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Background Given limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh. Methods Following D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2–4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography–tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer. Results SMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: −0.031, 0.038; n = 91). Conclusions The D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach. Impact The D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences.To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children.We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA.A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P 0.05).The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Background: Fortification of rice with slaked lime is an acceptable and inexpensive way to combat calcium (Ca) deficiency. However, bioavailability of calcium after intake of slaked lime fortified rice is yet to be investigated. Objective: To measure the fractional absorption of Ca (FAC) from slaked lime fortified cooked rice. Design: We conducted an experimental study using stable isotopes of Ca to measure FAC during a single morning test meal containing rice fortified with slaked lime. Participants (n = 22) were given slaked lime fortified rice 3 times a day for 4 days. On the morning of the fifth day, the participants were served the same amount of rice as previous the 4 days at the breakfast test meal with an accurately measured amount of 44Ca stable isotope oral tracer followed by an intravenous injection of 42Ca. Urine was collected over the next 24 hours in 3 consecutive 8-hour pools. Fractional absorption of Ca was calculated from the measurement of the relative enrichment of the of each administered tracer 44Ca and 42Ca using inductively coupled plasma mass spectrometry. Results: The mean Ca concentration in the test meal was 879.5 ± 152.9 µg/g with a coefficient of variance (CV) of 17.2%. Although Ca absorption efficiency decreases with higher calcium intake, the total amount of calcium absorbed from test meal using FAC = 0.391 calculated from the third 8-hour urine pool was 69.0 (CV of 15.6) mg. Conclusions: We showed that one-fifth of daily calcium recommendation for women of reproductive age could be met by ingesting ∼200 g cooked slake fortified rice.

BACKGROUND More than 30 million children worldwide suffer from moderate acute malnutrition (MAM). Current treatments have limited effectiveness and much remains unknown about pathogenesis. Children with MAM exhibit perturbed development of their gut microbiota. METHODS Slum-dwelling Bangladeshi children, aged 12 to 18 months, with moderate acute malnutrition (n=124) received a microbiota-directed complementary food (MDCF-2) or an existing ready-to-use supplementary food (RUSF), twice daily for three months followed by a 1-month period of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age Z-scores and mid-upper arm circumference at baseline and fortnightly, through four months. We compared the rate of change of these related phenotypes between baseline and three months, and between baseline and four months. We also measured levels of 4,977 proteins in plasma plus 209 bacterial taxa in fecal samples. RESULTS 118 children completed the intervention (n=59/arm). The rate of change in weight-for-length Z-score (β-WLZ), weight-for-age Z-score, and mid upper arm circumference is consistent with a benefit of MDCF-2 on growth over the course of the study including the one-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 β-WLZ-positively correlated plasma proteins including mediators of bone growth, neurodevelopment and inflammation (gene set enrichment analysis [GSEA];p

IntroductionDiarrhoea is one of the leading causes of under-5 childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. In severely malnourished children, diarrhoea progresses to shock, where the risk of mortality is even higher. At icddr,b Dhaka Hospital, the fatality rate is as high as 69% in children with severe malnutrition and fluid refractory septic shock. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhoea (eg, in cholera) and severe acute malnutrition (SAM) or severe underweight who are in shock and unresponsive to WHO-recommended fluid therapy. To reduce the mortality of severely malnourished children presenting with diarrhoea and fluid refractory shock, we aim to compare the efficacy of blood transfusion, dopamine and epinephrine in fluid refractory shock in children who do not respond to WHO-recommended fluid resuscitation.Methods and analysisIn this randomised, three-arm, controlled, non-masked clinical trial in children 1–59 months old with SAM or severe underweight and fluid refractory shock, we will compare the efficacy of dopamine or epinephrine administration versus blood transfusion in children who failed to respond to WHO-recommended fluid resuscitation. The primary outcome variable is the case fatality rate. The effect of the intervention will be assessed by performing an intention-to-treat analysis. Recruitment and data collection began in July 2021 and are now ongoing. Results are expected by May 2023.Ethics and disseminationThis study has been approved by the icddr,b Institutional Review Board. We adhere to the ‘Declaration of Helsinki’ (2000), guidelines for Good Clinical Practice. Before enrolment, we collect signed informed consent from the parents or caregivers of the children. We will publish the results in a peer-reviewed journal and will arrange a dissemination seminar.Trial registration numberNCT04750070.

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor–derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto- N -neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N -glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.

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

Objective:To estimate the total energy and micronutrient intakes of children 9–24 months of age and evaluate the probability of adequacy (PA) of the diet in seven MAL-ED sites.Design:Cohort study. Food intake was registered monthly using 24-h recalls beginning at 9 months. We estimated PA for thirteen nutrients and overall mean PA (MPA) by site and 3-month periods considering estimated breast milk intake.Setting:Seven sites in Asia, Africa and Latin America.Participants:1669 children followed from birth to 24 months of age.Results:Median estimated %energy from breast milk ranged from 4 to 70 % at 9–12 months, and declined to 0–39 % at 21–24 months. Iron bioavailability was low for all sites, but many diets were of moderate bioavailability for zinc. PA was optimal for most nutrients in Brazil and South Africa, except for iron and vitamin E (both), calcium and zinc (South Africa). PA for zinc increased only for children consuming a diet with moderate bioavailability. MPA increased 12–24 months as the quantity of complementary foods increased; however, PA for vitamin A remained low in Bangladesh and Tanzania. PA for vitamins D and E and iron was low for most sites and age groups.Conclusions:MPA increased from 12 to 24 months as children consumed higher quantities of food, while nutrient density remained constant for most nutrients. Ways to increase the consumption of foods containing vitamins D, E and A, and calcium are needed, as are ways to increase the bioavailability of iron and zinc.

