A systematic review of behaviour change interventions to improve maternal health outcomes in sub-Saharan Africa.

The rate of decline in the global burden of avoidable maternal deaths has stagnated and remains an issue of concern in many sub-Saharan Africa countries. As per the most recent evidence, an average maternal mortality ratio (MMR) of 223 deaths per 100,000 live births has been estimated globally, with sub-Saharan Africa's average MMR at 536 per 100,000 live births-more than twice the global average. Despite the high MMR, there is variation in MMR between and within sub-Saharan Africa countries. Differences in the behaviour of those accessing and/or delivering maternal healthcare may explain variations in outcomes and provide a basis for quality improvement in health systems. There is a gap in describing the landscape of interventions aimed at modifying the behaviours of those accessing and delivering maternal healthcare for improving maternal health outcomes in sub-Saharan Africa. Our objective was to extract and synthesise the target behaviours, component behaviour change strategies and outcomes of behaviour change interventions for improving maternal health outcomes in sub-Saharan Africa. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Our protocol was published a priori on PROSPERO (registration number CRD42022315130). We searched ten electronic databases (PsycINFO, Cochrane Database of Systematic Reviews, International Bibliography of Social Sciences, EMBASE, MEDLINE, Scopus, CINAHL PLUS, African Index Medicus, African Journals Online, and Web of Science) and included randomised trials and quasi-experimental studies. We extracted target behaviours and specified the behavioural interventions using the Action, Actor, Context, Time, and Target (AACTT) framework. We categorised the behaviour change strategies using the intervention functions described in the Behaviour Change Wheel (BCW). We reviewed 52 articles (26 randomized trials and 26 quasi-experimental studies). They had a mixed risk of bias. Out of these, 41 studies (78.8%) targeted behaviour change of those accessing maternal healthcare services, while seven studies (13.5%) focused on those delivering maternal healthcare. Four studies (7.7%) targeted mixed stakeholder groups. The studies employed a range of behaviour change strategies, including education 37 (33.3%), persuasion 20 (18%), training 19 (17.1%), enablement 16 (14.4%), environmental restructuring 8 (7.2%), modelling 6 (5.4%) and incentivisation 5 (4.5%). No studies used restriction or coercion strategies. Education was the most common strategy for changing the behaviour of those accessing maternal healthcare, while training was the most common strategy in studies targeting the behaviour of those delivering maternal healthcare. Of the 52 studies, 40 reported effective interventions, 7 were ineffective, and 5 were equivocal. A meta-analysis was not feasible due to methodological and clinical heterogeneity across the studies. In conclusion, there is evidence of effective behaviour change interventions targeted at those accessing and/or delivering maternal healthcare in sub-Saharan Africa. However, more focus should be placed on behaviour change by those delivering maternal healthcare within the health facilities to fast-track the reduction of the huge burden of avoidable maternal deaths in sub-Saharan Africa.

The use of network meta-analysis in updating WHO living maternal and perinatal health recommendations.

Drawing on two recent examples of WHO living guidelines in maternal and perinatal health, this paper elucidates a pragmatic, stepwise approach to using network meta-analysis (NMA) in guideline development in the presence of multiple treatment options. NMA has important advantages. These include the ability to compare multiple interventions in a single coherent analysis, provide direct estimates of the relative effects of all available interventions, infer indirect effect estimates for interventions not directly compared and generate rankings of the available treatment options. It can be difficult to harness these advantages in the face of a lack of current guidance on using NMA evidence in guideline development, with several challenges emerging. Challenges include the choice of conceptual approach, the volume and complexity of the evidence, the contribution of treatment rankings, and the fact that the preferable treatment is not always obvious. This paper describes a layered approach to resolving these challenges, which supports systematic guideline decision-making and development of trustworthy clinical guidelines when multiple treatment options are available.

Perceptions and experiences of the prevention, detection, and management of postpartum haemorrhage: a qualitative evidence synthesis.

