Effects of L-Carnitine Supplementation on the Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction in Children with Severe Acute Malnutrition: A Double-Blind Randomized Controlled Clinical Trial.

BACKGROUND: Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited. OBJECTIVES: We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM. METHODS: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9-24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < -3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis. RESULTS: The primary outcome variable, "rate of weight gain," was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression [ß: 0.37; 95% confidence interval (CI): -0.63,1.37; P = 0.465]. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) [ß: -1342.29; 95% CI: -2817.35, 132.77; P = 0.074], Neopterin (nmol/L) [ß: -153.33; 95% CI: -556.58, 249.91; P = 0.452], alpha-1-antitrypsin (mg/mL) [ß: 0.05; 95% CI: -0.15, 0.25; P = 0.627]. Initial L-carnitine (µmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203.7). CONCLUSIONS: Although our study findings suggest that L-carnitine bears no additional effect on SAM, we recommend clinical trials with a longer duration of supplementation, possibly with other combinations of interventions, to investigate further into this topic of interest. This trial was registered at clinicaltrials.gov as NCT05083637.

Prevalence and factors associated with undernutrition and overnutrition among ever-married adolescent girls in Bangladesh: an analysis of national surveys from 2004 to 2017.

Nutritional impairment during adolescence may result in adverse physical and reproductive health outcomes. We investigated the prevalence and determined the factors associated with underweight and overweight/obesity among ever-married adolescent girls in Bangladesh. We used Bangladesh Demographic and Health Surveys data conducted in 2004, 2007, 2011, 2014, and 2017. A total of 7040 ever-married adolescent girls aged 15-19 years were included in this analysis. Prevalence of underweight (body mass index [BMI]<18.5 kg/m2) significantly decreased from 39.53% (95% CI = 36.71, 42.43) to 23.62% (95% CI = 21.35, 26.05) during 2004-2017 (p < 0.001). However, prevalence of overweight/obesity (BMI ≥ 23 kg/m2) significantly increased from 5.9% (95% CI = 4.67, 7.43) to 22.71% (95% CI = 20.39, 25.20) during the same period (p < 0.001). The girls with higher age (OR = 0.94, 95% CI = 0.90, 0.99, p = 0.023), higher level of education (OR = 0.60, 95% CI = 0.43, 0.83, p = 0.002), and richest wealth quintile (OR = 0.78, 95% CI = 0.62, 0.98, p = 0.035) had significantly lower risk of being underweight. Adolescent girls having more than one child (OR = 1.41, 95% CI = 1.15, 1.73, p = 0.001) were more likely to be underweight. Elderly adolescents with better economic status were more at risk of being overweight/obese (OR = 2.57, 95% CI = 1.86, 3.55, p < 0.001). Girls married to skilled/unskilled workers (OR = 0.58, 95% CI = 0.44, 0.77, p < 0.001) and persons involved in small businesses (OR = 0.66, 95% CI = 0.49, 0.89, p = 0.007) had lower risk of having a high BMI. Using contraceptive (OR = 0.8, 95% CI = 0.69, 0.94, p = 0.006) was negatively associated with overweight/obese. Although prevalence of undernutrition among ever-married adolescent girls is declining, the proportion of being overweight/obese is increasing in Bangladesh warranting effective strategies to improve adolescent nutrition.

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy.

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS: Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED. CONCLUSIONS: These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).

Immune modulation by nutritional intervention in malnourished children: Identifying the phenotypic distribution and functional responses of peripheral blood mononuclear cells.

