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 ).

Ready-to-use foods for management of moderate acute malnutrition: considerations for scaling up production and use in programs.

Ready-to-use foods are one of the available strategies for the treatment of moderate acute malnutrition (MAM), but challenges remain in the use of these products in programs at scale. This paper focuses on two challenges: the need for cheaper formulations using locally available ingredients that are processed in a safe, reliable, and financially sustainable local production facility; and the effective use of these products in large-scale community-based programs. Linear programming tools can be used successfully to design local compositions that are in line with international guidelines, low in cost, and acceptable, and the efficacy of these local formulations in the treatment of MAM was recently demonstrated in Malawi. The production of local formulations for programs at scale relies on the existence of a reliable and efficient local production facility. Technical assistance may be required in the development of sustainable business models at an early stage in the process, taking into account the stringent product quality and safety criteria and the required investments. The use of ready-to-use products, as of any food supplement, in programs at scale will be affected by the practice of household sharing and diversion of these products for other uses. Additional measures can be considered to account for sharing. These products designed for the treatment and prevention of MAM are to be used in community-based programs and should therefore be used in conjunction with other interventions and designed so that they do not replace the intake of other foods and breastmilk. Remaining challenges and implications for the (operations) research agenda are discussed.

Tablets are preferred and more acceptable than powdered prenatal calcium supplements among pregnant women in Dhaka, Bangladesh.

Prenatal calcium supplementation is recommended by the WHO to decrease the risk of preeclampsia in women with low dietary calcium intake; yet, this recommendation has not been successfully implemented to date. One component of an effective population-based prenatal calcium intervention will be the selection of a widely accepted calcium vehicle to promote consistent, long-term consumption of the supplement. We aimed to evaluate preference and acceptability of 4 different options for delivering prenatal calcium (conventional tablets, chewable tablets, unflavored powder, and flavored powder) to pregnant women in urban Bangladesh. In a modified discrete-choice trial, pregnant women (n = 132) completed a 4-d "run-in period" in which each delivery vehicle was sampled once, followed by a 21-d "selection period" during which participants were instructed to freely select a single delivery vehicle of their choice each day. Preference was empirically defined as the probability that each delivery vehicle was selected on a given day, and measured from participants' daily delivery vehicle selections; acceptability was assessed by using mid- and post-trial questionnaires. Conventional tablets demonstrated the highest probability of selection (62%); the probability of selection of chewable tablets (19%), flavored powder (12%), and unflavored powder (5%) were all significantly lower than for conventional tablets (P < 0.001). The palatability and product characteristics of the conventional tablets were more acceptable than for the other 3 delivery vehicles. Our rigorous methodologic approach used both quantitative and self-reported measures that consistently identified the most preferred and accepted prenatal calcium delivery form. Through observation of pregnant women's actual supplement use, and perceptions of acceptability (i.e., ease of use, palatability), we demonstrated that conventional tablets are likely to be the most accepted and successful calcium delivery vehicle in future field studies and scale-up of the WHO recommendation in Bangladesh.

Discordance in exclusive breastfeeding between maternal recall and deuterium dose-to-mother technique during the first 6 months of infants: A multi-country study in Asia.

PURPOSE: This study aimed to assess the agreement in EBF between maternal recall and the dose-to-mother (DTM) technique. METHODS: Indonesia, Malaysia, Mongolia, Pakistan, Sri Lanka, Thailand, and Vietnam participated in the study. A total of 207 and 118 mother-infant pairs were assessed at 3 and 6 months of child's age. Using a standardized questionnaire, mothers were asked to recall child feeding during the previous 24 h, at 3 and 6 months. Those recalled to be EBF proceeded to be assessed using DTM technique. Non-milk oral intake (NMOI) cutoff of 86.6 g/d was used to classify EBF. RESULTS: According to DTM, 66% of infants were EBF at 3 months, while only 22% were EBF at 6 months. At 3 months, the overall % agreement between maternal recall and DTM method was 68%, kappa 0.06 (95% CI: 0.07-0.20), and at 6 months, the % agreement was only 21%, kappa -0.031 (95% CI -0.168 to 0.107). Human milk intakes were similar at 3 months and 6 months when expressed as g/d, but decreased when expressed as g/kg/d, with a large variation within and between countries; Pakistan being the lowest. CONCLUSION: This study showed there were declining levels of EBF from 3 to 6 months in the participating countries from Asia and the agreement between maternal recall and DTM technique to classify EBF was low. To ensure that the DTM technique can be more widely used in evaluating breastfeeding promotion programs, consensus on the appropriate NMOI cutoff and simplification of the DTM protocol is necessary.

