Exploring global barriers to optimal ovarian cancer care: thematic analysis.

OBJECTIVE: To explore the barriers to ovarian cancer care, as reported in the open ended responses of a global expert opinion survey, highlighting areas for improvement in global ovarian cancer care. Potential solutions to overcome these barriers are proposed. METHODS: Data from the expert opinion survey, designed to assess the organization of ovarian cancer care worldwide, were analyzed. The survey was distributed across a global network of physicians. We examined free text, open ended responses concerning the barriers to ovarian cancer care. A qualitative thematic analysis was conducted to identify, analyze, and report meaningful patterns within the data. RESULTS: A total of 1059 physicians from 115 countries completed the survey, with 438 physicians from 93 countries commenting on the barriers to ovarian cancer care. Thematic analysis gave five major themes, regardless of income category or location: societal factors, inadequate resources in hospital, economic barriers, organization of the specialty, and need for early detection. Suggested solutions include accessible resource stratified guidelines, multidisciplinary teamwork, public education, and development of gynecological oncology training pathways internationally. CONCLUSIONS: This analysis provides an international perspective on the main barriers to optimal ovarian cancer care. The themes derived from our analysis highlight key target areas to focus efforts to reduce inequalities in global care. Future regional analysis involving local representatives will enable country specific recommendations to improve the quality of care and ultimately to work towards closing the care gap.

Severe falciparum malaria in pregnancy in Southeast Asia: a multi-centre retrospective cohort study.

BACKGROUND: Severe malaria in pregnancy causes maternal mortality, morbidity, and adverse foetal outcomes. The factors contributing to adverse maternal and foetal outcomes are not well defined. We aimed to identify the factors predicting higher maternal mortality and to describe the foetal mortality and morbidity associated with severe falciparum malaria in pregnancy. METHODS: A retrospective cohort study was conducted of severe falciparum malaria in pregnancy, as defined by the World Health Organization severe malaria criteria. The patients were managed prospectively by the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border or were included in hospital-based clinical trials in six Southeast Asian countries. Fixed-effects multivariable penalised logistic regression was used for analysing maternal mortality. RESULTS: We included 213 (123 SMRU and 90 hospital-based) episodes of severe falciparum malaria in pregnancy managed between 1980 and 2020. The mean maternal age was 25.7 (SD 6.8) years, and the mean gestational age was 25.6 (SD 8.9) weeks. The overall maternal mortality was 12.2% (26/213). Coma (adjusted odds ratio [aOR], 7.18, 95% CI 2.01-25.57, p = 0.0002), hypotension (aOR 11.21, 95%CI 1.27-98.92, p = 0.03) and respiratory failure (aOR 4.98, 95%CI 1.13-22.01, p = 0.03) were associated with maternal mortality. Pregnant women with one or more of these three criteria had a mortality of 29.1% (25/86) (95%CI 19.5 to 38.7%) whereas there were no deaths in 88 pregnant women with hyperparasitaemia (> 10% parasitised erythrocytes) only or severe anaemia (haematocrit < 20%) only. In the SMRU prospective cohort, in which the pregnant women were followed up until delivery, the risks of foetal loss (23.3% by Kaplan-Meier estimator, 25/117) and small-for-gestational-age (38.3%, 23/60) after severe malaria were high. Maternal death, foetal loss and preterm birth occurred commonly within a week of diagnosis of severe malaria. CONCLUSIONS: Vital organ dysfunction in pregnant women with severe malaria was associated with a very high maternal and foetal mortality whereas severe anaemia or hyperparasitaemia alone were not associated with poor prognosis, which may explain the variation of reported mortality from severe malaria in pregnancy. Access to antenatal care must be promoted to reduce barriers to early diagnosis and treatment of both malaria and anaemia.

Vacuum extraction or caesarean section in the second stage of labour: A systematic review.

