Re-Defining the Population-Specific Cut-Off Mark for Vitamin A Deficiency in Pre-School Children of Malawi.

Retinol Binding Protein (RBP) is responsible for the transport of serum retinol (SR) to target tissue in the body. Since RBP is relatively easy and cheap to measure, it is widely used in national Micronutrient Surveys (MNS) as a proxy for SR to determine vitamin A status. By regressing RBP concentration against SR concentration measured in a subset of the survey population, one can define a population-specific threshold concentration of RBP that indicates vitamin A deficiency (VAD). However, the relationship between RBP and SR concentrations is affected by various factors including inflammation. This study, therefore, aimed to re-define the population-specific cut-off for VAD by examining the influence of inflammation on RBP and SR, among pre-school children (PSC) from the 2015-16 Malawi MNS. The initial association between RBP and SR concentrations was poor, and this remained the case despite applying various methods to correct for inflammation. The World Health Organization (WHO) recommends the threshold of 0.7 µmol/L to define VAD for SR concentrations. Applying this threshold to the RBP concentrations gave a VAD prevalence of 24%, which reduced to 10% after inflammation adjustments following methods developed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA). Further research is required to identify why SR and RBP were poorly associated in this population. Future MNS will need to account for the effect of inflammation on RBP to measure the prevalence of VAD in Malawi.

Biofortified Maize Improves Selenium Status of Women and Children in a Rural Community in Malawi: Results of the Addressing Hidden Hunger With Agronomy Randomized Controlled Trial.

Background: Selenium deficiency is widespread in the Malawi population. The selenium concentration in maize, the staple food crop of Malawi, can be increased by applying selenium-enriched fertilizers. It is unknown whether this strategy, called agronomic biofortification, is effective at alleviating selenium deficiency. Objectives: The aim of the Addressing Hidden Hunger with Agronomy (AHHA) trial was to determine whether consumption of maize flour, agronomically-biofortified with selenium, affected the serum selenium concentrations of women, and children in a rural community setting. Design: An individually-randomized, double-blind placebo-controlled trial was conducted in rural Malawi. Participants were randomly allocated in a 1:1 ratio to receive either intervention maize flour biofortified with selenium through application of selenium fertilizer, or control maize flour not biofortified with selenium. Participant households received enough flour to meet the typical consumption of all household members (330 g capita -1 day-1) for a period of 8 weeks. Baseline and endline serum selenium concentration (the primary outcome) was measured by inductively coupled plasma mass spectrometry (ICP-MS). Results: One woman of reproductive age (WRA) and one school-aged child (SAC) from each of 180 households were recruited and households were randomized to each group. The baseline demographic and socioeconomic status of participants were well-balanced between arms. No serious adverse events were reported. In the intervention arm, mean (standard deviation) serum selenium concentration increased over the intervention period from 57.6 (17.0) µg L-1 (n = 88) to 107.9 (16.4) µg L-1 (n = 88) among WRA and from 46.4 (14.8) µg L-1 (n = 86) to 97.1 (16.0) µg L-1 (n = 88) among SAC. There was no evidence of change in serum selenium concentration in the control groups. Conclusion: Consumption of maize flour biofortified through application of selenium-enriched fertilizer increased selenium status in this community providing strong proof of principle that agronomic biofortification could be an effective approach to address selenium deficiency in Malawi and similar settings. Clinical Trial Registration: http://www.isrctn.com/ISRCTN85899451, identifier: ISRCTN85899451.

Food purchasing decisions of Malawian mothers with young children in households experiencing the nutrition transition.

As overweight/obesity prevalence increases in sub-Saharan Africa, information is needed about factors influencing food purchases in households with overweight members. This study assessed food purchasing decisions of Malawian mothers with young children (N = 54 dry season, N = 55 rainy season) among whom the mother, child, or both were overweight. Research assistants completed structured observations of mothers shopping for food during the dry season and of the types and quantities of foods in mothers' homes during the rainy season. After each observation, research assistants conducted an in-depth interview about factors that influenced food purchases, including asking mothers to sort 12 factors into piles that always, sometimes, or never influence their food purchases. Observations showed mothers most often shopped at outdoor markets to buy foods needed to prepare relish, such as tomatoes (71%), green leafy vegetables (58%), cooking oil (58%), and fish (40%). At home, maize flour (80%) and salt (66%) were the most common foods. Pile sorts and in-depth interviews revealed cost, taste preferences, freshness, and healthiness were the strongest factors influencing food purchases. Mothers described buying a smaller quantity or making substitutions (e.g., fish instead of meat) if a food is too expensive. Many mothers reported buying foods their family likes and prioritizing children's preferences. Freshness of foods, especially fruits and vegetables, and whether foods were perceived to be healthy also influenced food purchases, but mothers' knowledge of which foods were healthy was mixed. Mothers used some of their minimal funds to buy unhealthy foods (e.g., packaged or fried snacks) for their children, despite their overall emphasis on food cost and healthiness. These findings can be used by programs to reinforce healthy and decrease unhealthy food purchases by mothers with young children in Malawi.

