Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes.

A package of care for all pregnant women within eight scheduled antenatal care contacts is recommended by WHO. Some interventions for reducing and managing the outcomes for small vulnerable newborns (SVNs) exist within the WHO package and need to be more fully implemented, but additional effective measures are needed. We summarise evidence-based antenatal and intrapartum interventions (up to and including clamping the umbilical cord) to prevent vulnerable births or improve outcomes, informed by systematic reviews. We estimate, using the Lives Saved Tool, that eight proven preventive interventions (multiple micronutrient supplementation, balanced protein and energy supplementation, low-dose aspirin, progesterone provided vaginally, education for smoking cessation, malaria prevention, treatment of asymptomatic bacteriuria, and treatment of syphilis), if fully implemented in 81 low-income and middle-income countries, could prevent 5·202 million SVN births (sensitivity bounds 2·398-7·903) and 0·566 million stillbirths (0·208-0·754) per year. These interventions, along with two that can reduce the complications of preterm (<37 weeks' gestation) births (antenatal corticosteroids and delayed cord clamping), could avert 0·476 million neonatal deaths (0·181-0·676) per year. If further research substantiates the preventive effect of three additional interventions (supplementation with omega-3 fatty acids, calcium, and zinc) on SVN births, about 8·369 million SVN births (2·398-13·857) and 0·652 million neonatal deaths (0·181-0·917) could be avoided per year. Scaling up the eight proven interventions and two intrapartum interventions would cost about US$1·1 billion in 2030 and the potential interventions would cost an additional $3·0 billion. Implementation of antenatal care recommendations is urgent and should include all interventions that have proven effects on SVN babies, within the context of access to family planning services and addressing social determinants of health. Attaining high effective coverage with these interventions will be necessary to achieve global targets for the reduction of low birthweight births and neonatal mortality, and long-term benefits on growth and human capital.

Small vulnerable newborns-big potential for impact.

Despite major achievements in child survival, the burden of neonatal mortality has remained high and even increased in some countries since 1990. Currently, most neonatal deaths are attributable to being born preterm, small for gestational age (SGA), or with low birthweight (LBW). Besides neonatal mortality, these conditions are associated with stillbirth and multiple morbidities, with short-term and long-term adverse consequences for the newborn, their families, and society, resulting in a major loss of human capital. Prevention of preterm birth, SGA, and LBW is thus critical for global child health and broader societal development. Progress has, however, been slow, largely because of the global community's failure to agree on the definition and magnitude of newborn vulnerability and best ways to address it, to frame the problem attractively, and to build a broad coalition of actors and a suitable governance structure to implement a change. We propose a new definition and a conceptual framework, bringing preterm birth, SGA, and LBW together under a broader umbrella term of the small vulnerable newborn (SVN). Adoption of the framework and the unified definition can facilitate improved problem definition and improved programming for SVN prevention. Interventions aiming at SVN prevention would result in a healthier start for live-born infants, while also reducing the number of stillbirths, improving maternal health, and contributing to a positive economic and social development in the society.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Maternal postures for fetal malposition in late pregnancy for improving the health of mothers and their infants.

BACKGROUND: The optimal relationship of the fetus to the mother's birth canal is when the fetus is in the longitudinal lie, cephalic presentation with well-flexed head (vertex presentation), and in the occipito-anterior position. Fetal malposition is described as occipito-posterior (OP) when the back of the fetal head lies posteriorly in the mother's pelvis, and occipito-transverse (OT) when the back of the fetal head lies transversely in the mother's pelvis. The fetal head will often be deflexed and may extend further to a mento-anterior or mento-transverse position, where the chin is anterior or transverse to the maternal pelvis. Fetal malposition is associated with both maternal and fetal complications, including prolonged labour, fetal distress, maternal exhaustion, need for caesarean section, operative vaginal birth, and increased risk of perineal trauma and anal sphincter injuries. This review considered positional interventions in late pregnancy to correct fetal malposition. A separate Cochrane review addresses maternal postural position for fetal malposition during labour. OBJECTIVES: To assess the effects of maternal posture for fetal malposition in women in late pregnancy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (24 October 2022), and reference lists of retrieved studies. SELECTION CRITERIA: Our selection criteria were randomised controlled trials and cluster-randomised controlled trials that included women in late pregnancy with a malposition of the fetus including OP and OT, mento-anterior and mento-transverse, or with uncertain fetal position, randomly allocated to use of specified maternal positioning in late pregnancy, compared with usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed potential studies for inclusion in the review. We used standardised methodology for assessment of risk of bias and trustworthiness developed by the Cochrane Pregnancy and Childbirth Group. MAIN RESULTS: We reviewed three full-text reports; we excluded one due to lack of a comparison group and listed two as awaiting classification. We needed further information from the report authors for both potentially suitable studies to account for substantial imbalances between the numbers allocated to each group in one, or identical numbers for all groups in the other. The failure to resolve these issues may have been due to the long interval since publication of the studies (2004 and 1983). AUTHORS' CONCLUSIONS: We did not identify evidence for guiding practice with respect to positional interventions for fetal malposition in late pregnancy. More studies are needed to understand the effect of positional interventions in late pregnancy. Future research on positional interventions for fetal malposition in late pregnancy should include follow-up to determine whether short-term correction of fetal position translates to improved pregnancy outcomes. This might include interventions commenced in late pregnancy and repeated as needed until the onset of labour. The latter would be included in the review on maternal positions during labour.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