Malnourished children are susceptible to an increased risk of mortality owing to impaired immune functions. However, the underlying mechanism of altered immune functions and its interaction with malnutrition is poorly understood. This study investigates the immune function and evaluates the effect of a particular nutritional intervention on the immune cells of undernourished children. Stunted (LAZ <-2) and at-risk of being stunted (length-for-age Z-scores, LAZ <-1 to -2) children aged between 12 and 18 months were enrolled and were provided with the daily nutritional intervention of one egg and 150 mL cow's milk for 90 days. Peripheral blood mononuclear cells (PBMCs) were isolated at enrolment and upon completion of the intervention. Phenotypic profiles for CD3+ cells, CD4+ cells, CD8+ cells, NKT cells, and B cells were similar in both cohorts, both before and after the intervention. However, activated B cells (CD25+) were increased after nutritional intervention in the at-risk of being stunted cohort. Several pro-inflammatory cytokines, IL-6, IFN-γ, and TNF-α, were elevated in the stunted children following the nutritional intervention. The results of the study indicate that nutritional intervention may have a role on activated B cells (CD25+) s in children who are at-risk of being stunted and may alter the capacity of PBMC to produce inflammatory cytokines in stunted children.

Alteration of stool pH and its association with biomarkers of gut enteropathy among slum-dwelling women of reproductive age in Bangladesh.

BACKGROUND: Recent evidence suggests that measures of maternal gut enteropathy are associated with unfavorable fetal outcomes. It is, therefore, crucial to identify and treat the features of intestinal enteropathy among reproductive-age women living in areas where enteropathy is highly prevalent. However, there is a lack of non-invasive diagnostic tests to determine EED, making it difficult to identify the disease in field settings. In this study, we tested the potential of fecal pH as a biomarker of gut enteropathy and investigated its relationship with fecal biomarkers of intestinal enteropathy in reproductive-age women living in resource-limited environments. METHODS: Data on socio-demographic information, anthropometry, and biological samples were collected from 78 apparently healthy women aged between 20 and 27 years from November 2018 to December 2019. The association of stool pH with two fecal biomarkers of gut enteropathy (i.e., intestinal alkaline phosphatase [IAP] and fecal lipocalin-2 [LCN-2] was investigated using multiple linear regression models after adjusting for relevant covariates. RESULTS: In the adjusted models, alkaline stool pH (pH > 7.2) was found to be significantly associated with a decrease in the fecal IAP level by 1.05 unit (95% CI: -1.68, -0.42; p < 0.001) in the log scale, and acidic stool pH (pH < 6) was found to be significantly associated with an increase in the fecal LCN-2 level by 0.89 units (95% CI: 0.12, 1.67; p < 0.025) in the log scale. CONCLUSIONS: The study findings demonstrated an association of fecal pH with biomarkers of gut enteropathy indicating its applicability as a simple tool for understanding intestinal enteropathy among reproductive-age women living in resource-limited settings.

A qualitative assessment of facility readiness and barriers to the facility-based management of childhood severe acute malnutrition in the public healthcare settings in Bangladesh.

OBJECTIVE: To assess facility readiness and identify barriers to the facility-based management of childhood severe acute malnutrition (SAM) in public healthcare settings. DESIGN: Qualitative methods were applied to assess readiness and identify different perspectives on barriers to the facility-based management of children with SAM. Data collection was done using in-depth interviews, key informant interviews, exit interviews and pre-tested observation tools. SETTINGS: Two tertiary care and four district hospitals in Rangpur and Sylhet Divisions of Bangladesh. PARTICIPANTS: Healthcare professionals and caregivers of children with SAM. RESULTS: Anthropometric tools, glucometer, medicines, F-75, F-100 and national guidelines for facility-based management of childhood SAM were found unavailable in some of the hospitals. Sitting and sleeping arrangements for the caregivers were absent in all of the chosen facilities. We identified a combination of health system and contextual barriers that inhibited the facility-based management of SAM. The health system barriers include inadequate manpower, rapid turnover of staff, increased workload, lack of training and lack of adherence to management protocol. The major facility barriers were insufficient space and unavailability of required equipment, medicines and foods for hospitalised children with SAM. The reluctance of caregivers to complete the treatment regimen, their insufficient knowledge regarding proper feeding, increased number of attendants and poverty of parents were the principal contextual barriers. CONCLUSIONS: The study findings provide insights on barriers that are curbing the facility-based management of SAM and emphasise policy efforts to develop feasible interventions to reduce the barriers and ensure the preparedness of the facilities for effective service delivery.

