Per Ashorn

Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy

Gut bacterial strains targeted by IgA in undernourished Malawian children produce severe enteropathy in gnotobiotic mice and correlate with health status. BugFACS Inc. In a new study, Kau et al. show that bacterial targets of gut immunoglobulin A (IgA) responses have diagnostic and therapeutic implications for childhood undernutrition. Purifying IgA-targeted microbes from fecal samples collected during the first 2 years of life from Malawian children using a method called BugFACS, these authors demonstrate that IgA responses to several types of bacteria, including Enterobacteriaceae, correlate with undernutrition. Transplanting IgA-bound bacteria from undernourished children to germ-free mice led to disruption of the gut lining (epithelium), weight loss, and sepsis in animals consuming a nutrient-deficient Malawian diet. This was prevented by a nutrient-sufficient diet or two IgA-targeted bacterial species from a healthy donor’s microbiota. Dissecting a collection of cultured IgA-targeted bacterial strains from an undernourished donor revealed that Enterobacteriaceae interacted with other community members to produce pathology. These findings have implications for the diagnosis and treatment of childhood undernutrition. To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA+ bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss, and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition.

Growth and change in blood haemoglobin concentration among underweight Malawian infants receiving fortified spreads for 12 weeks: a preliminary trial.

Objective: Fortified spreads (FSs) have proven effective in the rehabilitation of severely malnourished children. We examined acceptability, growth and change in blood haemoglobin (Hb) concentration among moderately underweight ambulatory infants given FS. Methods: This was a randomised, controlled, parallel-group, investigator-blind clinical trial in rural Malawi. Six- to 17-month-old underweight infants (weight for age <−2), whose weight was greater than 5.5 kg and weight-for-height z score greater than −3 received for 12 weeks at home 1 of 8 food supplementation schemes: nothing, 5, 25, 50, or 75 g/day milk-based FS or 25, 50, or 75 g/day soy-based FS. Outcome measures included change in weight, length and blood Hb concentration. Results: A total of 126 infants started and 125 completed the intervention. All infants accepted the spread well, and no intolerance was recorded. Average weight and length gains were higher among infants receiving daily 25 to 75 g FS than among those receiving only 0 to 5 g FS. Mean Hb concentration remained unchanged among unsupplemented controls but increased by 10 to 17 g/L among infants receiving any FS. All average gains were largest among infants receiving 50 g of FS daily: mean difference (95% confidence interval) in the 12-week gain between infants in 50 g milk-based FS group and the unsupplemented group was 290 g (range, −130 to 700 g), 0.9 cm (range, −0.3 to 2.2 cm), and 17 g/L (range, 0 to 34 g/L) for weight, length and blood Hb concentration, respectively. In soy- vs milk-based FS groups, average outcomes were comparable. Conclusions: Supplementation with 25 to 75 g/day of highly fortified spread is feasible and may promote growth and alleviate anaemia among moderately malnourished infants. Further trials should test this hypothesis.

Supplementary feeding of underweight, stunted malawian children with a ready-to-use food

Objective Maize and soy flour mixes are often used in the treatment of moderate malnutrition in Malawi. Their efficacy has not been formally evaluated. A recently developed ready-to-use food (RTUF) effectively promotes growth among severely malnourished children. The authors compared the effect of maize and soy flour with that of RTUF in the home treatment of moderately malnourished children. Methods Sixty-one underweight, stunted children 42 to 60 months of age were recruited in rural Malawi, in southeastern Africa. They received either RTUF or maize and soy flour for 12 weeks. Both supplements provided 2 MJ (500Kcal) of energy daily but had different energy and nutrient densities. Outcome variables were weight and height gain and dietary intake. Results Before intervention, the mean dietary intake and weight and height gain were similar in the two groups. During the supplementation phase, the consumption of staple food fell among children receiving maize and soy flour but not among those receiving RTUF. There was thus higher intake of energy, fat, iron, and zinc in the RTUF group. Both supplements resulted in modest weight gain, but the effect lasted longer after RTUF supplementation. Height gain was not affected in either group. Periodic 24-hour dietary recalls suggested that the children received only 30% and 43%, respectively, of the supplementary RTUF and maize and soy flour provided. Conclusions RTUF is an acceptable alternative to maize and soy flour for dietary supplementation of moderately malnourished children. Approaches aimed at increasing the consumption of supplementary food by the selected recipients are needed.