Tranexamic acid at cesarean delivery: drug-error deaths.

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.

Tranexamic acid at cesarean delivery: drug-error deaths.

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.

Novel concepts and improvisation for treating postpartum haemorrhage: a narrative review of emerging techniques.

BACKGROUND: Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access. NARRATIVE REVIEW: Pubmed 2020 to 2021 was searched on 'postpartum haemorrhage treatment', and novel reports among 755 citations were catalogued. New health care strategies included early diagnosis with a bundled first response and home-based treatment of PPH. A calibrated postpartum blood monitoring tray has been described. Oxytocin is more effective than misoprostol; addition of misoprostol to oxytocin does not improve treatment. Heat stable carbetocin has not been assessed for treatment. A thermostable microneedle oxytocin patch has been developed. Intravenous tranexamic acid reduces mortality but deaths have been reported from inadvertent intrathecal injection. New transvaginal uterine artery clamps have been described. Novel approaches to uterine balloon tamponade include improvised and purpose-designed free-flow (as opposed to fixed volume) devices and vaginal balloon tamponade. Uterine suction tamponade methods include purpose-designed and improvised devices. Restrictive fluid resuscitation, massive transfusion protocols, fibrinogen use, early cryopreciptate transfusion and point-of-care viscoelastic haemostatic assay-guided blood product transfusion have been reported. Pelvic artery embolization and endovascular balloon occlusion of the aorta and pelvic arteries are used where available. External aortic compression and direct compression of the aorta during laparotomy or aortic clamping (such as with the Paily clamp) are alternatives. Transvaginal haemostatic ligation and compression sutures, placental site sutures and a variety of novel compression sutures have been reported. These include Esike's technique, three vertical compression sutures, vertical plus horizontal compression sutures, parallel loop binding compression sutures, uterine isthmus vertical compression sutures, isthmic circumferential suture, circumferential compression sutures with intrauterine balloon, King's combined uterine suture and removable retropubic uterine compression suture. Innovative measures for placenta accreta spectrum include a lower uterine folding suture, a modified cervical inversion technique, bilateral uterine artery ligation with myometrial excision of the adherent placenta and cervico-isthmic sutures or a T-shaped lower segment repair. Technological advances include cell salvage, high frequency focussed ultrasound for placenta increta and extra-corporeal membrane oxygenation. CONCLUSIONS: Knowledge of innovative methods can equip clinicians with last-resort options when faced with haemorrhage unresponsive to conventional methods.

Unborn babies are nourished by the mother's blood supply to the afterbirth (placenta). After a baby's birth, contractions of the muscles of the womb (uterus) shear the placenta from its attachment and clamp off the mother's blood vessels. This process is assisted by giving an injection which contracts the womb, and pulling gently on the cord to remove the afterbirth. Usually, blood loss is minimal. Occasionally the womb fails to contract effectively or there is bleeding from tears of the birth canal. Bleeding in excess of 500 ml is called postpartum haemorrhage, which can be life-threatening. Excessive bleeding may be treated with medicines to contract the womb or help the blood to clot, rubbing or squeezing the womb, a 'drip' with fluids or blood replacement, placing a balloon or suction device in the womb, and operations to stop the bleeding or remove of the womb (hysterectomy). There is very little hard evidence for the effectiveness of each method. This review highlights recent innovations including approaches to quick diagnosis and rapid treatment, suturing the lower part of the womb via the vagina, improvements in balloon and suction methods, new designs of clamps to apply through the vagina and to clamp the aorta (the main artery of the body), new approaches to giving blood clotting factors, many new types of stitches to compress the uterus, and advanced technology such as ultrasound treatment and artificial oxygenation of the mother's blood. We call for more research to show which methods really work.