Drivers of food consumption among overweight mother-child dyads in Malawi.

To address the increase in overweight and obesity among mothers and children in sub-Saharan Africa, an understanding of the factors that drive their food consumption is needed. We hypothesized food consumption in Malawi is driven by a combination of factors, including season, food accessibility (area of residence, convenience of purchasing food, female autonomy), food affordability (household resources, food expenditures, household food insecurity), food desirability (taste preferences, body size preferences), demographics, and morbidity. Participants in Lilongwe and Kasungu Districts were enrolled across three types of mother-child dyads: either the mother (n = 120), child (n = 80), or both (n = 74) were overweight. Seven-day dietary intake was assessed using a quantitative food frequency questionnaire during the dry and rainy seasons. Drivers associated with intake of calories, macronutrients, and 11 food groups at p<0.1 in univariate models were entered into separate multivariate linear regression models for each dietary intake outcome. Mother-child dyads with an overweight child had a higher percent of calories from carbohydrates and lower percent of calories from fat compared to dyads with a normal weight child (both p<0.01). These mothers also had the highest intake of grains (p<0.01) and their children had the lowest intake of oil/fat (p = 0.01). Household food insecurity, maternal taste preferences, and maternal body size preferences were the most consistent predictors of food group consumption. Household food insecurity was associated with lower intake of grains, fruits, meat and eggs, oil/fat, and snacks. Maternal taste preferences predicted increased consumption of grains, legumes/nuts, vegetables, fish, and oil/fat. Maternal body size preferences for herself and her child were associated with consumption of grains, legumes/nuts, dairy, and sweets. Predictors of food consumption varied by season, across food groups, and for mothers and children. In conclusion, indicators of food affordability and desirability were the most common predictors of food consumption among overweight mother-child dyads in Malawi.

Body size preferences and food choice among mothers and children in Malawi.

Overweight in mothers and children in sub-Saharan Africa is rapidly increasing and may be related to body size perceptions and preferences. We enrolled 268 mother-child (6-59 months) pairs in central Malawi; 71% of mothers and 56% of children were overweight/obese, and the remainder were normal weight. Interviewers used seven body silhouette drawings and a questionnaire with open- and closed-ended questions to measure mothers' perceptions of current, preferred and healthy maternal and child body sizes and their relation to food choices. Overweight/obese and normal weight mothers' correct identification of their current weight status (72% vs. 64%), preference for overweight/obese body size (68% both) and selection of an overweight/obese silhouette as healthy (94% vs. 96%) did not differ by weight status. Fewer overweight/obese than normal weight mothers' preferred body silhouette was larger than their current silhouette (74% vs. 29%, p < .001). More mothers of overweight than normal weight children correctly identified the child's current weight status (55% vs. 42%, p < .05) and preferred an overweight/obese body size for the child (70% vs. 58%, p < .01), and both groups selected overweight/obese silhouettes as healthy for children. More than half of mothers in both groups wanted their child to be larger than the current size. Mothers said that increasing consumption of fruits, vegetables, meat, milk, grains, fizzy drinks and fatty foods could facilitate weight gain, but many cannot afford to purchase some of these foods. Their desired strategies for increasing weight indicate that body size preferences may drive food choice but could be limited by affordability.

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.

Urine selenium concentration is a useful biomarker for assessing population level selenium status.

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys.

Validation of a digitally displayed photographic food portion-size estimation aid among women in urban and rural Malawi.

