consent to a clinical trial after they received results showing adverse outcomes in some arms of the trial. METHOD: Semi-structured interviews were conducted with a purposive sample of 38 women in the UK who participated in a trial of antibiotics in pregnancy. All had received results from a follow-up study that reported increased risk of adverse outcomes for children of participants in some of the trial intervention arms. Data analysis was based on the constant comparative method. RESULTS: Participants' original decisions to consent to the trial had been based on hope of personal benefit and assumptions of safety. On receiving the results, most made sense of their experience in ways that enabled them to remain content with their decision to take part. But for some, the results provoked recognition that their original expectations might have been mistaken or that they had not understood the implications of their decision to participate. These participants experienced guilt, a sense of betrayal by the maternity staff and researchers involved in the trial, and damage to trust. CONCLUSIONS: Sharing of study results is not a wholly benign practice, and requires careful development of suitable approaches for further evaluation before widespread adoption.

Provision of interpreting support for cross-cultural communication in UK maternity services: A Freedom of Information request.

Background: Language, communication and understanding of information are central to safe, ethical and efficient maternity care. The National Health Service (NHS) commissioning board, NHS England, describes how healthcare providers should obtain language support through professionally trained interpreters. Providers of interpreters are commissioned to deliver remote/face to face interpretation across the NHS. Services can be booked in advance or calls can be made in real time. However, women report infrequent use of professionally trained interpreters during their maternity care, often relying on friends and family as interpreters which can compromise confidentiality, disclosure and accuracy. Methods: To determine the demand for, and provision of, professionally trained interpreters in practice, we sent a Freedom of Information (FOI) request to 119 NHS Trusts delivering maternity services in England in November 2022. For the financial years 2020/2021 and 2021/2022, we asked how many women in the maternity service were identified as needing an interpreter, the number and mode of interpreter sessions, and the annual spend on interpreting services. Data were analysed using descriptive statistics. Results: One hundred maternity Trusts responded by 21st April 2023 (response rate 100/119-84 %). Of these, 56 (56 %) recorded a woman's need for an interpreter. Nineteen Trusts relied on documentation in paper notes and 37 Trusts recorded the information on a digital system. From the 37 Trusts where this information could be digitally retrieved, women requiring interpreter support reflected between 1 and 25 % of the annual birth rate of the Trust (average 9 %) and received an average of three interpreter sessions across their pregnancy, birth and postnatal journey. Telephone was the dominant mode used for interpreting sessions, though 11 Trusts favoured face to face interpreting. Financial spend on interpreting services varied across Trusts; some funded their own in-house interpreting services, or worked with local community groups in addition to their contracted interpreting provider. Conclusion: Information obtained from this FOI request suggests that documentation of a woman's interpreting need is not complete or consistent across NHS maternity services. As a result, it is not clear how many women require an interpreter, the mode of provision or how frequently it is provided, and the cost involved. However, the limited information available suggests a failure to provide interpreter support to women at each scheduled care encounter. This raises questions about, the risk of women not understanding the care being offered, and the increased risk of uninformed, unconsented care as women traverse pregnancy and birth. Tweetable: There appears to be failure to provide interpreter support to women at each scheduled maternity care encounter increasing the risk of uninformed, unconsented care.

Community postnatal care delivery in England since Covid-19: A qualitative study of midwifery leaders' perspectives and strategies.

PROBLEM: COVID-19 impacted negatively on maternity care experiences of women and staff. Understanding the emergency response is key to inform future plans. BACKGROUND: Before the COVID-19 pandemic, experts highlighted concerns about UK community postnatal care, and its impact on long-term health, wellbeing, and inequalities. These appear to have been exacerbated by the pandemic. AIM: To explore community postnatal care provision during and since the pandemic across a large diverse UK region. METHODS: A descriptive qualitative approach. Virtual semi-structured interviews conducted November 2022-February 2023. All regional midwifery community postnatal care leaders were invited to participate. FINDINGS: 11/13 midwifery leaders participated. Three main themes were identified: Changes to postnatal care (strategic response, care on the ground); Impact of postnatal care changes (staff and women's experiences); and Drivers of postnatal care changes (COVID-19, workforce issues). DISCUSSION: Changes to postnatal care during the pandemic included introduction of virtual care, increased role of Maternity Support Workers, and moving away from home visits to clinic appointments. This has largely continued without evaluation. The number of care episodes provided for low and high-risk families appears to have changed little. Those requiring additional support but not deemed highest risk appear to have been most impacted. Staffing levels influenced amount and type of care provided. There was little inter-organisation collaboration in the postnatal pandemic response. CONCLUSION: Changes to postnatal care provision introduced more efficient working practices. However, evaluation is needed to ensure ongoing safe, equitable and individualised care provision post pandemic within limited resources.