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions.

BACKGROUND Persistent diarrhea (PD), diarrhea for ≥14 days, accounts for 36%-56% of all diarrhea-related death. Studies demonstrated that green banana helps in the resolution of diarrhea. OBJECTIVE We assessed whether a lactose-free diet rice suji (RS) or rice suji containing green banana (GB-RS), improves outcome compared with 3/4th strength rice suji (3/4th RS) in 6 to 35 months old children having PD in the icddr,b Dhaka hospital. METHODS In this open-labeled, randomized, controlled trial, children with PD not improving with milk suji (the initial diet) received any of the three study diets: GB-RS, RS, 3/4th RS. The primary outcome was the percentage of children who recovered from diarrhea by day 5 with an intention to treat analysis. RESULTS From 1st December 2017 to 31st August 2019, we randomly allocated 45 children to each group. By day 5, 66 children recovered from PD, of whom 26 (58%), 14 (31%), 26 (58%) received GB-RS, RS, and 3/4th RS respectively. Significantly more resolution of PD occurred in GB-RS and 3/4th RS groups compared to RS group [relative risk (RR) 1⸱71, 95% CI 1⸱19-2⸱60; p=0⸱019]. Two (10%) children died, one each in RS group and GB-RS group. TaqMan array card (TAC) identified EAEC, rotavirus, norovirus, EPEC, astrovirus, and Campylobacter as the major pathogens associated with PD. CONCLUSIONS GB-RS and 3/4th RS are efficacious in the management of PD in young children. We also demonstrated a wide range of entero-pathogen associated with PD by TAC which needs further study to find a causal link. CLINICALTRIAL ClinicalTrials.gov, ID: NCT03366740 Registered on 8th December 2017 INTERNATIONAL REGISTERED REPORT RR2-10.2196/15759

IntroductionThere is growing interest in assessing the impact of health interventions, particularly when women are the focus of the intervention, on women’s empowerment. Globally, research has shown that interventions targeting nutrition, health and economic development can affect women’s empowerment. Evidence suggests that women’s empowerment is also an underlying determinant of nutrition outcomes. Depending on the focus of the intervention, different domains of women’s empowerment will be influenced, for example, an increase in nutritional knowledge, or greater control over income and access to resources.ObjectiveThis study evaluates the impact of the Shonjibon Cash and Counselling (SCC) Trial that combines nutrition counselling and an unconditional cash transfer, delivered on a mobile platform, on women’s empowerment in rural Bangladesh.Methods and analysisWe will use a mixed-methods approach, combining statistical analysis of quantitative data from 2840 women in a cluster randomised controlled trial examining the impact of nutrition behaviour change communications (BCCs) and cash transfers on child undernutrition. Pregnant participants will be given a smartphone with a customised app, delivering nutrition BCC messages, and will receive nutrition counselling via a call centre and an unconditional cash transfer. This study is a component of the SCC Trial and will measure women’s empowerment using a composite indicator based on the Project-Level Women’s Empowerment in Agriculture Index, with quantitative data collection at baseline and endline. Thematic analysis of qualitative data, collected through longitudinal interviews with women, husbands and mothers-in-law, will elicit a local understanding of women’s empowerment and the linkages between the intervention and women’s empowerment outcomes. This paper describes the study protocol to evaluate women’s empowerment in a nutrition-specific and sensitive intervention using internationally validated, innovative tools and will help fill the evidence gap on pathways of impact, highlighting areas to target for future programming.Ethics and disseminationEthical approval has been obtained from the International Centre for Diarrhoeal Disease Research (Ref. PR 17106) and The University of Sydney (Ref: 2019/840). Findings from this study will be shared in Bangladesh with dissemination sessions in-country and internationally at conferences, and will be published in peer-reviewed journals.

