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Paediatric and adult resuscitation is often performed with family present. Current guidelines recommend deferred umbilical cord clamping as part of immediate neonatal care, requiring neonatal assessment next to the mother. This paper describes strategies for providing care beside the mother using both standard resuscitation equipment and a trolley designed for this purpose., Competing Interests: Competing interests: LD is principle investigator for the improving quality of care and outcome at very preterm birth programme funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0609-10107). CWY and LD contributed to development of the Lifestart trolley. The Cord Pilot Trial was registered (ISRCTN21456601) and the results have been accepted for publication in the Fetal and Neoanatal Edition of Archives of Disease in Childhood., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. Use of different tests and different criteria will influence which women are diagnosed with GDM. This is an update of a review published in 2011 and 2015., Objectives: To evaluate and compare different testing strategies for diagnosis of gestational diabetes mellitus to improve maternal and infant health while assessing their impact on healthcare service costs., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (9 January 2017) and reference lists of retrieved studies., Selection Criteria: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model, cluster-randomised or cross-over trials., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach., Main Results: We included a total of seven small trials, with 1420 women. One trial including 726 women was identified by this update and examined the two step versus one step approach. These trials were assessed as having varying risk of bias, with few outcomes reported. We prespecified six outcomes to be assessed for quality using the GRADE approach for one comparison: 75 g oral glucose tolerance test (OGTT) versus 100 g OGTT; data for only one outcome (diagnosis of gestational diabetes) were available for assessment. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50 g glucose polymer drink (40 women) and a 50 g glucose monomer drink (43 women). We have included the results reported by this trial as separate comparisons. No trial reported on measures of costs of health services.We examined six main comparisons. 75 g OGTT versus 100 g OGTT (1 trial, 248 women): women who received 75 g OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75; very-low quality evidence). No data were reported for the following additional outcomes prespecified for GRADE assessment: caesarean section, macrosomia > 4.5 kg or however defined in the trial, long-term type 2 diabetes maternal, long-term type 2 diabetes infant and economic costs. Candy bar versus 50 g glucose monomer drink (1 trial, 60 women): more women receiving the candy bar, rather than glucose monomer, preferred the taste of the candy bar (RR 0.60, 95% CI 0.42 to 0.86) and 1-hour glucose was less with the candy bar. There were no differences in the other outcomes reported (maternal side effects). No infant outcomes were reported or any review primary outcomes. 50 g glucose polymer drink versus 50 g glucose monomer drink (3 trials, 239 women): mean difference (MD) in gestation at birth was -0.80 weeks (1 trial, 100 women; 95% CI -1.69 to 0.09). Total side effects were less common with the glucose polymer drink (1 trial, 63 women; RR 0.21, 95% CI 0.07 to 0.59), and no clear difference in taste acceptability was reported (1 trial, 63 women; RR 0.99, 95% CI 0.76 to 1.29). Fewer women reported nausea following the 50 g glucose polymer drink compared with the 50 g glucose monomer drink (1 trial, 66 women; RR 0.29, 95% CI 0.11 to 0.78). No other measures of maternal morbidity or outcomes for the infant were reported. 50 g glucose food versus 50 g glucose drink (1 trial, 30 women): women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). No clear difference was noted in the number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome were reported for the infant or review primary outcomes. 75 g OGTT World Health Organization (WHO) criteria versus 75 g OGTT American Diabetes Association (ADA) criteria (1 trial, 116 women): no clear differences in included outcomes were observed between women who received the 75 g OGTT and were diagnosed using criteria based on WHO (1999) recommendations and women who received the 75 g OGTT and were diagnosed using criteria recommended by the ADA (1979). Outcomes measured included diagnosis of gestational diabetes (RR 1.47, 95% CI 0.66 to 3.25), caesarean section (RR 1.07, 95% CI 0.85 to 1.35), macrosomia defined as > 90th percentile by ultrasound or birthweight equal to or exceeding 4000 g (RR 0.73, 95% CI 0.19 to 2.79), stillbirth (RR 0.49, 95% CI 0.02 to 11.68) and instrumental birth (RR 0.21, 95% CI 0.01 to 3.94). No other secondary outcomes were reported. Two-step approach (50 g oral glucose challenge test followed by selective 100 g OGTT Carpenter and Coustan criteria) versus one-step approach (universal 75 g OGTT ADA criteria) (1 trial, 726 women): women allocated the two-step approach had a lower risk of being diagnosed with GDM at 11 to 14 weeks' gestation compared to women allocated the one-step approach (RR 0.51, 95% CI 0.28 to 0.95). No other primary or secondary outcomes were reported., Authors' Conclusions: There is insufficient evidence to suggest which strategy is best for diagnosing GDM. Large randomised trials are required to establish the best strategy for correctly identifying women with GDM.