OBJECTIVE: To validate digitally displayed photographic portion-size estimation aids (PSEA) against a weighed meal record and compare findings with an atlas of printed photographic PSEA and actual prepared-food PSEA in a low-income country. DESIGN: Participants served themselves water and five prepared foods, which were weighed separately before the meal and again after the meal to measure any leftovers. Participants returned the following day and completed a meal recall. They estimated the quantities of foods consumed three times using the different PSEA in a randomized order. SETTING: Two urban and two rural communities in southern Malawi. PARTICIPANTS: Women (n 300) aged 18-45 years, equally divided by urban/rural residence and years of education (≤4 years and ≥5 years). RESULTS: Responses for digital and printed PSEA were highly correlated (>91 % agreement for all foods, Cohen's κw = 0·78-0·93). Overall, at the individual level, digital and actual-food PSEA had a similar level of agreement with the weighed meal record. At the group level, the proportion of participants who estimated within 20 % of the weighed grams of food consumed ranged by type of food from 30 to 45 % for digital PSEA and 40-56 % for actual-food PSEA. Digital PSEA consistently underestimated grams and nutrients across foods, whereas actual-food PSEA provided a mix of under- and overestimates that balanced each other to produce accurate mean energy and nutrient intake estimates. Results did not differ by urban and rural location or participant education level. CONCLUSIONS: Digital PSEA require further testing in low-income settings to improve accuracy of estimations.

The risk of selenium deficiency in Malawi is large and varies over multiple spatial scales.

Selenium (Se) is an essential human micronutrient. Deficiency of Se decreases the activity of selenoproteins and can compromise immune and thyroid function and cognitive development, and increase risks from non-communicable diseases. The prevalence of Se deficiency is unknown in many countries, especially in sub-Saharan Africa (SSA). Here we report that the risk of Se deficiency in Malawi is large among a nationally representative population of 2,761 people. For example, 62.5% and 29.6% of women of reproductive age (WRA, n = 802) had plasma Se concentrations below the thresholds for the optimal activity of the selenoproteins glutathione peroxidase 3 (GPx3; <86.9 ng mL-1) and iodothyronine deiodinase (IDI; <64.8 ng mL-1), respectively. This is the first nationally representative evidence of widespread Se deficiency in SSA. Geostatistical modelling shows that Se deficiency risks are influenced by soil type, and also by proximity to Lake Malawi where more fish is likely to be consumed. Selenium deficiency should be quantified more widely in existing national micronutrient surveillance programmes in SSA given the marginal additional cost this would incur.

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial.

BACKGROUND: Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers - a process known as agronomic biofortification (agro-biofortification) - and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi. METHODS: A double-blind, randomised, controlled trial will be conducted in a rural community in Kasungu District, Central Region, Malawi. The hypothesis is that consumption of maize flour agro-biofortified with Se will increase serum Se concentration. We will recruit 180 women of reproductive age (WRA) (20-45 years) and 180 school-age children (SAC) (5-10 years) randomly assigned in a 1:1 ratio to receive either maize flour enriched through agro-biofortification with Se or a control flour not enriched with Se. Households will receive flour (330 g per capita per day) for 12 weeks. The primary outcome is Se concentration in serum (µg/L). Serum will be extracted from venous blood samples drawn at baseline (prior to flour distribution) and end-line. Selenium concentration will be measured by using inductively coupled plasma mass spectrometry. DISCUSSION: Findings will be communicated to policy stakeholders and participating communities and reported in peer-reviewed journals. TRIAL REGISTRATION: The Addressing Hidden Hunger with Agronomy (Malawi) trial is registered (5th March 2019; ISCRTN85899451).

Impact of lipid-based nutrient supplements and corn-soy blend on energy and nutrient intake among moderately underweight 8-18-month-old children participating in a clinical trial.

Nutrition interventions have an effect on growth, energy and nutrient intake, and development, but there are mixed reports on the effect of supplementation of energy-dense foods on dietary intake. This substudy aimed at assessing the effect of supplementation with corn-soy blend (CSB) or lipid-based nutrient supplement (LNS) on energy and nutrient intake in moderately underweight children participating in a clinical trial. A total of 188 children aged 8-18 months participated and received daily either 284 kcal from CSB or 220 kcal from LNS and no supplements (control). An interactive 24-h recall method was used to estimate energy and nutrient intakes in the groups. Total mean energy intake was 548 kcal, 551 kcal and 692 kcal in the control, CSB and LNS groups, respectively (P = 0.011). The mean (95% confidence interval) intake of energy and protein were 144 (37-250; P < 0.001) and 46 (1.5-7.6; P < 0.001) larger, respectively, in the LNS group than among the controls. No significant differences were observed between the control and CSB groups. Energy intake from non-supplement foods was significantly lower in the CSB group compared with the control group, but not in the LNS group, suggesting a lower displacement of non-supplement foods with LNS. Both CSB and LNS supplementation resulted in higher intakes of calcium, iron, zinc and vitamin C compared with controls (all P ≤ 0.001). This study indicates that LNS might be superior to CSB to supplement underweight children as it results in higher energy intake, but this requires confirmation in other settings.

