Associations of fish and meat intake with iron and anaemia in Malawian children.

Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6-month egg-feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7-day animal-source food screeners. Grams of intake were assessed through 24-h recalls conducted at 6-9, 9-12 and 12-15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6-9 and 12-15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by <5% of children in the past 24 h. Over the next 6 months, small fish, large fish and meat were consumed on 25%, 8% and 6% of days, respectively, with mean usual intakes of <5 g/day. More frequent small fish consumption was associated with lower sTfR (geometric mean ratio [95% CI]: 0.98 mg/L [0.96, 1.00] per 10 percentage point difference) but not ferritin (1.03 µg/L [0.98, 1.07]) or haemoglobin (1.01 g/dL [1.00, 1.01]). Large fish consumption was associated with higher anaemia (prevalence ratio [95% CI]: 1.09 [1.01, 1.19]) and lower iron deficiency (0.96 [0.93, 1.00]) prevalence. Gram intakes of flesh food categories were not associated with any iron or anaemia indicators. Small fish were a primary contributor to flesh food intake in this cohort of Malawian children, although usual portions were small. Fish was associated with modest improvements to iron status, but meat was too infrequent to be associated with anaemia and iron deficiency.

The Effects of One Egg Per Day on Vitamin A Status Among Young Malawian Children: A Secondary Analysis of a Randomized Controlled Trial.

Background: Vitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods. Objectives: This analysis aimed to determine the impact of supplementing children's diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD. Methods: Children age 6-9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol <0.7 µmol/L) were compared between groups using log-binomial or modified Poisson regression models. Results: After 6 mo of study participation, 489 were assessed for retinol (egg: n = 238; control: n = 251), and 575 (egg: n = 281; control: n = 294) were assessed for RBP. Prevalence of inflammation (CRP >5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 µmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 µmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)]. Conclusions: Provision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx.This trial was registered at [clinicaltrials.gov] as [NCT03385252].

The association between plasma choline, growth and neurodevelopment among Malawian children aged 6-15 months enroled in an egg intervention trial.

Choline is an essential micronutrient that may influence growth and development; however, few studies have examined postnatal choline status and children's growth and development in low- and middle-income countries. The aim of this observational analysis was to examine associations of plasma choline with growth and development among Malawian children aged 6-15 months enrolled in an egg intervention trial. Plasma choline and related metabolites (betaine, dimethylglycine and trimethylamine N-oxide) were measured at baseline and 6-month follow-up, along with anthropometric (length, weight, head circumference) and developmental assessments (the Malawi Developmental Assessment Tool [MDAT], the Infant Orienting with Attention task [IOWA], a visual paired comparison [VPC] task and an elicited imitation [EI] task). In cross-sectional covariate-adjusted models, each 1 SD higher plasma choline was associated with lower length-for-age z-score (-0.09 SD [95% confidence interval, CI -0.17 to -0.01]), slower IOWA response time (8.84 ms [1.66-16.03]) and faster processing speed on the VPC task (-203.5 ms [-366.2 to -40.7]). In predictive models, baseline plasma choline was negatively associated with MDAT fine motor z-score at 6-month follow-up (-0.13 SD [-0.22 to -0.04]). There were no other significant associations of plasma choline with child measures. Similarly, associations of choline metabolites with growth and development were null except higher trimethylamine N-oxide was associated with slower information processing on the VPC task and higher memory scores on the EI task. In this cohort of children with low dietary choline intake, we conclude that there were no strong or consistent associations between plasma choline and growth and development.

Community-based management of acute malnutrition for infants under 6 months of age is safe and effective: analysis of operational data.