BACKGROUND: Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent complications of PPH with timely and appropriate detection and management. However, implementing the best methods of PPH prevention, detection and management can be challenging, particularly in low- and middle-income countries. OBJECTIVES: Our overall objective was to explore the perceptions and experiences of women, community members, lay health workers, and skilled healthcare providers who have experience with PPH or with preventing, detecting, and managing PPH, in community or health facility settings. SEARCH METHODS: We searched MEDLINE, CINAHL, Scopus, and grey literature on 13 November 2022 with no language restrictions. We then performed reference checking and forward citation searching of the included studies. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored perceptions and experiences of PPH prevention, detection, and management among women, community members, traditional birth attendants, healthcare providers, and managers. DATA COLLECTION AND ANALYSIS: We used three-stage maximum variation sampling to ensure diversity in terms of relevance of the study to the review objectives, richness of data, and coverage of critical contextual elements: setting (region, country income level), perspective (type of participant), and topic (prevention, detection, management). We extracted data using a data extraction form designed for this review. We used thematic synthesis to analyse and synthesise the evidence, and we used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. To identify factors that may influence intervention implementation, we mapped each review finding to the Theoretical Domains Framework (TDF) and the Capability, Motivation, and Opportunity model of Behaviour change (COM-B). We used the Behaviour Change Wheel to explore implications for practice. MAIN RESULTS: We included 67 studies and sampled 43 studies for our analysis. Most were from low- or middle-income countries (33 studies), and most included the perspectives of women and health workers. We downgraded our confidence in several findings from high confidence to moderate, low, or very-low confidence, mainly due to concerns about how the studies were conducted (methodological limitations) or concerns about missing important perspectives from some types of participants or in some settings (relevance). In many communities, bleeding during and after childbirth is considered "normal" and necessary to expel "impurities" and restore and cleanse the woman's body after pregnancy and birth (moderate confidence). In some communities, people have misconceptions about causes of PPH or believe that PPH is caused by supernatural powers or evil spirits that punish women for ignoring or disobeying social rules or for past mistakes (high confidence). For women who give birth at home or in the community, female family members or traditional birth attendants are the first to recognise excess bleeding after birth (high confidence). Family members typically take the decision of whether and when to seek care if PPH is suspected, and these family members are often influenced by trusted traditional birth attendants or community midwives (high confidence). If PPH is identified for women birthing at home or in the community, decision-making about the subsequent referral and care pathway can be multifaceted and complex (high confidence). First responders to PPH are not always skilled or trained healthcare providers (high confidence). In health facilities, midwives may consider it easy to implement visual estimation of blood loss with a kidney dish or under-pad, but difficult to accurately interpret the amount of blood loss (very low confidence). Quantifying (rather than estimating) blood loss may be a complex and contentious change of practice for health workers (low confidence). Women who gave birth in health facilities and experienced PPH described it as painful, embarrassing, and traumatic. Partners or other family members also found the experience stressful. While some women were dissatisfied with their level of involvement in decision-making for PPH management, others felt health workers were best placed to make decisions (moderate confidence). Inconsistent availability of resources (drugs, medical supplies, blood) causes delays in the timely management of PPH (high confidence). There is limited availability of misoprostol in the community owing to stockouts, poor supply systems, and the difficulty of navigating misoprostol procurement for community health workers (moderate confidence). Health workers described working on the maternity ward as stressful and intense due to short staffing, long shifts, and the unpredictability of emergencies. Exhausted and overwhelmed staff may be unable to appropriately monitor all women, particularly when multiple women are giving birth simultaneously or on the floor of the health facility; this could lead to delays in detecting PPH (moderate confidence). Inadequate staffing, high turnover of skilled health workers, and appointment of lower-level cadres of health workers are key challenges to the provision of quality PPH care (high confidence). Through team-based simulation training, health workers of different cadres (doctors, midwives, lay health workers) can develop a shared mental model to help them work quickly, efficiently, and amicably as a team when managing women with PPH (moderate confidence). AUTHORS' CONCLUSIONS: Our findings highlight how improving PPH prevention, detection, and management is underpinned by a complex system of interacting roles and behaviours (community, women, health workers of different types and with different experiences). Multiple individual, sociocultural, and environmental factors influence the decisions and behaviours of women, families, communities, health workers, and managers. It is crucial to consider the broader health and social systems when designing and implementing PPH interventions to change or influence these behaviours. We have developed a set of prompts that may help programme managers, policymakers, researchers, and other key stakeholders to identify and address factors that affect implementation and scale-up of interventions to improve PPH prevention, detection, and management.

The compatibility of oxytocin and tranexamic acid injection products when mixed for co-administration by infusion for the treatment of postpartum haemorrhage: An in vitro investigation.