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

BACKGROUNDnTherapeutic 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.nnnOBJECTIVEnOur objective was to assess whether a reduction in stunting seen with 12-mo LNS supplementation was sustained over a subsequent 2-y nonintervention period.nnnDESIGNnOne 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnTwelve-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.

Effect of complementary feeding with lipid‐based nutrient supplements and corn–soy blend on the incidence of stunting and linear growth among 6‐ to 18‐month‐old infants and children in rural Malawi

Low nutritional value of complementary foods is associated with high incidence of childhood growth stunting in low-income countries. This study was done to test a hypothesis that dietary complementation with lipid-based nutrient supplements (LNS) promotes linear growth and reduces the incidence of severe stunting among at-risk infants. A total of 840 6-month-old healthy infants in rural Malawi were enrolled to a randomised assessor-blinded trial. The participants received 12-month supplementation with nothing, milk-LNS, soy-LNS, or corn-soy blend (CSB). Supplements provided micronutrients and approximately 280u2009kcal energy per day. Outcomes were incidence of severe and very severe stunting [length-for-age z-score, (LAZ)u2009<u2009-3.00 and <-3.50, respectively], and change in LAZ. The incidence of severe stunting was 11.8%, 8.2%, 9.1% and 15.5% (Pu2009=u20090.098) and that of very severe stunting 7.4%, 2.9%, 8.0% and 6.4% (Pu2009=u20090.138) in control, milk-LNS, soy-LNS and CSB groups, respectively. Between 9 and 12 months of age, the mean change in LAZ was -0.15, -0.02, -0.12 and -0.18 (Pu2009=u20090.045) for control, milk-LNS, soy-LNS and CSB groups, respectively. There was no significant between-group difference in linear growth during other age-intervals. Although participants who received milk-LNS had the lowest incidence of severe and very severe stunting, the differences between the groups were smaller than expected. Thus, the results do not provide conclusive evidence on a causal association between the LNS supplementation and the lower incidence of stunting. Exploratory analyses suggest that provision of milk-LNS, but not soy-LNS promotes linear growth among at-risk infants mainly between 9 and 12 months of age.

Supplementary feeding with fortified spread among moderately underweight 6–18-month-old rural Malawian children

We aimed to analyse growth and recovery from undernutrition among moderately underweight ambulatory children receiving micronutrient-fortified maize-soy flour (Likuni Phala, LP) or ready-to-use fortified spread (FS) supplementary diet. One hundred and seventy-six 6-18-month-old individuals were randomized to receive 500 g LP or 350 g FS weekly for 12 weeks. Baseline and end of intervention measurements were used to calculate anthropometric gains and recovery from underweight, wasting and stunting. Mean weight-for-age increased by 0.22 (95% CI 0.07-0.37) and 0.28 (0.18-0.40) Z-score units in the LP and FS groups respectively. Comparable increase for mean weight-for-length was 0.39 (0.20-0.57) and 0.52 (0.38-0.65) Z-score units. Recovery from underweight and wasting was 20% and 93% in LP group and 16% and 75% in FS group. Few individuals recovered from stunting and mean length-for-age was not markedly changed. There were no statistically significant differences between the outcomes in the two intervention groups. In a poor food-security setting, underweight infants and children receiving supplementary feeding for 12 weeks with ready-to-use FS or maize-soy flour porridge show similar recovery from moderate wasting and underweight. Neither intervention, if limited to a 12-week duration, appears to have significant impact on the process of linear growth or stunting.