Background: The optimum time for commencing antiplatelet therapy for the prevention of preeclampsia and its complications is unclear. Aggregate data meta-analyses suggest that aspirin is more effective if given prior to 16 weeks' gestation, but data are limited because of an inability to place women in the correct gestational age subgroup from relevant trials., Objective: The objective of the study was to use the large existing individual participant data set from the Perinatal Antiplatelet Review of International Studies Collaboration to assess whether the treatment effects of antiplatelet agents on preeclampsia and its complications vary based on whether treatment is started before or after 16 weeks' gestation., Study Design: A meta-analysis of individual participant data including 32,217 women and 32,819 babies recruited to 31 randomized trials comparing low-dose aspirin or other antiplatelet agents with placebo or no treatment for the prevention of preeclampsia has been published previously. Using this existing data set, we performed a prespecified subgroup analysis based on gestation at randomization to antiplatelet agents before 16 weeks, compared with at or after 16 weeks, for 4 of the main outcomes prespecified in the Perinatal Antiplatelet Review of International Studies protocol: preeclampsia, death of baby, preterm birth before 34 weeks, and small-for-gestational-age baby. Individual participant data for the subgroups were combined in a meta-analysis using RevMan software. Heterogeneity was assessed with the I 2 statistic. The χ 2 test for interaction was used to assess statistically significant (P < .05) differences in treatment effect between subgroups., Results: There was no significant difference in the effects of antiplatelet therapy for women randomized before 16 weeks' gestation compared with those randomized at or after 16 weeks for any of the 4 prespecified outcomes: preeclampsia, relative risk, 0.90, (95% confidence interval, 0.79-1.03; 17 trials, 9241 women) for <16 weeks and relative risk, 0.90 (95% confidence interval, 0.83-0.98; 22 trials, 21,429 women) for ≥16 weeks (interaction test, P = .98); death of baby, relative risk, 0.89 (95% confidence interval, 0.73-1.09; 15 trials, 8626 women) for <16 weeks and relative risk, 0.92 (95% confidence interval, 0.79-1.07; 21 trials, 22,336 women) for ≥16 weeks (interaction test, P = .80); preterm birth prior to 34 weeks, relative risk, 0.90 (95% confidence interval, 0.77-1.04; 19 trials, 9155 women) for <16 weeks and relative risk, 0.91 (95% confidence interval, 0.82-1.00; 25 trials, 22,117 women) for ≥16 weeks (interaction test, P = .91); and small-for-gestational-age baby, relative risk, 0.76 (95% confidence interval, 0.61-0.94; 13 trials, 6393 women) for <16 weeks and relative risk, 0.95 (95% confidence interval, 0.84-1.08; 18 trials, 14,996 women) for ≥16 weeks (interaction test, P = .08)., Conclusion: The effect of low-dose aspirin and other antiplatelet agents on preeclampsia and its complications is consistent, regardless of whether treatment is started before or after 16 weeks' gestation. Women at an increased risk of preeclampsia should be offered antiplatelet therapy, regardless of whether they are first seen before or after 16 weeks' gestation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The placenta has an essential role in determining the outcome of pregnancy. Consequently, biochemical measurement of placentally-derived factors has been suggested as a means to improve fetal and maternal outcome of pregnancy., Objectives: To assess whether clinicians' knowledge of the results of biochemical tests of placental function is associated with improvement in fetal or maternal outcome of pregnancy., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015) and reference lists of retrieved studies., Selection Criteria: Randomised, cluster-randomised or quasi-randomised controlled trials assessing the merits of the use of biochemical tests of placental function to improve pregnancy outcome.Studies were eligible if they compared women who had placental function tests and the results were available to their clinicians with women who either did not have the tests, or the tests were done but the results were not available to the clinicians. The placental function tests were any biochemical test of placental function carried out using the woman's maternal biofluid, either alone or in combination with other placental function test/s., Data Collection and Analysis: Two review authors independently assessed trials for inclusion, extracted data and assessed trial quality. Authors of published trials were contacted for further information., Main Results: Three trials were included, two quasi-randomised controlled trials and one randomised controlled trial. One trial was deemed to be at low risk of bias while the other two were at high risk of bias. Different biochemical analytes were measured - oestrogen was measured in one trial and the other two measured human placental lactogen (hPL). One trial did not contribute outcome data, therefore, the results of this review are based on two trials with 740 participants.There was no evidence of a difference in the incidence of death of a baby (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.36 to 2.13, two trials, 740 participants (very low quality evidence)) or the frequency of a small-for-gestational-age infant (RR 0.44, 95% CI 0.16 to 1.19, one trial, 118 participants (low quality evidence)).In terms of this review's secondary outcomes, there was no evidence of a clear difference between women who had biochemical tests of placental function compared with standard antenatal care for the incidence of stillbirth (RR 0.56, 95% CI 0.16 to 1.88, two trials, 740 participants (very low quality evidence)) or neonatal death (RR 1.62, 95% CI 0.39 to 6.74, two trials, 740 participants, very low quality evidence)) although the directions of any potential effect were in opposing directions. There was no evidence of a difference between groups in elective delivery (RR 0.98, 95% CI 0.84 to 1.14, two trials, 740 participants (low quality evidence)), caesarean section (one trial, RR 0.48, 95% CI 0.15 to 1.52, one trial, 118 participants (low quality evidence)), change in anxiety score (mean difference -2.40, 95% CI -4.78 to -0.02, one trial, 118 participants), admissions to neonatal intensive care (RR 0.32, 95% CI 0.03 to 3.01, one trial, 118 participants), and preterm birth before 37 weeks' gestation (RR 2.90, 95% CI 0.12 to 69.81, one trial, 118 participants). One trial (118 participants) reported that there were no cases of serious neonatal morbidity. Maternal death was not reported.A number of this review's secondary outcomes relating to the baby were not reported in the included studies, namely: umbilical artery pH < 7.0, neonatal intensive care for more than seven days, very preterm birth (< 32 weeks' gestation), need for ventilation, organ failure, fetal abnormality, neurodevelopment in childhood (cerebral palsy, neurodevelopmental delay). Similarly, a number of this review's maternal secondary outcomes were not reported in the included studies (admission to intensive care, high dependency unit admission, hospital admission for > seven days, pre-eclampsia, eclampsia, and women's perception of care)., Authors' Conclusions: There is insufficient evidence to support the use of biochemical tests of placental function to reduce perinatal mortality or increase identification of small-for-gestational-age infants. However, we were only able to include data from two studies that measured oestrogens and hPL. The quality of the evidence was low or very low.Two of the trials were performed in the 1970s on women with a variety of antenatal complications and this evidence cannot be generalised to women at low-risk of complications or groups of women with specific pregnancy complications (e.g. fetal growth restriction). Furthermore, outcomes described in the 1970s may not reflect what would be expected at present. For example, neonatal mortality rates have fallen substantially, such that an infant delivered at 28 weeks would have a greater chance of survival were those studies repeated; this may affect the primary outcome of the meta-analysis.With data from just two studies (740 women), this review is underpowered to detect a difference in the incidence of death of a baby or the frequency of a small-for-gestational-age infant as these have a background incidence of approximately 0.75% and 10% of pregnancies respectively. Similarly, this review is underpowered to detect differences between serious and/or rare adverse events such as severe neonatal morbidity. Two of the three included studies were quasi-randomised, with significant risk of bias from group allocation. Additionally, there may be performance bias as in one of the two studies contributing data, participants receiving standard care did not have venepuncture, so clinicians treating participants could identify which arm of the study they were in. Future studies should consider more robust randomisation methods and concealment of group allocation and should be adequately powered to detect differences in rare adverse events.The studies identified in this review examined two different analytes: oestrogens and hPL. There are many other placental products that could be employed as surrogates of placental function, including: placental growth factor (PlGF), human chorionic gonadotrophin (hCG), plasma protein A (PAPP-A), placental protein 13 (PP-13), pregnancy-specific glycoproteins and progesterone metabolites and further studies should be encouraged to investigate these other placental products. Future randomised controlled trials should test analytes identified as having the best predictive reliability for placental dysfunction leading to small-for-gestational-age infants and perinatal mortality.

Rationale: The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event., Hypothesis: Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective., Sample Size Estimates: The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance., Methods and Design: Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation., Study Outcome: The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events)., Discussion: The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack., (© 2015 The Author. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.)

Objectives: The aims of this study were to assess clinicians' views and experiences of providing immediate neonatal care at birth beside the mother, and of using a mobile trolley designed to facilitate this bedside care., Design: Qualitative interview study with semistructured interviews., Results: The results were analysed using thematic analysis., Setting: A large UK maternity unit., Participants: Clinicians (n=20) from a range of disciplines who were present when the trolley was used to provide neonatal care at birth at the bedside. Five clinicians provided/observed advanced resuscitation by the bedside., Results: Five themes were identified: (1) Parents' involvement, which included 'Contact and involvement', 'Positive emotions for parents' and 'Staff communication'; (2) Reservations about neonatal care at birth beside the mother, which included 'Impact on clinicians' and 'Impact on parents'; (3) Practical challenges in providing neonatal care at the bedside, which included 'Cord length' and 'Caesarean section'; (4) Comparison of the trolley with usual resuscitation equipment and (5) Training and integration of bedside care into clinical routine, which included 'Teething problems' and 'Training'., Conclusions: Overall, most clinicians were positive about providing immediate neonatal care at the maternal bedside, particularly in terms of the clinicians' perceptions of the parents' experience. Clinicians also perceived that their close proximity to parents improved communication. However, there was some concern about performing more intensive interventions in front of parents. Providing immediate neonatal care and resuscitation at the bedside requires staff training and support., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: The aims of this study were to assess parents' views of immediate neonatal care and resuscitation at birth being provided beside the mother, and their experiences of a mobile trolley designed to facilitate this bedside care., Design: Qualitative study with semistructured interviews. Results were analysed using thematic analysis., Setting: Large UK maternity hospital., Participants: Mothers whose baby received initial neonatal care in the first few minutes of life at the bedside, and their birth partners, were eligible. 30 participants were interviewed (19 mothers, 10 partners and 1 grandmother). 5 babies required advanced neonatal resuscitation., Results: 5 themes were identified: (1) Reassurance, which included 'Baby is OK', 'Having baby close', 'Confidence in care', 'Knowing what's going on' and 'Dad as informant'; (2) Involvement of the family, which included 'Opportunity for contact', 'Family involvement' and 'Normality'; (3) Staff communication, which included 'Communication' and 'Experience'; (4) Reservations, which included 'Reservations about witnessing resuscitation', 'Negative emotions' and 'Worries about the impact on staff' and (5) Experiences of the trolley, which included 'Practical issues' and 'Comparisons with standard resuscitation equipment'., Conclusions: Families were positive about neonatal care being provided at the bedside, and felt it gave reassurance about their baby's health and care. They also reported feeling involved as a family. Some parents reported experiencing negative emotions as a result of witnessing resuscitation of their baby. Parents were positive about the trolley., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The number of visits for antenatal (prenatal) care developed without evidence of how many visits are necessary. The content of each visit also needs evaluation., Objectives: To compare the effects of antenatal care programmes with reduced visits for low-risk women with standard care., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 March 2015), reference lists of articles and contacted researchers in the field., Selection Criteria: Randomised trials comparing a reduced number of antenatal visits, with or without goal-oriented care, versus standard care., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked for accuracy. We assessed studies for risk of bias and graded the quality of the evidence., Main Results: We included seven trials (more than 60,000 women): four in high-income countries with individual randomisation; three in low- and middle-income countries with cluster randomisation (clinics as the unit of randomisation). Most of the data included in the review came from the three large, well-designed cluster-randomised trials that took place in Argentina, Cuba, Saudi Arabia, Thailand and Zimbabwe. All results have been adjusted for the cluster design effect. All of the trials were at some risk of bias as blinding of women and staff was not feasible with this type of intervention. For primary outcomes, evidence was graded as being of moderate or low quality, with downgrading decisions due to risks of bias and imprecision of effects.The number of visits for standard care varied, with fewer visits in low- and middle- income country trials. In studies in high-income countries, women in the reduced visits groups, on average, attended between 8.2 and 12 times. In low- and middle- income country trials, many women in the reduced visits group attended on fewer than five occasions, although in these trials the content as well as the number of visits was changed, so as to be more 'goal-oriented'.Perinatal mortality was increased for those randomised to reduced visits rather than standard care, and this difference was borderline for statistical significance (risk ratio (RR) 1.14; 95% confidence interval (CI) 1.00 to 1.31; five trials, 56,431 babies; moderate-quality evidence). In the subgroup analysis, for high-income countries the number of deaths was small (32/5108), and there was no clear difference between the groups (RR 0.90; 95% CI 0.45 to 1.80, two trials); for low- and middle-income countries perinatal mortality was significantly higher in the reduced visits group (RR 1.15; 95% CI 1.01 to 1.32, three trials).There was no clear difference between groups for our other primary outcomes: maternal death (RR 1.13, 95%CI 0.50 to 2.57, three cluster-randomised trials, 51,504 women, low-quality evidence); hypertensive disorders of pregnancy (various definitions including pre-eclampsia) (RR 0.95, 95% CI 0.80 to 1.12, six studies, 54,108 women, low-quality evidence); preterm birth (RR 1.02, 95% CI 0.94 to 1.11; seven studies, 53,661 women, moderate-quality evidence); and small-for-gestational age (RR 0.99, 95% CI 0.91 to 1.09, four studies 43,045 babies, moderate-quality evidence).Reduced visits were associated with a reduction in admission to neonatal intensive care that was borderline for significance (RR 0.89; 95% CI 0.79 to 1.02, five studies, 43,048 babies, moderate quality evidence). There were no clear differences between the groups for the other secondary clinical outcomes.Women in all settings were less satisfied with the reduced visits schedule and perceived the gap between visits as too long. Reduced visits may be associated with lower costs., Authors' Conclusions: In settings with limited resources where the number of visits is already low, reduced visits programmes of antenatal care are associated with an increase in perinatal mortality compared to standard care, although admission to neonatal intensive care may be reduced. Women prefer the standard visits schedule. Where the standard number of visits is low, visits should not be reduced without close monitoring of fetal and neonatal outcome.

