The Recognition of Excessive blood loss At ChildbirTh (REACT) Study: a two-phase exploratory, sequential mixed methods inquiry using focus groups, interviews and a pilot, randomised crossover study.

OBJECTIVES: To explore how childbirth-related blood loss is evaluated and excessive bleeding recognised; and to develop and test a theory of postpartum haemorrhage (PPH) diagnosis. DESIGN: Two-phase, exploratory, sequential mixed methods design using focus groups, interviews and a pilot, randomised crossover study. SETTING: Two hospitals in North West England. SAMPLE: Women (following vaginal birth with and without PPH), birth partners, midwives and obstetricians. METHODS: Phase 1 (qualitative): 8 focus groups and 20 one-to-one, semi-structured interviews were conducted with 15 women, 5 birth partners, 11 obstetricians, 1 obstetric anaesthetist and 19 midwives (n = 51). Phase 2 (quantitative): 11 obstetricians and ten midwives (n = 21) completed two simulations of fast and slow blood loss using a high-fidelity childbirth simulator. RESULTS: Responses to blood loss were described as automatic, intuitive reactions to the speed, nature and visibility of blood flow. Health professionals reported that quantifying volume was most useful after a PPH diagnosis, to validate intuitive decisions and guide ongoing management. During simulations, PPH treatment was initiated at volumes at or below 200 ml (fast mean blood loss 79.6 ml, SD 41.1; slow mean blood loss 62.6 ml, SD 27.7). All participants treated fast, visible blood loss, but only half treated slow blood loss, despite there being no difference in volumes (difference 18.2 ml, 95% CI -5.6 to 42.2 ml, P = 0.124). CONCLUSIONS: Experience and intuition, rather than blood loss volume, inform recognition of excessive blood loss after birth. Women and birth partners want more information and open communication about blood loss. Further research exploring clinical decision-making and how to support it is required. TWEETABLE ABSTRACT: During a PPH, clinical decision-making is intuitive with clinicians treating as soon as excessive loss is recognised.

Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study.

OBJECTIVE: To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of postpartum haemorrhage (PPH), and recommendations on how to report the COS. DESIGN: A two-round Delphi survey and face-to-face meeting. POPULATION: Healthcare professionals and women's representatives. METHODS: Outcomes were identified from systematic reviews of PPH studies and stakeholder consultation. Participants scored each outcome in the Delphi on a Likert scale between 1 (not important) and 9 (critically important). Results were discussed at the face-to-face meeting to agree the final COS. Consensus at the meeting was defined as ≥ 70% of participants scoring the outcome as critically important (7-9). Lectures, discussion and voting were used to agree how to report COS outcomes. MAIN OUTCOME MEASURES: Outcomes from systematic reviews and consultations. RESULTS: Both Delphi rounds were completed by 152/205 (74%) participants for prevention and 143/197 (73%) for treatment. For prevention of PPH, nine core outcomes were selected: blood loss, shock, maternal death, use of additional uterotonics, blood transfusion, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. For treatment of PPH, 12 core outcomes were selected: blood loss, shock, coagulopathy, hysterectomy, organ dysfunction, maternal death, blood transfusion, use of additional haemostatic intervention, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. Recommendations were developed on how to report these outcomes where possible. CONCLUSIONS: These COS will help standardise outcome reporting in PPH trials. TWEETABLE ABSTRACT: Core outcome sets for PPH: nine core outcomes for PPH prevention and 12 core outcomes for PPH treatment.

"We have to clean ourselves to ensure that our children are healthy and beautiful": findings from a qualitative assessment of a hand hygiene poster in rural Uganda.