OBJECTIVE: To assess the effectiveness of outpatient management with ready-to-use and supplementary foods for infants under 6 months (u6m) of age who were unable to be treated as inpatients due to social and economic barriers. DESIGN: Review of operational acute malnutrition treatment records. SETTING: Twenty-one outpatient therapeutic feeding clinics in rural Malawi. PARTICIPANTS: Infants u6m with acute malnutrition treated as outpatients because of barriers to inpatient treatment. The comparison group consisted of acutely malnourished children 6-9 months of age who were being treated at the same time in the same location in the context of two different randomised clinical trials. RESULTS: A total of 323 infants u6m were treated for acute malnutrition (130 severe and 193 moderate). A total of 357 infants 6-9 months old with acute malnutrition (seventy-four severe and 283 moderate) were included as contemporaneous controls. Among infants u6m with severe acute malnutrition, 98 (75·4 %) achieved nutritional recovery; in comparison, 56 (75·7 %) of those with severe acute malnutrition 6-9 months old recovered. Among infants u6m with moderate acute malnutrition, 157 (81·3 %) recovered; in comparison, 241 (85·2 %) of those aged 6-9 months recovered. CONCLUSIONS: In a rural Malawian population of infants u6m who had generally already stopped exclusive breast-feeding and were now acutely malnourished, treatment with therapeutic or supplementary foods under the community management of acute malnutrition model was safe and effective. In settings where social and financial factors make hospital admission challenging, consideration should be given to lowering the recommended age of ready-to-use therapeutic and supplementary foods to infants u6m.

The Effects of 1 Egg per Day on Iron and Anemia Status among Young Malawian Children: A Secondary Analysis of a Randomized Controlled Trial.

Background: Young children with diets lacking diversity with low consumption of animal source foods are at risk of iron deficiency anemia (IDA). Objectives: Our objectives were to determine the impact of supplementing diets with 1 egg/d on 1) plasma ferritin, soluble transferrin receptor (sTfR), body iron index (BII), and hemoglobin concentrations and 2) the prevalence of iron deficiency (ID), anemia, and IDA. Methods: Malawian 6-9-mo-old infants in the Mazira trial (clinicaltrials.gov; NCT03385252) were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329). In this secondary analysis, hemoglobin, plasma ferritin, sTfR, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) were measured at enrollment and 6-mo follow-up. Iron biomarkers were corrected for inflammation. Ferritin, sTfR, BII, and hemoglobin were compared between groups using linear regression. Prevalence ratios (PRs) for anemia (hemoglobin <11 g/dL) and ID (ferritin <12 µg/L, sTfR >8.3 mg/L, or BII <0 mg/kg) between groups were compared using log binomial or modified Poisson regression. Results: A total of 585 children were included in this analysis (Egg: n = 286; Control: n = 299). At enrollment, the total prevalence of anemia was 61% and did not differ between groups. At 6-mo follow-up, groups did not differ in geometric mean concentration of hemoglobin [mean (95% CI); Egg: 10.9 (10.7, 11.1) g/dL; Control: 11.1 (10.9, 11.2) g/dL] and inflammation-adjusted ferritin [Egg: 6.52 (5.98, 7.10) µg/L; Control: 6.82 (6.27, 7.42) µg/L], sTfR [Egg: 11.34 (10.92, 11.78) mg/L; Control: 11.46 (11.04, 11.89) mg/L] or BII [Egg: 0.07 (0.06, 0.09) mg/kg; Control: 0.07 (0.05, 0.08) mg/kg]. There were also no group differences in anemia [Egg: 46%; Control 40%; PR: 1.15 (95% CI: 0.96, 1.38)], ID [PR: 0.99 (0.94, 1.05)], or IDA [PR: 1.12 (0.92, 1.36)]. Conclusions: Providing eggs daily for 6 mo did not affect iron status or anemia prevalence in this context. Other interventions are needed to address the high prevalence of ID and anemia among young Malawian children. This trial is registered at http://www.clinicaltrials.gov as NCT03385252.

Plasma Choline Concentration Was Not Increased After a 6-Month Egg Intervention in 6-9-Month-Old Malawian Children: Results from a Randomized Controlled Trial.

BACKGROUND: Eggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of 1 egg/d in young children in Ecuador, an egg intervention led to significant improvements in growth, which were partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development. OBJECTIVES: We aimed to evaluate the effect of 1 egg/d for 6 mo on plasma choline concentrations in Malawian children enrolled in a randomized trial. METHODS: Infants aged 6-9 mo in rural Malawi were randomly assigned to receive 1 egg/d (n = 331) or serve as a nonintervention control (n = 329) for 6 mo. Anthropometric, developmental, and dietary data were collected at baseline and 6-mo follow-up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and DHA were measured at both time points using ultrahigh performance liquid chromatography-tandem MS (n = 200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 mo of intervention. RESULTS: Plasma choline, betaine, dimethylglycine, and DHA concentrations did not differ between groups at 6-mo follow-up. Plasma TMAO was significantly (26%; 95% CI: 7%, 48%) higher in the egg intervention group in a fully adjusted model. CONCLUSIONS: Provision of 1 egg/d for 6 mo did not result in increases in plasma choline or related metabolites, except TMAO. This could partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

Longitudinal Assessment of Prenatal, Perinatal, and Early-Life Aflatoxin B1 Exposure in 828 Mother-Child Dyads from Bangladesh and Malawi.