Background: Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial., Methods/design: Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face V s postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a larger trial., Discussion: To our knowledge, this is the first feasibility randomised controlled trial of a vocational rehabilitation health intervention specific to traumatic brain injury. The results will inform the design of a definitive trial., Trial Registration: The trial is registered ISRCTN Number 38581822.

Background: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias., Objectives: To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic., Design: Multicentre, pragmatic, blinded, randomised placebo-controlled trial., Setting: Thirty to 40 hospitals in the UK., Participants: Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic., Intervention: Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission., Main Outcome Measure: Admission to Intensive Care Unit, or death, within 30 days of admission to hospital., Results: This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified., Conclusions: This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies., Trial Registration: Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.

Background: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. Use of different tests and different criteria will influence which women are diagnosed with GDM., Objectives: To evaluate and compare different testing strategies for diagnosis of gestational diabetes mellitus to improve maternal and infant health while assessing their impact on healthcare service costs., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014) and reference lists of retrieved studies., Selection Criteria: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy., Main Results: We identified six small trials, including 694 women. These trials were assessed as having varying risk of bias, with few outcomes reported. We prespecified six outcomes to be assessed for quality using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach; data for only one outcome (diagnosis of gestational diabetes) were available for assessment. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50-gram glucose polymer drink (40 women) and a 50-gram glucose monomer drink (43 women). We have reported results reported by this trial as separate comparisons. 75-gram oral glucose tolerance test (OGTT) versus 100-gram OGTT (one trial, 248 women): Women given the 75-gram OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75). This difference was borderline in terms of statistical significance, and evidence was considered to be of very low quality when assessed by GRADE. No data were reported for the following additional outcomes prespecified for assessment in GRADE: caesarean section, macrosomia > 4.5 kg or however defined in the trial, long-term type 2 diabetes maternal, long-term type 2 diabetes infant and economic costs. Candy bar versus 50-gram glucose monomer drink (one trial, 60 women): More women receiving the candy bar, rather than glucose monomer, preferred the taste of the candy bar (RR 0.60, 95% CI 0.42 to 0.86). Infant outcomes were not reported. 50-gram glucose polymer drink versus 50-gram glucose monomer drink (three trials, 239 women): Mean difference (MD) in gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09). Total side effects were less common with the glucose polymer drink (one trial, 63 women; RR 0.21, 95% CI 0.07 to 0.59), and no clear difference in taste acceptability was reported (one trial, 63 women; RR 0.99, 95% CI 0.76 to 1.29). Significantly fewer women reported nausea following the 50-gram glucose polymer drink compared with the 50-gram glucose monomer drink (one trial, 66 women; RR 0.29, 95% CI 0.11 to 0.78). No other measures of maternal morbidity or outcomes for the infant were reported. 50-gram glucose food versus 50-gram glucose drink (one trial, 30 women): Women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). No clear difference was noted in the number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome were reported for the infant. 75-gram oral glucose tolerance test (OGTT) World Health Organization (WHO) criteria versus 75-gram OGTT American Diabetes Association (ADA) criteria (one trial, 116 women): No clear differences in included outcomes were observed between women who received the 75-gram OGTT and were diagnosed using criteria based on WHO (1999) recommendations and women who received the 75-gram OGTT and were diagnosed using criteria recommended by the ADA (1979). Outcomes measured included diagnosis of gestational diabetes (RR 1.47, 95% CI 0.66 to 3.25), caesarean birth (RR 1.07, 95% CI 0.85 to 1.35), macrosomia defined as > 90th percentile by ultrasound or birthweight equal to or exceeding 4000 g (RR 0.73, 95% CI 0.19 to 2.79), stillbirth (RR 0.49, 95% CI 0.02 to 11.68) and instrumental birth (RR 0.21, 95% CI 0.01 to 3.94)., Authors' Conclusions: Evidence is insufficient to permit assessment of which strategy is best for diagnosing GDM.

Background: A high level of resistance in Neisseria gonorrhoeae has developed against penicillins, sulphonamides, tetracyclines and quinolones, and recent surveillance data have shown a gradual reduction in sensitivity to current first-line agents with an upward drift in the minimum inhibitory concentration of ceftriaxone. Laboratory sensitivity testing suggests that gentamicin, an aminoglycoside, may be an effective treatment option for gonorrhoea infection when used as a single intramuscular dose., Methods: A search of electronic reference databases and grey literature was used to identify randomised trials and well-conducted prospective studies with concurrent controls evaluating single-dose gentamicin against placebo or a comparator regimen in the treatment of uncomplicated gonorrhoea infection in men and women aged 16 years and over. The primary outcome was microbiological cure of N. gonorrhoeae., Results: Eight hundred and thirty-nine studies were identified, of which five (1,063 total participants) were included. All five studies administered single-dose gentamicin via intramuscular injection to men with uncomplicated gonococcal urethritis. Three studies were randomised trials, one was quasi-randomised and one was non-randomised but included a comparator arm. Comparator antibiotics included an alternative aminoglycoside or antibiotic used in the syndromic management of male urethritis. Methodology was poorly described in all five included studies. The high risk of bias within studies and clinical heterogeneity between studies meant that it was inappropriate to pool data for meta-analysis. Cure rates of 62% to 98% were reported with gentamicin treatment. The relative risk of cure was comparable between gentamicin and comparator antibiotics., Conclusions: The studies identified provide insufficient data to support or refute the efficacy and safety of single-dose intramuscular gentamicin in the treatment of uncomplicated gonorrhoea infection. Additional randomised trials to evaluate gentamicin for this indication are therefore required., Systematic Review Registration: PROSPERO CRD42012002490.