BACKGROUND: Prolonged second stage of labour is an important cause of maternal and perinatal morbidity and mortality. Vacuum extraction (VE) and second-stage caesarean section (SSCS) are the most commonly performed obstetric interventions, but the procedure chosen varies widely globally. OBJECTIVES: To compare maternal and perinatal morbidity, mortality and other adverse outcomes after VE versus SSCS. SEARCH STRATEGY: A systematic search was conducted in PubMed, Cochrane and EMBASE. Studies were critically appraised using the Newcastle-Ottawa scale. SELECTION CRITERIA: All artictles including women in second stage of labour, giving birth by vacuum extraction or cesarean section and registering at least one perinatal or maternal outcome were selected. DATA COLLECTION AND ANALYSIS: The chi-square test, Fisher exact's test and binary logistic regression were used and various adverse outcome scores were calculated to evaluate maternal and perinatal outcomes. MAIN RESULTS: Fifteen articles were included, providing the outcomes for a total of 20 051 births by SSCS and 32 823 births by VE. All five maternal deaths resulted from complications of anaesthesia during SSCS. In total, 133 perinatal deaths occurred in all studies combined: 92/20 051 (0.45%) in the SSCS group and 41/32 823 (0.12%) in the VE group. In studies with more than one perinatal death, both conducted in low-resource settings, more perinatal deaths occurred during the decision-to-birth interval in the SSCS group than in the VE group (5.5% vs 1.4%, OR 4.00, 95% CI 1.17-13.70; 11% vs 8.4%, OR 1.39, 95% CI 0.85-2.26). All other adverse maternal and perinatal outcomes showed no statistically significant differences. CONCLUSIONS: Vacuum extraction should be the recommended mode of birth, both in high-income countries and in low- and middle-income countries, to prevent unnecessary SSCS and to reduce perinatal and maternal deaths when safe anaesthesia and surgery is not immediately available.

Exploring international differences in ovarian cancer care: a survey report on global patterns of care, current practices, and barriers.

OBJECTIVE: Although global disparities in survival rates for patients with ovarian cancer have been described, variation in care has not been assessed globally. This study aimed to evaluate global ovarian cancer care and barriers to care. METHODS: A survey was developed by international ovarian cancer specialists and was distributed through networks and organizational partners of the International Gynecologic Cancer Society, the Society of Gynecologic Oncology, and the European Society of Gynecological Oncology. Respondents received questions about care organization. Outcomes were stratified by World Bank Income category and analyzed using descriptive statistics and logistic regressions. RESULTS: A total of 1059 responses were received from 115 countries. Respondents were gynecological cancer surgeons (83%, n=887), obstetricians/gynecologists (8%, n=80), and other specialists (9%, n=92). Income category breakdown was as follows: high-income countries (46%), upper-middle-income countries (29%), and lower-middle/low-income countries (25%). Variation in care organization was observed across income categories. Respondents from lower-middle/low-income countries reported significantly less frequently that extensive resections were routinely performed during cytoreductive surgery. Furthermore, these countries had significantly fewer regional networks, cancer registries, quality registries, and patient advocacy groups. However, there is also scope for improvement in these components in upper-middle/high-income countries. The main barriers to optimal care for the entire group were patient co-morbidities, advanced presentation, and social factors (travel distance, support systems). High-income respondents stated that the main barriers were lack of surgical time/staff and patient preferences. Middle/low-income respondents additionally experienced treatment costs and lack of access to radiology/pathology/genetic services as main barriers. Lack of access to systemic agents was reported by one-third of lower-middle/low-income respondents. CONCLUSIONS: The current survey report highlights global disparities in the organization of ovarian cancer care. The main barriers to optimal care are experienced across all income categories, while additional barriers are specific to income levels. Taking action is crucial to improve global care and strive towards diminishing survival disparities and closing the care gap.

Exploring the shared decision making process of caesarean sections at a teaching hospital in Ghana: a mixed methods study.