BACKGROUND: In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation. OBJECTIVES: Aflatoxin exposure and selected determinants thereof were characterized in mother-child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh. METHODS: Circulating aflatoxin B1 (AFB1)-lysine albumin adducts were measured in dyads from Bangladesh (n = 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (n = 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry. We examined AFB1-lysine adduct magnitude, persistence, seasonality, and associations with infant feeding, and estimated daily AFB1 intake. RESULTS: Maternal AFB1-lysine was higher in Malawi (98% detectable; median: 0.469, IQR: 0.225-1.027 pg/µL) than in Bangladesh (59%; 0.030, nondetectable [nd]-0.077 pg/µL). Although estimated dietary exposure in Malawi was temporally stable (648 ng AFB1/day), estimated intake in Bangladesh was reduced by 94% between rainy and winter seasons (98 to 6 ng/day). AFB1-lysine was low in cord blood from Bangladesh (15% detectable; 0.045, 0.031-0.088 pg/µL among detectable) and in Malawian infants at 6 mo of age (0.072, nd-0.236 pg/µL), but reached maternal concentrations by 18 or 24 mo (Bangladesh: 0.034, nd-0.063 pg/µL; Malawi: 0.370, 0.195-0.964 pg/µL). In Malawian infants, exclusive breastfeeding at 3 mo was associated with 58% lower AFB1-lysine concentrations at 6 mo compared with other feeding modes (P = 0.010). CONCLUSIONS: Among pregnant women, aflatoxin exposure was persistently high in Malawi, while lower and seasonal in Bangladesh. Infants were partially protected from exposure in utero and with exclusive breastfeeding, but exposures reached adult levels by 18-24 mo of age. The Bangladesh and Malawi trials are registered at clinicaltrials.gov as NCT00860470 and NCT01239693.

Fecal biomarkers of environmental enteric dysfunction and the gut microbiota of rural Malawian children: An observational study.

Environmental enteric dysfunction (EED) is a subclinical condition of the gut characterized by changes in morphology and function with underlying chronic inflammatory responses. This study characterized composition and diversity of the gut microbiota in rural Malawian children with and without signs of EED. Fecal samples were collected from children aged 1-59 months. Neopterin, myeloperoxidase and alpha-1 antitrypsin concentrations were quantified by ELISA and combined to form a composite EED score using principal component analysis. DNA was extracted from fecal samples and V4-16S rRNA gene sequencing was used to characterize the gut microbiota. The concentrations of all three biomarkers decreased with increasing age, which is consistent with other studies of children living in similar low-income settings. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were the dominant phyla while Faecalibacterium and Bifidobacterium were the most prevalent genera. Increased alpha diversity was associated with a reduction in neopterin concentration. Microbiota composition was different between fecal samples with low and high composite EED scores; increased abundance of Succinivibrio was associated with reduced composite EED scores.

Impacts of an egg intervention on nutrient adequacy among young Malawian children.

Eggs are a rich source of multiple nutrients that support child growth and development. Provision of eggs as a complementary food may improve dietary adequacy among young children at risk for undernutrition. Our objective was to test the impact of an egg intervention on the adequacy of total nutrient intakes and micronutrient density among 6- to 15-month-old Malawian children. Children 6 to 9 months old, living in Mangochi District, Malawi, were randomly assigned to the intervention group (n = 331) receiving an egg per day or a control group (n = 329) consuming their usual diet. Dietary intakes of macronutrients, vitamins and minerals were assessed using 24-h recalls at baseline, 3-month midline and 6-month endline, with repeat recalls in a subsample. Usual nutrient intake and micronutrient density distributions were modelled to estimate group means and prevalence of inadequacy. Group differences at midline and endline were tested using unequal variance t tests with bootstrapped standard errors. The egg intervention resulted in higher intakes of fat and protein and lower intakes of carbohydrates. The egg group had lower prevalence of inadequacy for selenium, vitamin A, riboflavin, vitamin B5 , vitamin B12 and choline. Micronutrient density inadequacy was lower in the egg group for vitamin A and choline at midline and endline, riboflavin at midline and vitamin B5 at endline. Inadequacy of nutrient intakes or density remained highly prevalent in both groups for multiple micronutrients. Though the egg intervention increased intakes of protein and several micronutrients, total intakes and micronutrient density of multiple micronutrients remained far below recommendations.