Women's participation in household decision-making: Qualitative findings from the Shonjibon Trial in rural Bangladesh.

A key element of women's empowerment is the ability to participate in household decision-making. This study presents the qualitative results from the Shonjibon Cash and Counselling Trial baseline process evaluation with the aim of exploring the status of women's decision-making at the trial's outset and to facilitate the exploration of any changes in women's empowerment over the course of the trial. Between January and March 2021, we conducted forty-one in-depth interviews with pregnant women in rural Bangladesh. The research team translated, transcribed, coded, and discussed the interviews. We used thematic analysis to examine women's experience and perceptions on household decision-making. The key findings that emerged; women jointly participated in financial decision-making with their husbands; men made the final decision regarding seeking healthcare, and women solely made choices regarding infant and young child feeding. Our findings revealed that women felt that they needed to discuss their plans to go outside the house with their husbands, many perceived a lack of importance in the community towards women's participation in decision-making. This study documents current contextual information on the status of women's involvement in household decision-making and intrahousehold power dynamics at the start of the Shonjibon Cash and Counselling Trial.

Trajectories of resting energy expenditure and performance of predictive equations in children hospitalized with an acute illness and malnutrition: a longitudinal study.

There is scarce data on energy expenditure in ill children with different degrees of malnutrition. This study aimed to determine resting energy expenditure (REE) trajectories in hospitalized malnourished children during and after hospitalization. We followed a cohort of children in Bangladesh and Malawi (2-23 months) with: no wasting (NW); moderate wasting (MW), severe wasting (SW), or edematous malnutrition (EM). REE was measured by indirect calorimetry at admission, discharge, 14-and-45-days post-discharge. 125 children (NW, n = 23; MW, n = 29; SW, n = 51; EM, n = 22), median age 9 (IQR 6, 14) months, provided 401 REE measurements. At admission, the REE of children with NW and MW was 67 (95% CI [58, 75]) and 70 (95% CI [63, 76]) kcal/kg/day, respectively, while REE in children with SW was higher, 79 kcal/kg/day (95% CI [74, 84], p = 0.018), than NW. REE in these groups was stable over time. In children with EM, REE increased from admission to discharge (65 kcal/kg/day, 95% CI [56, 73]) to 79 (95% CI [72, 86], p = 0.0014) and was stable hereafter. Predictive equations underestimated REE in 92% of participants at all time points. Recommended feeding targets during the acute phase of illness in severely malnourished children exceeded REE. Acutely ill malnourished children are at risk of being overfed when implementing current international guidelines.

An Integrated Mother-Child Intervention on Child Development and Maternal Mental Health.

OBJECTIVES: To evaluate an integrated, low-cost, facility-based group intervention designed to promote child care, boost maternal mental-wellbeing, reduce harsh discipline, and improve children's health, nutrition, and early development. METHODS: In Dhaka, 30 neighborhood clusters of a low-income urban community were randomized to intervention or control groups. Mothers with children between 6 and 24 months (n = 300) who self-reported negative discipline were identified and enrolled. A 1-year group intervention included integration of responsive caregiving, nutritional supplementation, caregivers' mental health, child protection, and health advice. Child outcomes were cognition (primary) and language, motor and behavioral development, growth, and hemoglobin and iron status (secondary). Maternal outcomes were depressive symptoms, self-esteem, negative discipline, and child care knowledge and practices. RESULTS: Overall, 222 (74%) mother-child dyads participated in the 1-year follow-up. Intervention and control groups differed on wealth, with no other significant differences. The intervention resulted in a 0.75 SD effect on cognition, 0.77 SD on language, 0.41 SD on motor, and 0.43 to 0.66 SDs on behavior during testing (emotion, cooperation, and vocalization) in the intervention arm. Mothers in the intervention group had fewer depressive symptoms (effect size: -0.72 SD), higher self-esteem (0.62 SD), better child care knowledge (2.02 SD), fewer harsh discipline practices (0.25 SD), and better home stimulation (0.73 SD). The intervention showed no effect on child growth or hemoglobin, but significantly improved serum iron status (-0.36 SD). CONCLUSIONS: A comprehensive intervention, delivered through group sessions in health facilities, was effective in promoting child development and reducing maternal depressive symptoms among mothers who reported using negative or harsh discipline.