Clinical algorithms for management of fetal heart rate abnormalities during labour.

OBJECTIVE: To construct algorithms with a sequential decision analysis pathway for monitoring of the fetal heart rate and managing fetal heart rate bradycardia, late decelerations and tachycardia during labour. POPULATION: Low-risk pregnant women in labour with singleton cephalic term pregnancies. SETTING: Institutional births in low- and middle-income countries. SEARCH STRATEGY: We sought relevant published clinical algorithms, guidelines and randomised trials/reviews by searching the Cochrane Library, PubMed and Google on the terms: "fetal AND heart AND rate AND algorithm AND (labour OR intrapartum)", up to March 2020. CASE SCENARIOS: The two scenarios included were fetal heart rate bradycardia or late decelerations (potentially related to uterine rupture, placental abruption, cord prolapse, maternal hypotension, uterine hyperstimulation or unexplained) and fetal heart rate tachycardia (potentially related to maternal hyperthermia, infection, dehydration or unexplained). The algorithms provide pathways for definition, assessment, diagnosis, interventions to correct the abnormalities and ongoing monitoring leading to mode of birth, and linking to other algorithms in the series. CONCLUSIONS: The algorithms provide a framework for monitoring and managing fetal heart rate bradycardia, late decelerations and tachycardia during labour. We emphasise the inherent diagnostic inaccuracy of fetal heart rate monitoring, the tendency to over-diagnose fetal compromise, the need to consider fetal heart rate information in the context of other clinical features and the need to engage in informed, shared, family-centred decision-making. We note the need for further research on methods of fetal assessment during labour including clinical fetal arousal testing and the rapid biophysical profile test. TWEETABLE ABSTRACT: Decision analysis algorithms for fetal bradycardia, late decelerations and tachycardia highlight diagnostic limitations.

Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care.

BACKGROUND: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most. OBJECTIVES: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing. SEARCH STRATEGY: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239). SELECTION CRITERIA: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates. MAIN RESULTS: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake. CONCLUSIONS: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate. TWEETABLE ABSTRACT: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low.

Constructing evidence-based clinical intrapartum care algorithms for decision-support tools.

AIM: To describe standardised iterative methods used by a multidisciplinary group to develop evidence-based clinical intrapartum care algorithms for the management of uneventful and complicated labours. POPULATION: Singleton, term pregnancies considered to be at low risk of developing complications at admission to the birthing facility. SETTING: Health facilities in low- and middle-income countries. SEARCH STRATEGY: Literature reviews were conducted to identify standardised methods for algorithm development and examples from other fields, and evidence and guidelines for intrapartum care. Searches for different algorithm topics were last updated between January and October 2020 and included a combination of terms such as 'labour', 'intrapartum', 'algorithms' and specific topic terms, using Cochrane Library and MEDLINE/PubMED, CINAHL, National Guidelines Clearinghouse and Google. CASE SCENARIOS: Nine algorithm topics were identified for monitoring and management of uncomplicated labour and childbirth, identification and management of abnormalities of fetal heart rate, liquor, uterine contractions, labour progress, maternal pulse and blood pressure, temperature, urine and complicated third stage of labour. Each topic included between two and four case scenarios covering most common deviations, severity of related complications or critical clinical outcomes. CONCLUSIONS: Intrapartum care algorithms provide a framework for monitoring women, and identifying and managing complications during labour and childbirth. These algorithms will support implementation of WHO recommendations and facilitate the development by stakeholders of evidence-based, up to date, paper-based or digital reminders and decision-support tools. The algorithms need to be field tested and may need to be adapted to specific contexts. TWEETABLE ABSTRACT: Evidence-based intrapartum care clinical algorithms for a safe and positive childbirth experience.

Maternal postures for fetal malposition in labour for improving the health of mothers and their infants.