Developing shelf-stable Microbiota Directed Complementary Food (MDCF) prototypes for malnourished children: study protocol for a randomized, single-blinded, clinical study.

BACKGROUND: Childhood undernutrition is a major public health concern that needs special attention to achieve 2025 global nutrition targets. Moderate acute malnutrition (MAM), manifest as wasting (low weight-for-height), affects 33 million children under 5, yet there are currently no global guidelines for its treatment. We recently performed a randomized-controlled clinical study of a microbiota-directed complementary food formulation (MDCF-2) in 12-18-month-old Bangladeshi children with MAM. The results revealed that MDCF-2, freshly prepared each day, produced a significantly greater improvement in ponderal growth than a standard ready-to-use supplementary food (RUSF), an effect that is associated with repair of the disrupted gut microbial community development that occurs in children with MAM. To test the generalizability of these results in acutely malnourished children at other sites, there is a pressing need for a packaged, shelf-stable, organoleptically-acceptable formulation that is bioequivalent to MDCF-2. This report describes the protocol for a clinical study to evaluate candidate formulations designed to meet these criteria. METHODS: A randomized single-blind study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative shelf-stable MDCF prototypes versus the current MDCF-2 formulation that is produced fresh each day. V4-16S rDNA amplicon and shotgun sequencing datasets will be generated from faecal DNA samples collected from each child enrolled in each group prior to, during, and after treatment to determine the abundances of MDCF-2-responsive bacterial taxa. Efficacy will be assessed by quantifying the change in representation of MDCF-2-responsive gut bacterial taxa after 4-weeks of treatment with freshly prepared MDCF-2 compared to their changes in abundance after treatment with the prototype MDCFs. Equivalence will be defined as the absence of a statistically significant difference, after 4-weeks of treatment, in the representation of faecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF. DISCUSSION: This trial aims to establish acceptability and equivalence with respect to microbiota repair, of scalable, shelf-stable formulations of MDCF-2 in 8-12-month-old Bangladeshi children with moderate acute malnutrition. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021.

Nutrition and Food Security in Bangladesh: Achievements, Challenges, and Impact of the COVID-19 Pandemic.

BACKGROUND: Bangladesh has experienced remarkable transformation in demographic, health, and nutritional status of the population. The changes have exposed the population to a number of challenges, the detrimental effect of which on health and nutrition is likely to be increased by the coronavirus disease 2019 (COVID-19) pandemic. We provide an overview of health and nutritional challenges in Bangladesh in relation to demographic transition and the COVID-19 pandemic. METHODS: We identified and reviewed recent reports, published articles, and pertinent gray literature on nutrition and food security in Bangladesh to provide historical and contextual information. RESULTS: The review identifies the progress as well as existing burden regarding nutrition and food security in Bangladesh and highlights the challenges in the coming days in regard to population growth and the COVID-19 pandemic. The country is on track to reduce all forms of childhood undernutrition, while the proportion of nutrition-related noncommunicable diseases is rising owing to changes in dietary intake, low physical activity, and sedentary lifestyle. CONCLUSIONS: Despite remarkable progress, health and nutritional status of the population in Bangladesh faces challenges, particularly in relation to demographic transition and compounded by the COVID-19 pandemic, which require concerted attention from policymakers as well as stakeholders.

Association of plasma low-density lipoprotein receptor-related protein-1 (LRP1) with undernutrition: a case-control study in Bangladeshi adults.

