Young Infant Mortality Associated with Preterm and Small-for-Gestational-Age Births in Rural Bangladesh: A Prospective Cohort Study.

OBJECTIVE: To assess the relative risk of mortality in infants born preterm and small for gestational age (SGA) during the first and second months of life in rural Bangladesh. STUDY DESIGN: We analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother's reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios (HRs) and corresponding 95% CIs for babies born preterm and SGA separately for the first and second month of life using bivariate and multivariable weighted Cox regression models. RESULTS: The analysis included 17 643 singleton live birth babies. Compared with infants born at term-appropriate for gestational age, in both unadjusted and adjusted analyses, infants born preterm-SGA had the greatest risk of death in the first (HR 13.25, 95% CI 8.65-20.31; adjusted HR 12.05, 95% CI 7.82-18.57) and second month of life (HR 4.65, 95% CI 1.93-11.23; adjusted HR 4.1, 95% CI 1.66-10.15), followed by infants born preterm-appropriate for gestational age and term-SGA. CONCLUSIONS: The risk of mortality in infants born preterm and/or SGA is increased and extends through the second month of life. Appropriate interventions to prevent and manage complications caused by prematurity and SGA could improve survival during and beyond the neonatal period.

Incidence and risk factors of preterm birth in a rural Bangladeshi cohort.

BACKGROUND: Globally, about 15 million neonates are born preterm and about 85% of global preterm birth occurs in Asia and Africa regions. We aimed to estimate the incidence and risk factors for preterm birth in a rural Bangladeshi cohort. METHODS: Between June 2007 and September 2009, community health workers prospectively collected data from 32,126 mother-live-born baby pairs on household socio-demographic status, pregnancy history, antenatal care seeking and newborn gestational age determined by recall of date of last menstrual period. RESULTS: Among all live births, 22.3% were delivered prior to 37 weeks of gestation (i.e. preterm); of which 12.3% were born at 35-36 weeks of gestation (late preterm), 7.1% were born at 32-34 weeks (moderate preterm), and 2.9% were born at 28-31 weeks of gestation (very preterm). Overall, the majority of preterm births (55.1%) were late preterm. Risk of preterm birth was lower among women with primary or higher level of education (RR: 0.92; 95% CI: 0.88, 0.97), women who sought antenatal care at least once during the index pregnancy (RR: 0.86; 95% CI: 0.83, 0.90), and women who had completed all birth preparedness steps (RR: 0.32; 95% CI: 0.30, 0.34). In contrast, risk of preterm birth was higher among women with a history of child death (RR: 1.05; 95% CI: 1.01, 1.10), who had mid-upper arm circumference (MUAC) ≤250 mm, indicative of under nutrition (for women having MUAC <214 mm the risk was higher; RR: 1.26; 95% CI: 1.17, 1.35), who reported an antenatal complication (RR: 1.32; 95% CI: 1.14, 1.53), and who received iron-folic acid supplementation for 2-6 months during the index pregnancy (RR: 1.33; 95% CI: 1.24, 1.44). CONCLUSIONS: In resource poor settings with high burden of preterm birth, alike Bangladesh, preterm birth risk could be reduced by close monitoring and/or frequent follow-up of women with history of child death and antenatal complications, by encouraging women to seek antenatal care from qualified providers, to adopt birth preparedness planning and to maintain good nutritional status. Additional research is needed to further explore the associations of antenatal iron supplementation and maternal nutritional status on preterm birth.

Systematic review of probiotics for the treatment of community-acquired acute diarrhea in children.

BACKGROUND: Oral rehydration salts (ORS), zinc, and continued feeding are the recommended treatments for community-acquired acute diarrhea among young children. However, probiotics are becoming increasingly popular treatments for diarrhea in some countries. We sought to estimate the effect of probiotics on diarrhea morbidity and mortality in children < 5 years of age. METHODS: We conducted a systematic review of randomized controlled trials to estimate the effect of probiotic microorganisms for the treatment of community-acquired acute diarrhea in children. Data were abstracted into a standardized table and study quality was assessed using the Child Health Epidemiology Reference Group (CHERG) adaption of the GRADE technique. We measured the relative effect of probiotic treatment in addition to recommended rehydration on hospitalizations, duration and severity. We then calculated the average percent difference for all continuous outcomes and performed a meta-analysis for discrete outcomes. RESULTS: We identified 8 studies for inclusion in the final database. No studies reported diarrhea mortality and overall the evidence was low to moderate quality. Probiotics reduced diarrhea duration by 14.0% (95% CI: 3.8-24.2%) and stool frequency on the second day of treatment by 13.1% (95% CI: 0.8 - 25.3%). There was no effect on the risk of diarrhea hospitalizations. CONCLUSION: Probiotics may be efficacious in reducing diarrhea duration and stool frequency during a diarrhea episode. However, only few studies have been conducted in low-income countries and none used zinc (the current recommendation) thus additional research is needed to understand the effect of probiotics as adjunct therapy for diarrhea among children in developing countries.