BACKGROUND: Caesarean section (CS) rates are rising. Shared decision making (SDM) is a component of patient-centered communication which requires adequate information and awareness. Women in Ghana have varying perceptions about the procedure. We sought to explore mothers' knowledge. perceptions and SDM-influencing factors about CSs. METHODS: A transdisciplinary mixed-methods study was conducted at the maternity unit of Korle-Bu Teaching Hospital in Accra, Ghana from March to May, 2019. Data collection was done in four phases: in-depth interviews (n = 38), pretesting questionnaires (n = 15), three focus group discussions (n = 18) and 180 interviewer administered questionnaires about SDM preferences. Factors associated with SDM were analyzed using Pearson's Chi-square test and multiple logistic regression. RESULTS: Mothers depicted a high level of knowledge regarding medical indications for their CS but had low level of awareness of SDM. The perception of a CS varied from dangerous, unnatural and taking away their strength to a life-saving procedure. The mothers had poor knowledge about pain relief in labour and at Caesarean section. Health care professionals attributed the willingness of mothers to be involved in SDM to their level of education. Husbands and religious leaders are key stakeholders in SDM. Insufficient consultation time was a challenge to SDM according to health care professionals and post-partum mothers. Women with parity ≥ 5 have a reduced desire to be more involved in shared decision making for Caesarean section. AOR = 0.09, CI (0.02-0.46). CONCLUSION: There is a high knowledge about the indications for CS but low level of awareness of and barriers to SDM. The fewer antenatal care visits mothers had, the more likely they were to desire more involvement in decision making. Aligned to respectful maternity care principles, greater involvement of pregnant women and their partners in decision making process could contribute to a positive pregnancy experience. Education, including religious leaders and decision- making tools could contribute to the process of SDM.

Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study.

OBJECTIVE: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. DESIGN: Prospective cohort. SETTING: Kagadi Hospital, Uganda. POPULATION: Non-anomalous singleton pregnancies. METHODS: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. RESULTS: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09-21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18-11.88). CONCLUSION: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. TWEETABLE ABSTRACT: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings.

Falciparum but not vivax malaria increases the risk of hypertensive disorders of pregnancy in women followed prospectively from the first trimester.

BACKGROUND: Malaria and hypertensive disorders of pregnancy (HDoP) affect millions of pregnancies worldwide, particularly those of young, first-time mothers. Small case-control studies suggest a positive association between falciparum malaria and risk of pre-eclampsia but large prospective analyses are lacking. METHODS: We characterized the relationship between malaria in pregnancy and the development of HDoP in a large, prospectively followed cohort. Pregnant women living along the Thailand-Myanmar border, an area of low seasonal malaria transmission, were followed at antenatal clinics between 1986 and 2016. The relationships between falciparum and vivax malaria during pregnancy and the odds of gestational hypertension, pre-eclampsia, or eclampsia were examined using logistic regression amongst all women and then stratified by gravidity. RESULTS: There were 23,262 singleton pregnancies in women who presented during the first trimester and were followed fortnightly. Falciparum malaria was associated with gestational hypertension amongst multigravidae (adjusted odds ratio (AOR) 2.59, 95%CI 1.59-4.23), whereas amongst primigravidae, it was associated with the combined outcome of pre-eclampsia/eclampsia (AOR 2.61, 95%CI 1.01-6.79). In contrast, there was no association between vivax malaria and HDoP. CONCLUSIONS: Falciparum but not vivax malaria during pregnancy is associated with hypertensive disorders of pregnancy.

The relation between maternal obesity and placenta accreta spectrum: A multinational database study.

INTRODUCTION: It has been suggested that women with obesity have increased risk of developing placenta accreta spectrum (PAS). It is unclear if this is independent of the increased risk of cesarean delivery seen with obesity itself. The aim of this study was to explore the association between maternal obesity and PAS, particularly severe PAS (percreta). MATERIAL AND METHODS: This is a cohort study based on cases recorded in the International Society for Placenta Accreta Spectrum (IS-PAS) database between April 2008 and May 2019. Multivariable logistic regression was used to explore the effect of maternal obesity on severity of PAS; this model was adjusted for other known risk factors including previous cesarean deliveries, maternal age, and placenta previa. The estimated rate of obesity in a hypothetical cohort with similar characteristics (previous cesarean delivery and same parity) was calculated and compared with the observed rate of obesity in the women of the PAS cohort (one sample test of proportions). RESULTS: Of the 386 included women with PAS, 227 (58.8%) had severe disease (percreta). In univariable analysis, maternal obesity initially appeared to be associated with increased odds of developing the most severe type of PAS, percreta (odds ratio [OR] 1.87; 95% CI 1.14-3.09); however, this association was lost after adjustment for other risk factors including previous cesarean delivery (OR 1.44; 95% CI 0.85-2.44). There was no difference in the observed rate of obesity and the rate estimated based on the risk of cesarean delivery from obesity alone (31.3% vs 36.8%, respectively; P = .07). CONCLUSIONS: Obesity does not seem to be an independent risk factor for PAS or severity for PAS. These findings are relevant for clinicians to provide accurate counseling to women with obesity regarding increased risks related to pregnancy.