In December 2012, the American College of Obstetricians and Gynecologists published a Committee Opinion entitled "Timing of umbilical cord clamping after birth." It stated that "evidence exists to support delayed cord clamping in preterm infants, when feasible. The single most important benefit for preterm infants is the possibility for a nearly 50% reduction in IVH." However, the Committee Opinion added that the ideal timing of umbilical cord clamping has yet to be determined and recommended that large clinical trials be conducted in the most preterm infants. Published randomized controlled trials include <200 infants of <30 weeks' gestation, with assessments of neurodevelopmental outcome in less than one-half of the children. This is a major gap in the evidence. Without reliable data from randomized controlled trials that optimally include childhood follow-up evaluations, we will not know whether delayed cord clamping may do more overall harm than good. Ongoing trials of delayed cord clamping plan to report childhood outcomes in >2000 additional very preterm infants. Current recommendations may need to change when these results become available. Greater international collaboration could accelerate resolution of whether this promising intervention will improve disability-free survival in about 1 million infants who will be born very preterm globally each year., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth., Objectives: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review., Selection Criteria: Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium., Data Collection and Analysis: We assessed eligibility and trial quality, extracted and double-entered data., Main Results: High-dose calcium supplementation (≥1 g/day)We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias.The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the calcium group, however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of stillbirth or infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%).One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose calcium supplementation (< 1 g/day)We included 10 trials (2234 women) that evaluated low-dose supplementation with calcium alone (4) or in association with vitamin D (3), linoleic acid (2), or antioxidants (1). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium significantly reduced the risk of pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in hypertension, low birthweight and neonatal intensive care unit admission., Authors' Conclusions: Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of pre-eclampsia, particularly for women with low calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces preterm birth and the occurrence of the composite outcome 'maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends calcium 1.5 g to 2 g daily for pregnant women with low dietary calcium intake.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.

Background: Mild to moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve the outcome., Objectives: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and reference lists of retrieved studies., Selection Criteria: All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy defined, whenever possible, as systolic blood pressure 140 to 169 mmHg and diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days., Data Collection and Analysis: Two review authors independently extracted data., Main Results: Forty-nine trials (4723 women) were included. Twenty-nine trials compared an antihypertensive drug with placebo/no antihypertensive drug (3350 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) (20 trials, 2558 women; risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; risk difference (RD) -0.10 (-0.13 to -0.07); number needed to treat to harm (NNTH) 10 (8 to 13)) but little evidence of a difference in the risk of pre-eclampsia (23 trials, 2851 women; RR 0.93; 95% CI 0.80 to 1.08). Similarly, there is no clear effect on the risk of the baby dying (27 trials, 3230 women; RR 0.71; 95% CI 0.49 to 1.02), preterm birth (15 trials, 2141 women; RR 0.96; 95% CI 0.85 to 1.10), or small-for-gestational-age babies (20 trials, 2586 women; RR 0.97; 95% CI 0.80 to 1.17). There were no clear differences in any other outcomes.Twenty-two trials (1723 women) compared one antihypertensive drug with another. Alternative drugs seem better than methyldopa for reducing the risk of severe hypertension (11 trials, 638 women; RR (random-effects) 0.54; 95% CI 0.30 to 0.95; RD -0.11 (-0.20 to -0.02); NNTH 7 (5 to 69)). There is also a reduction in the overall risk of developing proteinuria/pre-eclampsia when beta blockers and calcium channel blockers considered together are compared with methyldopa (11 trials, 997 women; RR 0.73; 95% CI 0.54 to 0.99). However, the effect on both severe hypertension and proteinuria is not seen in the individual drugs. Other outcomes were only reported by a small proportion of studies, and there were no clear differences., Authors' Conclusions: It remains unclear whether antihypertensive drug therapy for mild to moderate hypertension during pregnancy is worthwhile.

Deferring cord clamping allows blood flow between baby and placenta to continue for a few moments. This often leads to increased neonatal blood volume at birth. It also allows for longer transition to the neonatal circulation. Optimal timing for clamping the cord remains uncertain. This paper discusses the physiology of placental transfusion and presents the evidence from systematic reviews of randomised trials comparing alternative strategies for cord clamping for both term and preterm births. For healthy term infants, deferring cord clamping increases iron stores in infancy. Therefore, a more liberal approach to deferring cord clamping appears to be warranted, provided screening and treatment for jaundice requiring phototherapy is available. For preterm births, although there are few data on the main clinical outcomes, the evidence is promising that deferred cord clamping may be beneficial. For both term and preterm infants there is little information about long term development., (© 2013.)

Background: Very high blood pressure during pregnancy poses a serious threat to women and their babies. The aim of antihypertensive therapy is to lower blood pressure quickly but safety, to avoid complications. Antihypertensive drugs lower blood pressure but their comparative effectiveness and safety, and impact on other substantive outcomes is uncertain., Objectives: To compare different antihypertensive drugs for very high blood pressure during pregnancy., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (9 January 2013)., Selection Criteria: Studies were randomised trials. Participants were women with severe hypertension during pregnancy. Interventions were comparisons of one antihypertensive drug with another., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data and checked them for accuracy., Main Results: Thirty-five trials (3573 women) with 15 comparisons were included. Women allocated calcium channel blockers were less likely to have persistent high blood pressure compared to those allocated hydralazine (six trials, 313 women; 8% versus 22%; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66). Ketanserin was associated with more persistent high blood pressure than hydralazine (three trials, 180 women; 27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73), but fewer side-effects (three trials, 120 women; RR 0.32, 95% CI 0.19 to 0.53) and a lower risk of HELLP (haemolysis, elevated liver enzymes and lowered platelets) syndrome (one trial, 44 women; RR 0.20, 95% CI 0.05 to 0.81).Labetalol was associated with a lower risk of hypotension compared to diazoxide (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and a lower risk of caesarean section (RR 0.43, 95% CI 0.18 to 1.02), although both were borderline for statistical significance.Both nimodipine and magnesium sulphate were associated with a high incidence of persistent high blood pressure, but this risk was lower for nimodipine compared to magnesium sulphate (one trial, 1650 women; 47% versus 65%; RR 0.84, 95% CI 0.76 to 0.93). Nimodipine was associated with a lower risk of respiratory difficulties (RR 0.28, 95% CI 0.08 to 0.99), fewer side-effects (RR 0.68, 95% CI 0.55 to 0.85) and less postpartum haemorrhage (RR 0.41, 95% CI 0.18 to 0.92) than magnesium sulphate. Stillbirths and neonatal deaths were not reported.There are insufficient data for reliable conclusions about the comparative effects of any other drugs., Authors' Conclusions: Until better evidence is available the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug; on what is known about adverse effects; and on women's preferences. Exceptions are nimodipine, magnesium sulphate (although this is indicated for women who require an anticonvulsant for prevention or treatment of eclampsia), diazoxide and ketanserin, which are probably best avoided.

Background: Severe pre-eclampsia can cause significant mortality and morbidity for both mother and child, particularly when it occurs remote from term, between 24 and 34 weeks' gestation. The only known cure for this disease is delivery. Some obstetricians advocate early delivery to ensure that the development of serious maternal complications, such as eclampsia (fits) and kidney failure are prevented. Others prefer a more expectant approach delaying delivery in an attempt to reduce the mortality and morbidity for the child associated with being born too early., Objectives: The objective of the review was to compare the effects of a policy of interventionist care and early delivery with a policy of expectant care and delayed delivery for women with early onset severe pre-eclampsia., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2013)., Selection Criteria: Randomised trials comparing the two intervention strategies for women with early onset severe pre-eclampsia., Data Collection and Analysis: Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. Data were checked for accuracy., Main Results: Four trials, with a total of 425 women are included in this review. Trials were at low risk of bias for methods of randomisation and allocation concealment; high risk for blinding; unclear risk for incomplete outcome data and other bias; and low risk for selective reporting. There are insufficient data for reliable conclusions about the comparative effects on most outcomes for the mother. For the baby, there is insufficient evidence for reliable conclusions about the effects on stillbirth or death after delivery (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.69 to 1.71; four studies; 425 women). Babies whose mothers had been allocated to the interventionist group had more intraventricular haemorrhage (RR 1.82, 95% CI 1.06 to 3.14; one study; 262 women), more hyaline membrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), require more ventilation (RR 1.50, 95% CI 1.11 to 2.02; two studies; 300 women) and were more likely to have a lower gestation at birth in days (average mean difference (MD) -9.91, 95% CI -16.37 to -3.45; four studies; 425 women), more likely to be admitted to neonatal intensive care (RR 1.35, 95% CI 1.16 to 1.58) and have a longer stay in the neonatal intensive care unit (average MD 11.14 days, 95% CI 1.57 to 20.72 days; two studies; 125 women) than those allocated an expectant policy. Nevertheless, babies allocated to the interventionist policy were less likely to be small-for-gestational age (RR 0.30, 95% CI 0.14 to 0.65; two studies; 125 women). Women who had been allocated to the interventionist group were more likely to have a caesarean section (RR 1.09, 95% CI 1.01 to 1.18; four studies; 425 women) than those allocated an expectant policy. There were no statistically significant differences between the two strategies for any other outcomes., Authors' Conclusions: This review suggests that an expectant approach to the management of women with severe early onset pre-eclampsia may be associated with decreased morbidity for the baby. However, this evidence is based on data from only four trials. Further large trials are needed to confirm or refute these findings and establish if this approach is safe for the mother.

