• Alterations in maternally perceived fetal movement and their association with late stillbirth: findings from the Midland and North of England stillbirth case-control study.

      Sherwood Forest Hospitals NHS Foundation Trust (2018-07)
      OBJECTIVE: To report perception of fetal movements in women who experienced a stillbirth compared with controls at a similar gestation with a live birth. DESIGN: Case-control study. SETTING: 41 maternity units in the UK. PARTICIPANTS: Cases were women who had a late stillbirth >/=28 weeks gestation (n=291) and controls were women with an ongoing pregnancy at the time of the interview (n=733). Controls were frequency matched to cases by obstetric unit and gestational age. METHODS: Data were collected using an interviewer-administered questionnaire which included questions on maternal perception of fetal movement (frequency, strength, increased and decreased movements and hiccups) in the 2 weeks before the interview/stillbirth. Five fetal movement patterns were identified incorporating the changes in strength and frequency in the last 2 weeks by combining groups of similar pattern and risk. Multivariable analysis adjusted for known confounders. PRIMARY OUTCOME MEASURE: Association of maternally perceived fetal movements in relation to late stillbirth. RESULTS: In multivariable analyses, women who reported increased strength of movements in the last 2 weeks had decreased risk of late stillbirth compared with those whose movements were unchanged (adjusted OR (aOR) 0.18, 95% CI 0.13 to 0.26). Women with decreased frequency (without increase in strength) of fetal movements were at increased risk (aOR 4.51, 95% CI 2.38 to 8.55). Daily perception of fetal hiccups was protective (aOR 0.31, 95% CI 0.17 to 0.56). CONCLUSIONS: Increased strength of fetal movements and fetal hiccups is associated with decreased risk of stillbirth. Alterations in frequency of fetal movements are important in identifying pregnancies at increased risk of stillbirth, with the greatest risk in women noting a reduction in fetal activity. Clinical guidance should be updated to reflect that increase in strength and frequency of fetal movements is associated with the lowest risk of stillbirth, and that decreased fetal movements are associated with stillbirth.
    • Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial.

      Sherwood Forest Hospitals NHS Foundation Trust (2015-07)
      BACKGROUND: Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. METHODS: We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged >/=16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m(2) or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30-39 vs >/=40 kg/m(2)). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. FINDINGS: Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference -0.029, 95% CI -0.217 to 0.158; p=0.7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3.60, 95% CI 0.74-17.50; p=0.11). INTERPRETATION: Metformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes.
    • Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial.

      HALT-IT Trial Collaborators; Sherwood Forest Hospitals NHS Foundation Trust (2020-06)
      Summary Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.
    • Efficacy of metformin in pregnant obese women: a randomised controlled trial.

      Sherwood Forest Hospitals NHS Foundation Trust (2015-01-14)
      INTRODUCTION: Increasing evidence suggests obesity has its origins prior to birth. There is clear correlation between maternal obesity, high birthweight and offspring risk of obesity in later life. It is also clear that women who are obese during pregnancy are at greater risk of adverse outcomes, including gestational diabetes and stillbirth. The mechanism(s) by which obesity causes these problems is unknown, although hyperglycaemia and insulin resistance are strongly implicated. We present a protocol for a study to test the hypothesis that metformin will improve insulin sensitivity in obese pregnant women, thereby reducing the incidence of high birthweight babies and other pregnancy complications. METHODS AND ANALYSIS: The Efficacy of Metformin in Pregnant Obese Women, a Randomised controlled (EMPOWaR) trial is a double-masked randomised placebo-controlled trial to determine whether metformin given to obese (body mass index >30 kg/m(2)) pregnant women from 16 weeks' gestation until delivery reduces the incidence of high birthweight babies. A secondary aim is to test the mechanism(s) of any effect. Obese women with a singleton pregnancy and normal glucose tolerance will be recruited prior to 16 weeks' gestation and prescribed study medication, metformin or placebo, to be taken until delivery. Further study visits will occur at 28 and 36 weeks' gestation for glucose tolerance testing and to record anthropometric measurements. Birth weight and other measurements will be recorded at time of delivery. Anthropometry of mother and baby will be performed at 3 months postdelivery. As of January 2014, 449 women had been randomised across the UK. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. A favourable ethical opinion was obtained from Scotland A Research Ethics Committee, reference number 10/MRE00/12. Results will be disseminated at conferences and published in peer-reviewed journals.
    • . Evaluation of the Implementation of the Saving Babies’ Lives Care Bundle in early adopter NHS Trusts in England.

