Childhood Stunting in South Asian Slums

Puolet maailman lapsista, jotka kärsivät lyhytkasvuisuudesta, asuu Etelä-Aasiassa. Näiden maiden slummeissa jopa puolet lapsista on lyhytkasvuisia eli he eivät saavuta kasvupotentiaaliaan. Lyhytkasvuisuutta käsittelevä kirjallisuuskatsaus osoitti kolme puutetta aikaisemmassa tutkimustiedossa, joiden pohjalta tämän tutkimuksen kolme tavoitetta kehitettiin. Ensimmäisenä tavoitteena oli selvittää, ennustaako krooninen altistuminen aflatoksiinille Etelä-Aasian slummeissa asuvien lapsille lyhytkasvuisuutta. Toisena tavoitteena oli tunnistaa anemian ja yleisten hivenravinteiden puutosten yleisyys slummissa asuvilla lapsilla syntymästä 5-vuotiaaksi sekä selvittää, voivatko hemoglobiinitaso sekä plasmasta mitattu sinkin, ferritiinin ja retinolin pitoisuus varhaislapsuudessa ennustaa lasten tilan 5-vuotiaana. Kolmas tavoite oli testata, voiko slummeissa tehtävä ruokainterventio, jossa päivittäin lisätään ruokavalioon kananmuna, maitoa ja hivenaineita, parantaa slummissa elävien lasten pituuskasvua. Ensimmäisessä tutkimuksessa käytettiin MAL-ED syntymäkohortti-tutkimuksessa kerättyä slummissa asuvien lasten aineistoa. Aflatoksiini -pitoisuus mitattiin massaspektrometri -menetelmää käyttäen plasma-näytteistä, jotka oli kerätty lasten ollessa 7, 15, 24 ja 36 kuukauden ikäisiä. Lapsista 62 prosenttia oli altistunut aflatoksiinille 36 kuukauden ikäisinä. Kun analyysissa otettiin huomioon mahdolliset sekoittavat tekijät, yhteyttä aflatoksiini-altistuksen ja lyhytkasvuisuuden välillä ei havaittu. Toinen tutkimus oli pitkittäiskohortti, jossa lapsia seurattiin syntymästä 60 kuukauden ikään (MAL-ED Bangladesh). Tässä tutkimuksessa havaittiin, että kahden ensimmäisen ikävuoden aikana suuri osa lapsista on aneemisia ja kärsii sinkin ja vitamiini A:n puutteista. Viiden vuoden iässä näistä puutoksista kärsivien lasten määrä vähenee huomattavasti. Tämä tutkimus osoitti myös, että lapsilla, joilla veren rauta-arvot ja plasman sinkki-, ferritiini- ja retinoli-tasot olivat korkealla 7 ja 24 kuukauden välillä, verrattuna lapsiin, joilla nämä arvot olivat matalat, plasmasta mitattujen hivenaineiden pitoisuudet 60 kuukauden iässä olivat korkeammat. Kolmannessa tutkimuksessa slummeissa asuville lapsille annettiin päivittäin lisäruokaa 12 kuukauden iästä 18 kuukauden ikään. Lisäruokaan kuului yksi kananmuna, 150 millilitraa maitoa ja yksi pussillisen pulveria, joka sisälsi useita hivenaineita kolmen kuukauden ajan. Tutkimuksen loputtua, lisäruokintaa saaneet lapset olivat suhteellisesti pitempiä (length-for-age z-score) kuin historiallisen vertailuryhmän lapset, jotka eivät olleet saaneet lisäruokintaa. Yhteenvetona voidaan sanoa, että aflatoksiini ei ennusta lasten lyhytkasvuisuutta Etelä-Aasiassa. Kuitenkin suuri osa lapsista on altistunut aflatoksiinille, ja altistuksen lähde pitäisi selvittää. Lisäksi anemia ja monien hivenaineiden puutteet ovat yleisiä slummeissa asuvilla lapsilla. Lapset, jotka jo ovat lyhytkasvuisia, lisäruokapaketti, joka sisältää useita hivenaineita, kananmunaa ja maitoa, voi tehokkaasti vähentää lasten lyhytkasvuisuutta Etelä-Aasian slummeissa.Accommodating the half of the global caseload, stunting in children is ubiquitous in South Asian countries, and the prevalence is as high as 50% among city slum dwellers. A review of the literature identified the existing gaps in determinants of childhood stunting and interventions to improve this condition in this population. This review identified three different research gaps and also developed three aims to address these issues. The first aim was to explore whether chronic aflatoxin exposure is a predictor of childhood stunting in the slum children of South Asia. The second aim was to identify the burden of anemia and common micronutrient deficiencies among the slum children at different time points from birth to 5 years of age, and to investigate if the Hb and plasma levels of zinc, ferritin, and retinol in early childhood can predict their status at 5 years of age. The third aim was to test if a community-based dietary intervention with daily supplementation with egg, milk, and multiple micronutrients can improve the linear growth of stunted children living in slum settings. The first study used birth cohort data (MAL-ED aflatoxin study) of slum children, where aflatoxin concentrations were measured from plasma samples collected at 7, 15, 24, and 36 months of age using mass spectrometry. This study observed that 62% of the children were exposed to aflatoxin at 36 months of age. However, no association between aflatoxin exposure and childhood stunting was detected in this study after adjusting the potential confounders. The second study was a longitudinal cohort study (MAL-ED Bangladesh), where children were followed from birth to 60 months of age. This study observed that the proportion of children with anemia, and zinc, iron, and vitamin A deficiencies were high in the first couple of years and then the burdens were markedly reduced at 5 years of age. This study also revealed that children who had consistent upper levels of Hb and plasma zinc, ferritin, and retinol between 7 months to 24 months of age compared to children who had consistently lower levels of the Hb and other micronutrients for the same period as detected by latent class growth modeling, had better concentrations of plasma micronutrient status at 60 months of age. The third study was a community-based intervention study where stunted slum children aged from 12 months to 18 months were supplemented daily with one egg, 150 ml of milk, and 1 sachet of multiple micronutrient powder for three months. At the end of the diet, children in the intervention group had a significant improvement in length-for-age z-score, compared with the age, anthropometry, and area of residence matched historical comparison group, who did not receive any dietary intervention. In conclusion, aflatoxin is not a predictor of childhood stunting in slum children of South Asia. However, as a substantial number of children are exposed to aflatoxin the source of exposure needs to be identified. In addition, anemia and multiple micronutrient deficiencies are common in young slum children. For children who already developed stunting, a nutrition package consisting of multiple micronutrient powder, egg, and milk may be effective to ameliorate the stunting burden in the slums of South Asia

