Publications by authors named "Joyce L Browne"

54 Publications

Vaccine equity: Past, present, and future.

Cell Rep Med 2022 Mar 11;3(3):100551. Epub 2022 Feb 11.

Médecins Sans Frontiers, Luxembourg Operational Research Unit (LuxOR), Luxembourg.

The term "vaccine equity" primarily points to the enormous imbalance in global COVID-19 vaccine distribution. Vaccine equity should adopt a normative approach toward "health equity," and various stakeholders across the vaccine life cycle must practice it. The momentum gathered during this pandemic must be used to correct these structural imbalances.
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http://dx.doi.org/10.1016/j.xcrm.2022.100551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831140PMC
March 2022

Development of a clinical prediction model for perinatal deaths in low resource settings.

EClinicalMedicine 2022 Feb 7;44:101288. Epub 2022 Feb 7.

Julius Global Health, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, The Netherlands.

Background: Most pregnancy-related deaths in low and middle income countries occur around the time of birth and are avoidable with timely care. This study aimed to develop a prognostic model to identify women at risk of intrapartum-related perinatal deaths in low-resourced settings, by (1) external validation of an existing prediction model, and subsequently (2) development of a novel model.

Methods: A prospective cohort study was conducted among pregnant women who presented consecutively for delivery at the maternity unit of Zanzibar's tertiary hospital, Mnazi Mmoja Hospital, the Republic of Tanzania between October 2017 and May 2018. Candidate predictors of perinatal deaths included maternal and foetal characteristics obtained from routine history and physical examination at the time of admission to the labour ward. The outcomes were intrapartum stillbirths and neonatal death before hospital discharge. An existing stillbirth prediction model with six predictors from Nigeria was applied to the Zanzibar cohort to assess its discrimination and calibration performance. Subsequently, a new prediction model was developed using multivariable logistic regression. Model performance was evaluated through internal validation and corrected for overfitting using bootstrapping methods.

Findings: 5747 mother-baby pairs were analysed. The existing model showed poor discrimination performance (c-statistic 0·57). The new model included 15 clinical predictors and showed promising discriminative and calibration performance after internal validation (optimism adjusted c-statistic of 0·78, optimism adjusted calibration slope =0·94).

Interpretation: The new model consisted of predictors easily obtained through history-taking and physical examination at the time of admission to the labour ward. It had good performance in predicting risk of perinatal death in women admitted in labour wards. Therefore, it has the potential to assist skilled birth attendance to triage women for appropriate management during labour. Before routine implementation, external validation and usefulness should be determined in future studies.

Funding: The study received funding from Laerdal Foundation, Otto Kranendonk Fund and UMC Global Health Fellowship. TD acknowledges financial support from the Netherlands Organisation for Health Research and Development (grant 91617050).
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http://dx.doi.org/10.1016/j.eclinm.2022.101288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888338PMC
February 2022

Diagnostic accuracy of urine dipstick tests for proteinuria in pregnant women suspected of preeclampsia: A systematic review and meta-analysis.

Pregnancy Hypertens 2022 Mar 4;27:123-130. Epub 2022 Jan 4.

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Postbus 85500, 3508 GA Utrecht, The Netherlands.

Objectives: Dipstick tests are frequently used as bedside proteinuria tests to evaluate women suspected of preeclampsia and may inform diagnosis in low resource settings lacking laboratory facilities. This systematic review and meta-analysis aimed to (1) estimate the diagnostic accuracy of urine dipsticks in diagnosing proteinuria, (2) compare performance of different dipstick types and (3) estimate their related costs.

Methods: MEDLINE and EMBASE were searched up to August 1, 2020 for primary studies with cross-sectional diagnostic accuracy data on dipstick test(s) compared to a laboratory reference standard (24-hour protein ≥ 300 mg or protein-creatinine ratio ≥ 30 mg/mmol) in pregnant women ≥ 20 weeks of gestation suspected of preeclampsia. Risk of bias and applicability was assessed with QUADAS-2. Data were analysed using a bivariate model with hierarchical addition of covariates for subgroups.

Results: Nineteen studies were included. Protein-only dipsticks at 1 + threshold had a pooled sensitivity of 0.68 [95%CI: 0.57-0.77] and specificity of 0.85 [95% CI: 0.73-0.93] (n = 3700 urine samples, 18 studies). Higher specificity was found with automatedly (0.93 [95% CI: 0.82-0.98]) compared to visually (0.81 [95% CI: 0.65-0.91]) read dipsticks, whereas sensitivity was similar and costs were higher. The use of albumin-creatinine ratio (ACR) dipsticks was only reported in two studies and did not improve accuracy. Heterogeneity in study design and prevalence of preeclampsia amongst studies complicated interpretation of pooled estimates.

Conclusion: Urine dipsticks performed poorly at excluding preeclampsia in hypertensive pregnant women. Further development of accurate and low-cost bedside proteinuria tests is warranted.
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http://dx.doi.org/10.1016/j.preghy.2021.12.015DOI Listing
March 2022

Persistent Hypertension Up to One Year Postpartum among Women with Hypertensive Disorders in Pregnancy in a Low-Resource Setting: A Prospective Cohort Study.