Inflammation Adjustment by Two Methods Decreases the Estimated Prevalence of Zinc Deficiency in Malawi.

Serum zinc concentration (SZC) is used widely to assess population-level zinc status. Its concentration decreases during inflammatory responses, which can affect the interpretation of the results. This study aimed to re-estimate the prevalence of zinc deficiency in Malawi based on the 2015-2016 Malawi Micronutrient Survey (MNS) data, by adjusting SZC measures with markers of inflammation. SZC and inflammation data from 2760 participants were analysed. Adjustments were made using: (1) The Internal Correction Factor (ICF) method which used geometric means, and (2) The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) method, which used linear regression. Mean SZC values increased significantly when adjustments were made by either ICF or BRINDA (p < 0.001). The national prevalence of zinc deficiency decreased from 62% to 59%, after ICF adjustment, and to 52% after BRINDA adjustment. ICF and BRINDA values of SZC were highly correlated (p < 0.001, r = 0.99), but a Bland-Altman plot showed a lack of agreement between the two methods (bias of 2.07 µg/dL). There was no association between the adjusted SZC and stunting, which is a proxy indicator for zinc deficiency. Inflammation adjustment of SZC, using ICF or BRINDA, produces lower estimates of zinc deficiency prevalence, but the lack of agreement between the adjustment methods warrants further research. Furthermore, the lack of association between SZC and stunting highlights the need to explore other biomarkers and proxies of population zinc assessment. This study demonstrates the importance of considering inflammatory confounders when reporting SZC, to ensure accuracy and to support policy decision making.

Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

Consumption of Animal-Source Protein is Associated with Improved Height-for-Age z Scores in Rural Malawian Children Aged 12⁻36 Months.

Linear growth faltering, caused by insufficient diet, recurrent infections and environmental enteric dysfunction (EED), continues to plague young children in low- and middle-income countries (LMICs). Diets in LMICs are primarily plant based, and thus have poor-quality protein and low levels of essential micronutrients. The aim of this study was to assess the association of the type and protein quality of food consumed with stunting, EED and acute malnutrition in children aged 6⁻36 months in Limera and Masenjere, two rural Southern Malawian communities. This is a secondary analysis of two randomized controlled trials that tested the effects of common bean and cowpea flour on stunting in children aged 6⁻36 months. We used data from two interactive 24-h dietary recalls conducted 12 weeks after enrolment into each trial. Food intakes were compared between the regions using Chi-square and Student's t-test. There were 355 children that participated in the dietary recalls. The diets of children were of poor quality, but the children from Limera consumed more fish (54% vs. 35%, p = 0.009) and more bioavailable protein (26.0 ± 10.3 g/day vs. 23.1 ± 8.1 g/day, p = 0.018, respectively) than children in Masenjere. Food type and protein quality were not associated with any of the outcomes except an association between animal protein consumption and improvement in height-for-age z scores in children aged 12⁻36 months (p = 0.047). These findings support the notion that animal-source food (ASF) consumption in this vulnerable population promotes linear growth.

Effect of cowpea flour processing on the chemical properties and acceptability of a novel cowpea blended maize porridge.

Childhood growth stunting is a pervasive problem in Malawi and is in large part due to low quality complementary foods and chronic gut inflammation. Introducing legumes such as cowpea (Vigna unguiculata) into the complementary diet has the potential to improve childhood growth by improving diet quality through improvements in macro- and micronutrients and also by reducing gut inflammation. However, cowpea is relatively underutilized in complementary feeding in Malawi due to its strong taste, long processing time, and high energy requirements for processing. Effective utilization of cowpea in complementary feeding requires processing which may affect chemical composition as well as sensory quality. The present study evaluated the effect of processing on the retention of zinc, crude fibre, and flavonoid in roasted, boiled, and dehulled cowpea flours, and assessed the acceptability of maize porridge (70%) enriched with one of the three cowpea flours (30%). Roasting, dehulling, and boiling did not have any effect on zinc content. Crude fibre content increased after processing by all methods. Processing had no effect on measurable flavonoids. Roasted, boiled, and dehulled cowpea blended maize porridges were acceptable to children with mean quantities of leftover food of less than 3g from the given 100g. Caregivers also rated the blended flours to be highly acceptable to them as well, with maize porridge blended with dehulled cowpea flour the most acceptable to both children and caregivers. These results demonstrate that cowpea flour, processed by any of these three different methods, could serve as a useful addition to maize porridge for complementary feeding of children in sub-Saharan Africa.