Site-Specific Incidence Rate of \u3ci\u3eBlastocystis hominis\u3c/i\u3e and Its Association with Childhood Malnutrition: Findings from a Multi-Country Birth Cohort Study

In this study, we investigated the potential association between the burden of asymptomatic Blastocystis spp. (Blastocystis hominis) infection and nutritional status among children under 2 years of age using the data collected from 1,715 children from eight distinct geographic locations, including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. Childhood stunting, wasting, and underweight were the outcome variables, and B. hominis infection was the exposure variable of this present study. The presence of B. hominis in nondiarrheal stools was evaluated by TaqMan Array Cards. Site-specific incidence rates were estimated using Poisson regression, and multiple generalized estimating equation was used to assess the association between the B. hominis infection and nutritional status. The site-specific incidence rates of asymptomatic B. hominis infections per 100 child-months were higher in Tanzania, Peru, and South Africa when compared with the other study sites. Moreover, in terms of site-specific association, childhood stunting was significantly associated with asymptomatic B. hominis infection in Bangladesh (odds ratio [OR]: 1.62; 95% CI: 1.26–2.08), India (OR: 1.78; 95% CI: 1.46–2.16), Nepal (OR: 2.26; 95% CI: 1.60–3.21), Peru (OR: 1.47; 95% CI: 1.26–1.71), South Africa (OR: 1.57; 95% CI: 1.35–1.83), and Tanzania (OR: 2.46; 95% CI: 2.18–2.79) sites. Wasting was associated with B. hominis in the Brazil site only (OR: 3.19; 95% CI: 1.31–7.77). On the other hand, underweight was associated in the Bangladesh (OR: 1.89; 95% CI: 1.48–2.42), Brazil (OR: 4.41; 95% CI: 1.57–12.4), Nepal (OR: 2.25; 95% CI: 1.52–3.35), and Tanzania (OR: 1.68; 95% CI: 1.42–1.99) sites. Our analysis further reveals that the presence of additional pathogens may play a pathogenic role in children who have B. hominis infection

Preparation, GIAO NMR Calculations and Acidic Properties of Some Novel 4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives with Their Antioxidant Activities

Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, 1H-NMR, 13C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic 1H and 13C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a–c,e,f) were screened for their antioxidant activities

Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition

BACKGROUND: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3 months. METHODS: Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (pre-intervention), after 1 month, at the end of intervention (3 months), 1 month after cessation of intervention, and every 6 months thereafter for 4 years. DISCUSSION: This study will determine whether daily, controlled administration of MDCF-2 for 3 months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices. TRIAL REGISTRATION: The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered)

Site-Specific Analysis of the Incidence Rate of Enterotoxigenic \u3ci\u3eEscherichia coli\u3c/i\u3e Infection Elucidates an Association with Childhood Stunting, Wasting, and Being Underweight: A Secondary Analysis of the MAL-ED Birth Cohort

Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, andmultiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites

Site-Specific Analysis of the Incidence Rate of Enterotoxigenic \u3ci\u3eEscherichia coli\u3c/i\u3e Infection Elucidates an Association with Childhood Stunting, Wasting, and Being Underweight: A Secondary Analysis of the MAL-ED Birth Cohort

Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, andmultiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites

Children living in the slums of Bangladesh face risks from unsafe food and water and stunted growth is common

Aim: This study investigated the microbial quality of food and water consumed by children in four slums in Dhaka, the capital of Bangladesh, together with the associated risk factors. Methods: This cross-sectional study took place from December 2015 to May 2016 and focused on 360 children under the age of five. We recorded household food security, namely adequate food for a healthy life, socio-economic and nutritional status, hygiene and feeding practices. Food and water samples were analysed. Results: We found that 63% of the children were malnourished and 58% were stunted. Yeast and moulds were detected in 86% of the food samples and coliforms in 73%. All the water samples were contaminated with faecal coliforms, yeasts and moulds and Staphylococcus. Food insecurity affected 83% of households. Children were twice as likely to be malnourished if they were born with a perceived low birth weight or their mothers did not wash their hands with soap after cleaning the child’s bottom following defecation. Exclusively breast-fed children were less likely to develop malnutrition. Conclusion: Children from the Dhaka slums were frequently stunted and malnourished and contaminated food and water was common. Integrated efforts are essential to create public awareness about hygiene

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

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