Glob Heart 2021 9;16(1):62. Epub 2021 Sep 9.

Julius Global Health, Julius Center for Health Science and Primary Care, UMC Utrecht, Utrecht University, NL.

Background: Hypertensive disorders in pregnancy (HDPs) are associated with lifelong cardiovascular disease risk. Persistent postpartum hypertension in HDPs could suggest progression to chronic hypertension. This phenomenon has not been well examined in low- and middle-income countries (LIMCs), and most previous follow-ups typically last for maximally six weeks postpartum. We assessed the prevalence of persistent hypertension up to one year in women with HDPs in a low resource setting and determined associated risk factors.

Methodology: A prospective cohort study of women conducted at eight tertiary health care facilities in seven states of Nigeria. Four hundred and ten women with any HDP were enrolled within 24 hours of delivery and followed up at intervals until one year postpartum. Descriptive statistics were performed to express the participants' characteristics. Univariable and multivariable logistic regressions were conducted to identify associated risk factors.

Results: Of the 410 women enrolled, 278 were followed up to one year after delivery (follow-up rate 68%). Among women diagnosed with gestational hypertension and pre-eclampsia/eclampsia, 22.3% (95% CI; 8.3-36.3) and 62.1% (95% CI; 52.5-71.9), respectively, had persistent hypertension at six months and this remained similar at one year 22.3% (95% CI; 5.6-54.4) and 61.2% (95% CI; 40.6-77.8). Maternal age and body mass index were significant risk factors for persistent hypertension at one year [aORs = 1.07/year (95% CI; 1.02-1.13) and 1.06/kg/m (95% CI; 1.01-1.10)], respectively.

Conclusion: This study showed a substantial prevalence of persistent hypertension beyond puerperium. Health systems in LMICs need to be organized to anticipate and maintain postpartum monitoring until blood pressure is normalized, or women referred or discharged to family physicians as appropriate. In particular, attention should be given to women who are obese, and or of higher maternal age.
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http://dx.doi.org/10.5334/gh.854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428291PMC
November 2021

Navigating with logics: Care for women with hypertensive disorders of pregnancy in a tertiary hospital in Ghana.

Soc Sci Med 2021 11 14;289:114402. Epub 2021 Sep 14.

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands; Department of Obstetrics and Gynaecology, School of Medicine and Dentistry, University of Ghana, Accra, Ghana.

This paper explores how care for women with hypertensive disorders of pregnancy (HDP) is practiced in a tertiary hospital in Ghana. Partly in response to the persistently high maternal and neonatal mortality rates in Low- and Middle-income countries, efforts to improve quality of maternity care have increased. Quality improvement initiatives are shaped by the underlying conceptualisation of quality of care, often driven by global (WHO) standards and protocols. However, there are tensions between global standards of care and local clients' and providers' understandings of care practices and quality of care. Implementation of standards is further complicated by structural and organisational restrictions that influence providers' possibilities and priorities. Based on ethnographic fieldwork, we explore how clinical guidelines and professionals' and patients' perspectives converge and, more importantly, diverge. We illuminate local, situated care practices and show how professionals creatively deal with tensions that arise on the ground. In this middle-income setting, caring for women with HDP involves tinkering and navigating in contexts of uncertainty, scarcity, varying responsibilities and conflicting interests. We unravelled a complex web of, at times, contradictory logics, from which various forms of care arise and in which different notions of good care co-exist. While practitioners navigated through and with these varying logics of care, the logic of survival permeated all practices. This study provides important initial insights into how professionals might implement and innovatively adapt the latest quality of maternity care guidelines which seek to marry clinical standards and patients' needs, preferences and experiences.
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http://dx.doi.org/10.1016/j.socscimed.2021.114402DOI Listing
November 2021

Prevalence and determinants of chronic kidney disease in women with hypertensive disorders in pregnancy in Nigeria: a cohort study.

BMC Nephrol 2021 06 18;22(1):229. Epub 2021 Jun 18.

Population Council, Washington DC, USA.

Background: Worldwide, hypertensive disorders in pregnancy (HDPs) complicate between 5 and 10% of pregnancies. Sub-Saharan Africa (SSA) is disproportionately affected by a high burden of HDPs and chronic kidney disease (CKD). Despite mounting evidence associating HDPs with the development of CKD, data from SSA are scarce.

Methods: Women with HDPs (n = 410) and normotensive women (n = 78) were recruited at delivery and prospectively followed-up at 9 weeks, 6 months and 1 year postpartum. Serum creatinine was measured at all time points and the estimated glomerular filtration rates (eGFR) using CKD-Epidemiology equation determined. CKD was defined as decreased eGFR< 60 mL/min/1.73m lasting for ≥ 3 months. Prevalence of CKD at 6 months and 1 year after delivery was estimated. Logistic regression analyses were conducted to evaluate risk factors for CKD at 6 months and 1 year postpartum.

