Modeling maternal mortality in Bangladesh: the role of misoprostol in postpartum hemorrhage prevention.

BACKGROUND: Bangladesh is one of the few countries that may actually achieve the fifth Millennium Development Goal (MDG) in time, despite skilled birth attendance remaining low. The purpose of this paper is to examine the potential role misoprostol can play in the decline of maternal deaths attributed to postpartum hemorrhage (PPH) in Bangladesh. METHODS: Using data from a misoprostol and blood loss measurement tool feasibility study in Bangladesh, observed cause specific maternal mortality ratios (MMRs) were estimated and contrasted with expected ratios using estimates from the Bangladesh Maternal Mortality Survey (BMMS) data. Using Crystal Ball 7 we employ Monte Carlo simulation techniques to estimate maternal deaths in four scenarios, each with different levels of misoprostol coverage. These scenarios include project level misoprostol coverage (69%), no (0%), low (40%), and high (80%) misoprostol coverage. Data on receipt of clean delivery kit, use of misoprostol, experience of PPH, and cause of death were used in model assumptions. RESULTS: Using project level misoprostol coverage (69%), the mean number of PPH deaths expected was 40 (standard deviation = 8.01) per 100,000 live births. Assuming no misoprostol coverage (0%), the mean number of PPH deaths expected was 51 (standard deviation = 9.30) per 100,000 live births. For low misoprostol coverage (40%), the mean number of PPH deaths expected was 45 (standard deviation = 8.26) per 100,000 live births, and for high misoprostol coverage (80%), the mean number of PPH deaths expected was 38 (standard deviation = 7.04) per 100,000 live births. CONCLUSION: This theoretical exercise hypothesizes that prophylactic use of misoprostol at home births may contribute to a reduction in the risk of death due to PPH, in addition to reducing the incidence of PPH. If findings from this modeling exercise are accurate and uterotonics can prevent maternal death, misoprostol could be the tool countries need to further reduce maternal mortality at home births.

Performance of a validated spontaneous preterm delivery predictor in South Asian and Sub-Saharan African women: a nested case control study.

OBJECTIVES: To address the disproportionate burden of preterm birth (PTB) in low- and middle-income countries, this study aimed to (1) verify the performance of the United States-validated spontaneous PTB (sPTB) predictor, comprised of the IBP4/SHBG protein ratio, in subjects from Bangladesh, Pakistan and Tanzania enrolled in the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, and (2) discover biomarkers that improve performance of IBP4/SHBG in the AMANHI cohort. STUDY DESIGN: The performance of the IBP4/SHBG biomarker was first evaluated in a nested case control validation study, then utilized in a follow-on discovery study performed on the same samples. Levels of serum proteins were measured by targeted mass spectrometry. Differences between the AMANHI and U.S. cohorts were adjusted using body mass index (BMI) and gestational age (GA) at blood draw as covariates. Prediction of sPTB < 37 weeks and < 34 weeks was assessed by area under the receiver operator curve (AUC). In the discovery phase, an artificial intelligence method selected additional protein biomarkers complementary to IBP4/SHBG in the AMANHI cohort. RESULTS: The IBP4/SHBG biomarker significantly predicted sPTB < 37 weeks (n = 88 vs. 171 terms ≥ 37 weeks) after adjusting for BMI and GA at blood draw (AUC= 0.64, 95% CI: 0.57-0.71, p < .001). Performance was similar for sPTB < 34 weeks (n = 17 vs. 184 ≥ 34 weeks): AUC = 0.66, 95% CI: 0.51-0.82, p = .012. The discovery phase of the study showed that the addition of endoglin, prolactin, and tetranectin to the above model resulted in the prediction of sPTB < 37 with an AUC= 0.72 (95% CI: 0.66-0.79, p-value < .001) and prediction of sPTB < 34 with an AUC of 0.78 (95% CI: 0.67-0.90, p < .001). CONCLUSION: A protein biomarker pair developed in the U.S. may have broader application in diverse non-U.S. populations.

Population-based incidence and serotype distribution of invasive pneumococcal disease prior to introduction of conjugate pneumococcal vaccine in Bangladesh.

BACKGROUND: Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV-10) in 2015. We measured population-based incidence of invasive pneumococcal disease (IPD) prior to introduction of PCV-10 to provide a benchmark against which the impact of PCV-10 can be assessed. METHODS: We conducted population, facility and laboratory-based surveillance in children 0-59 months of age in three rural sub-districts of Sylhet district of Bangladesh from January 2014 to June 2015. All children received two-monthly home visits with one week recall for morbidity and care seeking. Children attending the three Upazilla Health Complexes (UHC, sub-district hospitals) in the surveillance area were screened for suspected IPD. Blood samples were collected from suspected IPD cases for culture and additionally, cerebrospinal fluid (CSF) was collected from suspected meningitis cases for culture and molecular testing. Pneumococcal isolates were serotyped by Quellung. Serotyping of cases detected by molecular testing was done by sequential multiplex polymerase chain reaction. RESULTS: Children under surveillance contributed to 126,657 child years of observations. Sixty-three thousand three hundred eighty-four illness episodes were assessed in the UHCs. Blood specimens were collected from 8,668 suspected IPD cases and CSF from 177 suspected meningitis cases. Streptococcus pneumoniae was isolated from 46 cases; 32 (70%) were vaccine serotype. The population-based incidence of IPD was 36.3/100,000 child years of observations. About 80% of the cases occurred in children below two years of age. DISCUSSION: IPD was common in rural Bangladesh suggesting the potential benefit of an effective vaccine. Measurement of the burden of IPD requires multiple surveillance modalities.