An effectiveness trial showed lipid-based nutrient supplementation but not corn-soya blend offered a modest benefit in weight gain among 6- to 18-month-old underweight children in rural Malawi.

OBJECTIVE: To determine if supplementation with corn-soya blend (CSB) or lipid-based nutrient supplement (LNS) improved the weight gain of moderately underweight infants and children when provided through the national health service. DESIGN: A randomised, controlled, assessor-blinded clinical trial. Infants and children were randomised to receive for 12 weeks an average daily ration of 71 g CSB or 43 g LNS, providing 1188 kJ and 920 kJ, respectively, or no supplement (control). Main outcome was weight gain. Secondary outcomes included changes in anthropometric indices and incidence of serious adverse events. Intention-to-treat analyses were used. SETTING: Kukalanga, Koche, Katema and Jalasi health centres in Mangochi District, rural Malawi. SUBJECTS: Underweight (weight-for-age Z-score <-2) infants and children aged 6-15 months (n 299). RESULTS: Mean weight gain was 630 g, 680 g and 750 g in control, CSB and LNS groups, respectively (P = 0·21). When adjusted for baseline age, children receiving LNS gained on average 90 g more weight (P = 0·185) and their weight-for-length Z-score increased 0·22 more (P = 0·049) compared with those receiving no supplementation. No statistically significant differences were observed between the CSB and control groups in mean weight and length gain. CONCLUSIONS: LNS supplementation provided during the lean season via through the national health service was associated with a modest increase in weight. However, the effect size was lower than that previously reported under more controlled research settings.

Developmental outcomes among 18-month-old Malawians after a year of complementary feeding with lipid-based nutrient supplements or corn-soy flour.

The major aim of this trial was to compare the development of 18-month-old infants who received complementary feeding for 1 year either with lipid-based nutrient supplements or micronutrient fortified corn-soy porridge. Our secondary aim was to determine the socio-economic factors associated with developmental outcomes in the same population. A total of 163 six-month-old rural Malawian children were enrolled in a randomized controlled trial where the control population received daily supplementation with 71 g corn-soy flour [Likuni Phala (LP)] (282 kcal) and individuals in the intervention groups received daily either 50 g of lipid-based nutrient supplement (FS50) (264 kcal) or 25 g of lipid-based nutrient supplement (FS25) (130 kcal). The main outcome measures were Griffiths' developmental scores at 0-2 years. Independent comparison of study groups was carried out using analysis of variance (ANOVA) statistics where mean raw scores, quotients, or mental ages were compared. Association of developmental outcome with predictor variables were examined using multiple regression. At 18 months of chronological age, the mean ± standard deviation (SD) mental ages in the LP, FS50, and FS25 groups were 17.9 ± 1.3, 17.9 ± 1.3, and 17.9 ± 1.2 (P > 0.99), respectively. Likewise, the mean raw developmental scores and mean developmental quotients did not differ significantly. Length-for-age z-score gain during the intervention period, and maternal education were associated with developmental outcome at 18 months (P = 0.03 and P = 0.04; respectively). In conclusion, rural Malawian infants receiving 12-month daily supplementation of their diet either with the tested lipid-based nutrient supplements or fortified corn-soy flour have comparable development outcomes by 18 months of age.

The validity of a structured interactive 24-hour recall in estimating energy and nutrient intakes in 15-month-old rural Malawian children.