Impact of maternal risk factors on ethnic disparities in maternal mortality: a national population-based cohort study.

Background: Ethnic disparities in maternal mortality are consistently reported. This study aimed to investigate the contribution of known risk factors including age, socioeconomic status, and medical comorbidities to observed ethnic disparities in the United Kingdom (UK). Methods: A cohort of all women who died during or up to six weeks after pregnancy in the UK 2009-2019 were identified through national surveillance. No single denominator population included data on all risk factors, therefore we used logistic regression modelling to compare to 1) routine population birth and demographic data (2015-19) (routine data comparator) and 2) combined control groups of four UK Obstetric Surveillance System studies (UKOSS) control comparator)). Findings: There were 801 maternal deaths in the UK between 2009 and 2019 (White: 70%, Asian: 13%, Black: 12%, Chinese/Other: 3%, Mixed: 2%). Using the routine data comparator (n = 3,519,931 maternities) to adjust for demographics, including social deprivation, women of Black ethnicity remained at significantly increased risk of maternal death compared with women of white ethnicity (adjusted OR 2.43 (95% Confidence Interval 1.92-3.08)). The risk was greatest in women of Caribbean ethnicity (aOR 3.55 (2.30-5.48)). Among women of White ethnicity, risk of mortality increased as deprivation increased, but women of Black ethnicity had greater risk irrespective of deprivation. Using the UKOSS control comparator (n = 2210), after multiple adjustments including smoking, body mass index, and comorbidities, women of Black and Asian ethnicity remained at increased risk (aOR 3.13 (2.21-4.43) and 1.57 (1.16-2.12) respectively). Interpretation: Known risk factors do not fully explain ethnic disparities in maternal mortality. The impact of socioeconomic deprivation appears to differ between ethnic groups. Funding: This research is funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-127-21202.

Induction of labour care in the UK: A cross-sectional survey of maternity units.

OBJECTIVES: To explore local induction of labour pathways in the UK National Health Service to provide insight into current practice. DESIGN: National survey. SETTING: Hospital maternity services in all four nations of the UK. SAMPLE: Convenience sample of 71 UK maternity units. METHODS: An online cross-sectional survey was disseminated and completed via a national network of obstetrics and gynaecology specialist trainees (October 2021-March 2022). Results were analysed descriptively, with associations explored using Fisher's Exact and ANOVA. MAIN OUTCOME MEASURES: Induction rates, criteria, processes, delays, incidents, safety concerns. RESULTS: 54/71 units responded (76%, 35% of UK units). Induction rate range 19.2%-53.4%, median 36.3%. 72% (39/54) had agreed induction criteria: these varied widely and were not all in national guidance. Multidisciplinary booking decision-making was not reported by 38/54 (70%). Delays reported 'often/always' in hospital admission for induction (19%, 10/54) and Delivery Suite transfer once induction in progress (63%, 34/54). Staffing was frequently reported cause of delay (76%, 41/54 'often/always'). Delays triggered incident reports in 36/54 (67%) and resulted in harm in 3/54 (6%). Induction was an area of concern (44%, 24/54); 61% (33/54) reported induction-focused quality improvement work. CONCLUSIONS: There is substantial variation in induction rates, processes and policies across UK maternity services. Delays appear to be common and are a cause of safety concerns. With induction rates likely to increase, improved guidance and pathways are critically needed to improve safety and experience of care.

Unblinding following trial participation: qualitative study of participants' perspectives.

BACKGROUND: The implications of offering unblinding to trial participants to treatment arm after trial completion have been little explored. PURPOSE: We sought to explore trial participants' perspectives on whether they would like to be unblinded as to the treatment arm to which they were allocated following involvement in a large randomised controlled trial (RCT). METHODS: We conducted semi-structured interviews with 38 women who had participated in a trial during suspected preterm labour and had received the results of a long-term follow-up study that identified adverse outcomes for children in some of the treatment groups. Participants were sampled purposively. Analysis was based on the constant comparative method. RESULTS: Most women reported that they wanted to know the treatment arm to which they had been allocated. While the primary motive for some was curiosity, many others wanted to know as part of an attempt to understand or explain their child's current health problems. These women were motivated by a search for a coherent causal narrative, even though unblinding was unlikely to be able to meet their aspirations. Some participants identified potential disadvantages in discovering their treatment allocation, including feeling responsible for their child's health status, and some women were very clear that they did not want to know their treatment group. LIMITATIONS: A purposive sample was used and the extent to which it represents the views of all participants in the study is not established. CONCLUSIONS: Important challenges arise in offering to unblind trial participants, whatever the trial results. Participants may need help and support to understand the limitations of the knowledge they gain through being unblinded and to decide whether they wish to know to which treatment arm they were allocated.