Ginger (ZingiberofficinaleL.) belongs to family Zingiberaceae is an important oriental spice crop. Ginger is high value crop which grows well in warm and humid climate and is cultivated from sea level to an altitude of 1500 meters above sea level (Kandinnan, et al. 1996). It has special significance for tropical countries where it is produced and consumed in large quantities (Islam, 2017; BARI, 2012, 2013 and 2014). The aromatic rhizomes are used as spice and medicine. Major producers of ginger in the world are India, Jamaica, Sierra Leone, Nigeria, China, Japan, Taiwan and Australia (Rana and Sharma, 1998). Ginger is much more used in Bangladesh as a spice and is cultivated more or less all over the country. In the country produced only 74380 metric tons of ginger from 9120 ha of land and the yield per hectare was 8.15 kg (BBS, 2011). But average yield is low as compared to other ginger growing countries of the world. The production is not enough to fulfill the annual requirement of the country. So every year a good amount of ginger is imported in exchange of foreign currency. Like many countries diseases are the major limiting factors for ginger cultivation in Bangladesh. Among the diseases, rhizome rot is the most devastating one caused by Pythium aphanidermatum, Fusariumoxysporum, Sclerotiumrolfsiiand Ralstoniasolanacearumthroughout the world (Chauhan and Patel, 1990; Dohrooet al. 1987 and Iyer, 1987). The pathogens involved decide the nature of the damage and symptom expression .The major pathogens involved with rhizome rot are viz., species of Pythium causing soft rot, Fusariumspp. causing yellows or wilt and Ralstoniasolanacearumcausing bacterial wilt (Elliot, 2003). Basal rot caused by Sclerotiumrolfsiiwhich appears later in the season in some cases. All these pathogens are known to form complexes with nematodes leading to synergistic effect on the severity of the disease. They predispose the crops to secondary pathogens (Sarma, 1994).Loss due to rhizome rot is estimated in many countries and the main pathogens associated with rhizome rot are the fungi such as Pythium spp. and Fusariumspp, bacteria like Ralstoniasolanacearumand nematode (Elliot, 2003). It may cause losses to the extent of 50% or more due to soft rot ((Islam, 2017; BARI, 2012, 2013 and 2014; Joshi and Sharma, 1982) and sometimes total failure of the crops in the tropical regions of India (Fageriaet al, 2006); 70% rhizomeproduction is reduced due to the infection caused by Pythium spp. and Fusariumspp. in Nepal (Anon., 2012) and 5-30% losses occurred in Fiji and Australia by Pythium myriotylum(Stirlinget al., 2009). Soil, water and infected planting materials are the main source of perpetuation of these pathogens (Dohroo, 2005). Pythium spp. is able to persist in soil over decay by means of encysted zoospores, oospores and sporangia. Pythium spp also can survive in air dry muck soil for up to 12 years (Hoppe, 1966). Pythium spread via infested rhizomes (Trujillo, 1964) and as oospores surviving in debris in the soil (Dohroo, 2005). Infection started from contaminated planting materials, saprophytically living fungus in the soil or on trash of previous ginger crops. The soft rot pathogen generally have quite a wide host range and can survive on other host plants so this makes it difficult to control in the field. In the past Pythium aphanidermatumwas known as the sole causal agent of rhizome rot of ginger and was successfully controlled by the technology developed by Plant Pathology Division, BARI. But during the last few years that technology was not working well and it was noticed that some other fungal and bacterial association were involved with such rot. As the crop is cash crop so it is prime need to identify the causal agents of rhizome rot through intensive survey which will help to modify the existing technology for managing the disease in future. The present research work was undertaken to determine the incidence of rhizome rot of ginger and its causal agents.Bangladesh J. Agril. Res. 44(3): 569-576, September 2019

Objective: To determine the MIC of Imipenem against Salmonella Typhi. Study Design: An interventional study. Place of Study: Department of Pharmacology & Therapeutics in collaboration with Department of Microbiology atAd-din Sakina Women’s Medical College, Jashore. Study Duration: January 2018 to May 2018. Methodology: MIC of Imipenem was determined by Broth Dilution Technique against standard strain of Salmonellatyphi ATCC 24683. Result: The MIC of Imipenem against Salmonella typhi was 0.75 μg/ml. Conclusion: Imipenem is a potential therapeutic agent for Salmonella typhi infection. Bangladesh Crit Care J September 2019; 7(2): 102-105

Background Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. Objective We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. Results A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. Conclusions EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED.

To assess the efficacy and safety of F-100, diluted F-100 (F100D), and infant formula (IF) for dietary management in the rehabilitation phase of severe acute malnutrition (SAM) of infants aged under 6 months (u6m). Double-blind randomized clinical trial was conducted to assess the efficacy and safety of F-100, F-100D, and IF at the Nutrition Rehabilitation Unit, icddr,b. Infants (n = 153) u6m with SAM were enrolled and randomly assigned to any of the three diets after stabilization. Two ml blood was collected on study days 1, 3, and 7 for measuring serum electrolytes, creatinine and osmolality, urine samples for specific gravity and osmolality creatinine ratio. Renal Solute Load (RSL) and Potential Renal Solute Load (PRSL) were calculated. Infants were discharged when gained 15% of the admission bodyweight or had edema-free weight-for-length Z-score ≥ − 2. Infants fed F-100 and F-100D had higher weight gain than infants who received IF. Mean difference between F-100 and IF was 4.6 g/kg/d (95% CI 1.5–7.6, P = 0.004) and between F-100D and IF was 3.1 g/kg/d (95% CI 0.6–5.5, P = 0.015). Total energy intake from study diet and breast milk was significantly higher in infants fed F-100 compared with other two diets (P = 0.001 in each case). RSL was highest in infants fed F-100 but serum sodium showed no sign of elevation. Urinary specific gravity and serum sodium values were within normal range. F-100 can be safely used in the rehabilitation phase for infants u6m with SAM and there is no need to prepare alternative formulations.