Tenofovir disoproxil fumarate in pregnancy for prevention of mother to child transmission of hepatitis B in a rural setting on the Thailand-Myanmar border: a cost-effectiveness analysis.

BACKGROUND: Hepatitis B Virus (HBV) is transmitted from mother to child which can be prevented via birth dose vaccine combined with three follow up hepatitis B vaccines, hepatitis B immunoglobulins (HBIG), and maternal antiviral treatment with Tenofovir Disoproxil Fumarate (TDF). This study evaluates the cost effectiveness of six strategies to prevent perinatal HBV transmission in a resource limited setting (RLS) on the Thailand-Myanmar border. METHODS: The cost effectiveness of six strategies was tested by a decision tree model in R. All strategies included birth and follow up vaccinations and compared cost per infection averted against two willingness to pay thresholds: one-half and one gross domestic product (GDP) per capita. Strategies were: 1) Vaccine only, 2) HBIG after rapid diagnostic test (RDT): infants born to HBsAg+ are given HBIG, 3) TDF after RDT: HBsAg+ women are given TDF, 4) TDF after HBeAg test: HBeAg+ women are given TDF, 5) TDF after high HBV DNA: women with HBV DNA > 200,000 are given TDF, 6) HBIG & TDF after high HBV DNA: women with HBV DNA > 200,000 are given TDF and their infants are given HBIG. One-way and probabilistic sensitivity analyses were conducted on the cost-effective strategies. RESULTS: Vaccine only was the least costly option with TDF after HBeAg test strategy as the only cost-effective alternative. TDF after HBeAg test had an incremental cost-effectiveness ratio of US$1062; which would not be considered cost-effective with the lower threshold of one-half GDP per capita. The one-way sensitivity analysis demonstrated that the results were reasonably robust to changes in single parameter values. The PSA showed that TDF after HBeAg test had an 84% likelihood of being cost effective at a willingness to pay threshold of one GDP per capita per infection averted. CONCLUSIONS: We found that TDF after HBeAg test has the potential to be cost-effective if TDF proves effective locally to prevent perinatal HBV transmission. The cost of TDF treatment and reliability of the RDT could be barriers to implementing this strategy. While TDF after RDT may be a more feasible strategy to implement in RLS, TDF after HBeAg test is a less costly option.

Association of peripartum management and high maternal blood loss at cesarean delivery for placenta accreta spectrum (PAS): A multinational database study.

INTRODUCTION: Placenta accreta spectrum (PAS) carries a high burden of adverse maternal outcomes, especially significant blood loss, which can be life-threatening. Different management strategies have been proposed but the association of clinical risk factors and surgical management options during cesarean delivery with high blood loss is not clear. MATERIAL AND METHODS: In this international multicenter study, 338 women with PAS undergoing cesarean delivery were included. Fourteen European and one non-European center (USA) provided cases treated retrospectively between 2008 and 2014 and prospectively from 2014 to 2019. Peripartum blood loss was estimated visually and/or by weighing and measuring of volume. Participants were grouped based on blood loss above or below the 75th percentile (>3500 ml) and the 90th percentile (>5500 ml). RESULTS: Placenta percreta was found in 58% of cases. Median blood loss was 2000 ml (range: 150-20 000 ml). Unplanned hysterectomy was associated with an increased risk of blood loss >3500 ml when compared with planned hysterectomy (adjusted OR [aOR] 3.7 [1.5-9.4], p = 0.01). Focal resection was associated with blood loss comparable to that of planned hysterectomy (crude OR 0.7 [0.2-2.1], p = 0.49). Blood loss >3500 ml was less common in patients undergoing successful conservative management (placenta left in situ, aOR 0.1 [0.0-0.6], p = 0.02) but was more common in patients who required delayed hysterectomy (aOR 6.5 [1.7-24.4], p = 0.001). Arterial occlusion methods (uterine or iliac artery ligation, embolization or intravascular balloons), application of uterotonic medication or tranexamic acid showed no significant effect on blood loss >3500 ml. Patients delivered by surgeons without experience in PAS were more likely to experience blood loss >3500 ml (aOR 3.0 [1.4-6.4], p = 0.01). CONCLUSIONS: In pregnant women with PAS, the likelihood of blood loss >3500 ml was reduced in planned vs unplanned cesarean delivery, and when the surgery was performed by a specialist experienced in the management of PAS. This reinforces the necessity of delivery by an expert team. Conservative management was also associated with less blood loss, but only if successful. Therefore, careful patient selection is of great importance. Our study showed no consistent benefit of other adjunct measures such as arterial occlusion techniques, uterotonics or tranexamic acid.