Antibiotics for preterm rupture of membranes.

BACKGROUND: Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection. OBJECTIVES: To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). SELECTION CRITERIA: Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone. DATA COLLECTION AND ANALYSIS: We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors. MAIN RESULTS: We included 22 trials, involving 6872 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found antibiotics seemed to have little effect on the health of children. AUTHORS' CONCLUSIONS: Routine prescription of antibiotics for women with preterm rupture of the membranes is associated with prolongation of pregnancy and improvements in a number of short-term neonatal morbidities, but no significant reduction in perinatal mortality. Despite lack of evidence of longer-term benefit in childhood, the advantages on short-term morbidities are such that we would recommend antibiotics are routinely prescribed. The antibiotic of choice is not clear but co-amoxiclav should be avoided in women due to increased risk of neonatal necrotising enterocolitis.

High-dose versus low-dose oxytocin for augmentation of delayed labour.

BACKGROUND: A major cause of failure to achieve spontaneous vaginal birth is delay in labour due to presumed inefficient uterine action. Oxytocin is given to increase contractions and high-dose regimens may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. OBJECTIVES: To compare starting dose and increment dose of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high-dose regimens of oxytocin improves labour outcomes and to examine the effect on both maternal/neonatal outcomes and women's birth experiences. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials for women in delayed labour requiring augmentation by oxytocin comparing high-dose regimens (defined as starting dose and increment of equal to or more than 4 mU per minute) with low-dose regimens (defined as starting dose and an increment of less than 4 mU per minute). Increase interval: between 15 and 40 minutes. The separation of low- and high-dose regimens is based on an arbitrary decision. DATA COLLECTION AND ANALYSIS: Four review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. MAIN RESULTS: We included four studies involving 644 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in the rate of caesarean section (risk ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in the rate of spontaneous vaginal birth in the high-dose group (RR 1.35; 95% CI 1.13 to 1.62, three trials, 444 women), although for both of these outcomes there were inconsistencies between studies in the size of effect. When we carried out sensitivity analysis (temporarily removing a study at high risk of bias) the differences between groups were no longer statistically significantThere were no significant differences between high- and low-dose regimens for instrumental vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage, chorioamnionitis or women's perceptions of experiences. For neonatal outcomes, there was no significant difference between groups for Apgar scores, umbilical cord pH, admission to special care baby unit, or neonatal mortality. The following outcomes were not evaluated in the included studies: perinatal mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. AUTHORS' CONCLUSIONS: Higher-dose regimens of oxytocin (4 mU per minute or more) were associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence to recommend that high-dose regimens are advised routinely for women with delay in the first stage of labour. Further research should evaluate the effect of high-dose regimens of oxytocin for women delayed in labour and should include maternal and neonatal outcomes as well as the effects on women.

Prophylactic antibiotics for inhibiting preterm labour with intact membranes.

