Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

Binding Energy of Triplet Excitons in Nonfullerene Acceptors: The Effects of Fluorination and Chlorination.

One strategy to improve the photovoltaic properties of nonfullerene acceptors (NFAs), employed in state-of-art organic solar cells, is the rational fluorination or chlorination of these molecules. Although this modification improves important acceptor properties, little is known about the effects on the triplet states. Here, we combine the polarizable continuum model with an optimally tuned range-separated hybrid functional to investigate this issue. We find that fluorination or chlorination of NFAs decreases the degree of the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) overlap along these molecules. Consequently, the energy gap between T1 and S1 states, ΔEST = ES1 - ET1, also decreases. This effect reduces the binding energy of triplet excitons, which favors their dissociation into free charges. Furthermore, the reduction of ΔEST can contribute to mitigating the losses produced by the nonradiative deactivation of the T1 excitons. Interestingly, although Cl has a lower electronegativity than F, chlorination is more effective to reduce ΔEST. Since the chlorination of NFAs is easier than fluorination, Cl substitution can be a useful approach to enhance solar energy harvesting using triplet excitons.

Development of the FAST-M maternal sepsis bundle for use in low-resource settings: a modified Delphi process.

OBJECTIVE: To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. DESIGN: Modified Delphi process. SETTING: Participants from 34 countries. POPULATION: Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. METHODS: We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. MAIN OUTCOME MEASURE: Consensus on bundle items. RESULTS: Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher-level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym 'FAST-M'. CONCLUSION: A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. TWEETABLE ABSTRACT: A maternal sepsis bundle for low resource settings has been developed by international consensus.

Diagnostic accuracy of the partograph alert and action lines to predict adverse birth outcomes: a systematic review.

BACKGROUND: There are questions about the use of the 'one-centimetre per hour rule' as a valid benchmark for assessing the adequacy of labour progress. OBJECTIVES: To determine the accuracy of the alert (1-cm/hour) and action lines of the cervicograph in the partograph to predict adverse birth outcomes among women in first stage of labour. SEARCH STRATEGY: PubMed, EMBASE, CINAHL, POPLINE, Global Health Library, and reference lists of eligible studies. SELECTION CRITERIA: Observational studies and other study designs reporting data on the correlation between the alert line status of women in labour and the occurrence of adverse birth outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers at a time independently identified eligible studies and independently abstracted data including population characteristics and maternal and perinatal outcomes. MAIN RESULTS: Thirteen studies in which 20 471 women participated were included in the review. The percentage of women crossing the alert line varied from 8 to 76% for all maternal or perinatal outcomes. No study showed a robust diagnostic test accuracy profile for any of the selected outcomes. CONCLUSIONS: This systematic review does not support the use of the cervical dilatation over time (at a threshold of 1 cm/h during active first stage) to identify women at risk of adverse birth outcomes. TWEETABLE ABSTRACT: Alert line of partograph does not identify women at risk of adverse birth outcomes.

Postpartum hemorrhage: new insights for definition and diagnosis.

The current definition of is inadequate for early recognition of this important cause of maternal death that is responsible for >80,000 deaths worldwide in 2015. A stronger definition of postpartum hemorrhage should include both blood loss and clinical signs of cardiovascular changes after delivery, which would help providers to identify postpartum hemorrhage more promptly and accurately. Along with the amount of blood loss, clinical signs, and specifically the shock index (heart rate divided by systolic blood pressure) appear to aid in more accurate diagnosis of postpartum hemorrhage.

Cervical dilatation patterns of 'low-risk' women with spontaneous labour and normal perinatal outcomes: a systematic review.