A multicenter observational survey of management strategies in 442 pregnancies with suspected placenta accreta spectrum.

INTRODUCTION: Management options for women with placenta accreta spectrum (PAS) comprise termination of pregnancy before the viable gestational age, leaving the placenta in situ for subsequent reabsorption of the placenta or delayed hysterectomy, manual removal of placenta after vaginal delivery or during cesarean section, focal resection of the affected uterine wall, and peripartum hysterectomy. The aim of this observational study was to describe actual clinical management and outcomes in PAS in a large international cohort. MATERIAL AND METHODS: Data from women in 15 referral centers of the International Society of PAS (IS-PAS) were analyzed and correlated with the clinical classification of the IS-PAS: From Grade 1 (no PAS) to Grade 6 (invasion into pelvic organs other than the bladder). PAS was usually diagnosed antenatally and the operators performing ultrasound rated the likelihood of PAS on a Likert scale of 1 to 10. RESULTS: In total, 442 women were registered in the database. No maternal deaths occurred. Mean blood loss was 2600 mL (range 150-20 000 mL). Placenta previa was present in 375 (84.8%) women and there was a history of a previous cesarean in 329 (74.4%) women. The PAS likelihood score was strongly correlated with the PAS grade (P < .001). The mode of delivery in the majority of women (n = 252, 57.0%) was cesarean hysterectomy, with a repeat laparotomy in 20 (7.9%) due to complications. In 48 women (10.8%), the placenta was intentionally left in situ, of those, 20 (41.7%) had a delayed hysterectomy. In 26 women (5.9%), focal resection was performed. Termination of pregnancy was performed in 9 (2.0%), of whom 5 had fetal abnormalities. The placenta could be removed in 90 women (20.4%) at cesarean, and in 17 (3.9%) after vaginal delivery indicating mild or no PAS. In 34 women (7.7%) with an antenatal diagnosis of PAS, the placenta spontaneously separated (false positives). We found lower blood loss (P < .002) in 2018-2019 compared with 2009-2017, suggesting a positive learning curve. CONCLUSIONS: In referral centers, the most common management for severe PAS was cesarean hysterectomy, followed by leaving the placenta in situ and focal resection. Prenatal diagnosis correlated with clinical PAS grade. No maternal deaths occurred.

Antenatal Doppler ultrasound implementation in a rural sub-Saharan African setting: exploring the perspectives of women and healthcare providers.

BACKGROUND: The World Health Organization recommends research to evaluate the effects of a single third trimester Doppler ultrasound examination on preventable deaths in unselected-risk pregnancies, particularly in low- and middle-income countries (LMICs) where the evidence base is scarce. While evaluating such technologies, researchers often ignore women and health care provider perspectives. This study explored the views and experiences of women and healthcare providers regarding the use of advanced ultrasound technology to optimize the health of mothers and their babies in a rural community in mid-western Uganda. METHODS: We enrolled 53 mothers and 10 healthcare providers, and captured data on their perceptions, barriers, and facilitators to the use of Doppler ultrasound technology using focus group discussions, semi-structured interviews and observations. Using qualitative content analysis, we inductively coded the transcripts in ATLAS.ti 8.0, detecting emerging themes. RESULTS: Women were afraid that ultrasound would harm them or their fetuses and many of them had never seen an ultrasound scan. The majority of the women found their partners supportive to attend antenatal care and use ultrasound services. Healthcare providers in Kagadi Hospital were unfamiliar with Doppler technology and using it to guide clinical decisions. Other barriers to the implementation of Doppler ultrasound included shortage of trained local staff, insufficient equipment, long distance to and from the hospital, and frequent power cuts. CONCLUSIONS: We found limited exposure to Doppler ultrasound technology among women and healthcare providers in mid-western Uganda. Engaging male partners may potentially influence the likelihood of accepting and using it to improve the health of women and their fetuses while wide spread myths and misconceptions about it may be changed by community engagement. Healthcare workers experienced difficulties in offering follow-up care to mothers detected with complications and Doppler ultrasound required a high level of training. While introducing advanced ultrasound machines to weak health systems, it is important to adequately train healthcare providers to avoid inappropriate interventions based on misinterpretation of the findings, consider where it is likely to be most beneficial, and embed it with realistic clinical practice guidelines.