This study aimed to compare the nutritional intake values among 15-month-old rural Malawian children obtained by weighed food record (WFR) with those obtained by modified 24-hour recall (mod 24-HR), and to develop algorithm for adjusting mod 24-HR values so as to predict mean intake based on WFRs. The study participants were 169 15-month-old children who participated in a clinical trial. Food consumption on one day was observed and weighed (established criterion) by a research assistant to provide the estimates of energy and nutrient intakes. On the following day, another research assistant, blinded to the direct observation, conducted the structured interactive 24-hour recall (24-HR) interview (test method). Paired t-tests and scatter-plots were used to compare intake values of the two methods. The structured interactive 24-HR method tended to overestimate energy and nutrient intakes (each P < 0.001). The regression-through-the-origin method was used to develop adjustment algorithms. Results showed that multiplying the mean energy, protein, fat, iron, zinc and vitamin A intake estimates based on the test method by 0.86, 0.80, 0.68, 0.69, 0.72 and 0.76, respectively, provides an approximation of the mean values based on WFRs.

Postintervention growth of Malawian children who received 12-mo dietary complementation with a lipid-based nutrient supplement or maize-soy flour.

BACKGROUND: Therapeutic feeding with micronutrient-fortified lipid-based nutrient supplements (LNSs) has proven useful in the rehabilitation of severely malnourished children. We recently reported that complementary feeding of 6-18-mo-old infants with an LNS known as FS50 was associated with improved linear growth and a reduction in the incidence of severe stunting during the supplementation period. OBJECTIVE: Our objective was to assess whether a reduction in stunting seen with 12-mo LNS supplementation was sustained over a subsequent 2-y nonintervention period. DESIGN: One hundred eighty-two 6-mo-old healthy rural Malawian infants were randomly assigned to receive daily supplementation for 12 mo with 71 g of maize-soy flour [likuni phala (LP); control group, 282 kcal] or either 50 g of FS50 (264 kcal; main intervention group), or 25 g of FS25 (130 kcal). Main outcome measures were incidence of severe stunting and mean z score changes in weight-for-age, length-for-age, and weight-for-length during a 36-mo follow-up period. RESULTS: The cumulative 36-mo incidence of severe stunting was 19.6% in LP, 3.6% in FS50, and 10.3% in FS25 groups (P = 0.03). Mean weight-for-age changes were -1.09, -0.76, and -1.22 (P = 0.04); mean length-for-age changes were -0.47, -0.37, and -0.71 (P = 0.10); and mean weight-for-length changes were -1.52, -1.18, and -1.48 (P = 0.27). All differences were more marked among individuals with baseline length-for-age below the median. Differences in length developed during the intervention at age 10-18 mo, whereas weight differences continued to increase after the intervention. CONCLUSIONS: Twelve-month-long complementary feeding with 50 g/d FS50 is likely to have a positive and sustained impact on the incidence of severe stunting in rural Malawi. Half-dose intervention may not have the same effect. This trial was registered at (clinicaltrials.gov) as NCT00131209.

Complementary feeding with fortified spread and incidence of severe stunting in 6- to 18-month-old rural Malawians.

OBJECTIVE: To compare growth and incidence of malnutrition in infants receiving long-term dietary supplementation with ready-to-use fortified spread (FS) or micronutrient-fortified maize-soy flour (likuni phala [LP]). DESIGN: Randomized, controlled, single-blind trial. SETTING: Rural Malawi. PARTICIPANTS: A total of 182 six-month-old infants. INTERVENTION: Participants were randomized to receive 1 year of daily supplementation with 71 g of LP (282 kcal), 50 g of FS (FS50) (256 kcal), or 25 g of FS (FS25) (130 [corrected] kcal). OUTCOME MEASURES: Weight and length gains and the incidences of severe stunting, underweight, and wasting. RESULTS: Mean weight and length gains in the LP, FS50, and FS25 groups were 2.37, 2.47, and 2.37 kg (P = .66) and 12.7, 13.5, and 13.2 cm (P = .23), respectively. In the same groups, the cumulative 12-month incidence of severe stunting was 13.3%, 0.0%, and 3.5% (P = .01), of severe underweight was 15.0%, 22.5%, and 16.9% (P = .71), and of severe wasting was 1.8%, 1.9%, and 1.8% (P > .99). Compared with LP-supplemented infants, those given FS50 gained a mean of 100 g more weight and 0.8 cm more length. There was a significant interaction between baseline length and intervention (P = .04); in children with below-median length at enrollment, those given FS50 gained a mean of 1.9 cm more than individuals receiving LP. CONCLUSION: One-year-long complementary feeding with FS does not have a significantly larger effect than LP on mean weight gain in all infants, but it is likely to boost linear growth in the most disadvantaged individuals and, hence, decrease the incidence of severe stunting.