Objectives: To assess parents' first experiences of their very preterm babies and the neonatal intensive care unit (NICU)., Design: Qualitative study using semistructured interviews., Participants: 32 mothers and 7 fathers of very preterm babies (<32 weeks gestation)., Setting: Three neonatal units in tertiary care hospitals in South East England., Results: Five themes were identified. The first describes parents' blurred recall of the birth. The second shows the anticipation of seeing and touching their baby for the first time was characterised by contrasting emotions, with some parents feeling scared and others excited about the event. The third theme describes parents' first sight and touch of their babies and their 'rollercoaster' of emotions during this time. It also highlights the importance of touch to trigger and strengthen the parent-baby bond. However, some parents were worried that touching or holding the baby might transmit infection or interfere with care. The fourth theme captures parents' impressions of NICU and how overwhelming this was particularly for parents who had not toured NICU beforehand or whose first sight of their baby was on NICU. The final theme captures unique experiences of fathers, in particular that many felt excluded and confused about their role., Conclusions: This study informs family-centred care by providing insight into the experiences of parents of very preterm infants at a time when they are most in need of support. Clinical implications include the importance of offering parents preparatory tours of the NICU and including fathers.

Background: For patients with early breast cancer and lymph node metastasis, axillary treatment is widely recommended. This is either surgical removal of the axillary lymph nodes, or axillary radiotherapy. The rationale for axillary treatment is that it will reduce the risk of recurrence in the axilla, and may improve survival. However, both treatments are associated with adverse effects, such as lymphedema, pain and sensory loss, and are costly to the health services and to patients. With improvements in adjuvant therapy, routine axillary treatment may no longer offer any overall advantage., Objectives: To assess the short and long term benefits and adverse effects of routine axillary treatment (axillary lymph node clearance or axillary radiotherapy) for patients with lymph node positive early-stage breast cancer., Methods/design: Criteria for potentially eligibility for the study will be that the participants are men and women with early breast cancer and lymph nodes with metastasis. The study compares either axillary treatment with no axillary treatment, or axillary node clearance with axillary radiotherapy, and the study is a randomized trial. Primary outcomes are axillary recurrence, disease-free and overall survival. Secondary outcomes include breast or chest wall recurrence, distant metastasis, time to axillary recurrence, axillary recurrence-free survival, arm morbidity, quality of life and health economic costs. The search strategy will include the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) search portal. Two independent reviewers will assess studies for inclusion in the review, assess study quality and extract data. Characteristics of included studies will be described. Meta-analysis will be conducted using ReVman software., Comment: This review addresses an important clinical question, and results will inform clinical practice and health care policy.

Background: Optimal timing for clamping the umbilical cord at preterm birth is unclear. Early clamping allows for immediate transfer of the infant to the neonatologist. Delaying clamping allows blood flow between the placenta, the umbilical cord and the baby to continue. The blood which transfers to the baby between birth and cord clamping is called placental transfusion. Placental transfusion may improve circulating volume at birth, which may in turn improve outcome for preterm infants., Objectives: To assess the short- and long-term effects of early rather than delaying clamping or milking of the umbilical cord for infants born at less than 37 completed weeks' gestation, and their mothers., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 May 2011). We updated this search on 26 June 2012 and added the results to the awaiting classification section., Selection Criteria: Randomised controlled trials comparing early with delayed clamping of the umbilical cord and other strategies to influence placental transfusion for births before 37 completed weeks' gestation., Data Collection and Analysis: Three review authors assessed eligibility and trial quality., Main Results: Fifteen studies (738 infants) were eligible for inclusion. Participants were between 24 and 36 weeks' gestation at birth. The maximum delay in cord clamping was 180 seconds. Delaying cord clamping was associated with fewer infants requiring transfusions for anaemia (seven trials, 392 infants; risk ratio (RR) 0.61, 95% confidence interval (CI) 0.46 to 0.81), less intraventricular haemorrhage (ultrasound diagnosis all grades) 10 trials, 539 infants (RR 0.59, 95% CI 0.41 to 0.85) and lower risk for necrotising enterocolitis (five trials, 241 infants, RR 0.62, 95% CI 0.43 to 0.90) compared with immediate clamping. However, the peak bilirubin concentration was higher for infants allocated to delayed cord clamping compared with immediate clamping (seven trials, 320 infants, mean difference 15.01 mmol/L, 95% CI 5.62 to 24.40). For most other outcomes (including the primary outcomes infant death, severe (grade three to four) intraventricular haemorrhage and periventricular leukomalacia) there were no clear differences identified between groups; but for many there was incomplete reporting and wide CIs. Outcome after discharge from hospital was reported for one small study; there were no significant differences between the groups in mean Bayley II scores at age seven months (corrected for gestation at birth (58 children)).No studies reported outcomes for the women., Authors' Conclusions: Providing additional placental blood to the preterm baby by either delaying cord clamping for 30 to 120 seconds, rather than early clamping, seems to be associated with less need for transfusion, better circulatory stability, less intraventricular haemorrhage (all grades) and lower risk for necrotising enterocolitis. However, there were insufficient data for reliable conclusions about the comparative effects on any of the primary outcomes for this review.

Background: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment., Objectives: To evaluate and compare alternative tests for diagnosis of GDM, in terms of maternal and infant health and use of health service resources., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2011)., Selection Criteria: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model., Data Collection and Analysis: Two review authors independently assessed trials for inclusion, trial quality and extracted data., Main Results: We identified five small trials, including 578 women. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50 g glucose polymer drink (40 women) and a 50 g glucose monomer drink (43 women). We have reported results for this trial as two separate comparisons.75 g oral glucose tolerance test (OGTT) versus a 100 g OGTT (one trial, 248 women): women given the 75 g OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75).This difference was borderline for statistical significance. No other measures of maternal morbidity, or outcome for the baby were reported.Candy bar versus 50 g glucose monomer drink (one trial, 82 women): women receiving the candy bar, rather than glucose monomer, reported fewer side effects (RR 0.50, 95% CI 0.26 to 0.97) and preferred the taste (RR 0.62, 95% CI 0.44 to 0.87). No outcomes were reported for the baby.50 g glucose polymer versus 50 g glucose monomer (three trials, 259 women): mean difference (MD) in gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09). Side effects were less common with the glucose polymer (one trial 82 women; RR 0.20 95% CI 0.07 to 0.54), with no clear difference in taste acceptability (one trial 83 women; RR 0.96; 95% CI 0.78 to 1.18). Significantly fewer women reported nausea following the 50 g glucose polymer drink compared to the 50 g glucose monomer drink (one trial 66 women; RR 0.29; 95% CI 0.11 to 0.78) and bloatedness (two trials 149 women; RR 0.22; 95% CI 0.08 to 0.60). No other measures of maternal morbidity or outcome for the baby were reported.50 g glucose in food versus 50 g glucose drink (one trial, 30 women): women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). There was no clear difference in number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome for the baby were reported., Authors' Conclusions: There is insufficient evidence to assess which is the best strategy for diagnosing GDM.

Introduction: Pre-eclampsia (raised blood pressure and proteinuria) complicates 2% to 8% of pregnancies, and raises morbidity and mortality in the mother and child. Pre-eclampsia is more common in women with multiple pregnancy and in those who have conditions associated with microvascular disease., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: what are the effects of preventive interventions in women at risk of pre-eclampsia? What are the effects of interventions in women who develop mild to moderate hypertension during pregnancy? What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy? What is the best choice of anticonvulsant for women with eclampsia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants, antihypertensive drugs, antioxidants, antiplatelet drugs, atenolol, bed rest, hospital admission, or day care, calcium supplementation, choice of analgesia during labour, early delivery (interventionist care), evening primrose oil, fish oil, glyceryl trinitrate, magnesium supplementation, plasma volume expansion, and salt restriction.