OBJECTIVE: To investigate the compatibility of oxytocin and tranexamic acid injection products when mixed for the purpose of co-administration by intravenous infusion. DESIGN: Compatibility testing. SETTING: Hospitals taking part in a multicentre postpartum haemorrhage treatment (E-MOTIVE) trial in Kenya, Nigeria, Tanzania and South Africa. SAMPLE: Oxytocin and tranexamic acid products. METHODS: The compatibility of two sentinel products of oxytocin injection and tranexamic acid injection in 200-mL infusion bags of both 0.9% w/v saline and Ringer's lactate solution was assessed. We analysed all tranexamic acid-oxytocin combinations, and each evaluation was conducted for up to 3 h. Subsequently, the compatibility of multiple tranexamic acid products with reference oxytocin products when mixed in 0.9% w/v saline over a period of 1 h was investigated. MAIN OUTCOME MEASURES: Concentration of oxytocin over time after mixing with tranexamic acid products. RESULTS: We found significant interaction between certain oxytocin and tranexamic acid products after mixing them in vitro and observing for 1 h. The interaction substantially impacted oxytocin content leading to reduction in concentration (14.8%-29.0%) immediately on mixing (t = 0 min). In some combinations, the concentration continued to decline throughout the stability assessment period. Oxytocin loss was observed in 7 out of 22 (32%) of combinations tested. CONCLUSIONS: In a clinical setting, mixing certain oxytocin and tranexamic acid products before administration may result in an underdosing of oxytocin, compromising care in an emergency life-threatening situation. The mixing of oxytocin and tranexamic acid injection products for co-administration with intravenous infusion fluids should be avoided until the exact nature of the observed interaction and its implications are understood.

A comprehensive analysis of chromosomal polymorphic variants on reproductive outcomes after intracytoplasmic sperm injection treatment.

Recent studies suggest that chromosomal polymorphic variations are associated with infertility. A systematic review of chromosomal polymorphisms in assisted reproduction found an association with higher rates of miscarriage. Aim of this study is to analyse the influence of specific types or number of chromosomal polymorphic variations on reproductive outcomes of couples undergoing ICSI treatment. We analysed data from 929 fresh and frozen embryo transfer cycles of 692 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman (GTL) banding prior to the ICSI procedure at the Fertility Centre of Lanka Hospitals Corporation Plc, Sri Lanka, from January 2016 to December 2018. The outcomes of interest were the pregnancy, miscarriage and live birth rate per cycle. There was no evidence of a difference in the reproductive outcomes between carriers or non-carriers of any type or number of chromosomal polymorphic variation. Our data, in contrast to previous studies, does not support a deleterious effect for the type or number of chromosomal polymorphic variations on reproductive outcomes. However, additional prospective, adequately powered studies, conducted in multiethnic populations, are required to further investigate whether the detection of chromosomal polymorphic variants prior to assisted conception may in fact be a futile diagnostic tool.

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.

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.

Tocolytics for delaying preterm birth: a network meta-analysis (0924).