BACKGROUND: The aetiology of preterm birth is complex and there is evidence that subclinical genital tract infection influences preterm labour in some women but the role of prophylactic antibiotic treatment in the management of preterm labour is controversial. Since rupture of the membranes is an important factor in the progression of preterm labour, it is important to see if the routine administration of antibiotics confers any benefit or causes harm, prior to membrane rupture. OBJECTIVES: To assess the effects of prophylactic antibiotics administered to women in preterm labour with intact membranes, on maternal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013). SELECTION CRITERIA: Randomised trials that compared antibiotic treatment with placebo or no treatment for women in preterm labour (between 20 and 36 weeks' gestation) with intact membranes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, and undertook quality assessment and data extraction. We contacted study authors for additional information. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with their respective 95% confidence intervals (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) was calculated where appropriate. MAIN RESULTS: In this update (2013), with the addition of three trials (305 women), the large ORACLE II 2001 trial continues to dominate the results of this review. This review now includes a total of 14 studies randomising 7837 women. No significant difference was shown in perinatal or infant mortality for infants of women allocated to any prophylactic antibiotics compared with no antibiotics. However, an increase in neonatal deaths was shown for infants of women receiving any prophylactic antibiotics when compared with placebo (RR 1.57, 95% CI 1.03 to 2.40; NNTH 149, 95% CI 2500 to 61). No reduction in preterm birth or other clinically important short-term outcomes for the infant were shown.Long-term child outcomes to seven years of age were available for infants in the UK enrolled in the ORACLE II trial. Comparing any antibiotics with placebo, a marginally non-statistically significant increase was shown in any functional impairment (RR 1.10, 95% CI 0.99 to 1.23) and cerebral palsy (CP) (RR 1.82, 95% CI 0.99 to 3.34). In subgroup analysis, CP was statistically significantly increased for infants of women allocated to macrolide and beta-lactam antibiotics combined compared with placebo (RR 2.83, 95% CI 1.02 to 7.88; NNTH 35, 95% CI 333 to 9).Further, exposure to any macrolide antibiotics (including erythromycin alone or erythromycin plus co-amoxiclav) versus no macrolide antibiotics (including placebo and co-amoxiclav alone) was shown to increase neonatal death (RR 1.52, 95% CI 1.05 to 2.19; NNTH 139, 95% CI 1429 to 61), any functional impairment (RR 1.11, 95% CI 1.01 to 1.20; NNTH 24, 95% CI 263 to 13) and CP (RR 1.90, 95% CI 1.20 to 3.01; NNTH 64, 95% CI 286 to 29). Exposure to any beta-lactam (beta-lactam alone or in combination with macrolide antibiotics) versus no beta-lactam antibiotics resulted in more neonatal deaths (RR 1.51, 95% CI 1.06 to 2.15; NNTH 143, 95% CI 1250 to 63) and CP (RR 1.67, 95% CI 1.06 to 2.61; NNTH 79, 95% CI 909 to 33), however no difference was shown in functional impairment.Maternal infection was reduced with the use of any prophylactic antibiotics compared with placebo (RR 0.74, 95% CI 0.63 to 0.86; NNTB 34, 95% CI 24 to 63) and any beta-lactam compared with no beta-lactam antibiotics (RR 0.80, 95% CI 0.69 to 0.92; NNTB 47, 95% CI 31 to 119). However, caution should be exercised with this finding due to the possibility of bias shown by funnel plot asymmetry. Any beta-lactam compared with no beta-lactam antibiotics was associated with an increase in maternal adverse drug reaction (RR 1.61, 95% CI 1.02 to 2.54; NNTH 17, 95% CI 526 to 7). AUTHORS' CONCLUSIONS: This review did not demonstrate any benefit in important neonatal outcomes with the use of prophylactic antibiotics for women in preterm labour with intact membranes, although maternal infection may be reduced. Of concern, is the finding of short- and longer-term harm for children of mothers exposed to antibiotics. The evidence supports not giving antibiotics routinely to women in preterm labour with intact membranes in the absence of overt signs of infection.Further research is required to develop sensitive markers of subclinical infection for women in preterm labour with intact membranes, as this is a group that might benefit from future novel interventions, including new modalities of antibiotic therapy. The results of this review demonstrate the need for future trials in the area of preterm birth to include assessment of long-term neurodevelopmental outcome.

IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination.

Previously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since TH17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A-/- and three of its receptors on HSV-IL-2-induced CNS demyelination. IL-17A-/- mice did not develop CNS demyelination, while IL-17RA-/-, IL-17RC-/-, IL-17RD-/- and IL-17RA-/-RC-/- mice developed CNS demyelination. Adoptive transfer of T cells from wild-type (WT) mice to IL-17A-/- mice or T cells from IL-17A-/- mice to Rag-/- mice induced CNS demyelination in infected mice. Adoptive T cell experiments suggest that both T cells and non-T cells expressing IL-17A contribute to HSV-IL-2-induced CNS demyelination with no difference in the severity of demyelination between the two groups of IL-17A producing cells. IL-6, IL-10, or TGFß did not contribute to CNS demyelination in infected mice. Transcriptome analysis between IL-17A-/- brain and spinal cord of infected mice with and without T cell transfer from WT mice revealed that "neuron projection extension involved in neuron projection guidance" and "ensheathment of neurons" pathways were associated with CNS demyelination. Collectively, the results indicate the importance of IL-17A in CNS demyelination and the possible involvement of more than three of IL-17 receptors in CNS demyelination.