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.

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.

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.

An Optimized Dose of Therapeutic Feeding Results in Noninferior Growth in Midupper Arm Circumference Compared with a Standard Dose in Children in Sierra Leone Recovering from Acute Malnutrition.

BACKGROUND: Ready-to-use therapeutic food (RUTF) given at 175 kcal/kg per day throughout severe acute malnutrition (SAM) treatment is recommended. Some treatment programs have diverged from this paradigm in 2 ways: reducing the supplemental food dose to 75 kcal/kg per day when midupper arm circumference (MUAC) is >11.4 cm or simplifying to a fixed-dose regimen. OBJECTIVE: The objective was to determine if transitioning to an optimized, fixed-dose supplementary feeding regimen during SAM treatment when MUAC is >11.4 cm would result in noninferior gain in MUAC compared with standard treatment. METHODS: Using data from 2 clinical trials conducted in Sierra Leone, a retrospective dual-cohort study was performed. The 2 cohorts included children with SAM who had improved to meet criteria for moderate acute malnutrition (MAM). The standard dose cohort continued to receive weight-based RUTF at 175 kcal/kg per day, while the optimized dose cohort received fixed-dose, 500 kcal/d of supplementary feeding. The primary outcome was a noninferiority margin of 1 mm of MUAC after 4 wk of treatment, while secondary outcomes included rate of anthropometric changes as well as time-to-relapse to SAM or death. RESULTS: MUAC after 4 wk was noninferior (Δ: -0.1 mm; 95% CI: -0.05, 0.03; inferiority rejected P = 0.008). Rates of weight gain and MUAC gain were the same in the optimized-dose and standard-dose groups, whereas the rate of length gain was slower in the optimized-dose cohort. Time-to-relapse to SAM or death was not different (HR: 1.05; P = 0.71). CONCLUSIONS: This study supports the practice of treating children with SAM who have recovered to meet criteria for MAM with a reduced and fixed-dose regimen of RUTF. The results also raise the question of whether this strategy might adversely impact linear growth during SAM treatment.

Use of a novel supplementary food and measures to control inflammation in malnourished pregnant women in Sierra Leone to improve birth outcomes: study protocol for a prospective, randomized, controlled clinical effectiveness trial.

BACKGROUND: The negative synergy between poor nutritional status and infectious diseases is doubly detrimental in pregnancy. In Sierra Leone, maternal malnutrition is amongst the highest in the world, while maternal mortality is high at 1320/100,000 live births and stunting in under-five is 37.9%, ranked 110/132 worldwide. Maternal malnutrition has been associated with preterm birth, small-for-gestational age infants, and poor maternal outcomes. Infants born prematurely or small-for-gestational age experience higher mortality and are at risk for stunting and decreased cognitive performance. Nutritional interventions alone during pregnancy may not be as effective in the setting of increased inflammation from repeated infections. Interventions are needed to improve maternal outcomes and reduce stunting in this population. METHODS/DESIGN: This will be a prospective, randomized, controlled clinical effectiveness trial of an improved supplementary food plus anti-infective therapies compared to standard therapy in malnourished pregnant women. Pregnant women will be randomized to receive a low water activity, ready-to-use supplementary food plus five anti-infective interventions or the standard of care which is 3.5 kg corn/ soy blended flour with 350 mL vegetable oil every two weeks. The five anti-infective interventions are 1) insecticide-treated mosquito net at the time of enrollment into the study, 2) sulfadoxine-pyrimethamine given every 4 weeks, beginning at enrollment or at 13 weeks' gestation, whichever is later, 3)azithromycin at a dose of 1 g given once at enrollment (after first trimester)and again during 28-34 weeks of gestation, 4)single dose 400 mg albendazole given in second trimester, and 5) testing and treatment for bacterial vaginosis at enrollment and again at 28-34 weeks of gestation. Treatment will be provided for the duration of the pregnancy. The primary outcome measure will be birth length. Secondary outcomes in the mothers will include rates of maternal weight gain and increase in mid-upper arm circumference, and time to maternal anthropometric recovery. Secondary outcomes in the infants will include birth weight, birth head circumference, and linear and ponderal growth. DISCUSSION: Malnutrition remains a major problem in the developing world with lasting maternal and infant consequences. Maternal malnutrition has been associated with intrauterine growth retardation, low birth weight (LBW), pre-term delivery and poor cognitive development. Nutritional interventions alone have not been successful in reducing stunting. By bundling nutritional and anti-infective interventions, we aim to reduce intrauterine growth restriction and low birth weight in moderately malnourished pregnant women in Sierra Leone. If successful, this bundle can easily be implemented by governments or non-governmental organizations. TRIAL REGISTRATION: Clinicaltrials.gov NCT03079388; Date: March 5, 2017.