BACKGROUND: Preterm birth is the leading cause of death in newborns and children. Tocolytic drugs aim to delay preterm birth by suppressing uterine contractions to allow time for administration of corticosteroids for fetal lung maturation, magnesium sulphate for neuroprotection, and transport to a facility with appropriate neonatal care facilities. However, there is still uncertainty about their effectiveness and safety. OBJECTIVES: To estimate relative effectiveness and safety profiles for different classes of tocolytic drugs for delaying preterm birth, and provide rankings of the available drugs. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (21 April 2021) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials assessing effectiveness or adverse effects of tocolytic drugs for delaying preterm birth. We excluded quasi- and non-randomised trials. We evaluated all studies against predefined criteria to judge their trustworthiness. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials for inclusion and risk of bias, and extracted data. We performed pairwise and network meta-analyses, to determine the relative effects and rankings of all available tocolytics. We used GRADE to rate the certainty of the network meta-analysis effect estimates for each tocolytic versus placebo or no treatment. MAIN RESULTS: This network meta-analysis includes 122 trials (13,697 women) involving six tocolytic classes, combinations of tocolytics, and placebo or no treatment. Most trials included women with threatened preterm birth, singleton pregnancy, from 24 to 34 weeks of gestation. We judged 25 (20%) studies to be at low risk of bias. Overall, certainty in the evidence varied. Relative effects from network meta-analysis suggested that all tocolytics are probably effective in delaying preterm birth compared with placebo or no tocolytic treatment. Betamimetics are possibly effective in delaying preterm birth by 48 hours (risk ratio (RR) 1.12, 95% confidence interval (CI) 1.05 to 1.20; low-certainty evidence), and 7 days (RR 1.14, 95% CI 1.03 to 1.25; low-certainty evidence). COX inhibitors are possibly effective in delaying preterm birth by 48 hours (RR 1.11, 95% CI 1.01 to 1.23; low-certainty evidence). Calcium channel blockers are possibly effective in delaying preterm birth by 48 hours (RR 1.16, 95% CI 1.07 to 1.24; low-certainty evidence), probably effective in delaying preterm birth by 7 days (RR 1.15, 95% CI 1.04 to 1.27; moderate-certainty evidence), and prolong pregnancy by 5 days (0.1 more to 9.2 more; high-certainty evidence). Magnesium sulphate is probably effective in delaying preterm birth by 48 hours (RR 1.12, 95% CI 1.02 to 1.23; moderate-certainty evidence). Oxytocin receptor antagonists are probably effective in delaying preterm birth by 48 hours (RR 1.13, 95% CI 1.05 to 1.22; moderate-certainty evidence), are effective in delaying preterm birth by 7 days (RR 1.18, 95% CI 1.07 to 1.30; high-certainty evidence), and possibly prolong pregnancy by 10 days (95% CI 2.3 more to 16.7 more). Nitric oxide donors are probably effective in delaying preterm birth by 48 hours (RR 1.17, 95% CI 1.05 to 1.31; moderate-certainty evidence), and 7 days (RR 1.18, 95% CI 1.02 to 1.37; moderate-certainty evidence). Combinations of tocolytics are probably effective in delaying preterm birth by 48 hours (RR 1.17, 95% CI 1.07 to 1.27; moderate-certainty evidence), and 7 days (RR 1.19, 95% CI 1.05 to 1.34; moderate-certainty evidence). Nitric oxide donors ranked highest for delaying preterm birth by 48 hours and 7 days, and delay in birth (continuous outcome), followed by calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics. Betamimetics (RR 14.4, 95% CI 6.11 to 34.1; moderate-certainty evidence), calcium channel blockers (RR 2.96, 95% CI 1.23 to 7.11; moderate-certainty evidence), magnesium sulphate (RR 3.90, 95% CI 1.09 to 13.93; moderate-certainty evidence) and combinations of tocolytics (RR 6.87, 95% CI 2.08 to 22.7; low-certainty evidence) are probably more likely to result in cessation of treatment. Calcium channel blockers possibly reduce the risk of neurodevelopmental morbidity (RR 0.51, 95% CI 0.30 to 0.85; low-certainty evidence), and respiratory morbidity (RR 0.68, 95% CI 0.53 to 0.88; low-certainty evidence), and result in fewer neonates with birthweight less than 2000 g (RR 0.49, 95% CI 0.28 to 0.87; low-certainty evidence). Nitric oxide donors possibly result in neonates with higher birthweight (mean difference (MD) 425.53 g more, 95% CI 224.32 more to 626.74 more; low-certainty evidence), fewer neonates with birthweight less than 2500 g (RR 0.40, 95% CI 0.24 to 0.69; low-certainty evidence), and more advanced gestational age (MD 1.35 weeks more, 95% CI 0.37 more to 2.32 more; low-certainty evidence). Combinations of tocolytics possibly result in fewer neonates with birthweight less than 2500 g (RR 0.74, 95% CI 0.59 to 0.93; low-certainty evidence). In terms of maternal adverse effects, betamimetics probably cause dyspnoea (RR 12.09, 95% CI 4.66 to 31.39; moderate-certainty evidence), palpitations (RR 7.39, 95% CI 3.83 to 14.24; moderate-certainty evidence), vomiting (RR 1.91, 95% CI 1.25 to 2.91; moderate-certainty evidence), possibly headache (RR 1.91, 95% CI 1.07 to 3.42; low-certainty evidence) and tachycardia (RR 3.01, 95% CI 1.17 to 7.71; low-certainty evidence) compared with placebo or no treatment. COX inhibitors possibly cause vomiting (RR 2.54, 95% CI 1.18 to 5.48; low-certainty evidence). Calcium channel blockers (RR 2.59, 95% CI 1.39 to 4.83; low-certainty evidence), and nitric oxide donors probably cause headache (RR 4.20, 95% CI 2.13 to 8.25; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with placebo or no tocolytic treatment, all tocolytic drug classes that we assessed (betamimetics, calcium channel blockers, magnesium sulphate, oxytocin receptor antagonists, nitric oxide donors) and their combinations were probably or possibly effective in delaying preterm birth for 48 hours, and 7 days. Tocolytic drugs were associated with a range of adverse effects (from minor to potentially severe) compared with placebo or no tocolytic treatment, although betamimetics and combination tocolytics were more likely to result in cessation of treatment. The effects of tocolytic use on neonatal outcomes such as neonatal and perinatal mortality, and on safety outcomes such as maternal and neonatal infection were uncertain.