Background: Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants are used to control eclamptic fits and to prevent further fits., Objectives: The objective of this review was to assess the effects of magnesium sulphate compared with diazepam when used for the care of women with eclampsia. Magnesium sulphate is compared with phenytoin and with lytic cocktail in other Cochrane reviews., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2010) and CENTRAL (2010, Issue 3)., Selection Criteria: Randomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with diazepam for women with a clinical diagnosis of eclampsia., Data Collection and Analysis: Two authors assessed and extracted data independently., Main Results: We have included seven trials, involving 1396 women. Three trials (1030 women) were good quality. Magnesium sulphate was associated with a reduction in maternal death (seven trials;1396 women; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.38 to 0.92) and recurrence of seizures (seven trials;1390 women; RR 0.43, 95% CI 0.33 to 0.55) compared to diazepam. There were no clear differences in other measures of maternal morbidity.There was no clear difference in perinatal mortality (four trials; 788 infants; RR 1.04, 95% CI 0.81 to 1.34) or neonatal mortality (four trials; 759 infants; RR 1.18, 95% CI 0.75 to 1.84). In the magnesium sulphate group, fewer liveborn babies had an Apgar score less than seven at one minute (two trials; 597 babies; RR 0.75, 95% CI 0.65 to 0.87) or at five minutes (RR 0.70, 95% CI 0.54 to 0.90), and fewer appeared to need intubation at the place of birth (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00). There was no difference in admission to a special care nursery (four trials; 834 infants; RR 0.91, 95% CI 0.79 to 1.05), but fewer babies in the magnesium sulphate group had a length of stay more than seven days (three trials 631 babies; RR 0.66, 95% CI 0.46 to 0.96)., Authors' Conclusions: Magnesium sulphate for women with eclampsia reduces the risk ratio of maternal death and of recurrence of seizures, compared with diazepam.

Background: Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia., Objectives: To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3)., Selection Criteria: Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia., Data Collection and Analysis: Two authors assessed trial quality and extracted data independently., Main Results: We included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero there was no clear difference in death (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory disability (RR 0.77, 95% CI 0.38 to 1.58) at age 18 months.Magnesium sulphate reduced eclampsia compared to phenytoin (three trials, 2291 women; RR 0.08, 95% CI 0.01 to 0.60) and nimodipine (one trial, 1650 women; RR 0.33, 95% CI 0.14 to 0.77)., Authors' Conclusions: Magnesium sulphate more than halves the risk of eclampsia, and probably reduces maternal death. There is no clear effect on outcome after discharge from hospital. A quarter of women report side effects with magnesium sulphate.

Background: The third stage of labour is from birth of the baby until delivery of the placenta. Clamping the umbilical cord is one component of active management of the third stage. Deferring cord clamping allows blood flow between the baby and the placenta to continue; net transfer to the baby is called placental transfusion. If the cord is clamped immediately placental transfusion is restricted. Gravity is one of several factors that may influence the volume and duration of placental transfusion at both vaginal and caesarean births. Hence raising or lowering the baby whilst the cord is intact may influence placental transfusion, which in turn may affect outcome for the baby and the woman., Objectives: To compare the effects of alternative positions for the baby between birth and cord clamping on outcome for the baby, outcome for the mother and on use of health service resources., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010)., Selection Criteria: Randomised trials comparing alternative positions for the baby at vaginal and caesarean birth, before clamping of the umbilical cord., Data Collection and Analysis: We independently assessed trial eligibility and quality. When necessary, we contacted study authors for additional information., Main Results: Thirty-seven studies (7559 mother-infant pairs) were excluded: 33 (7296) because they did not compare alternative positions for the baby before clamping the umbilical cord and four (263) due to quasi-random allocation. No studies met the inclusion criteria. One additional trial is ongoing., Authors' Conclusions: No randomised trials have assessed the influence of gravity on placental transfusion. Large, well-designed randomised trials are needed to assess whether gravity influences placental transfusion at vaginal and caesarean births and, if so, whether this affects short-term and long-term outcome for the baby and for the mother.

Background: Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants have been used to control eclamptic fits and to prevent further seizures., Objectives: The objective of this review was to assess the effects of magnesium sulphate compared with phenytoin when used for the care of women with eclampsia. Magnesium sulphate is compared with diazepam and with lytic cocktail in other Cochrane reviews., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2010)., Selection Criteria: Randomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with phenytoin for women with a clinical diagnosis of eclampsia., Data Collection and Analysis: Two review authors assessed trial quality and extracted data., Main Results: We have included data from seven trials, involving 972 women. One large trial (775 women) was of good quality. Magnesium sulphate was associated with a substantial reduction in the recurrence of seizures, when compared to phenytoin (six trials, 972 women; risk ratio (RR) 0.34, 95% confidence interval (CI) 0.24 to 0.49). The trend in maternal mortality favours magnesium sulphate, but the difference does not reach statistical significance (three trials, 847 women; RR 0.50, 95% CI 0.24 to 1.05). There were reductions in the risk of pneumonia (one trial, RR 0.44, 95% CI 0.24 to 0.79), ventilation (one trial, RR 0.68, 95% CI 0.50 to 0.91) and admission to an intensive care unit (one trial, RR 0.67, 95% CI 0.50 to 0.89) associated with the use of magnesium sulphate rather than phenytoin.For the baby, magnesium sulphate was associated with fewer admissions to a special care baby unit (SCBU) (one trial, 518 babies; RR 0.73, 95% CI 0.58 to 0.91) and fewer babies who died or were in SCBU for more than seven days (one trial, 643 babies; RR 0.77, 95% CI 0.63 to 0.95) than phenytoin. There was no clear difference in perinatal deaths (two trials, 665 babies; (RR 0.85, 95% CI 0.67 to 1.09)., Authors' Conclusions: Magnesium sulphate, rather than phenytoin, for women with eclampsia reduces the risk ratio of recurrence of seizures, probably reduces the risk of maternal death, and improves outcome for the baby. Magnesium sulphate is the drug of choice for women with eclampsia. The use of phenytoin should be abandoned.

Background: The number of visits for antenatal (prenatal) care developed without evidence of how many visits are necessary. The content of each visit also needs evaluation., Objectives: To compare the effects of antenatal care programmes with reduced visits for low-risk women with standard care., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2010), reference lists of articles and contacted researchers in the field., Selection Criteria: Randomised trials comparing a reduced number of antenatal visits, with or without goal-oriented care, with standard care., Data Collection and Analysis: Two authors assessed trial quality and extracted data independently., Main Results: We included seven trials (more than 60,000 women): four in high-income countries with individual randomisation; three in low- and middle-income countries with cluster randomisation (clinics as the unit of randomisation). The number of visits for standard care varied, with fewer visits in low- and middle- income country trials. In studies in high-income countries, women in the reduced visits groups, on average, attended between 8.2 and 12 times. In low- and middle- income country trials, many women in the reduced visits group attended on fewer than five occasions, although in these trials the content as well as the number of visits was changed, so as to be more 'goal oriented'.Perinatal mortality was increased for those randomised to reduced visits rather than standard care, and this difference was borderline for statistical significance (five trials; risk ratio (RR) 1.14; 95% confidence interval (CI) 1.00 to 1.31). In the subgroup analysis, for high-income countries the number of deaths was small (32/5108), and there was no clear difference between the groups (2 trials; RR 0.90; 95% CI 0.45 to 1.80); for low- and middle-income countries perinatal mortality was significantly higher in the reduced visits group (3 trials RR 1.15; 95% CI 1.01 to 1.32). Reduced visits were associated with a reduction in admission to neonatal intensive care that was borderline for significance (RR 0.89; 95% CI 0.79 to 1.02). There were no clear differences between the groups for the other reported clinical outcomes.Women in all settings were less satisfied with the reduced visits schedule and perceived the gap between visits as too long. Reduced visits may be associated with lower costs., Authors' Conclusions: In settings with limited resources where the number of visits is already low, reduced visits programmes of antenatal care are associated with an increase in perinatal mortality compared to standard care, although admission to neonatal intensive care may be reduced. Women prefer the standard visits schedule. Where the standard number of visits is low, visits should not be reduced without close monitoring of fetal and neonatal outcome.