BACKGROUND: The call for women-centred approaches to reduce labour interventions, particularly primary caesarean section, has renewed an interest in gaining a better understanding of natural labour progression. OBJECTIVE: To synthesise available data on the cervical dilatation patterns during spontaneous labour of 'low-risk' women with normal perinatal outcomes. SEARCH STRATEGY: PubMed, EMBASE, CINAHL, POPLINE, Global Health Library, and reference lists of eligible studies. SELECTION CRITERIA: Observational studies and other study designs. DATA COLLECTION AND ANALYSIS: Two authors extracted data on: maternal characteristics; labour interventions; the duration of labour centimetre by centimetre; and the duration of labour from dilatation at admission through to 10 cm. We pooled data across studies using weighted medians and employed the Bootstrap-t method to generate the corresponding confidence bounds. MAIN RESULTS: Seven observational studies describing labour patterns for 99 971 women met our inclusion criteria. The median time to advance by 1 cm in nulliparous women was longer than 1 hour until a dilatation of 5 cm was reached, with markedly rapid progress after 6 cm. Similar labour progression patterns were observed in parous women. The 95th percentiles for both parity groups suggest that it was not uncommon for some women to reach 10 cm, despite dilatation rates that were much slower than the 1-cm/hour threshold for most part of their first stage of labours. CONCLUSION: An expectation of a minimum cervical dilatation threshold of 1 cm/hour throughout the first stage of labour is unrealistic for most healthy nulliparous and parous women. Our findings call into question the universal application of clinical standards that are conceptually based on an expectation of linear labour progress in all women. FUNDING: UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, and the United States Agency for International Development (USAID). TWEETABLE ABSTRACT: Cervical dilatation threshold of 1 cm/hour throughout labour is unrealistic for most women, regardless of parity.

Cervical dilatation over time is a poor predictor of severe adverse birth outcomes: a diagnostic accuracy study.

OBJECTIVE: To assess the accuracy of the World Health Organization (WHO) partograph alert line and other candidate predictors in the identification of women at risk of developing severe adverse birth outcomes. DESIGN: A facility-based, multicentre, prospective cohort study. SETTING: Thirteen maternity hospitals located in Nigeria and Uganda. POPULATION: A total of 9995 women with spontaneous onset of labour presenting at cervical dilatation of ≤6 cm or undergoing induction of labour. METHODS: Research assistants collected data on sociodemographic, anthropometric, obstetric, and medical characteristics of study participants at hospital admission, multiple assessments during labour, and interventions during labour and childbirth. The alert line and action line, intrapartum monitoring parameters, and customised labour curves were assessed using sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and the J statistic. OUTCOMES: Severe adverse birth outcomes. RESULTS: The rate of severe adverse birth outcomes was 2.2% (223 women with severe adverse birth outcomes), the rate of augmentation of labour was 35.1% (3506 women), and the caesarean section rate was 13.2% (1323 women). Forty-nine percent of women in labour crossed the alert line (4163/8489). All reference labour curves had a diagnostic odds ratio ranging from 1.29 to 1.60. The J statistic was less than 10% for all reference curves. CONCLUSIONS: Our findings suggest that labour is an extremely variable phenomenon, and the assessment of cervical dilatation over time is a poor predictor of severe adverse birth outcomes. The validity of a partograph alert line based on the 'one-centimetre per hour' rule should be re-evaluated. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development (USAID), UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), and WHO (A65879). TWEETABLE ABSTRACT: The alert line in check: results from a WHO study.

Respectful care during childbirth in health facilities globally: a qualitative evidence synthesis.

BACKGROUND: What constitutes respectful maternity care (RMC) operationally in research and programme implementation is often variable. OBJECTIVES: To develop a conceptualisation of RMC. SEARCH STRATEGY: Key databases, including PubMed, CINAHL, EMBASE, Global Health Library, grey literature, and reference lists of relevant studies. SELECTION CRITERIA: Primary qualitative studies focusing on care occurring during labour, childbirth, and/or immediately postpartum in health facilities, without any restrictions on locations or publication date. DATA COLLECTION AND ANALYSIS: A combined inductive and deductive approach was used to synthesise the data; the GRADE CERQual approach was used to assess the level of confidence in review findings. MAIN RESULTS: Sixty-seven studies from 32 countries met our inclusion criteria. Twelve domains of RMC were synthesised: being free from harm and mistreatment; maintaining privacy and confidentiality; preserving women's dignity; prospective provision of information and seeking of informed consent; ensuring continuous access to family and community support; enhancing quality of physical environment and resources; providing equitable maternity care; engaging with effective communication; respecting women's choices that strengthen their capabilities to give birth; availability of competent and motivated human resources; provision of efficient and effective care; and continuity of care. Globally, women's perspectives of what constitutes RMC are quite consistent. CONCLUSIONS: This review presents an evidence-based typology of RMC in health facilities globally, and demonstrates that the concept is broader than a reduction of disrespectful care or mistreatment of women during childbirth. Innovative approaches should be developed and tested to integrate RMC as a routine component of quality maternal and newborn care programmes. TWEETABLE ABSTRACT: Understanding respectful maternity care - synthesis of evidence from 67 qualitative studies.