Children with Poor Linear Growth Are at Risk for Repeated Relapse to Wasting after Recovery from Moderate Acute Malnutrition.

Background: Nutrition programs frequently approach wasting and stunting as 2 separate conditions with distinct causes and effects. Although several cross-sectional studies have identified an association between the 2 conditions, longitudinal studies are useful to quantify the risk of acute malnutrition based on the trajectory of linear growth. Objective: We analyzed data from a longitudinal study to explore associations between linear growth and relapse to acute malnutrition in high-risk children during the year after recovery from moderate acute malnutrition (MAM). Methods: This was a secondary data analysis from a cluster randomized trial involving 1487 Malawian children 6-62 mo old treated for MAM and enrolled upon recovery. Children were followed for 1 y, during which data were collected on anthropometric progress, symptoms of illness, and household food security. Multivariate fixed-effects logistic regression was used to identify associations between linear growth and relapse to acute malnutrition. Results: Children who have recovered from MAM proved to be a high-risk population, with nearly half experiencing a decrease in height-for-age z score (HAZ) for 12 mo. Children whose HAZ was declining were more likely to relapse to MAM or SAM than were those whose linear growth rate maintained or increased their HAZ (P < 0.001). Mean changes of +0.15, -0.03, -0.17, and -0.53 in HAZ were observed for those who sustained recovery, relapsed to MAM once, relapsed to MAM multiple times, and developed SAM, respectively. Conclusion: Our results add to the body of evidence suggesting that acute wasting is a harbinger of subsequent stunting. Children who experience poor linear growth after MAM are more likely to experience relapse. Given this bidirectional relation between wasting and stunting, supplementary feeding programs should consider both when designing protocols, aiming to optimize linear growth and achieve acute weight gain, as a means of reducing relapse. This trial was registered at clinicaltrials.gov as NCT02351687.

Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability.

Background: Chronic malnutrition, as manifested by linear growth faltering, is pervasive among rural African children. Improvements in complementary feeding may decrease the burden of environmental enteric dysfunction (EED) and thus improve growth in children during the critical first 1000 d of development. Objective: We tested the hypothesis that systematically including common bean or cowpea into complementary feeding would reduce EED and growth faltering among children in rural Malawi. Methods: This was a double-blind clinical trial in which children 12-23 mo of age were randomly assigned to receive complementary feeding with 1 of 3 foods: roasted cowpea or common bean flour, or an isoenergetic amount of corn-soy blend as a control food for 48 wk. Children aged 12-23 mo received 155 kcal/d and thereafter until 35 mo received 200 kcal/d. The primary outcomes were change in length-for-age z score (LAZ) and improvements in a biomarker of EED, the percentage of lactulose (%L) excreted as part of the lactulose:mannitol dual-sugar absorption test. Anthropometric measurements and urinary %L excretion were compared between the 2 intervention groups and the control group separately with the use of linear mixed model analyses for repeated measures. Results: A total of 331 children completed the clinical trial. Compliance with the study interventions was excellent, with >90% of the intervention flour consumed as intended. No significant effects on LAZ, change in LAZ, or weight-for-length z score were observed due to either intervention legume, compared to the control. %L was reduced with common bean consumption (effect estimate was -0.07 percentage points of lactulose, P = 0.0007). The lactulose:mannitol test was not affected by the legume intervention. Conclusion: The addition of common bean to complementary feeding of rural Malawian children during the second year of life led to an improvement in a biomarker of gut health, although this did not directly translate into improved linear growth. This trial was registered at clinicaltrials.gov as NCT02472301.

Household-level factors associated with relapse following discharge from treatment for moderate acute malnutrition.