Miscarriage syndrome: Linking early pregnancy loss to obstetric and age-related disorders.

Upon embryo implantation, the uterine mucosa - the endometrium - transforms into a robust decidual matrix that accommodates the fetal placenta throughout pregnancy. This transition is driven by the differentiation of endometrial fibroblasts into specialised decidual cells. A synchronised influx of circulating natural killer (NK) cells and bone marrow-derived mesenchymal stem/progenitor cells (BM-MSC) is pivotal for decidual homeostasis and expansion in early pregnancy. We hypothesise that pathological signals interfering with the recruitment or activity of extrauterine cells at the maternal-fetal interface link miscarriage to subsequent adverse pregnancy outcomes, including further pregnancy losses and preterm labour. NK cells and BM-MSC are key homeostatic regulators in multiple tissues, pointing towards a shared aetiology between recurrent miscarriage and age-related disorders, including cardiometabolic disease. We propose the term 'miscarriage syndrome' to capture the health risks associated with miscarriage and discuss how this paradigm can inform clinical practice and accelerate the development of preventative strategies.

Outcomes of ovarian transposition in cervical cancer; an updated meta-analysis.

BACKGROUND: Cervical cancer is the most common indication for ovarian transposition in reproductive-age women. Ovarian transposition should be performed in premenopausal women undergoing pelvic irradiation to preserve ovarian function, and prevent early menopause. As women become more knowledgeable about their fertility options, it is still unclear who will benefit from the intervention. We updated our previous meta-analysis of ovarian function preservation, symptomatic ovarian cysts, and metastases to the transposed ovaries following ovarian transposition in cervical cancer patients to further guide current clinical practice. METHODS: A systematic search of Medline, Embase, Web of Science, and The Cochrane Library databases, dating from January 1980 to July 2021, was conducted. We computed the summary proportions of women who had ovarian function preservation, non-ovarian cyst formation and metastases to the transposed ovaries following ovarian transposition by random-effects meta-analysis and we explored study heterogeneity by type of radiotherapy. RESULTS: There were 29 publications reporting on 1160 women with cervical cancer who underwent ovarian transposition. In the group that underwent surgery alone, 91% of the women had preserved ovarian function (95% CI 83-100), 89% (95% CI 80-99) of women who did not develop ovarian cysts, and 99% (95% CI 1-5) of women who did not suffer metastases to the transposed ovaries. In the surgery ± brachytherapy (BR) group, the proportion of women with the preserved ovarian function was 93% (95% CI 76-113), 84% (95% CI 69-103) of women who did not develop ovarian cysts, and 99% (95% CI 82-120) of women who did not suffer metastases to the transposed ovaries. In the external beam pelvic radiotherapy (EBRT) ± BR ± surgery group, the proportion of women with the preserved ovarian function was 61% (95% CI 55-69), and 95% (95% CI 85-107) of women who developed ovarian cysts. There were no metastases to the transposed ovaries in that group. CONCLUSIONS: In women with cervical cancer, ovarian transposition offers a significant preservation of the ovarian function. Despite an expected incidence of ovarian cyst formation, it carries almost no risk for metastases to the transposed ovaries.

Differences in obstetric practices and outcomes of postpartum hemorrhage across Nigerian health facilities.