BACKGROUND: Neonatal sepsis is a major cause of mortality worldwide, with most deaths occurring in low-income countries. The World Health Organisation (WHO) '5 Moments for Hand Hygiene' poster has been used to reduce hospital-acquired infections, but there is no similar tool to prevent community-acquired newborn infections in low-resource settings. This assessment, part of the BabyGel Pilot study, evaluated the acceptability of the 'Newborn Moments for Hand Hygiene in the Home' poster. This was an educational tool which aimed to remind mothers in rural Uganda to clean their hands to prevent neonatal infection. METHODS: The BabyGel pilot was a cluster randomised trial that assessed the post-partum use of alcohol-based hand rub (ABHR) to prevent neonatal infections in Mbale, Uganda. Fifty-five women in 5 village clusters received the ABHR and used it from birth to 3 months postnatally, with use guided by the new poster. Following the study, 5 focus group discussions (FGDs) were conducted consisting of 6-8 purposively sampled participants from intervention villages. FGDs were audio-recorded, transcribed then translated into English. Transcripts were inductively coded using ATLAS.ti® and qualitatively analysed using thematic content analysis. RESULTS: Most mothers reported that they understood the message in the poster ("The picture shows me you must use these drugs to keep your baby healthy") and that they could adhere to the moments from the poster. Some participants used the information from the poster to encourage other caregivers to use the ABHR ("after explaining to them, they liked it"). Other potential moments for hand hygiene were introduced by participants, such as after tending to domestic animals and gardening. CONCLUSION: The poster was well-received, and participants reported compliance with the moments for hand hygiene (although the full body wipe of the baby has since been removed). The poster will be adapted into a sticker format on the ABHR bottle. More focus could be put into an education tool for other caregivers who wish to hold the baby. Overall, the study demonstrated the acceptability of an adapted version of the WHO Moments for Hand Hygiene poster in the introduction of an intervention in the community. TRIAL REGISTRATION: ISRCTN67852437 , registered 02/03/2015. TRIAL FUNDING: Medical Research Council/ Wellcome Trust/ DfID (Global Health Trials Scheme).

Foley catheter vs. oral misoprostol to induce labour among hypertensive women in India: a cost-consequence analysis alongside a clinical trial.

OBJECTIVE: To determine the effectiveness and economic impact of two methods for induction of labour in hypertensive women, in low-resource settings. DESIGN: Cost-consequence analysis of a previously reported multicentre, parallel, open-label randomised trial. SETTING & POPULATION: A total of 602 women with a live fetus, aged ≥18 years requiring delivery for pre-eclampsia or hypertension, in two public hospitals in Nagpur, India. METHODS: We performed a formal economic evaluation alongside the INFORM clinical trial. Women were randomised to receive transcervical Foley catheterisation or oral misoprostol 25 mcg. Healthcare expenditure was calculated using a provider-side microcosting approach. MAIN OUTCOME MEASURES: Rates of vaginal this delivery within 24 hours of induction, healthcare expenditure per completed treatment episode. RESULTS: Induction with oral misoprostol resulted in a (mean difference) $20.6USD reduction in healthcare expenditure [95% CI (-) $123.59 (-) $72.49], and improved achievement of vaginal delivery within 24 hours of induction, mean difference 10% [95% CI (-2 to 17.9%), P = 0.016]. Oxytocin administration time was reduced by 135.3 minutes [95% CI (84.4-186.2 minutes), P < 0.01] and caesarean sections by 9.1% [95% CI (1.1-17%), P = 0.025] for those receiving oral misoprostol. Following probabilistic sensitivity analysis, oral misoprostol was cost-saving in 63% of 5,000 bootstrap replications and achieved superior rates of vaginal delivery, delivery within 24 hours of induction and vaginal delivery within 24 hours of induction in 98.7%, 90.7%, and 99.4% of bootstrap simulations. Based on univariate threshold analysis, the unit price of oral misoprostol 25 mcg could feasibly increase 31-fold from $0.24 to $7.50 per 25 mcg tablet and remain cost-saving. CONCLUSION: Compared to Foley catheterisation for the induction of high-risk hypertensive women, oral misoprostol improves rates of vaginal delivery within 24 hours of induction and may also reduce costs. Additional research performed in other low-resource settings is required to determine their relative cost-effectiveness. TWEETABLE ABSTRACT: Oral misoprostol less costly and more effective than Foley catheter for labour induction in hypertension.

Preventing neonatal sepsis in rural Uganda: a cross-over study comparing the tolerance and acceptability of three alcohol-based hand rub formulations.

BACKGROUND: Neonatal sepsis causes 0.5 million deaths annually, mostly in low resource settings. Babies born in African rural homes without running water or toilet facilities are especially vulnerable. Alcohol-based hand rub (ABHR) may be used by mothers and carers as an alternative to hand washing with soap to prevent neonatal infection. However, no definite study has established the preferred formulation of hand rub for the mothers. This study aimed to assess the effects of addition of bitterants and perfume towards the acceptability of the alcohol-based hand rubs by the mothers in their homes after childbirth. METHODS: This was a 3-way blinded cross-over study design. Mothers with children aged ≤3 months were recruited from immunisation clinics at 3 local health facilities in rural eastern Uganda and received 3-different ABHR formulations (in the order plain, bitterant and perfumed) packed in 100 ml bottles. Each ABHR was used for 5 consecutive days followed by a 2-day 'washout' period (evaluation period). Overall satisfaction with each hand rub was evaluated at the end of each week using a 7-point Likert scale. RESULTS: A total of 43 women were recruited, whose ages ranged from 16 to 45 years (mean 26.2 years old). None of the participants normally used a hand protective lotion/cream. The three formulations were used for a mean of 5 (range 3-7) days. A significantly greater volume of the "bitterant" and "perfumed" formulations (mean 91 and 83 ml respectively) were used in comparison to the "plain" formulation (mean 64 ml). Overall satisfaction was high with all the hand rubs, but the perfumed formulation had a significantly higher overall satisfaction score [mean 6.7, range 4-7] compared with the plain [6.4, 3-7] and bitterant [6.2, 2-7] formulations. CONCLUSIONS: All the 3 ABHR formulations were well accepted with little to choose between them. The ABHR with added perfume scored highest on overall satisfaction and was used significantly more often than plain ABHR. ABHR with bitterant additive did, however, score highly and may be a preferable choice to those with concern over alcohol misuse. TRIAL REGISTRATION: ISRCTN67852437 , prospectively registered on 18/03/2018.

Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed size. METHODS: Women with PPH 1000-1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused. RESULTS: Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3-1.7), P =0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th-75th centile) of 1 (0-4.5) unit of allogeneic blood products and had an additional 300 (100-350) ml blood loss whereas those who received placebo also received 3 (0-6) units of allogeneic blood products and had 700 (200-1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group. CONCLUSIONS: Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre -1 , but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis. TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 , last accessed 5 July 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-005511-11 , last accessed 5 July 2017).

Historical trends in the timing of informed consent for research into intrapartum complications.

Obtaining informed consent for clinical trials involving the management of intrapartum complications is complex. This article describes the strategies used to obtain consent over the last 60 years using data from the Cochrane Library. Of 138 intrapartum randomised studies, 37% had no record of the consent procedures. Of the remainder, 74% sought consent only when the complication developed, 11% sought consent from all women in early labour, and 13% gave all women antenatal information and then sought written consent when the complication arose. Despite the existence of ethics guidelines for intrapartum consent, many studies fail to follow their advice.

The effect of misoprostol on postpartum contractions: a randomised comparison of three sublingual doses.

OBJECTIVE: To compare the postpartum uterine activity and side effects of various doses of sublingual misoprostol and intramuscular oxytocin. DESIGN: Single centre, randomised trial. SETTING: Zliten Teaching Hospital in Libya. POPULATION: Forty-nine women who did not receive oxytocics in labour and who delivered vaginally. METHODS: Thirty-five women were randomised to receive 200, 400 or 600 mcg of sublingual misoprostol PPH prophylaxis immediately following delivery. These were compared with 14 consecutive women given 10 IU of intramuscular oxytocin. Immediately after placental delivery, a Koala intra uterine pressure catheter was inserted transcervically into the uterine cavity. MAIN OUTCOMES MEASURES: Main outcomes measures are the uterine pressure (in Montevideo units) measured over 120 minutes. Other outcomes included temperature and measured blood loss. RESULTS: Women's age, parity, gestational age and neonatal birth weight were not significantly different between the four groups. There was no difference in intrauterine pressure between the three misoprostol doses. However, the uterine pressure was significantly lower than oxytocin with all three doses for the first 10 minutes (P < 0.008) and significantly higher than oxytocin from 50 to 120 minutes (P < 0.008). A dose-related rise in the body temperature and chills was observed in the misoprostol groups, with 8.3%, 8.3% and 45% of women experiencing a fever >39 °C with the 200, 400, and 600 mcg doses respectively. CONCLUSION: Intramuscular oxytocin has the highest immediate post partum uterine activity. Lower doses of misoprostol may be as effective as high doses and with fewer side effects. Clinical outcomes with low-dose misoprostol should be further explored (ISRCTN97277056).

The retained placenta: historical and geographical rate variations.

In this study, we sought to explore the variation in reported rates of retained placenta around the world and over time in the UK. A systematic review of observational studies was performed to obtain retained placenta rates from around the world and annual hospital reports from the Royal College of Obstetricians and Gynaecologists archives were examined to obtain historical retained placenta rates. The data show that the median rate of retained placenta at 30 minutes was higher in developed countries (2.67% vs 1.46%, p < 0.02), as was the median manual removal rate (2.24% vs 0.45%, p < 0.001). In addition to this, there appears to have been a rise in rate of manual removal in the UK from a mean of 0.66% in the 1920s to 2.34% in the 1980s (p < 0.0001).

Why are women still dying from obstetric hemorrhage? A narrative review of perspectives from high and low resource settings.

The possibility of hemorrhage will always co-exist with pregnancy, whether anticipated or not. It remains the unwelcome guest in the corner of every delivery room, stealing the lives of young women every day across the globe. In 2014, the World Health Organization reported that hemorrhage was the leading contributor to maternal mortality worldwide, with nearly 75% of maternal deaths due to postpartum hemorrhage. In low resource settings, while maternal mortality is decreasing, hemorrhage remains the single most important contributor to maternal death. Hospital-based deliveries with skilled birth attendants have been encouraged to improve outcomes and, as a result, hospital births have dramatically increased. However, access to higher levels of emergency obstetric care as well as blood products and therapeutic resources remain limiting factors. Meanwhile, in high resource settings, maternal mortality from hemorrhage is increasing, particularly among women of color. While very rare, mortality from hemorrhage generally follows medical interventions such as surgical management of placenta accreta or emergency cesarean section. Primary prevention therefore requires careful selection and conduct of medical interventions, as well as the provision of high quality, supportive, and safe maternity care. It is clear that there is not one single solution in preventing obstetric hemorrhage on a global scale. The international community must employ creative solutions to reduce this ever-present problem.

The use of misoprostol in obstetrics and gynaecology.

Misoprostol, although originally introduced as a therapy for gastric ulcers, is now widely used in reproductive health. For some indications it is now the optimal choice, whilst for others it provides an important alternative, especially in low-resource settings. The optimal dose varies widely from 20 to 600 mcg depending on the indication and gestation. Use of the correct dose is important, too low a dose will be ineffective and overdosage can be dangerous for mother and baby. Evidence-based information about the safest regimens for multiple pregnancy indications are therefore provided in this review.

In search of a primary outcome for community-based newborn infection trials in Eastern Uganda: a nested cohort study within the BabyGel pilot trial.

BACKGROUND: Due to their immature immune system, neonates are at high risk of infection. This vulnerability when combined with limited resources and health education in developing countries can lead to sepsis, resulting in high global neonatal mortality rates. Many of these deaths are preventable. The BabyGel pilot trial tested the feasibility of conducting the main randomised trial, with the provision of alcohol handgel to postpartum mothers for prevention of neonatal infective morbidity in the rural community. This secondary analysis sought to evaluate the methods of detecting infections in babies up to 3 months of age. METHODS: The pilot two-arm cluster randomised controlled trial took place in 10 villages around Mbale, Eastern Uganda. Women were eligible and recruited antenatally if their gestation was ≥ 34 weeks. All infants of mothers participating in the BabyGel pilot trial were followed up for the first 3 months of life. Evidence for infant infection was collected using five different methods: clinician diagnosed infection, microbiologically confirmed infection, maternally reported infection, a positive infection screen using the World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) screening criteria, and reported antibiotic use identified during home and clinic visits. These methods were assessed quantitatively regarding the detection rates of suspected infections and qualitatively by exploring the challenges collecting data in the rural community setting. RESULTS: A total of 103 eligible women participated in the BabyGel pilot trial, with 1 woman delivering twins. Of the 99 mother-infant pairs who consented to participate in the study, 55 infants were identified with infection in total. Maternal report of illness provided the highest estimate, with mothers reporting suspected illness for 45 infants (81.8% of the total suspected infections identified). The WHO IMCI screening criteria identified 30 infants with suspected infection (54.5%), and evidence for antibiotic use was established in 22 infants (40%). Finally, clinician-diagnosed infection identified 19 cases (34.5%), which were also microbiologically confirmed in 5 cases (9.1%). Data collection in the rural setting was hindered by poor communication between mothers and the research team, limited staff awareness of the study in health centres resulting in reduced safeguarding of clinical notes, and widespread use of antibiotics prior to notification and clinical review. Furthermore, identification of suspected infection may not have been limited to severe infections, with ambiguity and no official clinical diagnosis being given to those identified solely by maternal report of infection. CONCLUSIONS: A high rate of suspected infection was identified spanning the five sources of data collection, but no ideal method was found for detection of community neonatal infection. Although maternal self-reports of infant infection provided the highest detection rate, data collection via each source was limited and may have identified minor rather than major infections. Future studies could utilise the IMCI screening tool to detect severe community infection leading to referral for clinical confirmation. This should be combined with weekly contact with mothers to detect maternally suspected illness. Obtaining more details of the symptoms and timescale will improve the accuracy when detecting the total burden of suspected disease, and advising participants to retain medication packaging and prescriptions will improve identification of antibiotic use. TRIAL REGISTRATION: Babygel pilot trial - trial registration: ISCRCTN 67852437. Registered 02/03/2015.