Globally, nearly three million babies are stillborn every year, but most especially in low- and middle-income countries like Uganda. One of the factors contributing to a high number of stillbirths in low-income countries is the difficulty in identifying complications and accessing high quality care during pregnancy. Although antenatal Doppler scans are being widely used to diagnose complications in high-risk pregnancies in developed countries, studies evaluating it in LMICs are needed before it is implemented on a wide scale. We engaged 53 mothers, eight health workers from a hospital and two healthcare managers from a local government in Uganda to attain their opinions about Doppler ultrasound. We found that spousal involvement may promote acceptance and use of ultrasound services. However, the health workers did not have adequate knowledge about Doppler technology and using it for the benefit of mothers and the mothers feared that ultrasound procedures might harm them or their unborn babies. Making matters worse, the hospital faced frequent power cuts that affected the use of the equipment. Further, mothers must cover a long distance to access the hospital and its services. To reduce the number of babies dying during pregnancy or a few days after birth in Uganda and similar low-resource settings using Doppler technology, it is essential to strengthen the health systems. Starting with the training of healthcare providers to equipping and stabilizing power supply in health facilities, and educating the public about critical health procedures to break myths and misconceptions.

Classifying maternal deaths in Suriname using WHO ICD-MM: different interpretation by Physicians, National and International Maternal Death Review Committees.

The World Health Organization (WHO) provides a framework (ICD-MM) to classify pregnancy-related deaths systematically, which enables global comparison among countries. We compared the classification of pregnancy-related deaths in Suriname by the attending physician and by the national maternal death review (MDR) committee and among the MDR committees of Suriname, Jamaica and the Netherlands. There were 89 possible pregnancy-related deaths in Suriname between 2010 and 2014. Nearly half (47%) were classified differently by the Surinamese MDR committee as compared to the classification of the attending physicians. All three MDR committees agreed that 18% (n = 16/89) of the cases were no maternal deaths. Out of the remaining 73 cases, there was disagreement regarding whether 15% (n = 11) were maternal deaths. The Surinamese and Jamaican MDR committees achieved greater consensus in classification than the Surinamese and the Netherlands MDR committees. The Netherlands MDR committee classified more deaths as unspecified than Surinamese and the Jamaican MDR committees. Underlying causes that achieved a high level of agreement among the three committees were abortive outcomes and obstetric hemorrhage, while little agreement was reported for unspecified and other direct causes. The issues encountered during maternal death classification using the ICD-MM guidelines included classification of suicide during early pregnancy; when to assume pregnancy without objective evidence; how to count maternal deaths occurring outside the country of residence; the relevance of direct or indirect cause attribution; and how to select the underlying cause when direct and indirect conditions or multiple comorbidities co-occur. Addressing these classification barriers in future revisions of the ICD-MM guidelines could enhance the feasibility of maternal death classification and facilitate global comparison. BACKGROUND: Insight into the underlying causes of pregnancy-related deaths is essential to develop policies to avert preventable deaths. The WHO International Classification of Diseases-Maternal Mortality (ICD-MM) guidelines provide a framework to standardize maternal death classifications and enable comparison in and among countries over time. However, despite the implementation of these guidelines, differences in classification remain. We evaluated consensus on maternal death classification using the ICD-MM guidelines. METHODS: The classification of pregnancy-related deaths in Suriname during 2010-2014 was compared in the country (between the attending physician and the national maternal death review (MDR) committee), and among the MDR committees from Suriname, Jamaica and the Netherlands. All reviewers applied the ICD-MM guidelines. The inter-rater reliability (Fleiss kappa [κ]) was used to measure agreement. RESULTS: Out of the 89 cases certified by attending physicians, 47% (n = 42) were classified differently by the Surinamese MDR committee. The three MDR committees agreed that 18% (n = 16/89) of these cases were no maternal deaths, and, therefore, excluded from further analyses. However, opinions differed whether 15% (n = 11) of the remaining 73 cases were maternal deaths. The MDR committees achieved moderate agreement classifying the deaths into type (direct, indirect and unspecified) (κ = 0.53) and underlying cause group (κ = 0.52). The Netherlands MDR committee classified more maternal deaths as unspecified (19%), than the Jamaican (7%) and Surinamese (4%) committees did. The mutual agreement between the Surinamese and Jamaican MDR committees (κ = 0.69 vs κ = 0.63) was better than between the Surinamese and the Netherlands MDR committees (κ = 0.48 vs κ = 0.49) for classification into type and underlying cause group, respectively. Agreement on the underlying cause category was excellent for abortive outcomes (κ = 0.85) and obstetric hemorrhage (κ = 0.74) and fair for unspecified (κ = 0.29) and other direct causes (κ = 0.32). CONCLUSIONS: Maternal death classification differs in Suriname and among MDR committees from different countries, despite using the ICD-MM guidelines on similar cases. Specific challenges in applying these guidelines included attribution of underlying cause when comorbidities occurred, the inclusion of deaths from suicides, and maternal deaths that occurred outside the country of residence.