Results: Within 24 h of delivery, 9 weeks, and 6 months postpartum, women with HDPs were more likely to have a decreased eGFR compared to normotensive women (12, 5.7, 4.3% versus 0, 2 and 2.4%, respectively). The prevalence of CKD in HDPs at 6 months and 1 year postpartum was 6.1 and 7.6%, respectively, as opposed to zero prevalence in the normotensive women for the corresponding periods. Proportions of decreased eGFR varied with HDP sub-types and intervening postpartum time since delivery, with pre-eclampsia/eclampsia showing higher prevalence than chronic and gestational hypertension. Only maternal age was independently shown to be a risk factor for decreased eGFR at 6 months postpartum (aOR = 1.18/year; 95%CI 1.04-1.34).

Conclusion: Prior HDP was associated with risk of future CKD, with prior HDPs being more likely to experience evidence of CKD over periods of postpartum follow-up. Routine screening of women following HDP-complicated pregnancies should be part of a postpartum monitoring program to identify women at higher risk. Future research should report on both the eGFR and total urinary albumin excretion to enable detection of women at risk of future deterioration of renal function.
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http://dx.doi.org/10.1186/s12882-021-02419-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212529PMC
June 2021

Metabolic syndrome following hypertensive disorders in pregnancy in a low-resource setting: A cohort study.

Pregnancy Hypertens 2021 Aug 4;25:129-135. Epub 2021 Jun 4.

Julius Global Health, Julius Center for Health Science and Primary Care, UMC Utrecht, Utrecht University, the Netherlands.

Objectives: Hypertensive disorders in pregnancy (HDPs) are associated with risk of future metabolic syndrome. Despite the huge burden of HDPs in sub-Saharan Africa, this association has not been adequately studied in this population.

Study Design: This was a prospective cohort study on pregnant women recruited between August 2017 - April 2018 and followed up to one year after their deliveries and evaluated for presence of metabolic syndrome at delivery, nine weeks, six months and one year.

Main Outcome Measures: Prevalence of metabolic syndrome RESULTS: A total of 488 pregnant women were included: 410 and 78 with HDPs and normotensive, respectively. None of the normotensive had metabolic syndrome until one year (1.7% = 1 out of 59 observations), while among those with HDPs were 17.4% (71 of 407), 8.7% (23 of 263), 4.7% (11 of 232) and 6.1% (17 of 278), at delivery, nine weeks, six months and one year postpartum, respectively. High BMI and blood pressure were the drivers of metabolic syndrome in this population. The incidence rate in HDPs versus normotensive at one year were, respectively, 57.5/1000 persons' year (95%CI; 35.8 - 92.6) and 16.9/1000 persons' years (95%CI; 2.4-118.3), with incidence rate ratio of 3.4/1000 person's years. Only parity significantly predicted the presence of metabolic syndrome at one year [(aOR= 3.26/delivery (95%CI; 1.21-8.79)].

Conclusion: HDPs were associated with a higher incidence of metabolic syndrome up to one year postpartum. Women with HDPs should be routinely screened for metabolic syndrome within the first year postpartum to reduce cardiometabolic risks.
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http://dx.doi.org/10.1016/j.preghy.2021.05.018DOI Listing
August 2021

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

Reprod Health 2021 Feb 19;18(1):46. Epub 2021 Feb 19.

Division Women and Baby, Department of Obstetrics, Wilhelmina's Children Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1186/s12978-020-01051-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893967PMC
February 2021

Evidence-based interventions to reduce mortality among preterm and low-birthweight neonates in low-income and middle-income countries: a systematic review and meta-analysis.

BMJ Glob Health 2021 02;6(2)

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Preterm birth is the leading cause of under-five-mortality worldwide, with the highest burden in low-income and middle-income countries (LMICs). The aim of this study was to synthesise evidence-based interventions for preterm and low birthweight (LBW) neonates in LMICs, their associated neonatal mortality rate (NMR), and barriers and facilitators to their implementation. This study updates all existing evidence on this topic and reviews evidence on interventions that have not been previously considered in current WHO recommendations.

Methods: Six electronic databases were searched until 3 March 2020 for randomised controlled trials reporting NMR of preterm and/or LBW newborns following any intervention in LMICs. Risk ratios for mortality outcomes were pooled where appropriate using a random effects model (PROSPERO registration number: CRD42019139267).

Results: 1236 studies were identified, of which 49 were narratively synthesised and 9 contributed to the meta-analysis. The studies included 39 interventions in 21 countries with 46 993 participants. High-quality evidence suggested significant reduction of NMR following antenatal corticosteroids (Pakistan risk ratio (RR) 0.89; 95% CI 0.80 to 0.99|Guatemala 0.74; 0.68 to 0.81), single cord (0.65; 0.50 to 0.86) and skin cleansing with chlorhexidine (0.72; 0.55 to 0.95), early BCG vaccine (0.64; 0.48 to 0.86; I 0%), community kangaroo mother care (OR 0.73; 0.55 to 0.97; I 0%) and home-based newborn care (preterm 0.25; 0.14 to 0.48|LBW 0.42; 0.27 to 0.65). No effects on perinatal (essential newborn care 1.02; 0.91 to 1.14|neonatal resuscitation 0.95; 0.84 to 1.07) or 7-day NMR (essential newborn care 1.03; 0.83 to 1.27|neonatal resuscitation 0.92; 0.77 to 1.09) were observed after training birth attendants.