Background: Eclampsia, the occurrence of a seizure in association with pre-eclampsia, is a rare but serious complication of pregnancy. A number of different anticonvulsants have been used to control eclamptic fits and to prevent further seizures., Objectives: The objective of this review was to assess the effects of magnesium sulphate compared with lytic cocktail (usually chlorpromazine, promethazine and pethidine) when used for the care of women with eclampsia. Magnesium sulphate is compared with diazepam and with phenytoin in other Cochrane reviews., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010) and the Cochrane Central Register of Trials (The Cochrane Library 2010, Issue 2)., Selection Criteria: Randomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with lytic cocktail for women with a clinical diagnosis of eclampsia., Data Collection and Analysis: Two review authors (L Duley and D Chou) assessed trial quality and extracted data., Main Results: We included three small trials (total 397 women) of average quality in the review. Magnesium sulphate was associated with fewer maternal deaths (risk ratio (RR) 0.14, 95% confidence interval (CI) 0.03 to 0.59; 3 trials, 397 women) and was better at preventing further seizures (RR 0.06, 95% CI 0.03 to 0.12; 3 trials, 397 women) than lytic cocktail. Magnesium sulphate was also associated with less respiratory depression (RR 0.12, 95% CI 0.02 to 0.91; 2 trials, 198 women), less coma (RR 0.04, 95% CI 0.00 to 0.74; 1 trial, 108 women), and less pneumonia (RR 0.20, 95% CI 0.06 to 0.67; 2 trials, 307 women). There was no clear difference in the RR for any death of the baby (RR 0.35, 95% CI 0.05 to 2.38, random effects; 2 trials, 177 babies)., Authors' Conclusions: Magnesium sulphate, rather than lytic cocktail, for women with eclampsia reduces the RR of maternal death, of further seizures and of serious maternal morbidity (respiratory depression, coma, pneumonia). Magnesium sulphate is the anticonvulsant of choice for women with eclampsia; the use of lytic cocktail should be abandoned.

Background: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia through a number of mechanisms, and may help to prevent preterm birth., Objectives: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2010) and contacted study authors., Selection Criteria: Randomised trials comparing at least 1 g daily of calcium during pregnancy with placebo., Data Collection and Analysis: We assessed eligibility and trial quality, extracted and double-entered data., Main Results: We included 13 studies of good quality (involving 15,730 women). The average risk of high blood pressure was reduced with calcium supplementation rather than placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81). There was also a reduction in the average risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65). The effect was greatest for high-risk women (five trials, 587 women: RR 0.22, 95% CI 0.12 to 0.42), and those with low baseline calcium intake (eight trials, 10,678 women: RR 0.36, 95% CI 0.20 to 0.65).The average risk of preterm birth was reduced in the calcium group overall (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97) and amongst women at high risk of developing pre-eclampsia recruited to four small trials (568 women: RR 0.45, 95% CI 0.24 to 0.83).There was no overall effect on the risk of stillbirth or death before discharge from hospital (11 trials 15,665 babies; RR 0.90, 95% CI 0.74 to 1.09). The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97). Most of the women in these trials were low risk and had a low calcium diet. Maternal deaths were reported in only one trial. One death occurred in the calcium group and six in the placebo group, a difference which was not statistically significant (RR 0.17, 95% CI 0.02 to 1.39).Blood pressure in childhood has been assessed in two studies, only one of which is currently included: childhood systolic blood pressure greater than 95th percentile was reduced (514 children: RR 0.59, 95% CI 0.39 to 0.91)., Authors' Conclusions: Calcium supplementation appears to approximately halve the risk of pre-eclampsia, to reduce the risk of preterm birth and to reduce the rare occurrence of the composite outcome 'death or serious morbidity'. There were no other clear benefits, or harms.

Background: Magnesium sulphate remains the drug of choice for both prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but have not yet been formally evaluated., Objectives: To assess the comparative effects of alternative regimens for the administration of magnesium sulphate when used for the care of women with pre-eclampsia or eclampsia, or both., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2010)., Selection Criteria: Randomised trials comparing different regimens for administration of magnesium sulphate used for the care of women with pre-eclampsia or eclampsia, or both., Data Collection and Analysis: All four review authors assessed trial quality and extracted data independently., Main Results: We identified 17 studies of which six (866 women) met the inclusion criteria: two trials (451 women) compared regimens for women with eclampsia and four (415 women) for women with pre-eclampsia.Treatment of eclampsia: one trial compared loading dose alone with loading dose plus maintenance therapy for 24 hours (401 women). There was no clear difference between the groups in the risk ratio (RR) of recurrence of convulsions (RR 1.13, 95% confidence interval (CI) 0.42 to 3.05) or stillbirth (RR 1.13, 95% CI 0.66 to 1.92), and the CIs are wide. One trial compared a low dose regimen with a standard dose regimen over 24 hours (50 women). This study was too small for any reliable conclusions about the comparative effects.Prevention of eclampsia: one trial compared intravenous with intramuscular maintenance regimen for 24 hours (17 women). This trial was too small for any reliable conclusions. Three trials compared short maintenance regimens postpartum with continuing for 24 hours after the birth (398 women), even taken together these trials were too small for any reliable conclusions., Authors' Conclusions: Although strong evidence supports the use of magnesium sulphate for prevention and treatment of eclampsia, trials comparing alternative treatment regimens are too small for reliable conclusions.

Background: The Magpie Trial compared magnesium sulfate with placebo for women with preeclampsia. The objective of this study was to explore women's views and experiences of participating in the Magpie Trial in the United Kingdom., Methods: Postal questionnaires were sent to 771 women participants in the Magpie Trial to assess long-term health of UK women and children. The questionnaire included three questions exploring women's experience of participating in the trial: (a) If time suddenly went backward, and you had to do it all over again, would you agree to participate in the Magpie Trial? (b) Please tell us if there was anything about the Magpie Trial that you think could have been done better; and (c) Please tell us if there was anything about the Magpie Trial, or your experience of joining the trial, that you think was particularly good., Results: Overall, 619 of the 771 women who were sent questionnaires returned them. In response to the three questions: (a) 58 percent (356) of women responded "definitely yes," 27 percent (169) "probably yes," 4 percent (23) "probably no," 5 percent (33) "definitely no," and 5 percent (34) "not sure." No clear evidence was shown of a relationship with allocated treatment, although women who responded "probably or definitely no" were more likely to have had side effects from trial treatment. (b) Although 44 percent of women stated that nothing could have been done better, free text suggestions related to content of recruitment information, and its timing, and wanting to know treatment allocation and trial results. c) Women were generally extremely positive about being followed up and receiving trial results., Conclusions: Women were largely positive about participation in the trial and its follow-up, but still reported ways they believed the study could have been improved, such as more information, given earlier, which also has implications for clinical care.

Over half a million women die each year from pregnancy related causes, 99% in low and middle income countries. In many low income countries, complications of pregnancy and childbirth are the leading cause of death amongst women of reproductive years. The Millennium Development Goals have placed maternal health at the core of the struggle against poverty and inequality, as a matter of human rights. Ten percent of women have high blood pressure during pregnancy, and preeclampsia complicates 2% to 8% of pregnancies. Preeclampsia can lead to problems in the liver, kidneys, brain and the clotting system. Risks for the baby include poor growth and prematurity. Although outcome is often good, preeclampsia can be devastating and life threatening. Overall, 10% to 15% of direct maternal deaths are associated with preeclampsia and eclampsia. Where maternal mortality is high, most of deaths are attributable to eclampsia, rather than preeclampsia. Perinatal mortality is high following preeclampsia, and even higher following eclampsia. In low and middle income countries many public hospitals have limited access to neonatal intensive care, and so the mortality and morbidity is likely to be considerably higher than in settings where such facilities are available. The only interventions shown to prevent preeclampsia are antiplatelet agents, primarily low dose aspirin, and calcium supplementation. Treatment is largely symptomatic. Antihypertensive drugs are mandatory for very high blood pressure. Plasma volume expansion, corticosteroids and antioxidant agents have been suggested for severe preeclampsia, but trials to date have not shown benefit. Optimal timing for delivery of women with severe preeclampsia before 32 to 34 weeks' gestation remains a dilemma. Magnesium sulfate can prevent and control eclamptic seizures. For preeclampsia, it more than halves the risk of eclampsia (number needed to treat 100, 95% confidence interval 50 to 100) and probably reduces the risk of maternal death. A quarter of women have side effects, primarily flushing. With clinical monitoring serious adverse effects are rare. Magnesium sulfate is the anticonvulsant of choice for treating eclampsia; more effective than diazepam, phenytoin, or lytic cocktail. Although it is a low cost effective treatment, magnesium sulfate is not available in all low and middle income countries; scaling up its use for eclampsia and severe preeclampsia will contribute to achieving the Millennium Development Goals.