BACKGROUND: Fetal malposition (occipito-posterior and persistent occipito-transverse) in labour is associated with adverse maternal and infant outcomes. Whether use of maternal postures can improve these outcomes is unclear. This Cochrane Review of maternal posture in labour is one of two new reviews replacing a 2007 review of maternal postures in pregnancy and labour. OBJECTIVES: To assess the effect of specified maternal postures for women with fetal malposition in labour on maternal and infant morbidity compared to other postures.  SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (13 July 2021), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or cluster-RCTs conducted among labouring women with a fetal malposition confirmed by ultrasound or clinical examination, comparing a specified maternal posture with another posture. Quasi-RCTs and cross-over trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, risk of bias, and performed data extraction. We used mean difference (MD) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included eight eligible studies with 1766 women.  All studies reported some form of random sequence generation but were at high risk of performance bias due to lack of blinding. There was a high risk of selection bias in one study, detection bias in two studies, attrition bias in two studies, and reporting bias in two studies. Hands and knees The use of hands and knees posture may have little to no effect on operative birth (average RR 1.14, 95% CI 0.87 to 1.50; 3 trials, 721 women; low-certainty evidence) and caesarean section (RR 1.34, 95% CI 0.96 to 1.87; 3 trials, 721 women; low-certainty evidence) but the evidence is uncertain; and very uncertain for epidural use (average RR 0.74, 95% CI 0.41 to 1.31; 2 trials, 282 women; very low-certainty evidence), instrumental vaginal birth (average RR 1.04, 95% CI 0.57 to 1.90; 3 trials, 721 women; very low-certainty evidence), severe perineal tears (average RR 0.88, 95% CI 0.03 to 22.30; 2 trials, 586 women; very low-certainty evidence), maternal satisfaction (average RR 1.02, 95% CI 0.68 to 1.54; 3 trials, 350 women; very low-certainty evidence), and Apgar scores less than seven at five minutes (RR 0.71, 95% CI 0.21 to 2.34; 2 trials, 586 babies; very low-certainty evidence).  No data were reported for the hands and knees comparisons for postpartum haemorrhage, serious neonatal morbidity, death (stillbirth or death of liveborn infant), admission to neonatal intensive care, neonatal encephalopathy, need for respiratory support, and neonatal jaundice requiring phototherapy.  Lateral postures The use of lateral postures may have little to no effect on reducing operative birth (average RR 0.72, 95% CI 0.43 to 1.19; 4 trials, 871 women; low-certainty evidence), caesarean section (average RR 0.78, 95% CI 0.44 to 1.39; 4 trials, 871 women; low-certainty evidence), instrumental vaginal birth (average RR 0.73, 95% CI 0.39 to 1.36; 4 trials, 871 women; low-certainty evidence), and maternal satisfaction (RR 0.96, 95% CI 0.84 to 1.09; 2 trials, 451 women; low-certainty evidence), but the evidence is uncertain. The evidence is very uncertain about the effect of lateral postures on severe perineal tears (RR 0.66, 95% CI 0.17 to 2.48; 3 trials, 609 women; very low-certainty evidence), postpartum haemorrhage (RR 0.90, 95% CI 0.48 to 1.70; 1 trial, 322 women; very low-certainty evidence), serious neonatal morbidity (RR 1.41, 95% CI 0.64 to 3.12; 3 trials, 752 babies; very low-certainty evidence), Apgar scores less than seven at five minutes (RR 0.25, 95% CI 0.03 to 2.24; 1 trial, 322 babies; very low-certainty evidence), admissions to neonatal intensive care (RR 1.41, 95% CI 0.64 to 3.12; 2 trials, 542 babies; very low-certainty evidence) and neonatal death (stillbirth or death of liveborn) (1 trial, 210 women and their babies; no events).  For the lateral posture comparisons, no data were reported for epidural use, neonatal encephalopathy, need for respiratory support, and neonatal jaundice requiring phototherapy. We were not able to estimate the outcome death (stillbirth or death of liveborn infant) due to no events (1 trial, 210 participants).  AUTHORS' CONCLUSIONS: We found low- and very low-certainty evidence which indicated that the use of hands and knees posture or lateral postures in women in labour with a fetal malposition may have little or no effect on health outcomes of the mother or her infant. If a woman finds the use of hands and knees or lateral postures in labour comfortable there is no reason why they should not choose to use them. Further research is needed on the use of hands and knees and lateral postures for women with a malposition in labour. Trials should include further assessment of semi-prone postures, same-side-as-fetus lateral postures with or without hip hyperflexion, or both, and consider interventions of longer duration or that involve the early second stage of labour.

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.

BACKGROUND: Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. METHODS: We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 µg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. RESULTS: A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups. CONCLUSIONS: Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).

Speciation in the deep: genomics and morphology reveal a new species of beaked whale Mesoplodon eueu.