Conclusion: The findings of this study encourage the implementation of additional, evidence-based interventions in the current (WHO) guidelines and to be selective in usage of antenatal corticosteroids, to reduce mortality among preterm and LBW neonates in LMICs. Given the global commitment to end all preventable neonatal deaths by 2030, continuous evaluation and improvement of the current guidelines should be a priority on the agenda.
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http://dx.doi.org/10.1136/bmjgh-2020-003618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896575PMC
February 2021

The application of WHO ICD-PM: Feasibility for the classification of timing and causes of perinatal deaths in a busy birth centre in a low-income country.

PLoS One 2021 14;16(1):e0245196. Epub 2021 Jan 14.

Division Woman and Baby, University Medical Centre Utrecht, Utrecht, The Netherlands.

Objective: To assess the feasibility of the application of International Classification of Diseases-10-to perinatal mortality (ICD-PM) in a busy low-income referral hospital and determine the timing and causes of perinatal deaths, and associated maternal conditions.

Design: Prospective application of ICD-PM.

Setting: Referral hospital of Mnazi Mmoja Hospital, Zanzibar, United Republic of Tanzania.

Population: Stillbirths and neonatal deaths with a birth weight above 1000 grams born between October 16th 2017 to May 31st 2018.

Methods: Clinical information and an adapted WHO ICD-PM interactive excel-based system were used to capture and classify the deaths according to timing, causes and associated maternal complications. Descriptive analysis was performed.

Main Outcome Measures: Timing and causes of perinatal mortality and their associated maternal conditions.

Results: There were 661 perinatal deaths of which 248 (37.5%) were neonatal deaths and 413 (62.5%) stillbirths. Of the stillbirths, 128 (31%) occurred antepartum, 129 (31%) intrapartum and for 156 (38%) the timing was unknown. Half (n = 64/128) of the antepartum stillbirths were unexplained. Two-thirds (67%, n = 87/129) of intrapartum stillbirths followed acute intrapartum events, and 30% (39/129) were unexplained. Of the neonatal deaths, 40% died after complications of intrapartum events.

Conclusion: Problems of documentation, lack of perinatal death audits, capacity for investigations, and guidelines for the unambiguous objective assignment of timing and primary causes of death are major threats for accurate determination of timing and specific primary causes of perinatal deaths.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245196PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808596PMC
May 2021

Postpartum hemorrhage in Suriname: A national descriptive study of hospital births and an audit of case management.

PLoS One 2020 18;15(12):e0244087. Epub 2020 Dec 18.

Board of Doctoral Graduations and Honorary Doctorate Awards, Anton de Kom University, Paramaribo, Suriname, South Africa.

Background: Postpartum hemorrhage (PPH) is the leading cause of direct maternal mortality globally and in Suriname. We aimed to study the prevalence, risk indicators, causes, and management of PPH to identify opportunities for PPH reduction.

Methods: A nationwide retrospective descriptive study of all hospital deliveries in Suriname in 2017 was performed. Logistic regression analysis was applied to identify risk indicators for PPH (≥ 500ml blood loss). Management of severe PPH (blood loss ≥1,000ml or ≥500ml with hypotension or at least three transfusions) was evaluated via a criteria-based audit using the national guideline.

Results: In 2017, the prevalence of PPH and severe PPH in Suriname was 9.2% (n = 808/8,747) and 2.5% (n = 220/8,747), respectively. PPH varied from 5.8% to 15.8% across the hospitals. Risk indicators associated with severe PPH included being of African descent (Maroon aOR 2.1[95%CI 1.3-3.3], Creole aOR 1.8[95%CI 1.1-3.0]), multiple pregnancy (aOR 3.4[95%CI 1.7-7.1]), delivery in Hospital D (aOR 2.4[95%CI 1.7-3.4]), cesarean section (aOR 3.9[95%CI 2.9-5.3]), stillbirth (aOR 6.4 [95%CI 3.4-12.2]), preterm birth (aOR 2.1[95%CI 1.3-3.2]), and macrosomia (aOR 2.8 [95%CI 1.5-5.0]). Uterine atony (56.7%, n = 102/180[missing 40]) and retained placenta (19.4%, n = 35/180[missing 40]), were the main causes of severe PPH. A criteria-based audit revealed that women with severe PPH received prophylactic oxytocin in 61.3% (n = 95/155[missing 65]), oxytocin treatment in 68.8% (n = 106/154[missing 66]), and tranexamic acid in 4.9% (n = 5/103[missing 117]).

Conclusions: PPH prevalence and risk indicators in Suriname were similar to international and regional reports. Inconsistent blood loss measurement, varied maternal and perinatal characteristics, and variable guideline adherence contributed to interhospital prevalence variation. PPH reduction in Suriname can be achieved through prevention by practicing active management of the third stage of labor in every birth and considering risk factors, early recognition by objective and consistent blood loss measurement, and prompt treatment by adequate administration of oxytocin and tranexamic acid according to national guidelines.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244087PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748130PMC
March 2021

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

Health Technol Assess 2020 12;24(72):1-252

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management.

Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers.

Design: This was an individual participant data meta-analysis of cohort studies.

Setting: Source data from secondary and tertiary care.

Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey.

Primary Outcomes: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia.

Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using and τ. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals.

Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia.

Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data.

Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings.

Future Work: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate.

Study Registration: This study is registered as PROSPERO CRD42015029349.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780127PMC
December 2020

Applicability of the WHO maternal near-miss tool: A nationwide surveillance study in Suriname.

J Glob Health 2020 Dec;10(2):020429

Department of Obstetrics, Division Women and Baby, Birth Centre Wilhelmina's Children Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: Maternal near-miss (MNM) is an important maternal health quality-of-care indicator. To facilitate comparison between countries, the World Health Organization (WHO) developed the "MNM-tool". However, several low- and middle-income countries have proposed adaptations to prevent underreporting, ie, Namibian and Sub-Sahara African (SSA)-criteria. This study aims to assess MNM and associated factors in middle-income country Suriname by applying the three different MNM tools.

Methods: A nationwide prospective population-based cohort study was conducted using the Suriname Obstetric Surveillance System (SurOSS). We included women with MNM-criteria defined by WHO-, Namibian- and SSA-tools during one year (March 2017-February 2018) and used hospital births (86% of total) as a reference group.

Results: There were 9114 hospital live births in Suriname in the one-year study period. SurOSS identified 71 women with WHO-MNM (8/1000 live births, mortality-index 12%), 118 with Namibian-MNM (13/1000 live births, mortality-index 8%), and 242 with SSA-MNM (27/1000 live births, mortality-index 4%). Namibian- and SSA-tools identified all women with WHO-criteria. Blood transfusion thresholds and eclampsia explained the majority of differences in MNM prevalence. Eclampsia was not considered a WHO-MNM in 80% (n = 35/44) of cases. Nevertheless, mortality-index for MNM with hypertensive disorders was 17% and the most frequent underlying cause of maternal deaths (n = 4/10, 40%) and MNM (n = 24/71, 34%). Women of advanced age and maroon ethnicity had twice the odds of WHO-MNM (respectively adjusted odds ratio (aOR) = 2.6, 95% confidence interval (CI) = 1.4-4.8 and aOR = 2.0, 95% CI = 1.2-3.6). The stillbirths rate among women with WHO-MNM was 193/1000births, with six times higher odds than women without MNM (aOR = 6.8, 95%CI = 3.0-15.8). While the prevalence and mortality-index differ between the three MNM tools, the underlying causes of and factors associated with MNM were comparable.

Conclusions: The MNM ratio in Suriname is comparable to other countries in the region. The WHO-tool underestimates the prevalence of MNM (high mortality-index), while the adapted tools may overestimate MNM and compromise global comparability. Contextualized MNM-criteria per obstetric transition stage may improve comparability and reduce underreporting. While MNM studies facilitate international comparison, audit will remain necessary to identify shortfalls in quality-of-care and improve maternal outcomes.
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http://dx.doi.org/10.7189/jogh.10.020429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649043PMC
December 2020

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BMC Med 2020 11 2;18(1):302. Epub 2020 Nov 2.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting.

Methods: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis.

Results: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%.

Conclusions: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice.

Trial Registration: PROSPERO ID: CRD42015029349 .
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http://dx.doi.org/10.1186/s12916-020-01766-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604970PMC
November 2020

Why magnesium sulfate 'coverage' only is not enough to reduce eclampsia: Lessons learned in a middle-income country.

Pregnancy Hypertens 2020 Oct 21;22:136-143. Epub 2020 Sep 21.

Department of Obstetrics, Birth Centre Wilhelmina's Children Hospital, Division Woman and Baby, University Medical Center Utrecht, the Netherlands; Julius Global Health, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Objectives: Determine the eclampsia prevalence and factors associated with eclampsia and recurrent seizures in Suriname and evaluate quality-of-care indicator 'magnesium sulfate (MgSO4) coverage'.

Study Design: A two-year prospective nationwide cohort study was conducted in Suriname and included women with eclampsia at home or in a healthcare facility.

Main Outcome Measures: We calculated the prevalence by the number of live births obtained from vital registration. Risk factor denominator data concerned hospital births. Descriptive statistics and multivariate regression analysis were performed.

Results: Seventy-two women with eclampsia (37/10.000 live births) were identified, including two maternal deaths (case-fatality 2.8%). Nulliparity, African-descent and adolescence were associated with eclampsia. Adolescents with eclampsia had significantly lower BPs (150/100 mmHg) than adult women (168/105 mmHg). The first seizure occurred antepartum in 54% (n = 39/72), intrapartum in 19% (n = 14/72) and postpartum in 26% (n = 19/72). Recurrent seizures were observed in 60% (n = 43/72). MgSO4 was administered to 99% (n = 69/70) of women; however 26% received no loading dosage and, in 22% of cases MgSO4 duration was <24 h, i.e. guideline adherence existed in only 43%. MgSO4 was ceased during CS in all women (n = 40). Stable BP was achieved before CS in 46%. The median seizure-to-delivery interval was 27 h, and ranged from four to 36 h.

Conclusion: Solely 'MgSO4 coverage' is not a reliable quality-of-care indicator, as it conceals inadequate MgSO4 dosage and timing, discontinuation during CS, stabilization before delivery, and seizure-to-delivery interval. These other quality-of-care indicators need attention from the international community in order to reduce the prevalence of eclampsia.
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http://dx.doi.org/10.1016/j.preghy.2020.09.006DOI Listing
October 2020

Mistreatment during childbirth.

Lancet 2020 09;396(10254):816-817

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, Netherlands.

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http://dx.doi.org/10.1016/S0140-6736(20)31556-7DOI Listing
September 2020

Investigation of stillbirth causes in Suriname: application of the WHO ICD-PM tool to national-level hospital data.

Glob Health Action 2020 12;13(1):1794105

Department of Obstetrics, Division Women and Baby, Birth Centre Wilhelmina's Children Hospital, University Medical Centre Utrecht, Utrecht University , Utrecht, The Netherlands.

Background: Suriname has one of the highest stillbirth rates in Latin America and the Caribbean. To facilitate data comparison of perinatal deaths, the World Health Organization developed the International Classification of Diseases-10 Perinatal Mortality (ICD-PM).

Objective: We aimed to (1) assess characteristics and risk indicators of women with a stillbirth, (2) determine the timing and causes of stillbirths according to the ICD-PM with critical evaluation of its application and (3) propose recommendations for the reduction of stillbirths in Suriname.

Methods: A hospital-based, nation-wide, cross-sectional study was conducted in all hospitals within Suriname during one-year (2017). The medical files of stillbirths (gestation ≥28 weeks/birth weight ≥1000 grams) were reviewed and classified using ICD-PM. We used descriptive statistics and multiple logistic regression analyses.

Results: The stillbirth rate in Suriname was 14.4/1000 births (n=131 stillbirths, n=9089 total births). Medical files were available for 86% (n=113/131) of stillbirths. Women of African descent had the highest stillbirth rate and two times the odds of stillbirth (OR 2.1, 95%CI 1.4-3.1) compared to women of other ethnicities. One third (33%, n=37/113) of stillbirths occurred after hospital admission. The timing was antepartum in 85% (n=96/113), intrapartum in 11% (n=12/113) and unknown in 4% (n=5/113). Antepartum stillbirths were caused by in 46% (n=44/96). In 41% (n=39/96) the cause was unspecified. were present in 50% (n=57/113), mostly hypertensive disorders.

Conclusion: Stillbirth reduction strategies in Suriname call for targeting ethnic disparities, improving antenatal services, implementing perinatal death audits and improving diagnostic post-mortem investigations. ICD-PM limited the formulation of recommendations due to many stillbirths of 'unspecified' causes. Based on our study findings, we also recommend addressing some challenges with applying the ICD-PM.

Abbreviations: CTG: Cardiotocography; ENAP: Every Newborn Action Plan (ENAP); ICD-PM: The WHO application of ICD-10 to deaths during the perinatal period - perinatal mortality; SBR: Stillbirth rate; SGA: Small for gestational age; WHO: World Health Organization; LMIC: Low- and middle-income countries; FHR: foetal heart rate.
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http://dx.doi.org/10.1080/16549716.2020.1794105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480654PMC
December 2020

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

Reprod Health 2020 May 7;17(1):62. Epub 2020 May 7.

Julius Global Health, The Julius Centre for Health Sciences, University Medical Centre Utrecht, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1186/s12978-020-0902-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206667PMC
May 2020

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

Reprod Health 2020 Mar 14;17(1):36. Epub 2020 Mar 14.

Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.

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.
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http://dx.doi.org/10.1186/s12978-020-0849-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071714PMC
March 2020

Household fuel use and adverse pregnancy outcomes in a Ghanaian cohort study.

Reprod Health 2020 Feb 22;17(1):29. Epub 2020 Feb 22.

Institute for Risk Assessment Science (IRAS), Division of Environmental Epidemiology (EEPI), Utrecht University, Utrecht, The Netherlands.

Background: Accruing epidemiological evidence suggests that prenatal exposure to emissions from cooking fuel is associated with increased risks of adverse maternal and perinatal outcomes including hypertensive disorders of pregnancy, low birth weight, stillbirth and infant mortality. We aimed to investigate the relationship between cooking fuel use and various pregnancy related outcomes in a cohort of urban women from the Accra region of Ghana.

Methods: Self-reported cooking fuel use was divided into "polluting" (wood, charcoal, crop residue and kerosene) and "clean" fuels (liquid petroleum gas and electricity) to examine 12 obstetric outcomes in a prospective cohort of pregnant women (N = 1010) recruited at < 17 weeks of gestation from Accra, Ghana. Logistic and multivariate linear regression analyses adjusted for BMI, maternal age, maternal education and socio-economic status asset index was conducted.

Results: 34% (n = 279) of 819 women with outcome data available for analysis used polluting fuel as their main cooking fuel. Using polluting cooking fuels was associated with perinatal mortality (aOR: 7.6, 95%CI: 1.67-36.0) and an adverse Apgar score (< 7) at 5 min (aOR:3.83, 95%CI: (1.44-10.11). The other outcomes (miscarriage, post-partum hemorrhage, pre-term birth, low birthweight, caesarian section, hypertensive disorders of pregnancy, small for gestational age, and Apgar score at 1 min) had non-statistically significant findings.

Conclusions: We report an increased likelihood of perinatal mortality, and adverse 5-min Apgar scores in association with polluting fuel use. Further research including details on extent of household fuel use exposure is recommended to better quantify the consequences of household fuel use.