Haemolytic-uraemic syndrome as a sequela of diarrhoeal disease.

Haemolytic-uraemic syndrome (HUS) is a serious sequela of diarrhoea and results in a high mortality rate. This systematic review aimed at estimating the proportion of HUS cases that are linked to prior infection due to Shiga toxin-producing Escherichia coli (STEC) or Shigella dysenteriae type 1. A systematic review of the existing literature was done to identify cohort and case-control studies that examined the relationship between STEC and S. dysenteriae type 1 and HUS. After screening 2,516 articles, 11 studies were found that met the inclusion/exclusion criteria. Findings of case-control studies suggest that 60.8% of the HUS cases may be attributable to a previous infection with STEC. In cohort studies, 7.8% of participants with STEC and 8% of participants with S. dysenteriae type 1 developed HUS during follow-up. HUS is linked to diarrhoea due to both STEC and S. dysenteriae type 1. Thus, preventing infections caused by both pathogens is critical for the prevention and control of HUS, especially in areas where timely and effective treatment is not available.

Provider performance and facility readiness for managing infections in young infants in primary care facilities in rural Bangladesh.

BACKGROUND: Neonatal infections remain a leading cause of newborn deaths globally. In 2015, WHO issued guidelines for managing possible serious bacterial infection (PSBI) in young infants (0-59 days) using simplified antibiotic regimens when compliance with hospital referral is not feasible. Bangladesh was one of the first countries to adopt WHO's guidelines for implementation. We report results of an implementation research study that assessed facility readiness and provider performance in three rural sub-districts of Bangladesh during August 2015-August 2016. METHODS: This study took place in 19 primary health centers. Facility readiness was assessed using checklists completed by study staff at three time points. To assess provider performance, we extracted data for all infection cases from facility registers and compared providers' diagnosis and treatment against the guidelines. We plotted classification and dosage errors across the study period and superimposed a locally weighted smoothed (LOWESS) curve to analyze changes in performance over time. Focus group discussions (N = 2) and in-depth interviews (N = 28) with providers were conducted to identify barriers and facilitators for facility readiness and provider performance. RESULTS: At baseline, none of the facilities had adequate supply of antibiotics. During the 10-month period, 606 sick infants with signs of infection presented at the study facilities. Classification errors were identified in 14.9% (N = 90/606) of records. For infants receiving the first dose(s) of antibiotic treatment (N = 551), dosage errors were identified in 22.9% (N = 126/551) of the records. Distribution of errors varied by facility (35.7% [IQR: 24.7-57.4%]) and infection severity. Errors were highest at the beginning of the study period and decreased over time. Qualitative data suggest errors in early implementation were due to changes in providers' assessment and treatment practices, including confusion about classifying an infant with multiple signs of infection, and some providers' concerns about the efficacy of simplified antibiotic regimens. CONCLUSIONS: Strategies to monitor early performance and targeted supports are important for enhancing implementation fidelity when introducing complex guidelines in new settings. Future research should examine providers' assessment of effectiveness of simplified treatment and address misconceptions about superiority of broader spectrum antibiotics for treating community-acquired neonatal infections in this context.

Caregiver acceptability of the guidelines for managing young infants with possible serious bacterial infections (PSBI) in primary care facilities in rural Bangladesh.

INTRODUCTION: Many infants with possible serious bacterial infections (PSBI) do not receive inpatient treatment because hospital care may not be affordable, accessible, or acceptable for families. In 2015, WHO issued guidelines for managing PSBI in young infants (0-59 days) with simpler antibiotic regimens when hospital care is not feasible. Bangladesh adopted WHO's guidelines for implementation in outpatient primary health centers. We report results of an implementation research study that assessed caregiver acceptability of the guidelines in three rural sub-districts of Bangladesh during early implementation (October 2015-August 2016). METHODS: We included 19 outpatient primary health centers involved in the initial rollout of the infection management guidelines. We extracted data for all PSBI cases (N = 192) from facility registers to identify gaps in referral feasibility, simplified antibiotic treatment, and follow-up. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with both caregivers (6 FGDs; 23 IDIs) and providers (2 FGDs; 28 IDIs) to assess caregiver acceptability of the guidelines. RESULTS: Referral to the hospital was not feasible for many families (83.3%; N = 160/192) and acceptance varied by infection severity. Barriers to referral feasibility included economic and household factors, and previous experiences with poor quality of care at the sub-district hospital. Conversely, providers and caregivers indicated high acceptability of simplified antibiotic treatment. 80% (N = 96/120) of infants with clinical severe infection for whom referral was not feasible returned to the facility for the second antibiotic injection. Some providers reported developing local solutions-including engaging informal providers in treatment of the infant-to address organizational barriers and promote treatment compliance. Follow-up of young infants receiving simplified treatment is critical, but only 67.4% (N = 87/129) of infants received fourth day follow-up. Some providers' reported deviations from the guidelines that shifted responsibility of follow-up to the caregiver, which may have contributed to lapses. CONCLUSION: Caregivers' perception of trust and communication with providers were influential in caregiver acceptability of care. Few caregivers accepted referral to the sub-district hospital, suggesting low acceptability of this option. When referral was not feasible, many caregivers reported satisfaction with simplified antibiotic treatment. Local solutions described by providers require further examination in this context to assess the safety and potential value of these strategies in outpatient treatment. Our findings suggest strengthening providers' interpersonal skills could improve caregiver acceptability of the guidelines.