Introduction: Pre-eclampsia (raised blood pressure and proteinuria) complicates 2-8% of pregnancies, and raises morbidity and mortality in the mother and child. Pre-eclampsia is more common in women with multiple pregnancy and in those who have conditions associates with microvascular disease., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in women at risk of pre-eclampsia? What are the effects of interventions in women who develop mild-moderate hypertension during pregnancy? What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy? What is the best choice of anticonvulsant for women with eclampsia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 53 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants, antihypertensive drugs, antioxidants, antiplatelet drugs, atenolol, bed rest, hospital admission or day care, calcium supplementation, choice of analgesia during labour, early delivery (interventionist care), evening primrose oil, fish oil, glyceryl trinitrate, magnesium supplementation, plasma volume expansion, and salt restriction.

Background: A substantial proportion of the psychiatric burden of disease falls on the world's poorest nations, yet relatively little is known about randomised trials conducted in these countries. Our aim was to identify and describe a representative sample of mental health trials from low and middle-income countries., Methods: 6107 electronic records, most with full text copies, were available following extensive searches for randomised or potentially randomised trials from low and middle-income countries published in 1991, 1995 and 2000. These records were searched to identify studies relevant to mental health. Data on study characteristics were extracted from the full text copies., Results: Trials relevant to mental health were reported in only 3% of the records. 176 records reporting 177 trials were identified: 25 were published in 1991, 45 in 1995, and 106 in 2000. Participants from China were represented in 46% of trials described. 68% of trials had <100 participants. The method of sequence generation was described in less than 20% of reports and adequate concealment of allocation was described in only 12% of reports. Participants were most frequently adults with unipolar depression (36/177) or schizophrenia (36/177). 80% of studies evaluated pharmacological interventions, a third of which were not listed by WHO as essential drugs. 41% of reports were indexed on PubMed; this proportion decreased from 68% in 1991 to 32% in 2000., Conclusion: In terms of overall health burden, trial research activity from low and middle-income countries in mental health appears to be low, and in no area adequately reflects need.

Large randomized trials are required to provide reliable evidence of the typically moderate benefit of most interventions. To be affordable, such trials need to be simple; to be widely applicable, they need to be close to normal clinical practice. However, current regulations and guidelines have hugely increased trial complexity, effectively becoming barriers to their design and conduct. Key barriers include inadequate funding, overly complex regulations producing needlessly complex trial procedures, excessive monitoring, over restrictive interpretation of privacy laws without evidence of subject benefit, and inadequate understanding of methodology. Complex regulations result in multiple ethics approvals for a multi-center study, unnecessary complexity in the study protocol, delays in securing regulatory approval, and cumbersome regulatory procedures, even for drugs widely used in clinical practice. The type of detailed safety monitoring currently needed in trials of new drugs is being applied indiscriminately to all studies including a simpler and basic level of monitoring that constitutes good practice in most trials could be agreed on, with that level being exceeded only in specific instances. More evidence about the pros and cons of alternative approaches to data quality monitoring would help inform this process. Complex procedures in the form of multiple-page consent forms, overzealous monitoring of side effects and adverse events, source data verification, and over-restrictive approaches to protocol amendments, can impede, rather than facilitate, trial objectives. Finally, further education on the nuances and functions of randomisation would facilitate trial conduct, and reduce the need for burdensome complexity. A radical re-evaluation of existing trial guidelines is needed, based on a clear understanding of the important principles of randomized trials, with the objective of eliminating unnecessary documentation and reporting without sacrificing validity or safety. Researchers should encourage public debate about how best to strike the balance between regulation and cost.

Background: Pre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most., Methods: We did a meta-analysis of individual patient data from 32,217 women, and their 32,819 babies, recruited to 31 randomised trials of pre-eclampsia primary prevention., Findings: For women assigned to receive antiplatelet agents rather than control, the relative risk of developing pre-eclampsia was 0.90 (95% CI 0.84-0.97), of delivering before 34 weeks was 0.90 (0.83-0.98), and of having a pregnancy with a serious adverse outcome was 0.90 (0.85-0.96). Antiplatelet agents had no significant effect on the risk of death of the fetus or baby, having a small for gestational age infant, or bleeding events for either the women or their babies. No particular subgroup of women was substantially more or less likely to benefit from antiplatelet agents than any other., Interpretation: Antiplatelet agents during pregnancy are associated with moderate but consistent reductions in the relative risk of pre-eclampsia, of birth before 34 weeks' gestation, and of having a pregnancy with a serious adverse outcome.

Maternal mortality remains the health statistic for which there is the greatest disparity between developing and developed countries. The risk of stillbirth or neonatal death is also high in developing countries. The inequality of research funding between rich and poor countries is dramatic, with only 10% of research funding directed towards diseases which contribute 90% of the global burden of disease. The need for high-quality, relevant perinatal research in developing countries is compelling. There are many examples of good perinatal research in developing countries. Nevertheless, significant challenges remain and are being tackled. We need better information about maternal and perinatal health, and about performance of the health services, we need more evaluation of what helps and what harms within the existing health services, and we need improved strategies for implementation of research findings.

There is now strong evidence from systematic reviews of randomised trials to support the use of magnesium sulphate for the prevention and treatment of eclampsia. Magnesium sulphate more than halves the risk of eclampsia for women with pre-eclampsia (relative risk (RR) 0.41, 95% confidence interval (CI) 0.29-0.58; number needed to treat (NNT) 102 (95% CI 72-173) compared to placebo. For treatment of eclampsia, magnesium sulphate lowers the risk of maternal death (RR 0.59, 95% CI 0.37-0.94) and of recurrence of further fits (RR 0.44, 95% CI 0.34-0.57) compared to diazepam. Magnesium sulphate also reduces the risk of further fits compared to phenytoin (RR 0.31, 95% CI 0.20-0.47) and to lytic cocktail (RR 0.09, 95% CI 0.03-0.24).

Pre-eclampsia is a multisystem disorder, of unknown aetiology, usually associated with raised blood pressure and proteinuria. Although outcome for most women and their babies is good, it remains a major cause of morbidity and mortality. A wide range of interventions for prevention and treatment of pre-eclampsia have been evaluated in randomized trials. This evidence provides the basis for a rational approach to care. Overall, there is insufficient evidence for any firm conclusion about the effects of any aspect of diet or lifestyle during pregnancy. Antiplatelet agents are associated with a 19% reduction in the risk of pre-eclampsia (relative risk 0.81; 95% CI 0.75, 0.88), a 7% reduction in the risk of preterm birth (RR 0.93; 95% CI 0.89, 0.98), a 16% reduction in the risk of stillbirth or neonatal death (RR 0.84; 95% CI 0.74, 0.96) and an 8% reduction in the risk of a small for gestational age baby (RR 0.92; 95% CI 0.85, 1.00). For mild to moderate hypertension, trials evaluating bed rest are too small for reliable conclusions about the potential benefits and hazards. Antihypertensive agents halve the risk of progression to severe hypertension (RR 0.52; 95% CI 0.41, 0.64), but with no clear effect on pre-eclampsia (RR 0.99; 95% CI 0.84, 1.18), or any other substantive outcome. For severe hypertension, there is no good evidence that one drug is any better than another. Plasma volume expansion for severe pre-eclampsia seems unlikely to be beneficial, although the trials are small. The optimum timing of delivery for pre-eclampsia before 34 weeks is unclear. Magnesium sulphate more than halves the risk of eclampsia (RR 0.41; 95% CI 0.29, 0.58) and probably reduces the risk of maternal death (RR 0.54; 95% CI 0.26, 1.10). It is also the drug of choice for treatment of eclampsia.

Background: Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate., Methods: Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat., Findings: Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89)., Interpretation: Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.