Acceptability of three novel lipid‐based nutrient supplements among Malawian infants and their caregivers

We tested the acceptability of three new lipid-based nutrient supplements (LNSs) in two independent phases among 18 8-12-month-old healthy rural Malawians and their caregivers. In phase 1, acceptability was assessed by offering three new LNSs in random order, and an LNS already determined to be acceptable, Nutributter(®), each added to 30 g of warm maize porridge over three consecutive days. In phase 2, infants from each village were provided one of the new supplements for a 2-week home-use trial. Outcome measures included the amount consumed, time completion of the dose and the maternal rating of likeability on a 5-point scale. The supplements were rated acceptable if consumption was over 50% of the offered dose in phase 1. The mean (95% confidence interval) proportion of the LNS test meals consumed under direct observation was 88% (82-94%) for LNS-10gM, 90% (84-95%) for LNS-20gM, 87% (79-95%) for LNS-20gNoM, and 86% (83-90%) for Nutributter. The median (25th and 75th centile) time (minutes) for completing the offered test meal was 4 (2, 7) for LNS-10gM, 5 (3, 6) for LNS-20gM, 4 (3, 8) for LNS-20gNoM and 4 (2, 6) for Nutributter. During both phases, almost all caregivers rated all study foods very likeable for themselves and their children, with mean scores slightly lower among the caregivers than among the infants. In the home-use phase, the test foods were almost exclusively used by the study participants with minimal sharing with siblings and other household members. Some infants were reported to prefer the new investigational products over traditional complementary food. Considering that the novel LNS was largely acceptable. Efficacy trials are now needed to assess their impact on child growth and development.

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.

Malawian mothers' attitudes towards the use of two supplementary foods for moderately malnourished children

The efficacy of lipid-based nutrient supplements (LNS) versus corn-soy blend (CSB) in promoting the growth of moderately malnourished children is currently being tested, but information about maternal attitudes towards the two supplements is lacking. This research studied 504 Malawian mothers attitudes about LNS and CSB through exit interviews completed at the end of three 12-week clinical trials and compared differences between the groups. Exploratory analyses of factors associated with withholding of supplements during fever, diarrhea, and cough were performed using logistic regression. Mothers generally had similar, positive attitudes towards LNS and CSB. Both supplements were said to be highly acceptable, children learned to eat them within two weeks, and mothers were willing to use them again. Mothers in the LNS group were reportedly more likely to withhold supplements from their children during cough, due to its sweetness, and were willing to pay more for a one-week supply of supplement than mothers in the CSB group. Maternal literacy was negatively and childs weight-for-height z-score was positively associated with withholding of supplements during illness. Our results indicate that the sweetness in LNS should be reduced, and programs using supplements in Malawi could include advice on appropriate feeding of supplements during illness.

Feeding patterns and behaviors during home supplementation of underweight Malawian children with lipid-based nutrient supplements or corn-soy blend

The way caregivers use supplementary food for undernourished children and integrate it into feeding patterns may influence the benefits achieved by supplementation. We studied feeding patterns and behaviors in 170 underweight 6-17-month-olds who received either lipid-based nutrient supplements (LNS) (n=85) or corn-soy blend (CSB) (n=85) during a 12-week intervention trial in southern Malawi. Observational data were collected during one 11h home visit per participant. Differences were assessed by study group and by mode of serving LNS. Associations between selected caregiver behaviors and child growth were also tested. We found no difference between the CSB and LNS groups in mean number of feeding episodes per day or mean daily feeding time. Caregivers fed the child with a spoon, washed their hands before feeding, and there were leftovers significantly more often in the CSB than LNS group and when LNS mixed with porridge and plain LNS were compared. This suggests that differences between the groups were linked to the mode of serving LNS. Presence of leftovers was negatively associated with change in childs WAZ. Programs promoting LNS in Malawi should consider behaviors related to mode of serving and provide advice to caregivers in order to minimize leftovers during supplement use.