Early implementation of guidelines for managing young infants with possible serious bacterial infection in Bangladesh.

Neonatal infections remain a leading cause of newborn deaths globally. In 2015, WHO issued guidelines for managing possible serious bacterial infection (PSBI) in young infants (0-59 days) with simpler antibiotic regimens if hospital referral is not feasible. Bangladesh was one of the first countries to adapt WHO guidance into national guidelines for implementation in primary healthcare facilities. Early implementation was led by the Ministry of Health and Family Welfare (MOHFW) in 10 subdistricts of Bangladesh with support from USAID's MaMoni Health System Strengthening project. This mixed methods implementation research case study explores programme feasibility and acceptability through analysis of service delivery data from 4590 sick young infants over a 15-month period, qualitative interviews with providers and MOHFW managers and documentation by project staff. Multistakeholder collaboration was key to ensuring facility readiness and feasibility of programme delivery. For the 514 (11%) infants classified as PSBI, provider adherence to prereferral treatment and follow-up varied across infection subcategories. Many clinical severe infection cases for whom referral was not feasible received the recommended two doses of injectable gentamicin and follow-up, suggesting delivery of simplified antibiotic treatment is feasible. However, prereferral antibiotic treatment was low for infants whose families accepted hospital referral, which highlights the need for additional focus on managing these cases in training and supervision. Systems for tracking sick infants that accept hospital referral are needed, and follow-up of all PSBI cases requires strengthening to ensure sick infants receive the recommended treatment, to monitor outcomes and assess the effectiveness of the programme. Only 11.2% (95% CI 10.3 to 12.1) of the expected PSBI cases sought care from the selected service delivery points in the programme period. However, increasing trends in utilisation suggest improved awareness and acceptability of services among families of young infants as the programme matured. Future programme activities should include interviews with caregivers to explore the complexities around referral feasibility and acceptability of simplified antibiotic treatment.

Implementation research to support Bangladesh Ministry of Health and Family Welfare to implement its national guidelines for management of infections in young infants in two rural districts.

BACKGROUND: World Health Organization revised the global guidelines for management of possible serious bacterial infection (PSBI) in young infants to recommend the use of simplified antibiotic therapy in settings where access to hospital care is not possible. The Bangladesh Ministry of Health and Family Welfare (MoHFW), Government of Bangladesh (GOB) adopted these guidelines, allowing treatment at first-level facilities. During the first year of implementation, the Projahnmo Study Group and USAID/MaMoni Health Systems Strengthening (HSS) Project supported the MoHFW to operationalize the new guidelines and conducted an implementation research study in selected districts to assess challenges and identify solutions to facilitate scale-up across the country. IMPLEMENTATION SUPPORT: Projahnmo and MaMoni HSS teams supported implementation in three areas: building capacity, strengthening service delivery, and mobilizing communities. Capacity building focused on training paramedics to conduct outpatient management of PSBI cases and developing monitoring and supervision systems. The teams also filled gaps in government supply of essential drugs, equipment, and logistics. Community mobilization strategies to promote care-seeking and referrals to facilities varied across districts; in one district community, health workers made home visits while in another district, the promotion was carried out through community volunteers, village doctors, and through existing community structures. METHODS: We followed a plan-do-study-act (PDSA) cycle to identify and address implementation challenges. Three cycles-1 every 4 months-were conducted. We collected data utilizing quantitative and qualitative methods in both the community and facilities. The total sample size for this study was 13,590. DISCUSSION: This article provides implementation research design details for program managers intending to implement new guidelines on management of young infant infections. Results of this research will be reported in the forthcoming papers. Preliminary findings indicate that the management of PSBI cases at the UH&FWCs is feasible. However, MoHFW, GOB needs to address the implementation challenges before scale-up of this policy to the national level.

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.