PURPOSE: Studies revealed that silencing of low-density lipoprotein receptor-related protein-1 (LRP1) expression can cause inhibition of adipogenesis in animal model and contribute to reduced body size. But there is no study that has explored the association of LRP1 with body mass index (BMI) of human adults. Therefore, the aim of this study was to investigate the relationship of LRP1 with undernutrition. METHODS: A total of 270 Bangladeshi slum-dwelling adults were enrolled as case control design. Their socio-economic, demographic, anthropometric and biomedical data were collected. Plasma LRP1, C-reactive protein (CRP), alpha-1 acid glycoprotein (AGP) and ferritin levels were measured by ELISA, haemoglobin by HemoCue and zinc by atomic absorption spectrometry. RESULTS: The median (IQR) values of plasma LRP1 were 1673.1 (1382.5-1886.2) ng/mL in healthy participants and 707.7 (588.6-839.9) ng/mL in undernourished participants, respectively. A strong positive correlation (r = 0.70, p < 0.05) between LRP1 and BMI was found. Multivariable logistic regression analysis revealed a positive association between low plasma LRP1 (Adj. OR = 0.98, CI = 0.98, 0.99 and p < 0.05) and undernutrition. CONCLUSIONS: The study found that increased level of LRP1 is associated with increased BMI, whereas lower level is associated with low BMI.

Not water, sanitation and hygiene practice, but timing of stunting is associated with recovery from stunting at 24 months: results from a multi-country birth cohort study.

OBJECTIVES: To measure the role of water, sanitation and hygiene (WASH) practices on recovery from stunting and assess the role of timing of stunting on the reversal of this phenomenon. DESIGN: Data from the MAL-ED multi-country birth cohort study was used for the current analysis. Generalised linear mixed-effects models were used to estimate the probability of reversal of stunting with WASH practice and timing of stunting as the exposures of interest. SETTING: Seven different countries across three continents. PARTICIPANTS: A total of 612 children <2 years of age. RESULTS: We found that not WASH practice but timing of stunting had statistically significant association with recovery from stunting. In comparison with the children who were stunted at 6 months, children who were stunted at 12 months had 1·9 times (ß = 0·63, P = 0·03) more chance of recovery at 24 months of age. And, children who were stunted at 18 months of age even had higher odds (adjusted OR = 3·01, ß = 1·10, P < 0·001) of recovery than children who were stunted at 6 months. Additionally, mother's height (ß = 0·59, P = 0·04) and household income (ß = 0·02, P < 0·05) showed statistically significant associations with the outcome. CONCLUSIONS: The study provided evidence for the role of timing of stunting on the recovery from the phenomenon. This novel finding indicates that the programmes to promote linear growth should be directed at the earliest possible timepoints in the course of life.

Aflatoxin exposure was not associated with childhood stunting: results from a birth cohort study in a resource-poor setting of Dhaka, Bangladesh.

OBJECTIVE: Chronic aflatoxin exposure has been associated with childhood stunting (length-for-age/height-for-age < -2 sd), while data lacks for Bangladesh, a country with substantial burden of childhood stunting. This paper examined the association between aflatoxin exposure and childhood stunting in a slum setting of Dhaka city. DESIGN: In this MAL-ED aflatoxin birth cohort study, plasma samples were assayed for aflatoxin B1-lysine adduct (AFB1-lys) by MS at 7, 15, 24 and 36 months of age for 208, 196, 173 and 167 children to assess chronic aflatoxin exposure. Relationship between aflatoxin exposure and anthropometric measures was examined by mixed-effects logistic regression models. SETTING AND PARTICIPANTS: The study was conducted in Mirpur, Dhaka, where children were followed from birth to 36 months. RESULTS: Prevalence of stunting increased from 21 % at 7 months to 49 % at 36 months of age. Mean AFB1-lys concentrations at 7, 15, 24 and 36 months were 1·30 (range 0·09-5·79), 1·52 (range 0·06-6·35), 3·43 (range 0·15-65·60) and 3·70 (range 0·09-126·54) pg/mg albumin, respectively, and the percentage of children with detectable AFB1-lys was 10, 21, 18 and 62 %, respectively. No association was observed between aflatoxin exposure and stunting in multivariable analyses. Factors associated with childhood stunting were age, low birth weight, maternal height, stool myeloperoxidase and number of people sleeping in one room. CONCLUSIONS: A relatively lower exposure to aflatoxin may not influence the linear growth of children. This finding indicates a threshold level of exposure for linear growth deficit and further investigation in other areas where higher concentrations of aflatoxin exposure exist.

Antibiotic exposure among young infants suffering from diarrhoea in Bangladesh.