Background: In order to improve calcium status, fortified rice should have acceptable organoleptic properties of that food. Objective: We aimed to assess whether home fortification of rice with slaked lime can increase calcium content of rice and whether this fortified rice is well tolerated in a nutritionally at-risk population. Methods: This experimental study measured the calcium content of rice cooked with different concentration of lime and assessed the acceptability of fortified rice among 400 women and children. Each participant received fortified rice with one of five concentrations of lime (0, 2.5, 5, 7.5 or 10 gm per 500 gm of rice), with or without additional foods (lentil soup or fried green papaya). All participants were asked to score the organoleptic qualities on a hedonic scale. Results: Analysis showed that rice calcium content increased in a dose- response manner with increased lime during cooking (76.03, 205.58, 427.55, 614.29 and 811.23 mg/kg for given lime concentrations). Acceptability of the meal was greater when additional foods were served with rice at all lime concentrations. In both groups, the 7.5M arm reported highest overall acceptability (children, 6.25; women 6.10). This study found significant association between overall acceptability (different concentrations of lime mixed rice; with/without additional foods) and between groups (women vs. children) ( p value = < 0.001) where-as no association was found within groups. Conclusions: Lime-fortified rice can be feasible considering the calcium uptake of rice and organoleptic character. Further research on bioavailability can establish a solid foundation that will support design of an effective intervention to reduce calcium deficiency in this population.

Field performance of low land weeder was evaluated in mechanically transplanted rice fieldat Bahirbagh and Provakordi representing the silty loam soil under Gopalganj district of Bangladesh during the non-irrigated wet season (Aman) 2016. Twenty-one-day-old seedlings were transplanted by walk behind type 4-rows mechanical rice transplanter (DP480) at a pre-set spacing of 300 × 170 mm. Randomized Complete Block (RCB) design with three replications was applied with weeding practices of BRRI weeder (BW) followed by (fb) one hand weeding (HW), BRRI power weeder (BPW) fb one HW, two HW, pyrazosulfuron-ethyl (PSE) fb one HW, weedy check, weed free and mulching fb two HW (farmers’ practice) in two locations. The common weed species were observed in experimental sites. Weeding efficiency (WE) of BPW and BW was 67 and 44, respectively. Field capacity of BPW and BW was obtained 0.07 and 0.03 ha hr-1, respectively. Operator’s skill influenced the performance of weeder. During operation, BPW damaged 14-15% tillers in both the locations. However, damaged plants were revived after few days. The labour requirement in BW fb one HW, BPW fb one HW, PSE fb one HW and two HW were 380, 362, 243 and 616 man-hr ha-1 respectively. Except weedy check, weed management practices showed identical grain yield in both the locations. The BCR was accounted in PSE fb one HW (1.35), BW fb one HW (1.21), BPW fb one HW (1.20) whereas the lowest BCR was observed in weedy (0.83) and two HW (1.00). It can be concluded that pyrazosulfuron-ethyl, BRRI power weeder followed by one hand weeding and BRRI weeder followed by one hand weeding appeared as the cost effective weed control methods in mechanically transplanted Aman rice production. Bangladesh Rice j. 2018, 22(1): 25-34

Objectives: Environmental enteric dysfunction (EED) impairs zinc absorption from food, and zinc deficiency may contribute to the poor growth associated with EED. We examined zinc absorption from a standardized aqueous zinc dose, and habitual daily endogenous fecal zinc excretion (EFZ) and compared these outcomes between children grouped by the lactulose to mannitol ratio (L:M). Methods: Bangladeshi toddlers (18–24 months) with low (

Background Variability in the 25-hydroxyvitamin D [25(OH)D] response to prenatal and postpartum vitamin D supplementation is an important consideration for establishing vitamin D deficiency prevention regimens. Objectives We aimed to examine interindividual variation in maternal and infant 25(OH)D following maternal vitamin D supplementation. Methods In a randomized trial of maternal vitamin D supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) received a prenatal cholecalciferol (vitamin D-3) dose of 0, 4200, 16,800, or 28,000 IU/wk from 17 to 24 wk of gestation followed by placebo to 6 mo postpartum. A fifth group received 28,000 IU cholecalciferol/wk both prenatally and postpartum. In a subset of participants, associations of 25(OH)D with hypothesized explanatory factors were estimated in women at delivery (n = 655) and 6 mo postpartum (n = 566), and in their infants at birth (n = 502) and 6 mo of age (n = 215). Base models included initial 25(OH)D and supplemental vitamin D dose. Multivariable models were extended to include other individual characteristics and specimen-related factors. The model coefficient of determination (R2) was used to express the percentage of total variance explained. Results Supplemental vitamin D intake and initial 25(OH)D accounted for the majority of variance in maternal 25(OH)D at delivery and postpartum (R2 = 70% and 79%, respectively). Additional characteristics, including BMI, contributed negligibly to remaining variance (

Background Causes of infant linear growth faltering in low-income settings remain poorly understood. Identifying age-specific risk factors in observational studies might be influenced by statistical model selection. Objectives To estimate associations of selected household factors and infant feeding behaviors within discrete age intervals with interval-specific changes in length-for-age z-scores (LAZs) or attained LAZ, using 5 statistical approaches. Methods Data from a birth cohort in Dhaka, Bangladesh (n = 1157) were analyzed. Multivariable-adjusted associations of infant feeding patterns or household factors with conditional LAZ (cLAZ) were estimated for 5 intervals in infancy. Two alternative approaches were used to estimate differences in interval changes in LAZ, and differences in end-interval attained LAZ and RRs of stunting (LAZ

