The Effect of Breastfeeding Practices of Undernourished Mothers in Rural Sierra Leone on Infant Growth and Mortality.

Breastfeeding provides optimal infant nutrition; however, <50% of infants are exclusively breastfed (EBF) for 6 months. We aimed to describe breastfeeding practices and their effects on growth and mortality among a high-risk mother-infant cohort in rural Sierra Leone. This was a secondary analysis of data from a randomized nutrition intervention trial among undernourished pregnant women. The study's primary outcomes were infant weight and length gains at 6 weeks of age. We included 1270 singleton infants in the analysis, with 1092 (85.6%) having 24-week outcome data. At 6 weeks, 88% were EBF, but the rate of EBF decreased to 17% at 24 weeks. The EBF infants at 6 weeks had improved length (difference of 0.9 mm/week; 95% CI 0.4 to 1.3; p < 0.001) and weight (difference of 40 g/week; 95% CI 24 to 53; p < 0.001) gains compared to the non-EBF infants. At 12 weeks, the EBF infants had improved weight (difference of 12 g/week; 95% CI 2 to 22; p = 0.024) gain. The EBF infants had lower mortality than the infants who were not EBF (hazard ratio of 0.39; 95% CI 0.18 to 0.84; p = 0.017). In summary, the infants who were EBF had greater weight and length gain and reduced mortality than those who were not EBF. Efforts to improve breastfeeding should thus be prioritized to improve infant health.

Effect of Peanut Paste-based Ready-to-use School Meals With and Without Milk on Fluid Cognition in Northern Ghana: A Randomized Controlled Trial.

BACKGROUND: Few studies have investigated the role of school feeding in low- and middle-income countries as a means of improving childhood cognition. Peanut/milk ready-to-use food (PM-RUF) or cowpea offers an affordable, scalable option that might improve cognition. OBJECTIVES: To determine whether micronutrient-fortified PM-RUF or peanut/cowpea ready-to-use food (PC-RUF) would improve fluid cognition as assessed by 4 tests from the National Institutes of Health Toolbox Cognitive Battery when compared with a micronutrient-fortified millet porridge (FP) after a year of school feeding. METHODS: An individually randomly assigned, investigator-blinded, controlled clinical trial was conducted at 6 schools in Mion District in rural northern Ghana. Eight hundred seventy-one school children aged 5-12 y were randomly assigned and allocated to receive PM-RUF (n = 282), PC-RUF (n = 292), or FP (n = 297), each providing ∼400 kcal/d. The primary outcomes were 4 fluid cognition test scores: Dimensional Change Card Sort test, Flanker Inhibitory Control and Attention test, Pattern Comparison Processing Speed test, and a modified List Sorting Working Memory test. Secondary outcomes included a composite median ranking of the 4 primary outcomes and anthropometry changes. RESULTS: Among the 871 participants (median age, 8.8 y; 47% female), 795 (91%) completed endline cognitive testing. Median attendance rates exceeded 87% in all groups. PM-RUF group demonstrated better fluid cognition on the Dimensional Change Card Sort test [odds ratio (OR): 1.5; 95% CI: 1.1, 2.0; P = 0.016] and Pattern Comparison Processing Speed test (OR: 1.4; 95% CI: 1.0, 1.9; P = 0.026) than FP, whereas there were no significant differences on Flanker Inhibitory Control and Attention or List Sorting Working Memory tests. PC-RUF group demonstrated no improvement over FP on any cognitive tests. PM-RUF group had superior fluid cognition composite median rankings (OR: 1.5; 95% CI: 1.1, 2.0; P = 0.007). CONCLUSIONS: Among rural Ghanaian children aged 5-12 y, PM-RUF compared with FP resulted in superior fluid cognition. This trial was registered at clinicaltrials.gov as NCT04349007.

Women's empowerment and child nutrition in a context of shifting livelihoods in Eastern Oromia, Ethiopia.