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. METHODS: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. RESULTS: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). CONCLUSIONS: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Childbirth outcomes and ethnic disparities in Suriname: a nationwide registry-based study in a middle-income country.

BACKGROUND: Our study aims to evaluate the current perinatal registry, analyze national childbirth outcomes and study ethnic disparities in middle-income country Suriname, South America. METHODS: A nationwide birth registry study was conducted in Suriname. Data were collected for 2016 and 2017 from the childbirth books of all five hospital maternity wards, covering 86% of all births in the country. Multinomial regression analyses were used to assess ethnic disparities in outcomes of maternal deaths, stillbirths, teenage pregnancy, cesarean delivery, low birth weight and preterm birth with Hindustani women as reference group. RESULTS: 18.290 women gave birth to 18.118 (98%) live born children in the five hospitals. Hospital-based maternal mortality ratio was 112 per 100.000 live births. Hospital-based late stillbirth rate was 16 per 1000 births. Stillbirth rate was highest among Maroon (African-descendent) women (25 per 1000 births, aOR 2.0 (95%CI 1.3-2.8) and lowest among Javanese women (6 stillbirths per 1000 births, aOR 0.5, 95%CI 0.2-1.2). Preterm birth and low birthweight occurred in 14 and 15% of all births. Teenage pregnancy accounted for 14% of all births and was higher in Maroon women (18%) compared to Hindustani women (10%, aOR 2.1, 95%CI 1.8-2.4). The national cesarean section rate was 24% and was lower in Maroon (17%) than in Hindustani (32%) women (aOR 0.5 (95%CI 0.5-0.6)). Cesarean section rates varied between the hospitals from 17 to 36%. CONCLUSION: This is the first nationwide comprehensive overview of maternal and perinatal health in a middle income country. Disaggregated perinatal health data in Suriname shows substantial inequities in outcomes by ethnicity which need to be targetted by health professionals, researchers and policy makers.

Quality of intrapartum care: direct observations in a low-resource tertiary hospital.