Impact of stillbirths on international comparisons of preterm birth rates: a secondary analysis of the WHO multi-country survey of Maternal and Newborn Health.

OBJECTIVE: To evaluate the extent to which stillbirths affect international comparisons of preterm birth rates in low- and middle-income countries. DESIGN: Secondary analysis of a multi-country cross-sectional study. SETTING: 29 countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 258 215 singleton deliveries in 286 hospitals. METHODS: We describe how inclusion or exclusion of stillbirth affect rates of preterm births in 29 countries. MAIN OUTCOME MEASURES: Preterm delivery. RESULTS: In all countries, preterm birth rates were substantially lower when based on live births only, than when based on total births. However, the increase in preterm birth rates with inclusion of stillbirths was substantially higher in low Human Development Index (HDI) countries [median 18.2%, interquartile range (17.2-34.6%)] compared with medium (4.3%, 3.0-6.7%), and high-HDI countries (4.8%, 4.4-5.5%). CONCLUSION: Inclusion of stillbirths leads to higher estimates of preterm birth rate in all countries, with a disproportionately large effect in low-HDI countries. Preterm birth rates based on live births alone do not accurately reflect international disparities in perinatal health; thus improved registration and reporting of stillbirths are necessary. TWEETABLE ABSTRACT: Inclusion of stillbirths increases preterm birth rates estimates, especially in low-HDI countries.

The role of infection and sepsis in the Brazilian Network for Surveillance of Severe Maternal Morbidity.

OBJECTIVE: To identify the burden of severe infection within the Brazilian Network for Surveillance of Severe Maternal Morbidity and factors associated with worse maternal outcomes. METHODS: This was a multicentre cross-sectional study involving 27 referral maternity hospitals in Brazil. WHO's standardised criteria for potentially life-threatening conditions and maternal near miss were used to identify cases through prospective surveillance and the main cause of morbidity was identified as infection or other causes (hypertension, haemorrhage or clinical/surgical). Complications due to infection were compared to complications due to the remaining causes of morbidity. Factors associated with a severe maternal outcome were assessed for the cases of infection. RESULTS: A total of 502 (5.3%) cases of maternal morbidity were associated with severe infection vs. 9053 cases (94.7%) with other causes. Considering increased severity of cases, infection was responsible for one-fourth of all maternal near miss (23.6%) and nearly half (46.4%) of maternal deaths, with a maternal near miss to maternal death ratio three times (2.8:1) that of cases without infection (7.8:1) and a high mortality index (26.3%). Within cases of infection, substandard care was present in over one half of the severe maternal outcome cases. Factors independently associated with worse maternal outcomes were HIV/AIDS, hysterectomy, prolonged hospitalisation, intensive care admission and delays in medical care. CONCLUSIONS: Infection is an alarming cause of maternal morbidity and mortality and timely diagnosis and adequate management are key to improving outcomes during pregnancy. Delays should be addressed, risk factors identified, and specific protocols of surveillance and care developed for use during pregnancy.

Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study.

BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. METHODS: A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. RESULTS: Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. CONCLUSIONS: Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

BACKGROUND: The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established. OBJECTIVES: To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies. SELECTION CRITERIA: All study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia. DATA COLLECTION AND ANALYSIS: Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens. MAIN RESULTS: Twenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations. CONCLUSION: The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens. TWEETABLE ABSTRACT: Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.