Agriculture, and particularly livestock and animal source foods, has been closely linked to improvements in human nutrition. Production, income, and women's empowerment improve household food security and child nutritional outcomes in interacting ways. Khat production in Eastern Ethiopia is changing the economic and livelihood landscape for communities that have traditionally relied upon small-scale mixed agriculture and livestock production. How this shifting livelihood landscape and the empowerment of women in these communities are affecting nutritional outcomes has not been investigated. Using cross-sectional data collected during formative research for the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) project, we developed models to examine the roles of livelihood activities, including livestock production, staple crop production, and khat production, and women's empowerment in child nutrition outcomes. Survey participants were randomly selected mothers of children aged 10-15 months from Haramaya district, Eastern Hararghe, Oromia, Ethiopia. Nested logistic regression models were performed for each nutrition outcome: children's animal source food consumption, children's dietary diversity, and child stunting, wasting, and underweight. Explanatory variables included those for livelihood (tropical livestock unit, crop production, and khat production ladder) and women's empowerment (as indicated by domains of the Women's Empowerment in Agriculture Index), and covariates including child sex, mother's age, mother's education, assets, income, and kebele. Results indicated that khat production and tropical livestock units were not significantly associated with any of the child nutrition outcomes. However, results did indicate that the odds of reporting child animal source food consumption in households where the mother was empowered in the leadership domain was 3.33 times that in households where the mother wasn't (p < 0.05). In addition, the odds of having a stunted child in households where the mother was empowered in the time domain was 2.68 times that in households where the mother wasn't (p < 0.05). The results from this study both support and complicate the existing literature on the associations between women's empowerment in agriculture and child nutrition outcomes, underscoring the important role that livelihood, contextual factors, and location may have on the complex relationship between empowerment domains and nutritional outcomes.

Prevalence and Load of the Campylobacter Genus in Infants and Associated Household Contacts in Rural Eastern Ethiopia: a Longitudinal Study from the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) Project.

In our previous cross-sectional study, multiple species of Campylobacter were detected (88%) in stool samples from children (12 to 14 months of age) in rural eastern Ethiopia. This study assessed the temporal fecal carriage of Campylobacter in infants and identified putative reservoirs associated with these infections in infants from the same region. The prevalence and load of Campylobacter were determined using genus-specific real-time PCR. Stool samples from 106 infants (n = 1,073) were collected monthly from birth until 376 days of age (DOA). Human stool samples (mothers and siblings), livestock feces (cattle, chickens, goats, and sheep), and environmental samples (soil and drinking water) from the 106 households were collected twice per household (n = 1,644). Campylobacter was most prevalent in livestock feces (goats, 99%; sheep, 98%; cattle, 99%; chickens, 93%), followed by human stool samples (siblings, 91%; mothers, 83%; infants, 64%) and environmental samples (soil, 58%; drinking water, 43%). The prevalence of Campylobacter in infant stool samples significantly increased with age, from 30% at 27 DOA to 89% at 360 DOA (1% increase/day in the odds of being colonized) (P < 0.001). The Campylobacter load increased linearly (P < 0.001) with age from 2.95 logs at 25 DOA to 4.13 logs at 360 DOA. Within a household, the Campylobacter load in infant stool samples was positively correlated with the load in mother stool samples (r2 = 0.18) and soil collected inside the house (r2 = 0.36), which were in turn both correlated with Campylobacter loads in chicken and cattle feces (0.60 < r2 < 0.63) (P < 0.01). In conclusion, a high proportion of infants are infected with Campylobacter in eastern Ethiopia, and contact with the mother and contaminated soil may be associated with early infections. IMPORTANCE A high Campylobacter prevalence during early childhood has been associated with environmental enteric dysfunction (EED) and stunting, especially in low-resource settings. Our previous study demonstrated that Campylobacter was frequently found (88%) in children from eastern Ethiopia; however, little is known about potential Campylobacter reservoirs and transmission pathways leading to infection of infants by Campylobacter during early growth. In the longitudinal study presented here, Campylobacter was frequently detected in infants within the 106 surveyed households from eastern Ethiopia, and the prevalence was age dependent. Furthermore, preliminary analyses highlighted the potential role of the mother, soil, and livestock in the transmission of Campylobacter to the infant. Further work will explore the species and genetic composition of Campylobacter in infants and putative reservoirs using PCR and whole-genome and metagenomic sequencing. The findings from these studies can lead to the development of interventions to minimize the risk of transmission of Campylobacter to infants and, potentially, EED and stunting.

Docosahexaenoic Acid Stability in Ready-to-Use Therapeutic Food.