Factors associated with relapse among children who are discharged after reaching a threshold denoted 'recovered' from moderate acute malnutrition (MAM) are not well understood. The aim of this study was to identify factors associated with sustained recovery, defined as maintaining a mid-upper-arm circumference≥12·5 cm for 1 year after release from treatment. On the basis of an observational study design, we analysed data from an in-depth household (HH) survey on a sub-sample of participants within a larger cluster randomised controlled trial (cRCT) that followed up children for 1 year after recovery from MAM. Out of 1497 children participating in the cRCT, a subset of 315 children participated in this sub-study. Accounting for other factors, HH with fitted lids on water storage containers (P=0·004) was a significant predictor of sustained recovery. In addition, sustained recovery was better among children whose caregivers were observed to have clean hands (P=0·053) and in HH using an improved sanitation facility (P=0·083). By contrast, socio-economic status and infant and young child feeding practices at the time of discharge and HH food security throughout the follow-up period were not significant. Given these results, we hypothesise that improved water, sanitation and hygiene conditions in tandem with management of MAM through supplemental feeding programmes have the possibility to decrease relapse following recovery from MAM. Furthermore, the absence of associations between relapse and nearly all HH-level factors indicates that the causal factors of relapse may be related mostly to the child's individual, underlying health and nutrition status.

Complementary feeding with cowpea reduces growth faltering in rural Malawian infants: a blind, randomized controlled clinical trial.

Background: Growth faltering is common in rural African children and is attributed to inadequate dietary intake and environmental enteric dysfunction (EED).Objective: We tested the hypothesis that complementary feeding with cowpea or common bean flour would reduce growth faltering and EED in 6-mo-old rural Malawians compared with the control group receiving a corn-soy blend.Design: A prospective, double-blind, randomized controlled clinical trial was conducted in which children received daily feeding for 6 mo (200 kcal/d when 6-9 mo old and 300 kcal/d when 10-12 mo old). The primary outcomes were change in length-for-age z score (LAZ) and improvements in EED, as measured by percentage of lactulose excretion (%L). %L <0.2% was considered normal. Anthropometric measurements and %L through urine were compared between each legume group and the control group with Student's t test.Results: Of the 355 infants enrolled, 291 infants completed the trial, and 288 were breastfed throughout the duration of the study. Cowpea and common bean added 4.6-5.2 g protein/d and 4-5 g indigestible carbohydrate/d to the diet. LAZ and weight-for-height z score were reduced in all 3 groups from 6 to 12 mo of age. The changes in LAZ [mean (95% CI)] for the cowpea, common bean, and control groups from 6 to 9 mo were -0.14 (-0.24, -0.04), -0.27 (-0.38, -0.16), and -0.27 (-0.35, -0.19), respectively. LAZ was reduced less in infants receiving cowpea than in those receiving control food from 6 to 9 mo (P = 0.048). The absolute value of %L did not differ between the dietary groups at 9 mo of age (mean ± SD: 0.30 ± 0.43, 0.23 ± 0.21, and 0.26 ± 0.31 for cowpea, common bean, and control, respectively), nor did the change in %L from 6 to 9 mo.Conclusion: Addition of cowpea to complementary feeding in Malawian infants resulted in less linear growth faltering. This trial was registered at clinicaltrials.gov as NCT02472262.

Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: study protocol for a randomized controlled trial.

BACKGROUND: Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ultimately morbidity and mortality. Effective therapies against EED and stunting are lacking and further clinical trials are warranted to effectively identify and operationalize interventions. METHODS/DESIGN: A prospective randomized placebo-controlled parallel-group randomized controlled trial will be conducted to determine if a daily supplement of lactoferrin and lysozyme, two important proteins found in breast milk, can decrease the burden of EED and stunting in rural Malawian children aged 12-23 months old. The intervention and control groups will have a sample size of 86 subjects each. All field and laboratory researchers will be blinded to the assigned intervention group, as will the subjects and their caregivers. The percentage of ingested lactulose excreted in the urine (Δ%L) after 4 h will be used as the biomarker for EED and linear growth as the measure of chronic malnutrition (stunting). The primary outcomes of interest will be change in Δ%L from baseline to 8 weeks and to 16 weeks. Intention-to-treat analyses will be used. DISCUSSION: A rigorous clinical trial design will be used to assess the biologically plausible use of lactoferrin and lysozyme as dietary supplements for children at high risk for EED. If proven effective, these safe proteins may serve to markedly reduce the burden of childhood malnutrition and improve survival. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02925026 . Registered on 4 October 2016.

Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi.

Background: Stunting affects ∼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood.Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting.Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted.Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure.Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for ß-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.