The deep sea has been described as the last major ecological frontier, as much of its biodiversity is yet to be discovered and described. Beaked whales (ziphiids) are among the most visible inhabitants of the deep sea, due to their large size and worldwide distribution, and their taxonomic diversity and much about their natural history remain poorly understood. We combine genomic and morphometric analyses to reveal a new Southern Hemisphere ziphiid species, Ramari's beaked whale, Mesoplodon eueu, whose name is linked to the Indigenous peoples of the lands from which the species holotype and paratypes were recovered. Mitogenome and ddRAD-derived phylogenies demonstrate reciprocally monophyletic divergence between M. eueu and True's beaked whale (M. mirus) from the North Atlantic, with which it was previously subsumed. Morphometric analyses of skulls also distinguish the two species. A time-calibrated mitogenome phylogeny and analysis of two nuclear genomes indicate divergence began circa 2 million years ago (Ma), with geneflow ceasing 0.35-0.55 Ma. This is an example of how deep sea biodiversity can be unravelled through increasing international collaboration and genome sequencing of archival specimens. Our consultation and involvement with Indigenous peoples offers a model for broadening the cultural scope of the scientific naming process.

Effectiveness of uterine tamponade devices for refractory postpartum haemorrhage after vaginal birth: a systematic review.

OBJECTIVES: To evaluate uterine tamponade devices' effectiveness for atonic refractory postpartum haemorrhage (PPH) after vaginal birth and the effect of including them in institutional protocols. SEARCH STRATEGY: PubMed, EMBASE, CINAHL, LILACS, POPLINE, from inception to January 2021. STUDY SELECTION: Randomised and non-randomised comparative studies. OUTCOMES: Composite outcome including surgical interventions (artery ligations, compressive sutures or hysterectomy) or maternal death, and hysterectomy. RESULTS: All included studies were at high risk of bias. The certainty of the evidence was rated as very low to low. One randomised study measured the effect of the condom-catheter balloon compared with standard care and found unclear results for the composite outcome (relative risk [RR] 2.33, 95% CI 0.76-7.14) and hysterectomy (RR 4.14, 95% CI 0.48-35.93). Three comparative studies assessed the effect of including uterine balloon tamponade in institutional protocols. A stepped wedge cluster randomised controlled trial suggested an increase in the composite outcome (RR 4.08, 95% CI 1.07-15.58) and unclear results for hysterectomy (RR 4.38, 95% CI 0.47-41.09) with the use of the condom-catheter or surgical glove balloon. One non-randomised study showed unclear effects on the composite outcome (RR 0.33, 95% CI 0.11-1.03) and hysterectomy (RR 0.49, 95% CI 0.04-5.38) after the inclusion of the Bakri balloon. The second non-randomised study found unclear effects on the composite outcome (RR 0.95, 95% CI 0.32-2.81) and hysterectomy (RR 1.84, 95% CI 0.44-7.69) after the inclusion of Ebb or Bakri balloon. CONCLUSIONS: The effect of uterine tamponade devices for the management of atonic refractory PPH after vaginal delivery is unclear, as is the role of the type of device and the setting. TWEETABLE ABSTRACT: Unclear effects of uterine tamponade devices and their inclusion in institutional protocols for atonic refractory PPH after vaginal delivery.

Instruments for assisted vaginal birth.

BACKGROUND: Assisted vaginal births are carried out to expedite birth for the benefit of mothers and babies but are sometimes associated with significant morbidity for both. Various instruments are available, broadly divided into forceps and vacuum cups, and choice may be influenced by clinical circumstances, operator preference, experience and availability.  OBJECTIVES: To evaluate the different instruments in terms of success in achieving a vaginal birth, and the risk of morbidity for mother and baby. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (14 May 2021), and reference lists of retrieved studies. SELECTION CRITERIA: We selected randomised controlled trials of assisted vaginal birth using different instruments. The review did not include quasi-randomised trials, cluster-randomised trials or cross-over designs. The review included trials for which abstracts alone were available as long as there was sufficient information to assess eligibility.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used the GRADE approach to assess the certainty of evidence.  The main outcomes assessed included failed delivery with allocated instrument, any maternal trauma, third- and fourth-degree tears, postpartum haemorrhage, any neonatal trauma, low Apgar and low umbilical artery pH.  MAIN RESULTS: We included 31 studies involving a total of 5754 women.  Risk of bias criteria were largely assessed as 'unclear', due to a lack of detail in trial reports. Blinding would have been challenging for all trials due to their inability to conceal the type of instrument used from either the woman or the operator, which is reflected in the risk of bias assessment. Any type of forceps versus any type of vacuum cup (12 studies, 3129 women) Forceps may be less likely to fail in achieving vaginal birth: risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.88; 11 studies, 3080 women; low certainty. 'Any maternal trauma' may be slightly more likely with forceps: odds ratio (OR) 1.53, 95% CI 0.98 to 2.40; 5 studies, 1356 women; low certainty; and third- or fourth-degree tears may also be more likely with forceps: RR 1.83, 95% CI 1.32 to 2.55; 9 studies, 2493 women; low certainty. There is no evidence of a difference in the incidence of postpartum haemorrhage (PPH) between the two groups: RR 1.71, 95% CI 0.59 to 4.95; 2 studies, 523 women; low certainty, because the evidence is very imprecise due to a very wide CI.  More women in the forceps group reported requiring pain relief. There is probably no evidence of difference in rates of low Apgar: RR 0.83, 95% CI 0.46 to 1.51; 7 studies, 1644 women; moderate certainty; or low umbilical artery pH in the forceps group compared to any vacuum: RR 1.33, 95% CI 0.91 to 1.93; 2 studies, 789 women; low certainty; both of these outcomes are imprecise and have wide CIs that include both benefit and harm. There were also lower rates of fetal trauma with 'any forceps' (cephalhematoma, retinal haemorrhage and jaundice). The composite outcome of 'any neonatal trauma' was not reported. Low-cavity forceps versus any vacuum cup (2 studies, 218 women) We included two small studies with 218 participants in this comparison, but we judged most of the evidence as very low certainty, hence it was not feasible to make judgements on the difference in the rates of failed delivery, any maternal trauma or third- and fourth- degree tears. PPH and low umbilical artery pH were not reported. Soft vacuum cup versus any rigid cup (9 studies, 1148 women) Failed delivery may be more likely in the soft vacuum cup group: RR 1.62, 95% CI 1.21 to 2.17; 9 studies, 1148 women; low certainty. There may be no difference in the rates of 'any maternal trauma': OR 0.63, 95% CI 0.24 to 1.67; 2 studies, 348 women; low certainty, but the confidence interval is wide, indicating possible benefit or harm. There may be no difference in the rates of third- or fourth-degree tears: RR 0.93, 95% CI 0.35 to 2.44; 4 studies, 619 women; low certainty. There is probably no difference in the rates of PPH: RR 0.89, 95% CI 0.49 to 1.61; 5 studies, 737 women; moderate certainty between the soft and rigid cup groups.   There may be little or no difference in the incidence of low Apgar scores: RR 0.82, 95% CI 0.49 to 1.37; 9 studies, 1148; low certainty; or low umbilical artery pH: RR 0.80, 95% CI 0.47 to 1.36; 1 study, 100 women; low certainty. Handheld vacuum versus any vacuum cup (4 studies, 968 women) There may be no difference in the rates of failures with allocated instrument: RR 1.35, 95% CI 0.81 to 2.25; 4 studies, 962 women; low certainty, any maternal trauma: OR 1.16, 95% CI 0.71 to 1.88; 2 studies; 394 women; low certainty, PPH: RR 0.31, 95% CI 0.03 to 2.92; 1 study, 164 women; low certainty, low umbilical artery pH: RR 1.06, 95% CI 0.71 to 1.59; 1 study, 164 women; low certainty, or low Apgar scores: RR 1.25, 95% CI 0.34 to 4.61; 3 studies, 784 women; low certainty) between the two groups. There is probably no difference in the rates of third- or fourth-degree tears between the 'handheld vacuum' and 'any vacuum cup' groups: RR 1.15, 95% CI 0.62 to 2.12; 4 studies, 962 women; moderate certainty. AUTHORS' CONCLUSIONS: This review provides low-certainty evidence that forceps may be more likely to achieve vaginal birth and have lower rates of fetal trauma, but at a greater risk of perineal trauma and higher pain relief requirements compared with vacuum cups. There was low-certainty evidence that rigid vacuum cups may be more likely to achieve a vaginal birth than soft cups but with more fetal trauma, whilst handheld vacuum cups had similar success rates compared to other cups. There was no evidence of a difference in the rates of third- or fourth-degree tears or postpartum haemorrhages between types of cups, but wide confidence intervals around the estimates indicate further research is needed in this area.

Behavioral effects of different contraceptive methods and HIV acquisition: an ancillary study of the ECHO randomized trial.