AIMS: Appropriate rehydration has always been significant in treating diarrhoeal diseases in children. Irrational antibiotic use among diarrhoeal children has remained a major public health concern. Information regarding antibiotic use in young infants suffering from diarrhoea is very limited and a unique aspect of research. We aimed to investigate the prevalence of antibiotic use in the community among 2-6 months infants with diarrhoeal illnesses and having different nutritional status. METHODS: We investigated a total of 5279 infants aged 2-6 months at Dhaka hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, between September 2018 and June 2019. Among them, 257 infants were suffering from severe acute malnutrition (SAM). History of taking antibiotics was ascertained by direct observation of a prescription by a physician, the bottle of antibiotic or asking the caregiver about the name of antibiotic or its price that is very close to the usual market price of an antibiotic. RESULTS: Overall, 52% of infants received antibiotics before hospital admission. Non-SAM infants had higher odds of receiving antibiotics (adjusted odds ratio [aOR] = 1.52, 95% confidence interval: 1.18, 1.97, P value = 0.003) compared to infants with SAM and use of antibiotics increased with age (aOR = 1.11, 95% confidence interval: 1.06, 1.17, P value<0.001). Commonly used antibiotics were azithromycin (13.3%), ciprofloxacin (7.7%), erythromycin (7.7%) and metronidazole (2.6%). The proportion of receiving ciprofloxacin was significantly lower in infants with SAM compared to their non-SAM counterparts (2.7% vs. 7.97%, P value = 0.004). CONCLUSIONS: The study underscores the excessive use of antibiotics among diarrhoeal infants, which is already a major public health concern in low- and middle-income countries.

Asymptomatic Duodenitis and Helicobacter pylori associated Dyspepsia in 2-Year-Old Chronic Malnourished Bangladeshi Slum-Dwelling Children: A Cross-Sectional Study.

AIM: There is insufficient knowledge on the * duodenal histology and Helicobacter pylori infection in malnourished Bangladeshi children. Therefore, we attempted to explore the prevalence of H. pylori infection and duodenal histopathology in 2-year-old chronic malnourished Bangladeshi slum-dwelling children and investigate their association with dyspeptic symptoms. METHODS: This cross-sectional study was conducted using the data of the Bangladesh Environmental Enteric Dysfunction study in an urban slum of Dhaka, Bangladesh. With a view to address the association of environmental enteric dysfunction (EED) with stunting, upper gastrointestinal endoscopy was performed on 54 chronic malnourished children {31 stunted [length-for-age Z-scores (LAZ) <-2] and 23 at risk of stunting (LAZ <-1 to -2)} aged between 12-24 months and the mucosal biopsies were subjected to histopathological examination after obtaining proper clinical history. Stool antigen for H. pylori (HpSA) was assessed to determine H. pylori status. RESULTS: In all, 83.3% (45/54) of the children had histopathological evidence of duodenitis. Chronic mild duodenitis was found to be the most prevalent form of duodenitis (53.7%) in the children. Only 8.9% (4/45) of the children with duodenitis had dyspepsia (p < 0.05). The 14.8% (8/54) of the children were found positive for H. pylori infection. Logistic regression analysis revealed children positive for HpSA had significant association with dyspepsia (OR 9.34; 95% CI 1.54-56.80). CONCLUSIONS: The number of chronic malnourished children suffering from duodenitis was found to be very high. Majority of these children was asymptomatic. Children positive for HpSA had significant association with dyspeptic symptoms.

Daily Supplementation With Egg, Cow Milk, and Multiple Micronutrients Increases Linear Growth of Young Children with Short Stature.