Background: Persistent diarrhea (PD), diarrhea for ≥14 days, accounts for 36%-56% of all diarrhea-related death. Studies demonstrated that green banana helps in the resolution of diarrhea. We assessed whether a lactose-free diet rice suji (RS) or rice suji containing green banana (GB-RS), improves outcome compared with 3/4th strength rice suji (3/4th RS) in 6 to 35 months old children having PD in the icddr,b Dhaka hospital. Methods: In this open-labeled, randomized, controlled trial, children with PD not improving with milk suji (the initial diet) received any of the three study diets: GB-RS, RS, 3/4th RS. The primary outcome was the percentage of children who recovered from diarrhea by day 5 with an intention to treat analysis. Findings: From 1st December 2017 to 31st August 2019, we randomly allocated 45 children to each group. By day 5, 66 children recovered from PD, of whom 26 (58%), 14 (31%), 26 (58%) received GB-RS, RS, and 3/4th RS respectively. Significantly more resolution of PD occurred in GB-RS and 3/4th RS groups compared to RS group [relative risk (RR) 1⸱71, 95% CI 1⸱19-2⸱60; p=0⸱019]. Two (10%) children died, one each in RS group and GB-RS group. TaqMan array card (TAC) identified EAEC, rotavirus, norovirus, EPEC, astrovirus, and Campylobacter as the major pathogens associated with PD. Interpretation: GB-RS and 3/4th RS are efficacious in the management of PD in young children. We also demonstrated a wide range of entero-pathogen associated with PD by TAC which needs further study to find a causal link. Clinical Trial Registration Details: ClinicalTrials.gov, ID: NCT03366740, Registered on 8th December 2017. Funding Information: This protocol is supported by icddr,b’s core fund through capacity building for clinical research initiatives. We thank the governments of Bangladesh, Canada, Sweden, and the UK for providing unrestricted support to icddr,b. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: IRB of icddr,b approved the trial protocol (approval ID: PR 17075) which is available online. Written informed consent from parents or caregivers.

Background We examined the effect of maternal vitamin D supplementation during pregnancy and lactation on risk of acute respiratory infection (ARI) in infants up to 6 months of age in Bangladesh. Methods This study was nested in a randomized, double-blind, placebo-controlled, 5-arm dose-ranging trial of prenatal and postpartum vitamin D supplementation. One group of women received 0 IU vitamin D per week during pregnancy and for 26 weeks post delivery (“placebo” group), one group received high-dose prenatal vitamin D supplementation of 28 000 IU per week and 26 weeks post delivery, and there were 3 additional dose-ranging groups receiving vitamin D supplementation during pregnancy only (4200, 16 800, and 28 000 IU per week, respectively). Episodes of ARI were identified by active and passive surveillance. The primary outcome was microbiologically confirmed ARI, and the primary analysis compared the high-dose prenatal plus postpartum vitamin D vs placebo groups. Results In total, 1174 mother-infant pairs were included. Among infants born to mothers in the placebo group, 98% had a venous umbilical cord 25(OH)D level below 30 nmol/L compared with none in the high-dose prenatal plus postdelivery vitamin D group. Incidence of microbiologically confirmed ARI in the high-dose prenatal plus postpartum vitamin D (1.21 episodes per 6 person-months; N = 235) and placebo groups (1.07 episodes per 6 person-months; N = 234) was not significantly different (hazard ratio of 1.12 [95% confidence intervals: 0.90-1.40]). There were no differences in the incidence of microbiologically confirmed or clinical ARI, upper, lower, or hospitalized lower respiratory tract infection between high-dose prenatal plus postpartum vitamin D and placebo groups. Conclusions Despite a high prevalence of maternal baseline vitamin D deficiency and significant effects of maternal vitamin D supplementation on infant vitamin D status, the intervention did not reduce the risk of microbiologically confirmed ARI in infants up to 6 months of age.

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).

BackgroundSevere acute malnutrition (SAM) is associated with high levels of gamma Proteobacteria chronic gut inflammation and poor gut health. In this study, we aimed to assess the effects of probiotic and/or prebiotic supplementation on gut inflammation and fecal pH in young infants with SAM.MethodsThis study was a single-blind RCT where infants aged between 2 and 6 months were randomized to receive either: probiotic (B. infantis EVC001), synbiotic (prebiotic, Lacto-N-neotetraose [LNnT] plus probiotic [B. infantis EVC001]), or placebo (Lactose) for 28 days followed by 28 days of post-supplementation follow up. Stool samples were collected at baseline and at day 10, day 28 and day 56. Fecal myeloperoxidase (MPO), as an indicator of gut inflammation and fecal pH were measured and the change in the levels of these biochemical parameters between the sample collection time points were calculated and denoted as ∆MPO and ∆pH. Kruskal-Wallis test was done to assess the effect of the supplementations on ∆MPO and ∆pH. Multivariate quantile regression analysis was performed to analyze the association of the supplements with ∆MPO and ∆pH.ResultsIn comparison to the placebo group at day 10, a significant decrease in ∆MPO was found for the probiotic group (β-coefficient: -18.44; 95% CI: -31.62 µg/ml, -52.47 µg/ml; p = 0.007) and for the synbiotic group (β-coefficient: -17.24; 95% CI: -30.94 µg/ml, -35.36 µg/ml; p = 0.015). This reduction in ∆MPO in comparison to the placebo group was sustained only in the synbiotic group at other time points. Decrease in ∆pH was observed only in the synbiotic group at day 10 and day 28, but not at day 56 in comparison to the placebo group.ConclusionOur findings demonstrate that the use of this synbiotic supplementation may result in sustained effects in reduction of gut inflammation in young infants with SAM. However, further studies are required to fully evaluate the role of this synbiotic intervention for sustained reduction in fecal pH in this study population.Trial registrationThe trial is registered at ClinicalTrials.gov (NCT0366657). Registered on 12 September, 2018 (https://clinicaltrials.gov/ct2/show/NCT03666572)