Study Registration: Ghana Service Ethical Review Committee (GHS-ERC #: 07-9-11).
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http://dx.doi.org/10.1186/s12978-020-0878-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036189PMC
February 2020

Prognostic models for adverse pregnancy outcomes in low-income and middle-income countries: a systematic review.

BMJ Glob Health 2019 30;4(5):e001759. Epub 2019 Oct 30.

Julius Global Health, Julius Center for Health Sciences and Primary Care, Universitair Medisch Centrum Utrecht, Utrecht University, Utrecht, The Netherlands.

Introduction: Ninety-nine per cent of all maternal and neonatal deaths occur in low-income and middle-income countries (LMIC). Prognostic models can provide standardised risk assessment to guide clinical management and can be vital to reduce and prevent maternal and perinatal mortality and morbidity. This review provides a comprehensive summary of prognostic models for adverse maternal and perinatal outcomes developed and/or validated in LMIC.

Methods: A systematic search in four databases (PubMed/Medline, EMBASE, Global Health Library and The Cochrane Library) was conducted from inception (1970) up to 2 May 2018. Risk of bias was assessed with the PROBAST tool and narratively summarised.

Results: 1741 articles were screened and 21 prognostic models identified. Seventeen models focused on maternal outcomes and four on perinatal outcomes, of which hypertensive disorders of pregnancy (n=9) and perinatal death including stillbirth (n=4) was most reported. Only one model was externally validated. Thirty different predictors were used to develop the models. Risk of bias varied across studies, with the item 'quality of analysis' performing the least.

Conclusion: Prognostic models can be easy to use, informative and low cost with great potential to improve maternal and neonatal health in LMIC settings. However, the number of prognostic models developed or validated in LMIC settings is low and mirrors the 10/90 gap in which only 10% of resources are dedicated to 90% of the global disease burden. External validation of existing models developed in both LMIC and high-income countries instead of developing new models should be encouraged.

Prospero Registration Number: CRD42017058044.
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http://dx.doi.org/10.1136/bmjgh-2019-001759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830054PMC
October 2019

Birth asphyxia following delayed recognition and response to abnormal labour progress and fetal distress in a 31-year-old multiparous Malawian woman.

BMJ Case Rep 2019 Sep 11;12(9). Epub 2019 Sep 11.

Department of Vrouw & Baby, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands.

Reducing neonatal mortality is one of the targets of Sustainable Development Goal 3 on good health and well-being. The highest rates of neonatal death occur in sub-Saharan Africa. Birth asphyxia is one of the major preventable causes. Early detection and timely management of abnormal labour progress and fetal compromise are critical to reduce the global burden of birth asphyxia. Labour progress, maternal and fetal well-being are assessed using the WHO partograph and intermittent fetal heart rate monitoring. However, in low-resource settings adherence to labour guidelines and timely response to arising labour complications is generally poor. Reasons for this are multifactorial and include lack of resources and skilled health care staff. This case study in a Malawian hospital illustrates how delayed recognition of abnormal labour and prolonged decision-to-delivery interval contributed to birth asphyxia, as an example of many delivery rooms in low-income country settings.
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http://dx.doi.org/10.1136/bcr-2018-227973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738677PMC
September 2019

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

BMC Health Serv Res 2019 Sep 9;19(1):651. Epub 2019 Sep 9.

Department of Obstetrics, Division Women and Baby, Birth Centre Wilhelmina's Children Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.

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.
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http://dx.doi.org/10.1186/s12913-019-4377-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734520PMC
September 2019

Medical schools should ensure and improve global health education.

Lancet 2019 08;394(10200):731

Julius Global Health, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands; Netherlands Society for Tropical Medicine and International Health, Wijhe, Netherlands. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(19)31254-1DOI Listing
August 2019

Equity in maternal health outcomes in a middle-income urban setting: a cohort study.

Reprod Health 2019 Jun 18;16(1):84. Epub 2019 Jun 18.

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: Low socioeconomic status (SES) is associated with more adverse perinatal health outcomes, risk factors and lower access to and use of maternal health care services. However, evidence for the association between SES and maternal health outcomes is limited, particularly for middle-income countries like sub-Saharan Ghana. We assessed the association between parental SES and adverse maternal and perinatal outcomes of Ghanaian women during pregnancy, delivery and the postpartum period.

Methods: A prospective cohort study of 1010 women of two public hospitals in Accra, Ghana (2012-2014). SES was proxied by maternal and paternal education, wealth and employment status. The association of SES with maternal and perinatal outcomes was analyzed with multivariable logistic and linear regression.

Results: The analysis included 790 women with information on pregnancy outcomes. Average age was 28.2 years (standard deviation, SD 5.0). Over a third (n = 292, 37.0%) had low SES, 176 (22.3%) were classified to have high SES using the assets index. Nearly half (n = 374, 47.3%) of women had lower secondary school or vocational training as highest education level. Compared to women with middle assets SES, women with low assets SES were at higher risk for miscarriage (odds ratio, OR 1.61, 95% CI 1.06 to 2.45) and instrumental delivery (OR 1.74, 95% CI 1.03 to 2.94), but this association was not observed for the other SES proxies. For any of the maternal or perinatal outcomes and SES proxies, no other statistically significant differences were found.