BACKGROUND: The ECHO trial randomised 7829 women to depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant (1:1:1) and found no clear difference in HIV incidence between these three groups. We have previously hypothesized that oligo-amenorrhoea induced by DMPA-IM may have a protective effect on HIV acquisition. The aim of this ancillary study was to assess the effects of DMPA-IM, the IUD and the LNG implant on menstrual symptoms and sexual behavior and to correlate these with HIV acquisition. METHODS: At the Effective Care Research Unit (ECRU) in South Africa, of 615 women already randomised to DMPA-IM, the copper IUD and the LNG implant (1:1:1) 552 agreed to participate. Participants completed a 28-day symptom and behavior diary following their one-month ECHO trial visit and returning it at their 3-month follow-up visit. HIV acquisition data were retrieved from ECHO trial records. RESULTS: Of 552 women enrolled on the ancillary study, 390 (70.6%) completed their daily diary; 130, 133, and 127 received DMPA-IM, IUD, and LNG implant, respectively. Thirty-three (5.9%) of these women acquired HIV. Women on the progestin-only contraceptives were more likely to experience amenorrhoea, as expected, and were less likely to have intra-menstrual coitus than IUD users (p < 0.001 for DMPA-IM vs IUD and p = 0.002 for implant vs IUD). Overall coital frequency was highest and condom usage lowest among DMPA-IM users. Intra-menstrual coitus correlated positively, and duration of menstruation correlated negatively, with HIV acquisition, although these effects were not statistically significant (p = 0.09 and p = 0.079, respectively). CONCLUSIONS: Findings support the hypothesis that oligo-amenorrhoea and the associated reduced intra-menstrual coitus may mitigate the potential for an increased biological risk of HIV acquisition with DMPA-IM but more evidence is needed. Study registration number PACTR201706001651380.

There have been concerns that the depot-medroxyprogesterone acetate injection (DMPA-IM) may increase the risk of getting HIV infection. However, a large multicenter randomized study, the ECHO trial, recently compared HIV incidence among women randomized to DMPA-IM, the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant and found little difference in HIV risk between these methods. DMPA-IM often causes no or scanty menstruation; we hypothesized that this may have a protective effect on getting HIV, by reducing exposure to HIV during menstrual bleeding.This ancillary study was done among ECHO trial participants at one of the ECHO study sites in South Africa. The aim was to assess the effects of the three different contraceptives on menstrual symptoms and sexual behavior and to correlate these with the risk of getting HIV. The study required women to complete a 28-day daily symptom and behavior diary after their one-month ECHO trial follow-up visit.We found that fewer women had sex during their periods with DMPA-IM and the LNG implant than the copper IUD, probably because no or scanty menstruation is more common with both DMPA-IM and the implant. Although effects were not statistically significant, having sex during periods tended to have a higher risk of getting HIV and longer periods indicated a lower risk of getting HIV.We concluded that sexual behavior related to menstruation may influence HIV acquisition and may partially explain why the ECHO trial found little difference in HIV incidence between the three contraceptives assessed despite observational evidence of higher biological risk with DMPA related to immune suppression.

Duration of third stage labour and postpartum blood loss: a secondary analysis of the WHO CHAMPION trial data.

BACKGROUND: Obstetric haemorrhage continues to be a leading cause of maternal mortality, contributing to more than a quarter of the 2,443,000 maternal deaths reported between 2003 and 2009. During this period, about 70% of the haemorrhagic deaths occurred postpartum. In addition to other identifiable risk factors for greater postpartum blood loss, the duration of the third stage of labour (TSL) seems to be important, as literature shows that a longer TSL can be associated with more blood loss. To better describe the association between the duration of TSL and postpartum blood loss in women receiving active management of third stage of labour (AMTSL), this secondary analysis of the WHO CHAMPION trial data has been conducted. METHODS: This was a secondary analysis of the WHO CHAMPION trial conducted in twenty-three sites in ten countries. We studied the association between the TSL duration and blood loss in the sub cohort of women from the CHAMPION trial (all of whom received AMTSL), with TSL upto 60 min and no interventions for postpartum haemorrhage. We used a general linear model to fit blood loss as a function of TSL duration on the log scale, arm and center, using a normal distribution and the log link function. We showed this association separately for oxytocin and for Heat stable (HS) carbetocin. RESULTS: For the 10,040 women analysed, blood loss rose steeply with third stage duration in the first 10 min, but more slowly after 10 min. This trend was observed for both Oxytocin and HS carbetocin and the difference in the trends for both drugs was not statistically significant (p-value = 0.2070). CONCLUSIONS: There was a positive association between postpartum blood loss and TSL duration with either uterotonic. Blood loss rose steeply with TSL duration until 10 min, and more slowly after 10 min. Study registration The main trial was registered with Australian New Zealand Clinical Trials Registry ACTRN12614000870651 and Clinical Trial Registry of India CTRI/2016/05/006969.