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.

Background: Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations. Methods: Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by Inductively coupled plasma mass spectrometry (ICP-MS) analysis. The associations between maternal Se with PTB and gestational duration were analyzed using linear and logistic regressions. The results were then combined using fixed and random effect meta-analysis. Findings: In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/ml (range: 26.1 to 228.7 ng/ml) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB (p = 0.04) and gestational duration (p = 2.9e-6) with effect size estimates of an OR= 1.04 (95% CI: 1.0 to 1.07) for PTB per 10 ng/ml decrease in Se concentration and 0.44 days (95% CI: 0.26 – 0.62) longer gestation per 10 ng/ml increase in Se concentration. However, there was a substantial heterogeneity among study cohorts. The largest effect sizes were observed in UK (Liverpool) cohort, while the most statistically significant associations were observed in samples from Malawi. After excluding these two cohorts, the fixed effect meta-analysis was no longer significant, and the random-effect meta-analysis of all data sets also did not achieve statistical significance. Interpretation: While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalize across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Targeted Se supplementation could play a role in reducing PTB in some settings, however further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations are considered. Funding Statement: Payment for access to data and article-processing charges for this publication was covered by The Bill & Melinda Gates Foundation (Grant no: OPP1175128, OPP1152451). The NEST study acknowledges the support from National Institute of Environmental Health Sciences, the US Environmental Protection Agency, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Duke Cancer Institute. Th CPPOP study acknowledge support from the UCSF California Preterm Birth Initiative. The iLiNS-DYAD-M trial acknowledge the support by a grant to the University of California, Davis from The Bill & Melinda Gates Foundation [OPP49817] and a grant to the University of California, Davis from the Office of Health, Infectious Diseases, and Nutrition, Bureau for Global Health, U.S. Agency for International Development (USAID) through the Food and Nutrition Technical Assistance III Project (FANTA). MDIG, AMANHI, GAPPS and INTERBIO cohorts acknowledge the support by The Bill & Melinda Gates Foundation. Declaration of Interests: The authors declare no conflicts of interest regarding the content of this paper. Ethics Approval Statement: Our study protocol was approved by the Institute Review Board (IRB) of the CCHMC and by the corresponding Ethics Committees of each participating institution.

Background: With a prevalence of 3.1%, approximately, 450 000 children in Bangladesh are having severe acute malnutrition (SAM). There is currently no national community-based program run by government to take care of these children, one of the reasons being lack of access to ready-to-use therapeutic food (RUTF). Objective: To develop RUTF using locally available food ingredients and test its acceptability. Methods: A checklist was prepared for all food ingredients available and commonly consumed in Bangladesh that have the potential of being used for developing a RUTF. Linear programming was used to identify the combinations of nutrients that would result in an ideal RUTF. To test the acceptability of 2 local RUTFs compared to the prototype RUTF, Plumpy’Nut, a clinical trial with a crossover design was conducted among 30 children in the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. The acceptability was determined by using the mean proportion of offered food consumed by the children themselves. Results: Two RUTFs were developed, one based on chickpea and the other on rice–lentils. The total energy content of 100 g of chickpea and rice–lentil-based RUTF were 537.4 and 534.5 kcal, protein 12.9 and 13.5 g, and fat 31.8 and 31.1 g, respectively, without any significant difference among the group. On an average, 85.7% of the offered RUTF amount was consumed by the children in 3 different RUTF groups which implies that all types of RUTF were well accepted by the children. Conclusion: Ready-to-use therapeutic foods were developed using locally available food ingredients—rice, lentil, and chickpeas. Chickpea-based and rice–lentil-based RUTF were well accepted by children with SAM.

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., This article describes the protocol for an international study of human milk composition that will enable the construction of reference values for milk nutrient concentrations during lactation.