Child immunization coverage in rural hard-to-reach Haor areas of Bangladesh: possible alternative strategies.

This article assessed the status of childhood vaccination coverage and the possibility of using selected alternative vaccination strategies in rural hard-to-reach haor (low lying) areas of Bangladesh. Data were collected through survey, in-depth interviews, group discussion, and observations of vaccination sessions. Complete immunization coverage among 12- to 23-month-old children was found to be significantly lower in study areas when compared with the national coverage levels. The study identified reasons for low complete immunization coverage in hard-to-reach areas, including irregular/cancelled extended program on immunization (EPI) sessions, less time spent in EPI spots by field staff, and absence of any alternative strategy for remote areas. The findings indicated that the existing service delivery strategy is not sufficient to improve immunization coverage in hard-to-reach areas. However, most of the strategies assessed are considered possible to implement by health care providers in hard-to-reach areas. The study suggested that before implementing alternative strategies in hard-to-reach areas, feasibility and effectiveness of the possible strategies need to be tested to identify evidence-based strategies.

Effect of a package of integrated demand- and supply-side interventions on facility delivery rates in rural Bangladesh: Implications for large-scale programs.

BACKGROUND: According to the Bangladesh Demographic and Health Survey 2014, only approximately 37 percent of women deliver in a health facility. Among the eight administrative divisions of Bangladesh, the facility delivery rate is lowest in the Sylhet division (22.6 percent) where we assessed the effect of integrated supply- and demand-side interventions on the facility-based delivery rate. METHODS: Population-based cohort data of pregnant women from an ongoing maternal and newborn health improvement study being conducted in a population of ~120,000 in Sylhet district were used. The study required collection and processing of biological samples immediately after delivery. Therefore, the project assembled various strategies to increase institutional delivery rates. The supply-side intervention included capacity expansion of the health facilities through service provider refresher training, 24/7 service coverage, additions of drugs and supplies, and incentives to the providers. The demand-side component involved financial incentives to cover expenses, a provision of emergency transport, and referral support to a tertiary-level hospital. We conducted a before-and-after observational study to assess the impact of the intervention in a total of 1,861 deliveries between December 2014 and November 2016. RESULTS: Overall, implementation of the intervention package was associated with 52.6 percentage point increase in the proportions of facility-based deliveries from a baseline rate of 25.0 percent to 77.6 percent in 24 months. We observed lower rates of institutional deliveries when only supply-side interventions were implemented. The proportion rose to 47.1 percent and continued increasing when the project emphasized addressing the financial barriers to accessing obstetric care in a health facility. CONCLUSIONS: An integrated supply- and demand-side intervention was associated with a substantial increase in institutional delivery. The package can be tailored to identify which combination of interventions may produce the optimum result and be scaled. Rigorous implementation research studies are needed to draw confident conclusions and to provide information about the costs, feasibility for scale-up and sustainability.

Implementation of the ANISA Protocol in Sylhet, Bangladesh: Challenges and Solutions.

BACKGROUND: Despite the high rate of deaths in young infants (0-59 days) attributable to infections in resource-poor countries, data on bacterial and viral etiologies of community-acquired infections in this age group are limited. These data are needed to develop appropriate preventive strategies and suitable antibiotic treatment regimens for reducing the number of young infant deaths from infections. The Aetiology of Neonatal Infection in South Asia (ANISA) study is designed to generate these critical data and is being implemented in Bangladesh, India and Pakistan. The Sylhet site in Bangladesh was selected because neonatal mortality is high in this country and particularly in Sylhet District. In this article, we describe the contextual challenges in implementing the ANISA study in Sylhet, as well as the strategies developed by our team to address these challenges. CONTEXTUAL CHALLENGES: The major challenge in implementing the ANISA protocol in Sylhet is conducting the first postnatal visit within 24 hours of birth. This problem stems from several social, cultural and geographical characteristics of the study population and its demographic profile. In this area, most births take place at home, referral compliance for newborn illness to health facilities is low and the blood culture contamination rate is high. Community mobilization, cellphone-based birth notification by families, delivery of quality services at study hospitals and referral support to families in need were some of the strategies adopted by the Sylhet site team for overcoming these challenges during study implementation. Quality control in specimen collection, transportation and processing also plays a role in ensuring satisfactory performance. CONCLUSION: Our research team, with support from the ANISA coordination center, has successfully addressed these challenges and is implementing the study protocol while maintaining the high quality benchmark set by the coordination center.