Household food access and child malnutrition: results from the eight-country MAL-ED study.

BACKGROUND: Stunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites. METHODS: We administered a socioeconomic survey to 800 households in research sites in eight countries, including a recently validated nine-item food access insecurity questionnaire, and obtained anthropometric measurements from children aged 24 to 60 months. We used multivariable regression models to assess the relationship between household food access insecurity and anthropometry in children, and we assessed the invariance of that relationship across country sites. RESULTS: Average age of study children was 41 months. Mean food access insecurity score (range: 0-27) was 5.8, and varied from 2.4 in Nepal to 8.3 in Pakistan. Across sites, the prevalence of stunting (42%) was much higher than the prevalence of wasting (6%). In pooled regression analyses, a 10-point increase in food access insecurity score was associated with a 0.20 SD decrease in height-for-age Z score (95% CI 0.05 to 0.34 SD; p = 0.008). A likelihood ratio test for heterogeneity revealed that this relationship was consistent across countries (p = 0.17). CONCLUSIONS: Our study provides evidence of the validity of using a simple household food access insecurity score to investigate the etiology of childhood growth faltering across diverse geographic settings. Such a measure could be used to direct interventions by identifying children at risk of illness and death related to malnutrition.

Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries.

Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed approximately 6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage.

Distinct genomic signatures of adaptation in pre- and postnatal environments during human evolution.

The human genome evolution project seeks to reveal the genetic underpinnings of key phenotypic features that are distinctive of humans, such as a greatly enlarged cerebral cortex, slow development, and long life spans. This project has focused predominantly on genotypic changes during the 6-million-year descent from the last common ancestor (LCA) of humans and chimpanzees. Here, we argue that adaptive genotypic changes during earlier periods of evolutionary history also helped shape the distinctive human phenotype. Using comparative genome sequence data from 10 vertebrate species, we find a signature of human ancestry-specific adaptive evolution in 1,240 genes during their descent from the LCA with rodents. We also find that the signature of adaptive evolution is significantly different for highly expressed genes in human fetal and adult-stage tissues. Functional annotation clustering shows that on the ape stem lineage, an especially evident adaptively evolved biological pathway contains genes that function in mitochondria, are crucially involved in aerobic energy production, and are highly expressed in two energy-demanding tissues, heart and brain. Also, on this ape stem lineage, there was adaptive evolution among genes associated with human autoimmune and aging-related diseases. During more recent human descent, the adaptively evolving, highly expressed genes in fetal brain are involved in mediating neuronal connectivity. Comparing adaptively evolving genes from pre- and postnatal-stage tissues suggests that different selective pressures act on the development vs. the maintenance of the human phenotype.

The Mothers, Infants, and Lactation Quality (MILQ) Study: A Multi-Center Collaboration.