OBJECTIVE: To explore differences in obstetric practices and clinical outcomes of postpartum hemorrhage (PPH) in Nigerian facilities. METHODS: A descriptive cross-sectional study of public health facilities providing maternal healthcare services in Nigeria. Surveys were conducted across 38 purposively sampled facilities (January 2020-March 2021) to collect information on obstetric practices related to the management of the third stage of labor, treatment of postpartum hemorrhage, and clinical outcomes related to postpartum hemorrhage in the preceding 12 months. RESULTS: The median number of annual births per facility was 2230 (IQR, 1952-3283). The cesarean section rate was 21.6% (range 2.1%-52.6%). There was large variability in PPH rate (median 3%, range 0.4%-16.8%) and blood transfusions for PPH (median 2.8%, range 0.4%-48.6%) after vaginal birth. There was less variability for laparotomies (median 0.25%, range 0%-2.8%) and maternal deaths (median 0.11%, range 0%-0.64%) due to PPH after vaginal birth. The number of maternal deaths from all causes varied (median 0.27%, range 0%-3.5%). The rates of PPH and adverse maternal outcomes did not vary substantially between state or federal facilities, region, type of facility, and the number of clinical staff. CONCLUSION: Across the Nigerian facilities surveyed there was large variation in PPH rates and adverse maternal outcomes due to PPH. This variability remains largely unexplained and requires further insights and detailed data to gain a deeper understanding of the root causes and challenges to implement customized solutions to improve maternal outcomes.

Quality of oxytocin and tranexamic acid for the prevention and treatment of postpartum hemorrhage in Kenya, Nigeria, South Africa, and Tanzania.

OBJECTIVE: To check the quality of oxytocin and tranexamic acid-two recommended products for prevention and treatment of postpartum hemorrhage (PPH)-used in facilities taking part in an implementation research project to improve PPH diagnosis and management. METHODS: Between September 2020 and August 2021, oxytocin and tranexamic acid products used in the study facilities in Kenya, Nigeria, South Africa, and Tanzania were collected and transported in cold storage for analysis. Samples were analyzed according to the International (oxytocin) and British Pharmacopeia (tranexamic acid) standards. RESULTS: Of the 17 unique oxytocin products, 33 individual measurements were made. Only six unique products had adequate content and no related substances exceeding the recommended limits. Of 14 tranexamic acid samples, 10 showed adequate content. One product in Kenya and two products in Nigeria from different manufacturers had a high content of related substances, which classified them as substandard. CONCLUSION: While we were unable to investigate the origin regarding poor manufacturing or poor storage or both, the high number of substandard oxytocin samples is of great concern. Most of the tranexamic acid samples had adequate content but the presence of impurities in multiple products is worrying and requires further study.

Individual, health facility and wider health system factors contributing to maternal deaths in Africa: A scoping review.

The number of women dying during pregnancy and after childbirth remains unacceptably high, with African countries showing the slowest decline. The leading causes of maternal deaths in Africa are preventable direct obstetric causes such as haemorrhage, infection, hypertension, unsafe abortion, and obstructed labour. There is an information gap on factors contributing to maternal deaths in Africa. Our objective was to identify these contributing factors and assess the frequency of their reporting in published literature. We followed the Arksey and O'Malley methodological framework for scoping reviews. We searched six electronic bibliographic databases: MEDLINE, SCOPUS, African Index Medicus, African Journals Online (AJOL), French humanities and social sciences databases, and Web of Science. We included articles published between 1987 and 2021 without language restriction. Our conceptual framework was informed by a combination of the socio-ecological model, the three delays conceptual framework for analysing the determinants of maternal mortality and the signal functions of emergency obstetric care. We included 104 articles from 27 African countries. The most frequently reported contributory factors by level were: (1) Individual-level: Delay in deciding to seek help and in recognition of danger signs (37.5% of articles), (2) Health facility-level: Suboptimal service delivery relating to triage, monitoring, and referral (80.8% of articles) and (3) Wider health system-level: Transport to and between health facilities (84.6% of articles). Our findings indicate that health facility-level factors were the most frequently reported contributing factors to maternal deaths in Africa. There is a lack of data from some African countries, especially those countries with armed conflict currently or in the recent past. Information gaps exist in the following areas: Statistical significance of each contributing factor and whether contributing factors alone adequately explain the variations in maternal mortality ratios (MMR) seen between countries and at sub-national levels.