BACKGROUND: Childhood stunting is the most prevalent public health nutrition problem in low- and middle-income countries. OBJECTIVE: This study aimed to determine whether daily supplementation in 12-18-mo-old undernourished Bangladeshi children with egg, cow milk, and multiple micronutrients improves linear growth. METHODS: In the Bangladesh Environmental Enteric Dysfunction (BEED) study, a community-based intervention study, 12-18-mo-old children with length-for-age z score (LAZ) <1 were supplemented daily with an egg and 150 mL of milk for 90 feeding days, and 1 sachet of multiple micronutrient powder was provided daily for 60 feeding days. The change in LAZ over this period was compared with that in children of the same age and same baseline LAZ who were enrolled in the recently completed Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Dhaka birth cohort study conducted in the same community where no nutrition intervention was provided. Difference-in-difference (DID) analysis was done and the effect size was adjusted for other possible covariates using a generalized estimating equation in a regression model. RESULTS: A total of 472 children with LAZ <1 completed the intervention and data were available for 174 children in the comparison group. Compared with the comparison group, adjusted DID analysis revealed a change in LAZ in the intervention group of +0.23 (95% CI: 0.18, 0.29; P < 0.05). In a subgroup analysis, the changes were +0.27 (95% CI: 0.18, 0.35; P < 0.05) in stunted (LAZ <2) children and +0.19 (95% CI: 0.12, 0.27; P < 0.05) in children at risk of stunting (LAZ -1 to -2). No allergic reactions or other adverse events related to milk and egg consumption were observed. CONCLUSIONS: Daily directly observed milk, egg, and multiple micronutrient supplementation may improve linear growth of stunted children. A randomized controlled trial with longer duration of supplementation coupled with an additional intervention aimed at reducing pathogen burden is warranted to confirm these results. This trial was registered at clinicaltrials.gov as NCT02812615.

Prevalence and sociodemographic determinants of household-level double burden of malnutrition in Bangladesh.

OBJECTIVE: To investigate the prevalence and sociodemographic determinants of household-level mother-child double burden (MCDB) of malnutrition in Bangladesh. DESIGN: The analysis was done using Bangladesh Demographic and Health Survey 2014 data. Multivariable logistic regression identified the sociodemographic factors associated with double-burden households. SETTING: Nationally representative cross-sectional survey.ParticipantsA total of 5951 households were included in the analysis. RESULTS: A coexistence of overweight or obese mother and underweight or stunted or wasted child (OWOBM/USWC) was found in 6·3 % households. The prevalence of overweight or obese mother and underweight child (OWOBM/UWC) was 3·8 %, of overweight or obese mother and stunted child (OWOBM/STC) was 4·7 %, and of overweight or obese mother and wasted child (OWOBM/WSC) was 1·7 %. Mother's age 21-25 years at first birth, middle wealth index group, having two or three children and having four or more children showed statistically significant (P<0·05) associations with OWOBM/UWC. Households with mother's age 21-25 years at first birth, middle wealth index group, no exposure to information media, having two or three children and having four or more children had higher odds of OWOBM/STC and OWOBM/USWC which were statistically significant (P<0·05). Delivery of child through caesarean section was significantly associated with OWOBM/USWC (P<0·05). CONCLUSIONS: Although the prevalence of MCDB of malnutrition in Bangladesh is low, prevention programmes must consider the nutrition concerns of the entire household to prevent future risks. Such programmes also need to be tagged with family planning and increasing awareness through social and behaviour change counselling and exposure to information media.

Financing health care in Bangladesh: Policy responses and challenges towards achieving universal health coverage.

Bangladesh has attained notable progress in most of the health indicators, but still, health system of the country is suffering badly from poor funding. Issues like burden of out-of-pocket expenditure, low per capita share in health, inadequate service facilities, and financial barriers in reducing malnutrition are being overlooked due to inadequacy and inappropriate utilization of allocated funds. We aimed to review the current status of health care spending in Bangladesh in response to national health policy (NHP) and determine the future challenges towards achieving universal health coverage (UHC). National health policy suggested a substantial increase in budgetary allocation for health care, although government health care expenditures in proportion to total public spending plummeted down from 6.2% to 4.04% in the past 8 years. Overall, 67% of the health care cost is being paid by people, whereas global standard is below 32%. Only one hospital bed is allocated per 1667 people, and 34% of total posts in health sector are vacant due to scarcity of funds. The country is experiencing demographic dividend with a concurrent rise of aged people, but there seems no financial protection schemes for the aged and working age populations. Such situation results in multiple obstacles in achieving financial risk protection as well as UHC. Policy makers must think effectively to develop and adapt systems in order to achieve UHC and ensure health for all.

Association of intestinal pathogens with faecal markers of environmental enteric dysfunction among slum-dwelling children in the first 2 years of life in Bangladesh.

OBJECTIVE: Environmental Enteric Dysfunction (EED) can be assessed by faecal biomarkers such as Myeloperoxidase (MPO), Neopterin (NEO) and Alpha-1 anti-trypsin (AAT). We aimed to test the association of intestinal pathogens with faecal markers of EED among slum-dwelling children in first 2 years of life. METHODS: The MAL-ED birth cohort data of Bangladesh site were used to conduct this analysis. Multivariable analyses using Generalized Estimating Equations (GEE) were performed to test the association between intestinal pathogens and faecal markers of EED. RESULTS: Giardiasis, ascariasis and trichuriasis were the most frequent parasitic infections and Campylobacter spp., Enteroaggregative Escherichia coli (EAEC) and Enterotoxigenic Escherichia coli (ETEC) were the common bacterial pathogens observed in stool samples of the children. Overall, 71%, 97% and 58% of stool samples were above values considered normal in non-tropical settings for MPO, NEO and AAT respectively. Giardiasis was found to be significantly associated with MPO (Coefficient = 0.55; 95% CI = 0.15, 0.95; P-value = 0.008) and AAT concentrations (Coefficient = 0.34; 95% CI = 0.04, 0.63; P-value = 0.03). A significant association was found between trichuriasis and NEO (Coefficient = 0.90; 95% CI = 0.19, 1.61; P-value = 0.01). Trichuriasis (Coefficient = 1.71; 95% CI = 0.32, 3.11; P-value = 0.02) and giardiasis (Coefficient = 1.51; 95% CI = 0.79, 2.23; P-value <0.001) were significantly associated with EED score. Children with EAEC had significantly higher MPO concentrations (Coefficient = 0.33; 95% CI = 0.06, 0.61; P-value = 0.02). CONCLUSION: The study results imply the importance of intestinal pathogens in contributing to intestinal inflammation and increased intestinal permeability in young children.

Correction: Role of L-Carnitine supplementation on rate of weight gain and biomarkers of Environmental Enteric Dysfunction in children with severe acute malnutrition: A protocol for a double-blinded randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0275291.].

Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter.

Development of machine learning models predicting mortality using routinely collected observational health data from 0-59 months old children admitted to an intensive care unit in Bangladesh: critical role of biochemistry and haematology data.

INTRODUCTION: Treatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country. METHOD: We retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. Five commonly used ML models- logistic regression, least absolute shrinkage and selection operator, elastic net, gradient boosting trees (GBT) and random forest (RF), were evaluated using the area under the receiver operating characteristic curve (AUROC). Top predictors were selected using RF mean decrease Gini scores as the feature importance values. RESULTS: Data from 5669 children was used and was reduced to 3505 patients (10% death, 90% survived) following missing data removal. The mean patient age was 10.8 months (SD=10.5). The top performing models based on the validation performance measured by mean 10-fold cross-validation AUROC on the training data set were RF and GBT. Hyperparameters were selected using cross-validation and then tested in an unseen test set. The models developed used demographic, anthropometric, clinical, biochemistry and haematological data for mortality prediction. We found RF consistently outperformed GBT and predicted the mortality with AUROC of ≥0.87 in the test set when three or more laboratory measurements were included. However, after the inclusion of a fourth laboratory measurement, very minor predictive gains (AUROC 0.87 vs 0.88) resulted. The best predictors were the biochemistry and haematological measurements, with the top predictors being total CO2, potassium, creatinine and total calcium. CONCLUSIONS: Mortality in children admitted to ICU can be predicted with high accuracy using RF ML models in a real-life data set using multiple laboratory measurements with the most important features primarily coming from patient biochemistry and haematology.