Little valid information is available on human milk nutrient concentrations, especially for micronutrients (MNs), and there are no valid reference values (RVs) across lactation. In this multi-center collaborative study, RVs will be established for human milk nutrients across the first 8.5 mo postpartum. Well-nourished, unsupplemented women in Bangladesh, Brazil, Denmark, and The Gambia (n = 250/site) were recruited during the third trimester of pregnancy. Milk, blood, saliva, urine, and stool samples from mothers and their infants are collected identically at 3 visits (1-3.49, 3.5-5.99, 6.0-8.49 mo postpartum). Milk analyses include macronutrients, selected vitamins, trace elements and minerals, iodine, metabolomics, amino acids, human milk oligosaccharides, and bioactive peptides. We measure milk volume; maternal and infant diets, anthropometry, and morbidity; infant development, maternal genome, and the infant and maternal microbiome. RVs will be constructed based on methods for the WHO Child Growth Standards and the Intergrowth-21st Project. This trial was registered at clinical trials.gov as NCT03254329.

Development and evaluation of new mask protocols for gene expression profiling in humans and chimpanzees.

BACKGROUND: Cross-species gene expression analyses using oligonucleotide microarrays designed to evaluate a single species can provide spurious results due to mismatches between the interrogated transcriptome and arrayed probes. Based on the most recent human and chimpanzee genome assemblies, we developed updated and accessible probe masking methods that allow human Affymetrix oligonucleotide microarrays to be used for robust genome-wide expression analyses in both species. In this process, only data from oligonucleotide probes predicted to have robust hybridization sensitivity and specificity for both transcriptomes are retained for analysis. RESULTS: To characterize the utility of this resource, we applied our mask protocols to existing expression data from brains, livers, hearts, testes, and kidneys derived from both species and determined the effects probe numbers have on expression scores of specific transcripts. In all five tissues, probe sets with decreasing numbers of probes showed non-linear trends towards increased variation in expression scores. The relationships between expression variation and probe number in brain data closely matched those observed in simulated expression data sets subjected to random probe masking. However, there is evidence that additional factors affect the observed relationships between gene expression scores and probe number in tissues such as liver and kidney. In parallel, we observed that decreasing the number of probes within probe sets lead to linear increases in both gained and lost inferences of differential cross-species expression in all five tissues, which will affect the interpretation of expression data subject to masking. CONCLUSION: We introduce a readily implemented and updated resource for human and chimpanzee transcriptome analysis through a commonly used microarray platform. Based on empirical observations derived from the analysis of five distinct data sets, we provide novel guidelines for the interpretation of masked data that take the number of probes present in a given probe set into consideration. These guidelines are applicable to other customized applications that involve masking data from specific subsets of probes.

A sparse covarying unit that describes healthy and impaired human gut microbiota development.

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an "ecogroup" of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of ecogroup population dynamics were recapitulated in gnotobiotic piglets as they transitioned from exclusive milk feeding to a fully weaned state consuming a representative Bangladeshi diet.

Effects of microbiota-directed foods in gnotobiotic animals and undernourished children.

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.

Results with Complementary Food Using Local Food Ingredients.

Appropriate complementary food is a must for optimum growth of infants and children. The food should be diverse and be given in sufficient quantities 2-4 times a day depending upon age. Poverty, food insecurity, and lack of awareness regarding the choice of nutritious food ingredients are deterrents to optimum complementary feeding. In Bangladesh, 77% of children do not receive appropriate complementary food and, hence, the high prevalence of childhood malnutrition. We developed ready-to-use complementary foods (RUCFs) using locally available food ingredients, rice/lentil and chickpea, which conform to standard specifications. These foods were found to be acceptable by children and their mothers compared to the Pushti packet, the cereal-based supplement used in the erstwhile National Nutrition Program of Bangladesh. In a cluster-randomized community-based trial in rural Bangladesh among more than 5,000 children, the efficacy of rice/lentil- and chickpea-based RUCFs was compared with another commonly used supplementary food called wheat-soy blend++ (WSB++) and a commercial product called Plumpy'doz. Deceleration in length for age was significantly lower (by 0.02-0.04/month) in the rice/lentil, Plumpy'doz, and chickpea groups compared to the control group at 18 months of age. Weight-for-length z-score decline was lower only in Plumpy'doz and chickpea groups. WSB++ was not different from the control group. In children who received chickpea RUCF or Plumpy'doz, the prevalence of stunting was 5-6% lower at 18 months. These foods can be used to prevent or treat malnutrition among children, particularly those from food-insecure households.