Methods for managing miscarriage: a network meta-analysis.

BACKGROUND: Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option. OBJECTIVES: To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials. DATA COLLECTION AND ANALYSIS: At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods. MAIN RESULTS: Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods.  AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.

Progestogens for preventing miscarriage: a network meta-analysis.

BACKGROUND: Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage). OBJECTIVES: To estimate the relative effectiveness and safety profiles for the different progestogen treatments for threatened and recurrent miscarriage, and provide rankings of the available treatments according to their effectiveness, safety, and side-effect profile. SEARCH METHODS: We searched the following databases up to 15 December 2020: Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials assessing the effectiveness or safety of progestogen treatment for the prevention of miscarriage. Cluster-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded quasi- and non-randomised trials. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We performed pairwise meta-analyses and indirect comparisons, where possible, to determine the relative effects of all available treatments, but due to the limited number of included studies only direct or indirect comparisons were possible. We estimated the relative effects for the primary outcome of live birth and the secondary outcomes including miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy, congenital abnormalities, and adverse drug events. Relative effects for all outcomes are reported separately by the type of miscarriage (threatened and recurrent miscarriage). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Our meta-analysis included seven randomised trials involving 5,682 women, and all provided data for meta-analysis. All trials were conducted in hospital settings. Across seven trials (14 treatment arms), the following treatments were used: three arms (21%) used vaginal micronized progesterone; three arms (21%) used dydrogesterone; one arm (7%) used oral micronized progesterone; one arm (7%) used 17-α-hydroxyprogesterone, and six arms (43%) used placebo. Women with threatened miscarriage Based on the relative effects from the pairwise meta-analysis, vaginal micronized progesterone (two trials, 4090 women, risk ratio (RR) 1.03, 95% confidence interval (CI) 1.00 to 1.07, high-certainty evidence), and dydrogesterone (one trial, 406 women, RR 0.98, 95% CI 0.89 to 1.07, moderate-certainty evidence) probably make little or no difference to the live birth rate when compared with placebo for women with threatened miscarriage. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with threatened miscarriage. The pre-specified subgroup analysis by number of previous miscarriages is only possible for vaginal micronized progesterone in women with threatened miscarriage. In women with no previous miscarriages and early pregnancy bleeding, there is probably little or no improvement in the live birth rate (RR 0.99, 95% CI 0.95 to 1.04, high-certainty evidence) when treated with vaginal micronized progesterone compared to placebo. However, for women with one or more previous miscarriages and early pregnancy bleeding, vaginal micronized progesterone increases the live birth rate compared to placebo (RR 1.08, 95% CI 1.02 to 1.15, high-certainty evidence). Women with recurrent miscarriage Based on the results from one trial (826 women) vaginal micronized progesterone (RR 1.04, 95% CI 0.95 to 1.15, high-certainty evidence) probably makes little or no difference to the live birth rate when compared with placebo for women with recurrent miscarriage. The evidence for dydrogesterone compared with placebo for women with recurrent miscarriage is of very low-certainty evidence, therefore the effects remain unclear. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with recurrent miscarriage. Additional outcomes All progestogen treatments have a wide range of effects on the other pre-specified outcomes (miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy) in comparison to placebo for both threatened and recurrent miscarriage. Moderate- and low-certainty evidence with a wide range of effects suggests that there is probably no difference in congenital abnormalities and adverse drug events with vaginal micronized progesterone for threatened (congenital abnormalities RR 1.00, 95% CI 0.68 to 1.46, moderate-certainty evidence; adverse drug events RR 1.07 95% CI 0.81 to 1.39, moderate-certainty evidence) or recurrent miscarriage (congenital abnormalities 0.75, 95% CI 0.31 to 1.85, low-certainty evidence; adverse drug events RR 1.46, 95% CI 0.93 to 2.29, moderate-certainty evidence) compared with placebo. There are limited data and very low-certainty evidence on congenital abnormalities and adverse drug events for the other progestogens. AUTHORS' CONCLUSIONS: The overall available evidence suggests that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage. However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events. There is still uncertainty over the effectiveness and safety of alternative progestogen treatments for threatened and recurrent miscarriage.

Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss.

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5-18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.

Sporadic miscarriage: evidence to provide effective care.

The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units.