      Sherwood Forest Hospitals NHS Foundation Trust (Maternal and Fetal Health Research Centre, University of Manchester., 2018-11)
      This report presents the findings from the Saving Babies Lives Project Impact and Results Evaluation (SPiRE) conducted by the Tommy's Stillbirth Research Centre at the University of Manchester commissioned by NHS England in May 2016. The report describes the results of a comprehensive evaluation involving nineteen NHS trusts in England that have been implementing the Saving Babies' Lives Care Bundle (SBLCB) since April 2015, which aims to reduce the incidence of stillbirth by implementing best practice in four aspects of maternity care. This report describes the degree of implementation, the clinical and service outcomes and the economic impact(s) following a maximum two year implementation period in these early adopter Trusts and crucially, whether implementation of the SBLCB translates into fewer stillbirths. ... Stillbirth rates, clinical and service outcomes, element outcomes, estimated costs relating to SBLCB implementation and local guideline appraisal are reported. Information about the impact of implementation of the SBLCB on staff and services is described. participating trusts were assigned a letter for anonymization in the analysis. ... During the time period analysed in the early adopter Trusts there was a statistically significant reduction in stillbirth of 20%; this reduction was also seen in term stillbirths. Due to variations in the timing and level of implementation of the various elements of the SBLCB this reduction cannot be unambiguously related to its implementation. However, it is highly plausible that the SBLCB contributed to the fall in stillbirths.
    • Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models.

      Sherwood Forest Hospitals NHS Foundation Trust; PREP Collaborative Network (2017-03)
      Background Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. Method Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in the UK to a large prospective cohort study (PREP-946) for development of prognostic models for the overall risk of experiencing a complication using logistic regression (PREP-L), and for predicting the time to adverse maternal outcome using a survival model (PREP-S). External validation of the models were carried out in a multinational cohort (PIERS-634) and another cohort from the Netherlands (PETRA-216). Main outcome measures were C-statistics to summarise discrimination of the models and calibration plots and calibration slopes. Results A total of 169 mothers (18%) in the PREP dataset had adverse outcomes by 48 hours, and 633 (67%) by discharge. The C-statistics of the models for predicting complications by 48 hours and by discharge were 0.84 (95% CI, 0.81–0.87; PREP-S) and 0.82 (0.80–0.84; PREP-L), respectively. The PREP-S model included maternal age, gestation, medical history, systolic blood pressure, deep tendon reflexes, urine protein creatinine ratio, platelets, serum alanine amino transaminase, urea, creatinine, oxygen saturation and treatment with antihypertensives or magnesium sulfate. The PREP-L model included the above except deep tendon reflexes, serum alanine amino transaminase and creatinine. On validation in the external PIERS dataset, the reduced PREP-S model showed reasonable calibration (slope 0.80) and discrimination (C-statistic 0.75) for predicting adverse outcome by 48 hours. Reduced PREP-L model showed excellent calibration (slope: 0.93 PIERS, 0.90 PETRA) and discrimination (0.81 PIERS, 0.75 PETRA) for predicting risk by discharge in the two external datasets. Conclusions PREP models can be used to obtain predictions of adverse maternal outcome risk, including early preterm delivery, by 48 hours (PREP-S) and by discharge (PREP-L), in women with early onset pre-eclampsia in the context of current care. They have a potential role in triaging high-risk mothers who may need transfer to tertiary units for intensive maternal and neonatal care.