Patterns and Determinants of Care-Seeking for Antepartum and Intrapartum Complications in Rural Bangladesh: Results from a Cohort Study.

BACKGROUND: The burden of maternal complications during antepartum and intrapartum periods is high and care seeking from a trained provider is low, particularly in low middle income countries of sub-Saharan Africa and South Asia. Identification of barriers to access to trained care and development of strategies to address them will contribute to improvements in maternal health. Using data from a community-based cohort of pregnant women, this study identified the prevalence of antepartum and intrapartum complications and determinants of care-seeking for these complications in rural Bangladesh. METHODS: The study was conducted in 24,274 pregnant women between June 2011 and December 2013 in rural Sylhet district of Bangladesh. Women were interviewed during pregnancy to collect data on demographic and socioeconomic characteristics; prior miscarriages, stillbirths, live births, and neonatal deaths; as well as data on their ability to make decision to go to health center alone. They were interviewed within the first 7 days of child birth to collect data on self-reported antepartum and intrapartum complications and care seeking for those complications. Bivariate analysis was conducted to explore association between predisposing (socio-demographic), enabling (economic), perceived need, and service related factors with care-seeking for self-reported antepartum and intrapartum complications. Multivariable multinomial logistic regression was performed to examine the association of selected factors with care-seeking for self-reported antepartum and intrapartum complications adjusting for co-variates. RESULTS: Self-reported antepartum and intrapartum complications among women were 14.8% and 20.9% respectively. Among women with any antepartum complication, 58.9% sought care and of these 46.5% received care from a trained provider. Of the women with intrapartum complications, 61.4% sought care and of them 46.5% did so from a trained provider. Care-seeking for both antepartum and intrapartum complications from a trained provider was significantly higher for women with higher household wealth status, higher literacy level of both women and their husbands, and for those living close to a health facility (<10 km). Women's decision making ability to go to health centre alone was associated with untrained care only for antepartum complications, but was associated with both trained and untrained care for intrapartum complications. CONCLUSIONS: Nearly 40.0% of the women who experienced either an antepartum or intrapartum complications did not seek care from any provider and 11.5% -14.9% received care from untrained providers, primarily because of economic and geographic barriers to access. Development and evaluation of context specific, cost-effective, and sustainable strategies that will address these barriers to access to care for the maternal complications will enhance care seeking from trained health care providers and improve maternal health.

Training traditional birth attendants to use misoprostol and an absorbent delivery mat in home births.

A 50-fold disparity in maternal mortality exists between high- and low-income countries, and in most contexts, the single most common cause of maternal death is postpartum hemorrhage (PPH). In Bangladesh, as in many other low-income countries, the majority of deliveries are conducted at home by traditional birth attendants (TBAs) or family members. In the absence of skilled birth attendants, training TBAs in the use of misoprostol and an absorbent delivery mat to measure postpartum blood loss may strengthen the ability of TBAs to manage PPH. These complementary interventions were tested in operations research among 77,337 home births in rural Bangladesh. The purpose of this study was to evaluate TBAs' knowledge acquisition, knowledge retention, and changes in attitudes and practices related to PPH management in home births after undergoing training on the use of misoprostol and the blood collection delivery mat. We conclude that the training was highly effective and that the two interventions were safely and correctly used by TBAs at home births. Data on TBA practices indicate adherence to protocol, and 18 months after the interventions were implemented, TBA knowledge retention remained high. This program strengthens the case for community-based use of misoprostol and warrants consideration of this intervention as a potential model for scale-up in settings where complete coverage of skilled birth attendants (SBAs) remains a distant goal.

Programmatic aspects of dropouts in child vaccination in Bangladesh: findings from a prospective study.

The present study investigated prospectively programmatic factors relating to dropouts in child vaccination in 6 subdistricts of Bangladesh. A cross-sectional survey (n = 2700) was conducted estimating overall coverage of immunization using cluster sampling. The eligible subsample of children (n = 1064) was followed up prospectively to understand reasons for dropouts. In-depth interviews (n = 73) with mothers/caregivers and service providers were done and EPI (Expanded Programme on Immunization) sessions were observed (n = 131). Irregular EPI sessions were the prime cause of dropouts particularly in low-performing subdistricts. The other programmatic factors linked with dropouts were (a) no reminder about subsequent session/doses, (b) unfriendly behavior or absence of vaccinator, ( c) refusal due to lost card or vaccine exhausted, and (d) short duration of sessions. Providers highlighted constraints such as financial problems for transportation, particularly in the hard-to-reach areas and vacancies of the posts of health assistants. The barriers to completing full schedules of vaccination can be removed to a large extent through programmatic adjustments.