Conclusion: Women attending public maternal health care services in urban Ghana had overall equitable maternal and perinatal health outcomes, with the exception of a higher risk of miscarriage and instrumental delivery associated with low assets SES. This suggests known associations between SES, risk factors and outcomes could be mitigated with universal and accessible maternal health services.
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http://dx.doi.org/10.1186/s12978-019-0736-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580627PMC
June 2019

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

Eur J Public Health 2019 08;29(4):714-723

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1093/eurpub/ckz042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734941PMC
August 2019

Delphi consensus statement on intrapartum fetal monitoring in low-resource settings.

Int J Gynaecol Obstet 2019 Jul 24;146(1):8-16. Epub 2018 Dec 24.

Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands.

Objective: To determine acceptable and achievable strategies of intrapartum fetal monitoring in busy low-resource settings.

Methods: Three rounds of online Delphi surveys were conducted between January 1 and October 31, 2017. International experts with experience in low-resource settings scored the importance of intrapartum fetal monitoring methods.

Results: 71 experts completed all three rounds (28 midwives, 43 obstetricians). Consensus was reached on (1) need for an admission test, (2) handheld Doppler for intrapartum fetal monitoring, (3) intermittent auscultation (IA) every 30 minutes for low-risk pregnancies during the first stage of labor and after every contraction for high-risk pregnancies in the second stage, (4) contraction monitoring hourly for low-risk pregnancies in the first stage, and (5) adjunctive tests. Consensus was not reached on frequency of IA or contraction monitoring for high-risk women in the first stage or low-risk women in the second stage of labor.

Conclusion: There is a gap between international recommendations and what is physically possible in many labor wards in low-resource settings. Research on how to effectively implement the consensus on fetal assessment at admission and use of handheld Doppler during labor and delivery is crucial to support staff in achieving the best possible care in low-resource settings.
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http://dx.doi.org/10.1002/ijgo.12724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379246PMC
July 2019

The willingness to participate in biomedical research involving human beings in low- and middle-income countries: a systematic review.

Trop Med Int Health 2019 03 8;24(3):264-279. Epub 2019 Jan 8.

Department of Medical Humanities, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Objectives: To systematically review reasons for the willingness to participate in biomedical human subjects research in low- and middle-income countries (LMICs).

Methods: Five databases were systematically searched for articles published between 2000 and 2017 containing the domain of 'human subjects research' in 'LMICs' and determinant 'reasons for (non)participation'. Reasons mentioned were extracted, ranked and results narratively described.

Results: Ninety-four articles were included, 44 qualitative and 50 mixed-methods studies. Altruism, personal health benefits, access to health care, monetary benefit, knowledge, social support and trust were the most important reasons for participation. Primary reasons for non-participation were safety concerns, inconvenience, stigmatisation, lack of social support, confidentiality concerns, physical pain, efficacy concerns and distrust. Stigmatisation was a major concern in relation to HIV research. Reasons were similar across different regions, gender, non-patient or patient participants and real or hypothetical study designs.

Conclusions: Addressing factors that affect (non-)participation in the planning process and during the conduct of research may enhance voluntary consent to participation and reduce barriers for potential participants.
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http://dx.doi.org/10.1111/tmi.13195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850431PMC
March 2019

Strategies for intrapartum foetal surveillance in low- and middle-income countries: A systematic review.

PLoS One 2018 26;13(10):e0206295. Epub 2018 Oct 26.

Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: The majority of the five million perinatal deaths worldwide take place in low-resource settings. In contrast to high-resource settings, almost 50% of stillbirths occur intrapartum. The aim of this study was to synthesise available evidence of strategies for foetal surveillance in low-resource settings and associated neonatal and maternal outcomes, including barriers to their implementation.

Methods And Findings: The review was registered with Prospero (CRD42016038679). Five databases were searched up to May 1st, 2016 for studies related to intrapartum foetal monitoring strategies and neonatal outcomes in low-resource settings. Two authors extracted data and assessed the risk of bias for each study. The outcomes were narratively synthesised. Strengths, weaknesses, opportunities and threats analysis (SWOT) was conducted for each monitoring technique to analyse their implementation. There were 37 studies included: five intervention and 32 observational studies. Use of the partograph improved perinatal outcomes. Intermittent auscultation with Pinard was associated with lowest rates of caesarean sections (10-15%) but with comparable perinatal outcomes to hand-held Doppler and Cardiotocography (CTG). CTG was associated with the highest rates of caesarean sections (28-34%) without proven benefits for perinatal outcome. Several tests on admission (admission tests) and adjunctive tests including foetal stimulation tests improved the accuracy of foetal heart rate monitoring in predicting adverse perinatal outcomes.

Conclusions: From the available evidence, the partograph is associated with improved perinatal outcomes and is recommended for use with intermittent auscultation for intrapartum monitoring in low resource settings. CTG is associated with higher caesarean section rates without proven benefits for perinatal outcomes, and should not be recommended in low-resource settings. High-quality evidence considering implementation barriers and enablers is needed to determine the optimal foetal monitoring strategy in low-resource settings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206295PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203373PMC
April 2019
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