Ready-to-use therapeutic food (RUTF) is used to treat young children diagnosed with severe acute malnutrition. RUTF with low and balanced linoleic and alpha-linolenic acid, plus omega-3 docosahexaenoic acid (DHA), supports long-term cognitive recovery. DHA is prone to degradation due to peroxidation, possibly exacerbated by the iron inherently in RUTF. Our goals were to prepare benchtop and manufacturing scale of RUTF formulations that include DHA and measure its retention. Twenty-seven RUTF formulas with base ingredients, including oats, high oleic or commodity peanuts, and encapsulated or oil-based DHA at various levels were prepared at benchtop scale, followed by seven months of climate-controlled storage. These pilot samples had similar relative DHA retention. At the manufacturing scale, DHA was added at one of two stages in the process, either at the initial or the final mixing stage. Samples taken at preliminary or later steps show that less than 20% of DHA added at the early stages disappeared prior to packaging for any recipe tested. Overall, our data indicate that most DHA included in RUTF is retained in the final product and that DHA is best retained when added at the latest manufacturing stage.

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.

Supplementary feeding and infection control in pregnant adolescents-A secondary analysis of a randomized trial among malnourished women in Sierra Leone.

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

An Alternative Oat-Containing, Ready-To-Use, Therapeutic Food Does Not Alter Intestinal Permeability or the 16S Ribosomal RNA Fecal Microbiome Configuration Among Children With Severe Malnutrition in Sierra Leone: A Randomized Controlled Trial.

BACKGROUND: Previously, a novel oat ready-to-use therapeutic food (o-RUTF) resulted in improved recovery from severe acute malnutrition (SAM) when compared to a standard RUTF (s-RUTF). The o-RUTF contained 18% oat, while the s-RUTF has no cereal ingredients. OBJECTIVES: We determined the effects of o-RUTF on intestinal permeability, as measured by lactulose permeability, and the 16S ribosomal RNA (rRNA) fecal microbiome configuration of children with SAM. METHODS: This was a prospective, randomized, double-blinded, controlled clinical trial. Sierra Leonean children aged 6-59 mo with SAM, defined by a midupper arm circumference < 11.5 cm, were randomized to receive o-RUTF or s-RUTF. All children received 7 d of amoxicillin per guidelines. Lactulose permeability testing and fecal 16S rRNA sequencing were performed at baseline and after 4 wk of therapy. The change in lactulose permeability was the primary outcome, while the fecal 16S rRNA configuration at 4 wk was a secondary outcome. RESULTS: Of the 129 children enrolled, lactulose permeability testing was completed by 100 at baseline and 82 at week 4. After 4 wk of therapeutic feeding, there were no differences in lactulose permeability between the o-RUTF and s-RUTF groups (P = 0.84), and over half of children had increased lactulose permeability (50% s-RUTF compared with 58% o-RUTF, mean difference = -7.5%; 95% CI: -29.2, 15.2; P = 0.50). After 4 wk of feeding, there were no differences in the 16S rRNA configurations between the o-RUTF and s-RUTF groups (Permanova, 999 permutations; P = 0.648; pseudo-F = 0.581), nor were there differences in α or ß diversity. CONCLUSIONS: Despite remarkably different compositions of o-RUTF and s-RUTF, no differences were identified in lactulose permeability or the fecal 16S rRNA configuration among children with SAM receiving these foods. These results suggest that the o-RUTF exerts its beneficial effects through mechanisms other than reducing intestinal permeability or altering the fecal 16S configuration. This trial was registered at clinicaltrials.gov as NCT04334538.

Newborn Mid-Upper Arm Circumference Identifies Low-Birth Weight and Vulnerable Infants: A Secondary Analysis.

Background: Low birth weight (LBW) infants are at increased risk of morbidity and mortality. Identification of LBW may not occur in settings where access to reliable scales is limited. Mid-upper arm circumference (MUAC) may be an accessible, low-cost measure to identify LBW and vulnerable infants. Objectives: We explored the validity of newborn MUAC in identifying LBW and vulnerable newborns in rural Sierra Leone. Methods: This study was a secondary analysis of infant data from a randomized controlled clinical trial of supplementary food and anti-infective therapies compared with standard care for undernourished pregnant women. Data for singleton liveborn infants with birth measurement and 6-mo survival data were included in this analysis. The primary outcome was validity of MUAC in identifying low-birth weight (LBW) neonates. Secondary outcomes included validity of MUAC and head circumference (HC) in identifying weight-for-length z-score (WLZ) <-2, length-for-age z-score (LAZ) <-2, neonatal mortality, and mortality within the first 6 mo of life. Results: The study population included 1167 infants, 229 (19.6%) with LBW. Birth MUAC (r = 0.817) and HC (r = 0.752) were highly correlated with birth weight. MUAC (AUC: 0.905; 95% CI: 0.884, 0.925) performed superiorly to HC (AUC: 0.88; 95% CI: 0.856, 0.904) in identifying LBW. The MUAC for identifying LBW was 9.6 cm (sensitivity: 0.86; specificity: 0.78). Neither MUAC nor HC reliably identified newborns with WLZ <-2 or LAZ <-2. MUAC ≤9.0 cm was the ideal cutoff for neonatal mortality (sensitivity: 53.3%; specificity: 89.7%; HR: 9.57; 95% CI: 1.86, 49.30). Birth anthropometrics did not reliably identify infants at risk of death in the first 6 mo of life. Conclusions: MUAC was used successfully to identify LBW infants and infants at risk of neonatal mortality in Sierra Leone. Further evidence is needed to support increased use of newborn MUAC measurement to identify LBW infants and infants at risk of neonatal mortality in community settings where scales are not available. Primary trial was registered at clinicaltrials.gov as NCT03079388. Lay Summary: Mid-upper arm circumference (MUAC) can be used to identify infants with low birth weight and infants at risk for neonatal mortality, with an MUAC ≤9.0 cm indicating the highest risk.