Background: In clinical settings, wasting in childhood has primarily been assessed with the use of a weight-for-height z score (WHZ), and in community settings, it has been assessed via the midupper arm circumference (MUAC) with a cutoff

To determine factors associated with stunting among children aged 6 to 24 months in a slum of Dhaka, Bangladesh.We conducted this case control study during November 2009 to December 2012. Children were classified as case if length-for-age Z-score (LAZ) was-2 and as control if LAZ was-1 SD. The logistic regression model was used to find the factors associated with stunting.The significant risk factors for stunting were: child's age12 months, maternal undernutrition, mother's education5 years, consumption of untreated drinking water and monthly family income100 USD.The findings of this study reiterated the role of maternal undernutrition and less education, consumption of untreated drinking water and poor family income as important associated factors of childhood stunting in resource-poor setting.

It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common.We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group).Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose.In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

Human-milk-targeted metabolomics analysis offers novel insights into milk composition and relationships with maternal and infant phenotypes and nutritional status. The Biocrates AbsoluteIDQ&reg, p180 kit, targeting 40 acylcarnitines, 42 amino acids/biogenic amines, 91 phospholipids, 15 sphingolipids, and sum of hexoses, was evaluated for human milk using the AB Sciex 5500 QTRAP mass-spectrometer in liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and flow-injection analysis (FIA) mode. Milk (&lt, 6 months lactation) from (A) Bangladeshi apparently healthy mothers (body mass index (BMI) &gt, 18.5, n = 12) and (B) Bangladeshi mothers of stunted infants (height-for-age Z (HAZ)-score &lt, &minus, 2, n = 13) was analyzed. Overall, 123 of the possible 188 metabolites were detected in milk. New internal standards and adjusted calibrator levels were used for improved precision and concentration ranges for milk metabolites. Recoveries ranged between 43% and 120% (coefficient of variation (CV): 2.4%&ndash, 24.1%, 6 replicates). Milk consumed by stunted infants vs. that from mothers with BMI &gt, 18.5 was lower in 6 amino acids/biogenic amines but higher in isovalerylcarnitine, two phospholipids, and one sphingomyelin (p &lt, 0.05 for all). Associations between milk metabolites differed between groups. The AbsoluteIDQ&reg, p180 kit is a rapid analysis tool suitable for human milk analysis and reduces analytical bias by allowing the same technique for different specimens. More research is needed to examine milk metabolite relationships with maternal and infant phenotypes.

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. INTRODUCTION There is a dimension to post-natal human development that involves assembly of microbial communities in different body habitats, including the gut. Children with acute malnutrition have impaired development of their gut microbiota, leaving them with communities that appear younger (more immature) than those of chronologically age-matched healthy individuals. Current therapeutic foods given to children with acute malnutrition have not been formulated based on knowledge of how they affect the developmental biology of the gut microbiota. Moreover, they are largely ineffective in ameliorating the long-term sequelae of malnutrition that include persistent stunting, neurodevelopmental abnormalities, and immune dysfunction. RATIONALE Repairing microbiota immaturity and determining the degree to which such repair restores healthy growth requires identification of microbial targets that are not only biomarkers of community assembly but also mediators of various aspects of growth. Identifying ingredients in complementary foods, consumed during the transition from exclusive milk feeding to a fully weaned state, that increase the representation and expressed beneficial functions of growth-promoting bacterial taxa in the developing microbiota could provide an effective, affordable, culturally acceptable, and sustainable approach to treatment. RESULTS Metabolomic and proteomic analyses of serially collected plasma samples were combined with metagenomic analyses of serially collected fecal samples from Bangladeshi children with severe acute malnutrition (SAM) treated with standard therapy. The results provided a readout of their biological features as they transitioned from SAM to a state of persistent moderate acute malnutrition (MAM) with accompanying persistent microbiota immaturity. Significant correlations were identified between levels of plasma proteins, anthropometry, plasma metabolites, and the representation of bacteria in their microbiota. Gnotobiotic mice were subsequently colonized with a defined consortium of bacterial strains that represent various phases of microbiota development in healthy Bangladeshi children. Administration of different combinations of Bangladeshi complementary food ingredients to colonized mice and germ-free controls revealed diet-dependent increases in the abundance and changes in the metabolic activities of targeted weaning-phase strains as well as diet- and colonization-dependent augmentation of growth-promoting host signaling pathways. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes were subsequently examined in gnotobiotic mice colonized with immature microbiota from children with post-SAM MAM and in gnotobiotic piglets colonized with a defined consortium of targeted age- and growth-discriminatory taxa. A randomized, double-blind study of standard therapy versus various MDCF prototypes emerging from these preclinical models, conducted in Bangladeshi children with MAM, identified a lead MDCF that increased levels of biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function toward a state resembling healthy children. Using an approach inspired by statistical methods applied to financial markets, we show in the accompanying paper by Raman et al. that this lead MDCF was most effective in repairing the microbiota. CONCLUSION These findings demonstrate the translatability of results obtained from pre-clinical gnotobiotic animal models to humans, directly support the hypothesis that healthy microbiota development is causally linked to healthy growth, illustrate an approach for treating childhood undernutrition, and with the capacity to deliberately reconfigure immature microbiota, suggest a means to decipher how elements of the gut microbial community operate to regulate various host systems involved in healthy growth. Overview of therapeutic food discovery and testing. The approach used for integrating preclinical gnotobiotic animal models with human studies to understand the contributions of perturbed gut microbiota development to childhood malnutrition and to identify MDCFs.