BACKGROUND: The majority of the world's perinatal deaths occur in low- and middle-income countries. A substantial proportion occurs intrapartum and is avoidable with better care. At a low-resource tertiary hospital, this study assessed the quality of intrapartum care and adherence to locally-tailored clinical guidelines. METHODS: A non-participatory, structured, direct observation study was held at Mnazi Mmoja Hospital, Zanzibar, Tanzania, between October and November 2016. Women in active labour were followed and structure, processes of labour care and outcomes of care systematically recorded. Descriptive analyses were performed on the labour observations and compared to local guidelines and supplemented by qualitative findings. A Poisson regression analysis assessed factors affecting foetal heart rate monitoring (FHRM) guidelines adherence. RESULTS: 161 labouring women were observed. The nurse/midwife-to-labouring-women ratio of 1:4, resulted in doctors providing a significant part of intrapartum monitoring. Care during labour and two-thirds of deliveries was provided in a one-room labour ward with shared beds. Screening for privacy and communication of examination findings were done in 50 and 34%, respectively. For the majority, there was delayed recognition of labour progress and insufficient support in second stage of labour. While FHRM was generally performed suboptimally with a median interval of 105 (interquartile range 57-160) minutes, occurrence of an intrapartum risk event (non-reassuring FHR, oxytocin use or poor progress) increased assessment frequency significantly (rate ratio 1.32 (CI 1.09-1.58)). CONCLUSIONS: Neither international nor locally-adapted standards of intrapartum routine care were optimally achieved. This was most likely due to a grossly inadequate capacity of birth attendants; without whom innovative interventions at birth are unlikely to succeed. This calls for international and local stakeholders to address the root causes of unsafe intrafacility care in low-resource settings, including the number of skilled birth attendants required for safe and respectful births.

Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta.

The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians' understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.

Maternal and perinatal outcomes of asylum seekers and undocumented migrants in Europe: a systematic review.

BACKGROUND: Asylum seekers (AS) and undocumented migrants (UM) are at risk of adverse pregnancy outcomes due to adverse health determinants and compromised maternal healthcare access and service quality. Considering recent migratory patterns and the absence of a robust overview, a systematic review was conducted on maternal and perinatal outcomes in AS and UM in Europe. METHODS: Systematic literature searches were performed in MEDLINE and EMBASE (until 1 May 2017), complemented by a grey literature search (until 1 June 2017). Primary research articles reporting on any maternal or perinatal outcome, published between 2007 and 2017 in English/Dutch were eligible for inclusion. Review protocols were registered on Prospero: CRD42017062375 and CRD42017062477. Due to heterogeneity in study populations and outcomes, results were synthesized narratively. RESULTS: Of 4652 peer-reviewed articles and 145 grey literature sources screened, 11 were included from 4 European countries. Several studies reported adverse outcomes including higher maternal mortality (AS), severe acute maternal morbidity (AS), preterm birth (UM) and low birthweight (UM). Risk of bias was generally acceptable, although the limited number and quality of some studies preclude definite conclusions. CONCLUSION: Limited evidence is available on pregnancy outcomes in AS and UM in Europe. The adverse outcomes reported imply that removing barriers to high-quality maternal care should be a priority. More research focussing on migrant subpopulations, considering potential risk factors such as ethnicity and legal status, is needed to guide policy and optimize care.

Bottom-up development of national obstetric guidelines in middle-income country Suriname.

BACKGROUND: Obstetric guidelines are useful to improve the quality of care. Availability of international guidelines has rapidly increased, however the contextualization to enhance feasibility of implementation in health facilities in low and middle-income settings has only been described in literature in a few instances. This study describes the approach and lessons learned from the 'bottom-up' development process of context-tailored national obstetric guidelines in middle-income country Suriname. METHODS: Local obstetric health care providers initiated the guideline development process in Suriname in August 2016 for two common obstetric conditions: hypertensive disorders of pregnancy (HDP) and post partum haemorrhage (PPH). RESULTS: The process consisted of six steps: (1) determination of how and why women died, (2) interviews and observations of local clinical practice, (3) review of international guidelines, (4) development of a primary set of guidelines, (5) initiation of a national discussion on the guidelines content and (6) establishment of the final guidelines based on consensus. Maternal enquiry of HDP- and PPH-related maternal deaths revealed substandard care in 90 and 95% of cases, respectively. An assessment of the management through interviews and labour observations identified gaps in quality of the provided care and large discrepancies in the management of HDP and PPH between the hospitals. International recommendations were considered unfeasible and were inconsistent when compared to each other. Local health care providers and stakeholders convened to create national context-tailored guidelines based on adapted international recommendations. The guidelines were developed within four months and locally implemented. CONCLUSION: Development of national context-tailored guidelines is achievable in a middle-income country when using a 'bottom-up' approach that involves all obstetric health care providers and stakeholders in the earliest phase. We hope the descriptive process of guideline development is helpful for other countries in need of nationwide guidelines.

Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing.

Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.