Network for Surveillance of Severe Maternal Morbidity: a powerful national collaboration generating data on maternal health outcomes and care.

OBJECTIVE: To identify cases of severe maternal morbidity (SMM) during pregnancy and childbirth, their characteristics, and to test the feasibility of scaling up World Health Organization criteria for identifying women at risk of a worse outcome. DESIGN: Multicentre cross-sectional study. SETTING: Twenty-seven referral maternity hospitals from all regions of Brazil. POPULATION: Cases of SMM identified among 82 388 delivering women over a 1-year period. METHODS: Prospective surveillance using the World Health Organization's criteria for potentially life-threatening conditions (PLTC) and maternal near-miss (MNM) identified and assessed cases with severe morbidity or death. MAIN OUTCOME MEASURES: Indicators of maternal morbidity and mortality; sociodemographic, clinical and obstetric characteristics; gestational and perinatal outcomes; main causes of morbidity and delays in care. RESULTS: Among 9555 cases of SMM, there were 140 deaths and 770 cases of MNM. The main determining cause of maternal complication was hypertensive disease. Criteria for MNM conditions were more frequent as the severity of the outcome increased, all combined in over 75% of maternal deaths. CONCLUSIONS: This study identified around 9.5% of MNM or death among all cases developing any severe maternal complication. Multicentre studies on surveillance of SMM, with organised collaboration and adequate study protocols can be successfully implemented, even in low-income and middle-income settings, generating important information on maternal health and care to be used to implement appropriate health policies and interventions. TWEETABLE ABSTRACT: Surveillance of severe maternal morbidity was proved to be possible in a hospital network in Brazil.

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems.

Postpartum haemorrhage management, risks, and maternal outcomes: findings from the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To explore the clinical practices, risks, and maternal outcomes associated with postpartum haemorrhage (PPH). DESIGN: Secondary analysis of cross-sectional data. SETTING: A total of 352 health facilities in 28 countries. SAMPLE: A total of 274 985 women giving birth between 1 May 2010 and 31 December 2011. METHODS: We used multivariate logistic regression to examine factors associated with PPH among all births, and the Pearson chi-square test to examine correlates of severe maternal outcomes (SMOs) among women with PPH. All analyses adjust for facility- and country-level clustering. MAIN OUTCOME MEASURES: PPH, SMOs, and clinical practices for the management of PPH. RESULTS: Of all the women included in the analysis, 95.3% received uterotonic prophylaxis and the reported rate of PPH was 1.2%. Factors significantly associated with PPH diagnosis included age, parity, gestational age, induction of labour, caesarean section, and geographic region. Among those with PPH, 92.7% received uterotonics for treatment, and 17.2% had an SMO. There were significant differences in the incidence of SMOs by age, parity, gestational age, anaemia, education, receipt of uterotonics for prophylaxis or treatment, referral from another facility, and Human Development Index (HDI) group. The rates of death were highest in countries with low or medium HDIs. CONCLUSIONS: Among women with PPH, disparities in the incidence of severe maternal outcomes persist, even among facilities that report capacity to provide all essential emergency obstetric interventions. This highlights the need for better information about the role of institutional capacity, including quality of care, in PPH-related morbidity and mortality.

Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To assess the incidence of hypertensive disorders of pregnancy and related severe complications, identify other associated factors and compare maternal and perinatal outcomes in women with and without these conditions. DESIGN: Secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) database. SETTING: Cross-sectional study implemented at 357 health facilities conducting 1000 or more deliveries annually in 29 countries from Africa, Asia, Latin America and the Middle East. POPULATION: All women suffering from any hypertensive disorder during pregnancy, the intrapartum or early postpartum period in the participating hospitals during the study period. METHODS: We calculated the proportion of the pre-specified outcomes in the study population and their distribution according to hypertensive disorders' severity. We estimated the association between them and maternal deaths, near-miss cases, and severe maternal complications using a multilevel logit model. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy. Potentially life-threatening conditions among maternal near-miss cases, maternal deaths and cases without severe maternal outcomes. RESULTS: Overall, 8542 (2.73%) women suffered from hypertensive disorders. Incidences of pre-eclampsia, eclampsia and chronic hypertension were 2.16%, 0.28% and 0.29%, respectively. Maternal near-miss cases were eight times more frequent in women with pre-eclampsia, and increased to up to 60 times more frequent in women with eclampsia, when compared with women without these conditions. CONCLUSIONS: The analysis of this large database provides estimates of the global distribution of the incidence of hypertensive disorders of pregnancy. The information on the most frequent complications related to pre-eclampsia and eclampsia could be of interest to inform policies for health systems organisation.

Indirect causes of severe adverse maternal outcomes: a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To assess the proportion of severe maternal outcomes resulting from indirect causes, and to determine pregnancy outcomes of women with indirect causes. DESIGN: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health. SETTING: A total of 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East. SAMPLE: A total of 314 623 pregnant women admitted to the participating facilities. METHODS: We identified the percentage of women with severe maternal outcomes arising from indirect causes. We evaluated the risk of severe maternal and perinatal outcomes in women with, versus without, underlying indirect causes, using adjusted odds ratios and 95% confidence intervals, by a multilevel, multivariate logistic regression model, accounting for clustering effects within countries and health facilities. MAIN OUTCOME MEASURES: Severe maternal outcomes and preterm birth, fetal mortality, early neonatal mortality, perinatal mortality, low birthweight, and neonatal intensive care unit admission. RESULTS: Amongst 314 623 included women, 2822 were reported to suffer from severe maternal outcomes, out of which 20.9% (589/2822; 95% CI 20.1-21.6%) were associated with indirect causes. The most common indirect cause was anaemia (50%). Women with underlying indirect causes showed significantly higher risk of obstetric complications (adjusted odds ratio, aOR, 7.0; 95% CI 6.6-7.4), severe maternal outcomes (aOR 27.9; 95% CI 24.7-31.6), and perinatal mortality (aOR 3.8; 95% CI 3.5-4.1). CONCLUSIONS: Indirect causes were responsible for about one-fifth of severe maternal outcomes. Women with underlying indirect causes had significantly increased risks of severe maternal and perinatal outcomes.

Maternal and institutional characteristics associated with the administration of prophylactic antibiotics for caesarean section: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To illustrate the variability in the use of antibiotic prophylaxis for caesarean section, and its effect on the prevention of postoperative infections. DESIGN: Secondary analysis of a cross-sectional study. SETTING: Twenty-nine countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: Three hundred and fifty-nine health facilities with the capacity to perform caesarean section. METHODS: Descriptive analysis and effect estimates using multilevel logistic regression. MAIN OUTCOME MEASURES: Coverage of antibiotic prophylaxis for caesarean section. RESULTS: A total of 89 121 caesarean sections were performed in 332 of the 359 facilities included in the survey; 87% under prophylactic antibiotic coverage. Thirty five facilities provided 0-49% coverage and 77 facilities provided 50-89% coverage. Institutional coverage of prophylactic antibiotics varied greatly within most countries, and was related to guideline use and the practice of clinical audits, but not to the size, location of the institution or development index of the country. Mothers with complications, such as HIV infection, anaemia, or pre-eclampsia/eclampsia, were more likely to receive antibiotic prophylaxis. At the same time, mothers undergoing caesarean birth prior to labour and those with indication for scheduled deliveries were also more likely to receive antibiotic prophylaxis, despite their lower risk of infection, compared with mothers undergoing emergency caesarean section. CONCLUSIONS: Coverage of antibiotic prophylaxis for caesarean birth may be related to the perception of the importance of guidelines and clinical audits in the facility. There may also be a tendency to use antibiotics when caesarean section has been scheduled and antibiotic prophylaxis is already included in the routine clinical protocol. This study may act as a signal to re-evaluate institutional practices as a way to identify areas where improvement is possible.