The duration of the third stage of labour (TSL) seems to be an important risk factor for greater postpartum blood loss, as literature shows that a longer TSL can be associated with more blood loss. Active management of third stage of labour (AMTSL), included in the WHO guidelines for prevention of postpartum haemorrhage (PPH), is effective in reducing both the amount of postpartum blood loss and the duration of the third stage. To better describe the association between duration of TSL and postpartum blood loss in women receiving AMTSL, we conducted this secondary analysis of WHO CHAMPION trial data.To assess the association between the duration of third stage of labour and postpartum blood loss, a subcohort of the CHAMPION modified ITT population was selected by excluding women with missing blood loss or missing TSL duration or TSL duration more than 60 min and women with interventions. Thus, the subcohort consisted of 10,040 women.In women with vaginal birth and not receiving interventions for treating atonic PPH or other sources of bleeding, and with TSL duration up to 60 min, there was a positive association between duration of the TSL and postpartum blood loss. The blood loss rose steeply with duration in women with TSL of 10 min or less, while in women with longer TSL duration the slope was less steep.There was no evidence of a difference between oxytocin and HS carbetocin in the pattern of association of duration of the TSL and blood loss.

Formative research to design an implementation strategy for a postpartum hemorrhage initial response treatment bundle (E-MOTIVE): study protocol.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. When PPH occurs, early identification of bleeding and prompt management using evidence-based guidelines, can avert most PPH-related severe morbidities and deaths. However, adherence to the World Health Organization recommended practices remains a critical challenge. A potential solution to inefficient and inconsistent implementation of evidence-based practices is the application of a 'clinical care bundle' for PPH management. A clinical care bundle is a set of discrete, evidence-based interventions, administered concurrently, or in rapid succession, to every eligible person, along with teamwork, communication, and cooperation. Once triggered, all bundle components must be delivered. The E-MOTIVE project aims to improve the detection and first response management of PPH through the implementation of the "E-MOTIVE" bundle, which consists of (1) Early PPH detection using a calibrated drape, (2) uterine Massage, (3) Oxytocic drugs, (4) Tranexamic acid, (5) Intra Venous fluids, and (6) genital tract Examination and escalation when necessary. The objective of this paper is to describe the protocol for the formative phase of the E-MOTIVE project, which aims to design an implementation strategy to support the uptake of this bundle into practice. METHODS: We will use behavior change and implementation science frameworks [e.g. capability, opportunity, motivation and behavior (COM-B) and theoretical domains framework (TDF)] to guide data collection and analysis, in Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania. There are four methodological components: qualitative interviews; surveys; systematic reviews; and design workshops. We will triangulate findings across data sources, participant groups, and countries to explore factors influencing current PPH detection and management, and potentially influencing E-MOTIVE bundle implementation. We will use these findings to develop potential strategies to improve implementation, which will be discussed and agreed with key stakeholders from each country in intervention design workshops. DISCUSSION: This formative protocol outlines our strategy for the systematic development of the E-MOTIVE implementation strategy. This focus on implementation considers what it would take to support roll-out and implementation of the E-MOTIVE bundle. Our approach therefore aims to maximize internal validity in the trial alongside future scalability, and implementation of the E-MOTIVE bundle in routine practice, if proven to be effective. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04341662.

Excessive bleeding after birth is the leading cause of maternal death globally. The World Health Organization (WHO) has recommended several treatment options for bleeding after birth. However, these treatments are not used regularly, or consistently for all women. A key underlying issue is that it is challenging for health workers to identify when women are bleeding too much, because measuring the amount of blood loss is difficult.Maternal health experts have proposed a new clinical 'care bundle' for caring for women with excessive bleeding after birth. A care bundle is a way to group together multiple treatments (e.g. 3­5 treatments). These treatments are then given to the woman at the same time, or one after another in quick succession, and supported by strategies to improve teamwork, communication, and cooperation.This is a research protocol for the preliminary phase of our study ("E-MOTIVE"), which means that it is a description of what we plan to do and how we plan to do it. The aim of our study is to develop a strategy for how we will test whether the E-MOTIVE bundle works through collaborative activities with midwives and doctors in five countries (Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania) to develop a strategy for how we will test whether the E-MOTIVE bundle works. We plan to do this by conducting interviews and surveys with midwives and doctors, and reviewing other research conducted on PPH to understand what works in different settings. We will discuss our research findings in a workshop, with midwives and doctors in the study countries to co-create a strategy that will work for them, based on their needs and preferences.