Bioavailability of enteric-coated microencapsulated calcium during pregnancy: a randomized crossover trial in Bangladesh.

BACKGROUND: Prenatal calcium and iron supplements are recommended in settings of low dietary calcium intake and high prevalence of anemia. However, calcium administration may inhibit iron absorption. To overcome calcium-iron interactions, we developed a multi-micronutrient powder containing iron (60 mg), folic acid (400 µg), and calcium carbonate granules microencapsulated with a pH-sensitive enteric coating to delay intestinal release. OBJECTIVES: We aimed to establish in vivo evidence that enteric-coated (EC) calcium is bioavailable in pregnant women and to explore the dose-responsiveness of fractional calcium absorption (FCA) in pregnancy. DESIGN: This was a randomized crossover trial in pregnant women (26-28 wk of gestation) in Dhaka, Bangladesh. Participants were allocated to 1 of 3 dose groups (500, 1000, or 1500 mg elemental Ca). FCA was estimated in random order for EC and non-EC (control) granules by a dual-stable-isotope method ((44)Ca-labeled granules and intravenous (42)Ca) on the basis of the relative recovery of (44)Ca compared with (42)Ca in urine over 48 h. RESULTS: Forty-nine participants with FCA for both EC and non-EC granules were included in the primary analyses. FCA geometric means were as follows: 21.8% (500 mg), 9.2% (1000 mg), and 11.7% (1500 mg) for non-EC granules compared with 3.3% (500 mg), 1.2% (1000 mg), and 2.1% for EC granules. Cumulative 48-h FCA of EC calcium was 85% lower (P < 0.001) than that of non-EC calcium, after adjustment for dose. In comparison to 500 mg, the FCA for the 1000-mg dose was 61% lower (P < 0.001) and was 42% lower (P = 0.002) for the 1500-mg dose, after adjustment for formulation. CONCLUSIONS: A pH-sensitive enteric coating substantially reduced calcium absorption from a prenatal multi-micronutrient powder. In its current formulation, this novel supplement is not suitable for clinical use. FCA was highly dose-dependent, such that doses of 1000 and 1500 mg delivered only negligibly more bioavailable calcium than the 500-mg dose. This trial was registered at clinicaltrials.gov as NCT01678079.

OCPAT: an online codon-preserved alignment tool for evolutionary genomic analysis of protein coding sequences.

BACKGROUND: Rapidly accumulating genome sequence data from multiple species offer powerful opportunities for the detection of DNA sequence evolution. Phylogenetic tree construction and codon-based tests for natural selection are the prevailing tools used to detect functionally important evolutionary change in protein coding sequences. These analyses often require multiple DNA sequence alignments that maintain the correct reading frame for each collection of putative orthologous sequences. Since this feature is not available in most alignment tools, codon reading frames often must be checked manually before evolutionary analyses can commence. RESULTS: Here we report an online codon-preserved alignment tool (OCPAT) that generates multiple sequence alignments automatically from the coding sequences of any list of human gene IDs and their putative orthologs from genomes of other vertebrate tetrapods. OCPAT is programmed to extract putative orthologous genes from genomes and to align the orthologs with the reading frame maintained in all species. OCPAT also optimizes the alignment by trimming the most variable alignment regions at the 5' and 3' ends of each gene. The resulting output of alignments is returned in several formats, which facilitates further molecular evolutionary analyses by appropriate available software. Alignments are generally robust and reliable, retaining the correct reading frame. The tool can serve as the first step for comparative genomic analyses of protein-coding gene sequences including phylogenetic tree reconstruction and detection of natural selection. We aligned 20,658 human RefSeq mRNAs using OCPAT. Most alignments are missing sequence(s) from at least one species; however, functional annotation clustering of the ~1700 transcripts that were alignable to all species shows that genes involved in multi-subunit protein complexes are highly conserved. CONCLUSION: The OCPAT program facilitates large-scale evolutionary and phylogenetic analyses of entire biological processes, pathways, and diseases.