Socioecological predictors of breastfeeding practices in rural eastern Ethiopia.

BACKGROUND: Estimates by the World Health Organization indicate that over 800,000 global neonatal deaths each year are attributed to deviations from recommended best practices in infant feeding. Identifying factors promoting ideal breastfeeding practices may facilitate efforts to decrease neonatal and infant death rates and progress towards achieving the Sustainable Development Goals set for 2030. Though numerous studies have identified the benefits of breastfeeding in reducing the risk of childhood undernutrition, infection and illness, and mortality in low- and middle-income countries, no studies have explored predictors of breastfeeding practices in rural eastern Ethiopia, where undernutrition is widespread. The aim of this study is to examine predictors of infant feeding practices in Haramaya, Ethiopia, using a multi-level conceptual framework. METHODS: This study uses data collected from household questionnaires during the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) project among 102 households in the Haramaya woreda, Eastern Hararghe Zone, Eastern Ethiopia, and investigates factors influencing breastfeeding practices: early initiation, prelacteal feeding, and untimely complementary feeding. RESULTS: Nearly half (47.9%) of infants in this study were non-exclusively breastfed (n = 96). Generalized liner mixed effects models of breastfeeding practices revealed that prelacteal feeding may be a common practice in the region (43.9%, n = 98) and characterized by gender differences (p = .03). No factors evaluated were statistically significantly predictive of early initiation and untimely complementary feeding (82% and 14%, respectively). Severely food insecure mothers had more than 72% lower odds of early breastfeeding initiation, and participants who self-reported as being illiterate had 1.53 times greater odds of untimely complementary feeding (95% CI, [0.30,7.69]) followed by male children having 1.45 greater odds of being untimely complementary fed compared to female (95% CI,[0.40,5.37]). CONCLUSIONS: This study found high rates of prelacteal feeding and low prevalence of exclusive breastfeeding, with girls more likely to be exclusively breastfed. While no predictors evaluated in this multi-level framework were associated with prevalence of early initiation or complementary feeding, rates may be clinically meaningful in a region burdened by undernutrition. Findings raise questions about gendered breastfeeding norms, the under-examined role of khat consumption on infant feeding, and the complex factors that affect breastfeeding practices in this region. This information may be used to guide future research questions and inform intervention strategies.

Unravelling the reservoirs for colonisation of infants with Campylobacter spp. in rural Ethiopia: protocol for a longitudinal study during a global pandemic and political tensions.

INTRODUCTION: Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for Campylobacter bacteria, which are recognised as risk factors for child malnutrition. Increasing livestock production may be beneficial for improving nutrition of children but these benefits may be negated by increased exposure to Campylobacter and research is needed to evaluate the complex pathways of Campylobacter exposure and infection applicable to low-income and middle-income countries. We aim to identify reservoirs of infection with Campylobacter spp. of infants in rural Eastern Ethiopia and evaluate interactions with child health (environmental enteric dysfunction and stunting) in the context of their sociodemographic environment. METHODS AND ANALYSIS: This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water and soil. These samples are analysed by a range of phenotypic and genotypic microbiological methods to characterise the genetic structure of the Campylobacter population in each of these reservoirs, which will support inference about the main sources of exposure for infants. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Florida Internal Review Board (IRB201903141), the Haramaya University Institutional Health Research Ethics Committee (COHMS/1010/3796/20) and the Ethiopia National Research Ethics Review Committee (SM/14.1/1059/20). Written informed consent is obtained from all participating households. Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals and through the Feed the Future Innovation Lab for Livestock Systems.

Assessing infant cognition in field settings using eye-tracking: a pilot cohort trial in Sierra Leone.

OBJECTIVES: To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone. DESIGN: Prospective dual cohort study nested in a cluster-randomised trial. SETTING: 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM). PARTICIPANTS: For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control. INTERVENTIONS: Infants with MAM were provided with supplementary feeding. OUTCOME MEASURES: The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children. RESULTS: Infants exhibited consistent orienting to targets on a computer screen (>95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60-0.69) and across the 4-week test-retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI -2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=-14 ms, 95% CI -26.2 to -1.7, p=0.025) compared with age-matched controls. CONCLUSIONS: The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding.

Supplementary Feeding of Moderately Wasted Children in Sierra Leone Reduces Severe Acute Malnutrition and Death When Compared with Nutrition Counseling: A Retrospective Cohort Study.

BACKGROUND: There is uncertainty about whether children with moderate wasting should receive supplementary feeding. OBJECTIVES: We examined whether supplementary feeding compared with counseling alone in children with moderate wasting prevented progression to severe acute malnutrition (SAM) or death. METHODS: This was a retrospective, dual-cohort study in which 1791 children with moderate wasting were drawn from 2 prior randomized controlled trials that took place in the same location in rural Sierra Leone. A total of 1077 children received supplementary feeding, whereas 714 children received counseling alone. Children in both cohorts were followed for ≥24 wk from enrollment. The primary outcome was time to SAM or death using Kaplan-Meier analysis. Secondary outcomes included time to death as well as proportions of children with healthy midupper arm circumference (MUAC), moderate wasting, SAM, or death at 6, 12, and 24 wk from enrollment. RESULTS: Children who received supplementary feeding were less likely to develop SAM or die across the entire follow-up period (HR: 0.53; 95% CI: 0.44, 0.65; P < 0.001). Time to event for death alone also revealed a lower risk for children who received supplementary feeding (HR: 0.52; 95% CI: 0.28, 0.94; P = 0.03). Children who received supplementary feeding were more likely to have a healthy MUAC at 6 wk (RR: 2.0; 95% CI: 1.7, 2.2) and 12 wk (RR: 1.3; 95% CI: 1.2, 1.5), were less likely to develop SAM at 6 (RR: 0.7; 95% CI: 0.6, 0.9), 12 (RR: 0.5; 95% CI: 0.3, 0.8), and 24 wk (RR: 0.2; 95% CI: 0.1, 0.5), and had higher rates of gain in weight and MUAC at 6 and 12 wk. CONCLUSIONS: Supplementary feeding of children with moderate wasting reduces risk of SAM and death across 24 wk of follow-up.

Supplementary Feeding of Moderately Wasted Children in Sierra Leone Reduces Severe Acute Malnutrition and Death When Compared with Nutrition Counseling: A Retrospective Cohort Study.

BACKGROUND: There is uncertainty about whether children with moderate wasting should receive supplementary feeding. OBJECTIVES: We examined whether supplementary feeding compared with counseling alone in children with moderate wasting prevented progression to severe acute malnutrition (SAM) or death. METHODS: This was a retrospective, dual-cohort study in which 1791 children with moderate wasting were drawn from 2 prior randomized controlled trials that took place in the same location in rural Sierra Leone. A total of 1077 children received supplementary feeding, whereas 714 children received counseling alone. Children in both cohorts were followed for ≥24 wk from enrollment. The primary outcome was time to SAM or death using Kaplan-Meier analysis. Secondary outcomes included time to death as well as proportions of children with healthy midupper arm circumference (MUAC), moderate wasting, SAM, or death at 6, 12, and 24 wk from enrollment. RESULTS: Children who received supplementary feeding were less likely to develop SAM or die across the entire follow-up period (HR: 0.53; 95% CI: 0.44, 0.65; P < 0.001). Time to event for death alone also revealed a lower risk for children who received supplementary feeding (HR: 0.52; 95% CI: 0.28, 0.94; P = 0.03). Children who received supplementary feeding were more likely to have a healthy MUAC at 6 wk (RR: 2.0; 95% CI: 1.7, 2.2) and 12 wk (RR: 1.3; 95% CI: 1.2, 1.5), were less likely to develop SAM at 6 (RR: 0.7; 95% CI: 0.6, 0.9), 12 (RR: 0.5; 95% CI: 0.3, 0.8), and 24 wk (RR: 0.2; 95% CI: 0.1, 0.5), and had higher rates of gain in weight and MUAC at 6 and 12 wk. CONCLUSIONS: Supplementary feeding of children with moderate wasting reduces risk of SAM and death across 24 wk of follow-up.