OBJECTIVES: The effect of infection and inflammation on EZP size, a putative biomarker of Zn status, is unknown. We sought to evaluate the relationship of EZP to systemic inflammation in a group of toddlers with high risk of Zn deficiency and EED. METHODS: Subjects were 112 children from an urban slum area in Dhaka, Bangladesh, aged 18–24 months, at risk of EED and who participated in stable isotope studies of Zn homeostasis while on habitual diets. All children underwent screening for EED, using L: M ratio, and multiple markers of systemic and intestinal inflammation were obtained. EZP size was measured from intravenously administered stable isotope of Zn, with urine collections obtained over 4 days, starting 3 days after isotope administration. The size of EZP was calculated by dividing the mass (mg) of intravenous isotope dose ((67) Zn or (68) Zn) by the enrichment value at the y intercept of the linear regression: EZP (mg) = IV dose/y-intercept. The intercept is estimated from linear regression of a semi-log plot of urine enrichment data. Multiple regression analysis was applied to examine relationships among child size, serum Zn, markers of systemic and intestinal inflammation and EZP. EZP was also compared to previously published evaluation of EZP from multiple studies (Miller LV, J Nutr, 2016). RESULTS: Mean (± SD) age of subjects was 19 ± 2 months; mean weight 9.1 ± 1.0 kg; mean dietary Zn was 2.7 mg/d. Mean EZP was 3.7 ± 0.5 mg/kg, compared to an expected value of 4.1 mg/kg based on the previous published analysis of all child data; all data points were within the 90% prediction interval from those data (Figure). Compared to existing child data, these children weighed less and had smaller EZP. EZP/kg was directly associated with serum Zn concentration, and inversely associated with hemoglobin and dietary Zn (best model R(2 )= 0.24). The analyses indicated no evidence of an association of EZP/kg with any biomarkers of inflammation. CONCLUSIONS: The apparent absence of an effect of inflammation on EZP size may provide some advantage over serum Zn. The inverse relationship with dietary Zn suggests redistribution of Zn pools in chronic marginal Zn status. Evaluation of utility of EZP as a biomarker of Zn status will require measurement during controlled interventions. FUNDING SOURCES: Bill & Melinda Gates Foundation. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

To assess the efficacy and safety of F-100, diluted F-100 (F100D), and infant formula (IF) for dietary management in the rehabilitation phase of severe acute malnutrition (SAM) of infants aged under 6 months (u6m).Double-blind randomized clinical trial was conducted to assess the efficacy and safety of F-100, F-100D, and IF at the Nutrition Rehabilitation Unit, icddr,b. Infants (n = 153) u6m with SAM were enrolled and randomly assigned to any of the three diets after stabilization. Two ml blood was collected on study days 1, 3, and 7 for measuring serum electrolytes, creatinine and osmolality, urine samples for specific gravity and osmolality creatinine ratio. Renal Solute Load (RSL) and Potential Renal Solute Load (PRSL) were calculated. Infants were discharged when gained 15% of the admission bodyweight or had edema-free weight-for-length Z-score ≥ - 2.Infants fed F-100 and F-100D had higher weight gain than infants who received IF. Mean difference between F-100 and IF was 4.6 g/kg/d (95% CI 1.5-7.6, P = 0.004) and between F-100D and IF was 3.1 g/kg/d (95% CI 0.6-5.5, P = 0.015). Total energy intake from study diet and breast milk was significantly higher in infants fed F-100 compared with other two diets (P = 0.001 in each case). RSL was highest in infants fed F-100 but serum sodium showed no sign of elevation. Urinary specific gravity and serum sodium values were within normal range.F-100 can be safely used in the rehabilitation phase for infants u6m with SAM and there is no need to prepare alternative formulations.

Supplementery_tables for Home Fortification of Rice With Lime: A Novel Potential Way to Reduce Calcium Deficiency in Bangladesh by Nurun Nahar Naila, Prasenjit Mondal, Sabri Bromage, M. Munirul Islam, M. Mamun Huda, Mohammad Sohel Shomik, Dinesh Mondal, Wafaie Fawzi and Tahmeed Ahmed in Food and Nutrition Bulletin

The duration of exclusive breastfeeding (EBF) is often defined as the time from birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated by calculating the proportion of women at a given infant age who EBF in the previous 24 h (EBFDHS). Others have measured the total days or personal prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur, EBF can be re-initiated for extended periods. We compared breastfeeding metrics in the MAL-ED study; infants' breastfeeding trajectories were characterized from enrollment (median 7 days, IQR: 4, 12) to 180 days at eight sites. During twice-weekly surveillance, caretakers were queried about infant feeding the prior day. Overall, 101 833 visits and 356 764 child days of data were collected from 1957 infants. Median duration of EBFLONG was 33 days (95% CI: 32–36), compared to 49 days based on the EBFDHS. Median EBFPREV was 66 days (95% CI: 62–70). Differences were because of the return to EBF after a non-EBF period. The median number of returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode), infants gained an additional 18.8 days (SD: 25.1) of EBF, and gained 13.7 days (SD: 18.1) (third episode). In settings where women report short gaps in EBF, programmes should work with women to return to EBF. Interventions could positively influence the duration of these additional periods of EBF and their quantification should be considered in impact evaluation studies. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd