Assessing the cost-effectiveness of interventions for Hypertensive Disorder of Pregnancy and Diabetes Mellitus in Pregnancy in Bangladesh

Progress in reducing maternal mortality have stalled during the Sustainable Development Goals era both globally and in Bangladesh. Maternal mortality is often called the tip of the iceberg. The morbidities leading to maternal deaths often remain ignored. Long-term impact of these morbidities are rarely discussed. While hypertensive disorder is one of the leading causes of maternal deaths, there is a growing burden of diabetes in pregnancy. Economic evaluation models addressing either of the two Non-Communicable Diseases are scarce, especially in the context of low and middle income countries. Preventive interventions are highly recommended for addressing the burden of NCDs and are expected to be easier to implement given the capacity problems evidence in the Bangladesh health system. The aim of this thesis was to develop a cost-effectiveness model for interventions addressing hypertensive disorder and diabetes mellitus in pregnancy among Bangladeshi women. This was done in several steps including multiple reviews, stakeholder consultations and finally developing the model. First, a review of World Health Organisation and Bangladesh clinical guideline review was undertaken to understand the two diseases and their recommended treatment pathways. The clinical guideline review led to the identification of the risk factors of the two conditions, their symptoms or diagnostic criteria and the treatment to be undertaken once they are detected. This review also identified the individual level risk factors of the two diseases and revealed that diabetes mellitus, both pre-existing and gestational are risk factors for hypertensive disorder in pregnancy. The review recommendations suggested antenatal care to be the key stage of the pregnancy continuum of care to address the two disease conditions. It also indicated antenatal period to be the most crucial stage for delivering preventive interventions. Next, a systematic review of economic evaluation models assessing interventions related to hypertensive disorder and diabetes mellitus in pregnancy identified those methods that had been used previously. While decision trees represented the dominant model structures, markov state transition and microsimulation models had also been used. Interventions could be divided into several types; screening and diagnosis, treatment, diet and lifestyle, labour induction and others. Most models were built from a health system’s perspective while some were focused on the payer’s or societal perspective. Model time horizons ranged from pre-conception to the lifetime of the women and their offspring. A varied set of model outcomes were identified including immediate outcomes like development of hypertensive disorder to mortality and development of chronic conditions in the long-term. This review highlighted the lack of a consistent approach to modelling of these two disorders and the lack of a model that was suitable for decision making in Bangladesh. Both reviews also revealed the need for preventive care measures, specifically during the antenatal period. The reviews led to the development of a detailed list of interventions relevant for Bangladesh and a draft conceptual framework. These were presented to stakeholders and amended via interviews. Both the reviews and interviews with stakeholders identified the antenatal care related interventions as the key to address the two diseases conditions. The antenatal care package was deemed to be the most important intervention in addressing the two conditions which contains multiple preventive interventions. Rather than modelling the whole package of intervention, a single preventive intervention was selected as an exemplar. The final intervention selected for the model was calcium supplementation among pregnant women in Bangladesh scaled up from 18% to reach 80% coverage level. Calcium supplementation is a recommended preventive intervention that is supposed to be delivered as part of the antenatal care package through the Bangladeshi health system. Methods for incorporating multiple intervention effect were explored and documented. The model programming ensured flexibility in incorporating additional interventions for future work. The model took health system’s perspective as suggested by the stakeholders. Model outcomes covered the development of hypertensive disorders and gestational diabetes mellitus in pregnancy, c-section, preterm births, stillbirths, newborn and maternal deaths. Long-term outcomes needed to account for development of chronic conditions among women for a lifetime and developmental delay among children for 5 years. The model took into account two pre-existing chronic conditions as risk factors; pre-existing chronic hypertension and diabetes mellitus. An individual based markov microsimulation model was developed. Increased risks of events and outcomes were assigned from existing literature through ad hoc reviews. Costs of intervention and all downstream care-seeking were estimated based on Bangladesh national data. Disability Adjusted Life Years (DALYs) were estimated based on disability weights from Global Burden of Disease studies and country-specific life tables for women. DALYs were estimated both for pregnancy and long-term health conditions. Finally, a cost effectiveness analysis was undertaken and a probabilistic sensitivity analysis (PSA) was incorporated accounting for parameter uncertainty. The model was validated for the base case scenario against national prevalence levels and verified using a prescribed technical verification checklist. The model produced summary outputs in the form of Net Monetary Benefit, the Incremental Cost Effectiveness Ratio, the cost-effectiveness plane, cost-effectiveness acceptability curve. Selected scenario and sub-group analysis and deterministic sensitivity analyses were also conducted. The willingness to pay threshold was set at 1x and 3x Gross Domestic Product (GDP) per capita values based on stakeholder requirements. The intervention reduced adverse pregnancy and birth outcomes for mothers and their babies. The direct impact of the intervention led to a reduction in the number of women developing gestational hypertension, pre-eclampsia and eclampsia (23%, 40% and 36% reduction respectively). Caesarean-sections reduced by 7% through an indirect effect of the intervention. Preterm births and stillbirths reduced by 7% each and maternal deaths saw a 45% reduction through both direct and indirect impact. Newborn deaths were reduced by 8% through reduction in preterm births. Among the long-term outcomes, there was an 8% reduction in chronic hypertension while diabetes mellitus remained almost unchanged. The incremental cost per woman was estimated at BDT -5122 which indicates a cost saving for the scaled-up provision of care. The probability of the scaled-up provision to be cost-effective was 1 at both 1xGDP and 3xGDP per capita threshold level. The incremental net monetary benefit was positive at both threshold level and for all sub-group level analyses, which covered pre-existing conditions, age, education and wealth quintiles. The model is novel and added to the existing evidence base in several ways. It is the first model that took into account two cardio-metabolic diseases; hypertensive disorder and diabetes mellitus in pregnancy together. Pre-existing conditions and risks related to them were incorporated as risk factors in the model while interaction between the two pregnancy related conditions were also considered. The model was strengthened in terms of its validity and relevance by use of a large number of country specific data and involving stakeholders at an early stage. Findings from this thesis can add value to the existing evidence base of economic evaluation of calcium in the context of low and middle income countries. The thesis reemphasised the need for ensuring access to calcium supplementation during pregnancy in Bangladesh to prevent hypertensive disorders in pregnancy. It also highlighted that this simple intervention can release resources, which can then be redirected to other areas of need. In order to ensure successful implementation of this intervention, there is value in exploring the most effective channel for delivering the intervention. Further research should also consider ways to improve compliance in calcium intake, alternative sources of calcium like food fortification during pregnancy and pre-conception and explore the optimum dose of calcium for Bangladeshi women

Production and use of estimates for monitoring progress in the health sector: the case of Bangladesh

Background: In order to support the progress towards the post-2015 development agenda for the health sector, the importance of high-quality and timely estimates has become evident both globally and at the country level

Shonjibon cash and counselling : a community-based cluster randomised controlled trial to measure the effectiveness of unconditional cash transfers and mobile behaviour change communications to reduce child undernutrition in rural Bangladesh

Background: Undernutrition is strongly associated with poverty - levels of undernutrition are higher in poor countries than in better-off countries. Social protection especially cash transfer is increasingly recognized as an important strategy to accelerate progress in improving maternal and child nutrition. A critical method to improve nutrition knowledge and influence feeding practices is through behaviour change communication intervention. The Shonjibon Cash and Counselling study aims to assess the effectiveness of unconditional cash transfers combined with a mobile application on nutrition counselling and direct counselling through mobile phone in reducing the prevalence of stunting in children at 18 months. Method: The study is a longitudinal cluster randomised controlled trial, with two parallel groups, and cluster assignment by groups of villages. The cohort of mother-child dyads will be followed-up over the intervention period of approximately 24 months, starting from recruitment to 18 months of the child’s age. The study will take place in north-central Bangladesh. The primary trial outcome will be the percentage of stunted children at 18 m as measured in follow up assessments starting from birth. The secondary trial outcomes will include differences between treatment arms in (1) Mean birthweight, percentage with low birthweight and small for gestational age (2) Mean child length-for age, weight for age and weight-for-length Z scores (3) Prevalence of child wasting (4) Percentage of women exclusively breastfeeding and mean duration of exclusive breastfeeding (5) Percentage of children consuming > 4 food groups (6) Mean child intake of energy, protein, carbohydrate, fat and micronutrients (7) Percentage of women at risk of inadequate nutrient intakes in all three trimesters (8) Maternal weight gain (9) Household food security (10) Number of events for child suffering from diarrhoea, acute respiratory illness and fever (11) Average costs of mobile phone BCC and cash transfer, and benefit-cost ratio for primary and secondary outcomes. Discussion: The proposed trial will provide high-level evidence of the efficacy and cost-effectiveness of mobile phone nutrition behavior change communication, combined with unconditional cash transfers in reducing child undernutrition in rural Bangladesh. Trial registration: The study has been registered in the Australian New Zealand Clinical Trials Registry (ACTRN12618001975280)

Out-of-pocket expenditure for seeking health care for sick children younger than 5 years of age in Bangladesh: findings from cross-sectional surveys, 2009 and 2012

Background: Bangladesh has committed to universal health coverage, and options to decrease household out-of-pocket expenditure (OPE) are being explored. Understanding the determinants of OPE is an essential step. This study aimed to estimate and identify determinants of OPE in seeking health care for sick under-five children. Methods: Cross-sectional data was collected by structured questionnaire in 2009 (n = 7362) and 2012 (n = 6896) from mothers of the under-five children. OPE included consultation fees and costs of medicine, diagnostic tests, hospital admission, transport, accommodation, and food. Expenditure is expressed in US dollars and adjusted for inflation. Linear regression was used for ascertaining the determinants of OPE. Results: Between 2009 and 2012, the median OPE for seeking care for a sick under-five child increased by ~ 50%, from USD 0.82 (interquartile range 0.39\u20131.49) to USD 1.22 (0.63\u20132.36) per child/visit. Increases were observed in every component OPE measured, except for consultation fees which decreased by 12%. Medicine contributed the major portion of overall OPE. Higher overall OPE for care seeking was associated with a priority illness (20% increase), care from trained providers (90% public/~ 2-fold private), residing in hilly/wet lands areas (20%) , and for mothers with a secondary education (19%). Conclusion: OPE is a major barrier to quality health care services and access to appropriate medicine is increasing in rural Bangladesh. To support the goal of universal health care coverage, geographic imbalances as well as expanded health financing options need to be explored

EN-BIRTH Data Collector Training - Handbook and Manual

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains the EN-BIRTH_Trainer's Manual (14 June 2017) and EN-BIRTH_Training Handbook (23 May 2017)

EN-BIRTH Data Collector Training - Supporting Annexes

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains consent forms and participant information, in addition to standard operating procedures (SOP) for adverse clinical events, and managing distress in interviews. The full complement of annex files used during the training can be requested via this site if required

Chlorhexidine for facility-based umbilical cord care: EN-BIRTH multi-country validation study.

BACKGROUND: Umbilical cord hygiene prevents sepsis, a leading cause of neonatal mortality. The World Health Organization recommends 7.1% chlorhexidine digluconate (CHX) application to the umbilicus after home birth in high mortality contexts. In Bangladesh and Nepal, national policies recommend CHX use for all facility births. Population-based household surveys include optional questions on CHX use, but indicator validation studies are lacking. The Every Newborn Birth Indicators Research Tracking in Hospitals (EN-BIRTH) was an observational study assessing measurement validity for maternal and newborn indicators. This paper reports results regarding CHX. METHODS: The EN-BIRTH study (July 2017-July 2018) included three public hospitals in Bangladesh and Nepal where CHX cord application is routine. Clinical-observers collected tablet-based, time-stamped data regarding cord care during admission to labour and delivery wards as the gold standard to assess accuracy of women's report at exit survey, and of routine-register data. We calculated validity ratios and individual-level validation metrics; analysed coverage, quality and measurement gaps. We conducted qualitative interviews to assess barriers and enablers to routine register-recording. RESULTS: Umbilical cord care was observed for 12,379 live births. Observer-assessed CHX coverage was very high at 89.3-99.4% in all 3 hospitals, although slightly lower after caesarean births in Azimpur (86.8%), Bangladesh. Exit survey-reported coverage (0.4-45.9%) underestimated the observed coverage with substantial "don't know" responses (55.5-79.4%). Survey-reported validity ratios were all poor (0.01 to 0.38). Register-recorded coverage in the specific column in Bangladesh was underestimated by 0.2% in Kushtia but overestimated by 9.0% in Azimpur. Register-recorded validity ratios were good (0.9 to 1.1) in Bangladesh, and poor (0.8) in Nepal. The non-specific register column in Pokhara, Nepal substantially underestimated coverage (20.7%). CONCLUSIONS: Exit survey-report highly underestimated observed CHX coverage in all three hospitals. Routine register-recorded coverage was closer to observer-assessed coverage than survey reports in all hospitals, including for caesarean births, and was more accurately captured in hospitals with a specific register column. Inclusion of CHX cord care into registers, and tallied into health management information system platforms, is justified in countries with national policies for facility-based use, but requires implementation research to assess register design and data flow within health information systems

A community-based cluster randomised controlled trial in rural Bangladesh to evaluate the impact of the use of iron-folic acid supplements early in pregnancy on the risk of neonatal mortality: The Shonjibon trial

Abstract Background Iron-deficiency is the most common nutritional deficiency globally. Due to the high iron requirements for pregnancy, it is highly prevalent and severe in pregnant women. There is strong evidence that maternal iron deficiency anaemia increases the risk of adverse perinatal outcomes. However, most of the evidence is from observational epidemiological studies except for a very few randomised controlled trials. IFA supplements have also been found to reduce the preterm delivery rate and neonatal mortality attributable to prematurity and birth asphyxia. These results combined indicate that IFA supplements in populations of iron-deficient pregnant women could lead to a decrease in the number of neonatal deaths mediated by reduced rates of preterm delivery. In this paper, we describe the protocol of a community-based cluster randomised controlled trial that aims to evaluate the impact of maternal antenatal IFA supplements on perinatal outcomes. Methods/design The effect of the early use of iron-folic acid supplements on neonatal mortality will be examined using a community based, cluster randomised controlled trial in five districts with 30,000 live births. In intervention clusters trained BRAC village volunteers will identify pregnant women & provide iron-folic acid supplements. Groundwater iron levels will be measured in all study households using a validated test kit. The analysis will follow the intention to treat principle. We will compare neonatal mortality rates & their 95% confidence intervals adjusted for clustering between treatment groups in each groundwater iron-level group. Cox proportional hazards mixed models will be used for mortality outcomes & will include groundwater iron level as an interaction term in the mortality model. Discussion This paper aims to describe the study protocol of a community based randomised controlled trial evaluating the impact of the use of iron-folic acid supplements early in pregnancy on the risk of neonatal mortality. This study is critical because it will determine if antenatal IFA supplements commenced in the first trimester of pregnancy, rather than later, will significantly reduce neonatal deaths in the first month of life, and if this approach is cost-effective. Trial registration This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 31 May 2012. The registration ID is ACTRN12612000588897

Birth preparedness and complication readiness (BPCR) among pregnant women in hard-to-reach areas in Bangladesh:BPCR in hard-to-reach areas of Bangladesh

Birth preparedness and complication readiness aims to reduce delays in care seeking, promote skilled birth attendance, and facility deliveries. Little is known about birth preparedness practices among populations living in hard-to-reach areas in Bangladesh.To describe levels of birth preparedness and complication readiness among recently delivered women, identify determinants of being better prepared for birth, and assess the impact of greater birth preparedness on maternal and neonatal health practices.A cross-sectional survey with 2,897 recently delivered women was undertaken in 2012 as part of an evaluation trial done in five hard-to-reach districts in rural Bangladesh. Mothers were considered well prepared for birth if they adopted two or more of the four birth preparedness components. Descriptive statistics and multivariable logistic regression were used for analysis.Less than a quarter (24.5%) of women were considered well prepared for birth. Predictors of being well-prepared included: husband's education (OR = 1.3; CI: 1.1-1.7), district of residence, exposure to media in the form of reading a newspaper (OR = 2.2; CI: 1.2-3.9), receiving home visit by a health worker during pregnancy (OR = 1.5; CI: 1.2-1.8), and receiving at least 3 antenatal care visits from a qualified provider (OR = 1.4; CI: 1.0-1.9). Well-prepared women were more likely to deliver at a health facility (OR = 2.4; CI: 1.9-3.1), use a skilled birth attendant (OR = 2.4, CI: 1.9-3.1), practice clean cord care (OR = 1.3, CI: 1.0-1.5), receive post-natal care from a trained provider within two days of birth for themselves (OR = 2.6, CI: 2.0-3.2) or their newborn (OR = 2.6, CI: 2.1-3.3), and seek care for delivery complications (OR = 1.8, CI: 1.3-2.6).Greater emphasis on BPCR interventions tailored for hard to reach areas is needed to improve skilled birth attendance, care seeking for complications and essential newborn care and facilitate reductions in maternal and neonatal mortality in low performing districts in Bangladesh

EN-BIRTH Data Collection Tools

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains the following data collection tools: Register data extraction, Observation checklist (labour and delivery ward), Observation checklist (kangaroo mother care), Patient record verification tools for antenatal corticosteroid administration, Patient record verification tools for antibiotic administration, and the Maternal recall survey