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial.

BACKGROUND: There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for the treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. OBJECTIVES: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high-oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), improves cognition when compared with standard RUTF (S-RUTF). METHODS: A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF, and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem-solving assessment (PSA) intention score for 3 standardized problems, measured 6 mo and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, plasma fatty acid content, anthropometry, and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. RESULTS: Among the 2565 SAM children enrolled, mean global MDAT z-scores were -0.69 ± 1.19 and -0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI: 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (OR: 0.92, 95% CI: 0.67, 1.26 for DHA-HO-RUTF). After 4 wk of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared with S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF (P < 0.001). CONCLUSIONS: Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit 6 mo after completing diet therapy. This treatment should be explored in operational settings. This trial was registered at clinicaltrials.gov as NCT03094247.

A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial.

BACKGROUND: Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women. METHODS AND FINDINGS: This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020. Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention. CONCLUSIONS: In this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079388.

Host Fecal mRNAs Predicted Environmental Enteric Dysfunction among Children with Moderate Acute Malnutrition in Sierra Leone.

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.

Effectiveness and cost-effectiveness of 4 supplementary foods for treating moderate acute malnutrition: results from a cluster-randomized intervention trial in Sierra Leone.

BACKGROUND: Moderate acute malnutrition (MAM) affects 33 million children annually. Investments in formulations of corn-soy blended flours and lipid-based nutrient supplements have effectively improved MAM recovery rates. Information costs and cost-effectiveness differences are still needed. OBJECTIVES: We assessed recovery and sustained recovery rates of MAM children receiving a supplementary food: ready-to-use supplementary food (RUSF), corn soy whey blend with fortified vegetable oil (CSWB w/oil), or Super Cereal Plus with amylase (SC + A) compared to Corn Soy Blend Plus with fortified vegetable oil (CSB+ w/oil). We also estimated differences in costs and cost effectiveness of each supplement. METHODS: In Sierra Leone, we randomly assigned 29 health centers to provide a supplement containing 550 kcal/d for ∼12 wk to 2691 children with MAM aged 6-59 mo. We calculated cost per enrollee, cost per child who recovered, and cost per child who sustained recovery each from 2 perspectives: program perspective and caregiver perspective, combined. RESULTS: Of 2653 MAM children (98.6%) with complete data, 1676 children (63%) recovered. There were no significant differences in the odds of recovery compared to CSB+ w/oil [0.83 (95% CI: 0.64-1.08) for CSWB w/oil, 1.01 (95% CI: 0.78-1.3) for SC + A, 1.05 (95% CI: 0.82-1.34) for RUSF]. The odds of sustaining recovery were significantly lower for RUSF (0.7; 95% CI 0.49-0.99) but not CSWB w/oil or SC + A [1.08 (95% CI: 0.73-1.6) and 0.96 (95% CI: 0.67-1.4), respectively] when compared to CSB+ w/oil. Costs per enrollee [US dollars (USD)/child] ranged from $105/child in RUSF to $112/child in SC + A and costs per recovered child (USD/child) ranged from $163/child in RUSF to $179/child in CSWB w/oil, with overlapping uncertainty ranges. Costs were highest per sustained recovery (USD/child), ranging from $214/child with the CSB+ w/oil to $226/child with the SC + A, with overlapping uncertainty ranges. CONCLUSIONS: The 4 supplements performed similarly across recovery (but not sustained recovery) and costed measures. Analyses of posttreatment outcomes are necessary to estimate the full cost of MAM treatment. This trial was registered at clinicaltrials.gov as NCT03146897.

Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone.

BACKGROUND: Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified. OBJECTIVES: The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes. METHODS: In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations. RESULTS: The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (ß: -0.08; 95% CI: -0.14, -0.02) and WLZ (ß: -0.03; 95% CI: -0.06, -0.01) were negatively associated with GI score. A high GD score (ß: 0.36; 95% CI: 0.08, 0.64) and low AAT (ß: -1.35; 95% CI: -2.35, -0.36) were associated with recovery from MAM. CONCLUSIONS: Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.