This cluster randomized trial examined the effect of short-term, preventive supplementation with RUTF on the nutritional status, mortality, and morbidity children 6 to 60 mo of age. We found a protective effect of the intervention on WHZ change and a significant reduction in the incidence of wasting and severe wasting. There was a statistically non-significant reduction in mortality with RUTF supplementation.
This is the first population-based study to evaluate the effectiveness of RUTF in the prevention of wasting, but the protective effect of this intervention on WHZ decline and wasting incidence is consistent with the therapeutic use of RUTF in a variety of settings.3, 6, 8, 9, 18
RUTF has been shown to increase energy and micronutrient intake in children < 5 years.6, 18
The increase in energy intake associated with RUTF supplementation likely contributes to weight gain. The possibility of weight gain due to improved appetite from increased micronutrient intake has been suggested by others 19
but has not been consistent.20
This study found a mean adjusted difference in WHZ between the intervention and non-intervention groups from baseline to the end of follow-up of 0.22 Z. An increase of this magnitude in the mean WHZ will shift the population distribution of WHZ to the right and reduce the prevalence of wasting and severe wasting. The exponential relationship between the risk of mortality and nutritional status 21
suggests that the clinical importance of this intervention effect for mortality will be greatest on the left part of the WHZ distribution among children with low WHZ scores.
Sample sizes were not calculated to estimate differences in groups between the periods during and after supplementation. However, the data suggest that the intervention effect on WHZ change was greatest during the 3-month period that coincided with the actual administration of the supplement and a period of acute food insecurity preceding the harvest. Only a small benefit of supplementation appears to be sustained in the months after supplementation ceased. This suggests that short-term supplementation with RUTF may be targeted to suitably address specific, short-term nutrition needs, but further study is required to assess possible long-term improvements.
We found a limited effect of RUTF supplementation on HAZ, but the magnitude of difference in HAZ is in the range reported in trials assessing the effectiveness of complementary feeding practices in older infants.22
The small effect on HAZ change found here is likely due to the short duration of supplementation. The three-month intervention may have been too short to demonstrate an important impact on linear growth. A recent review of complementary feeding interventions suggests that the impact of similar programs on linear growth has been inconsistent, with significant improvements achieved in only some settings.23
Twenty-five children died during the study period, with less than half as many deaths in the intervention group than in the non-intervention group. A study from Malawi on the effectiveness of home-based treatment with RUTF found a similar non-significant decrease in mortality risk associated with RUTF supplementation compared to standard therapy.3
Data on the reported cause of death in this study suggest that the reduction in mortality with RUTF supplementation was achieved through protection against malnutrition (2/18 deaths in the non-intervention group vs. 0/7 deaths in the intervention group) and malaria (7/18 deaths in the non-intervention group vs. 2/7 deaths in the intervention group). Cause of death, however, was determined by verbal autopsy, which is not well-suited to distinguishing between causes of deaths with similar features and may suffer from misclassification.24
Interpretation of these data will therefore require caution.
There was no evidence of increased risk of malaria associated with RUTF supplementation. Findings of adverse health effects due to iron and folic acid supplementation in a large community-based randomized controlled trial in Zanzibar have suggested that iron supplementation proceed cautiously in settings where the prevalence of malaria and other infectious diseases is high.25
This study, however, suggests that RUTF, which is fortified with 11.5 g of iron / 100 g and other micronutrients, is unlikely to increase the prevalence of malaria. Further research is warranted to examine the impact of RUTF on the incidence of malaria.
The association of under-nutrition and increased susceptibility to infectious disease is well known,26
and evidence is accumulating on the possibly protective effect of some micronutrients, such as zinc, on diarrhea and respiratory infection.27, 28
The lack of a significant effect on diarrhea and respiratory infection in this study may be due to the non-specific nature of the diagnoses based on maternal report, the competing absorption of multiple micronutrients, such as zinc and iron, or insufficient dosages of these micronutrients in RUTF. Two studies have previously reported on the effect of RUTF on morbidity but results have been inconsistent.3, 18
There are several limitations to our study. First, the small number of clusters may have limited the benefits of randomization resulting in unmeasured confounding. Intervention groups did not significantly differ from each other for child, maternal and household characteristics, with the exception of a higher prevalence of stunting at recruitment in the intervention group. Imbalances in height-for-age were accounted for in all multivariate regression models. Consideration of the impact of differences in other specific baseline characteristics, including the frequency of hospitalization in the previous month and the prevalence of malaria, was also made. These factors were unlikely to strongly confound, or explain away, the observed differences attributed to the intervention due to their low prevalence. In multivariate regression models, the inclusion of these variables did not appreciably affect results. Potential measurement error of child’s age at recruitment and of anthropometric variables, such as length, may have resulted in residual confounding and reduced the statistical power to detect significant effects, respectively. This study was unblinded with respect to intervention assignment, however, we do not expect this to have had a differential impact on standardized anthropometric measurements. It did not appear to affect follow-up. This study also was not able to collect complete response data on all children, introducing the potential for bias if the mechanism for missingness is not ignorable. The proportion of missing data, however, is relatively small at each time point during follow-up and sensitivity analyses were used to assess the potential effect of missing response. Different strategies to account for the missing data did not appreciably change our conclusions. Finally, we were unable to measure dietary intakes at recruitment or during the intervention. We therefore did not have information on average energy intake, the macro- and micronutrient composition of baseline diets or information on energy received from the supplement vs. household foods during the intervention to indicate whether RUTF supplemented or displaced usual intake. Compliance was similarly not measured, limiting our understanding of how the supplement was used by each child and within the household.
The likelihood of contamination was reduced using village- rather than individual-level randomization. Contamination between intervention and non-intervention villages is also unlikely due to their geographic separation. There was no evidence of re-sale of the supplement in local markets to suggest that individuals from non-intervention villages would have been able to access the supplement provided in this study outside of the study. No secular changes in the health and nutritional status of children in the study villages were observed during the 8 mo of follow-up.
These results are applicable to other settings of acute food insecurity, where access to food is limited due to emergency or seasonal conditions, and short-term food supplementation is required for the prevention of wasting. The effectiveness of preventive supplementation with RUTF in other settings may depend on RUTF acceptability, the extent of re-sale after distribution, and the adequacy of the public health and nutrition systems in place. Further research is warranted to identify the minimal dose required to achieve an effect and to compare the impact of other formulations of RUTF and locally available diets, which also may be effective in improving nutritional status in children.29, 30
Information is also needed on the cost-effectiveness and feasibility of large-scale RUTF distribution. The relatively high costs of imported RUTF (USD 4.54 / kg before duties and shipping, written communication Guillaume Sauvage, Médecins Sans Frontières, Paris, France, July 2008) and locally produced RUTF (USD 3.66 / kg before duties, written communication Mark Manary, Department of Pediatrics, Washington University, School of Medicine, St Louis MO, USA, July 2008) may challenge the effective scaling up of short-term experiences such as these.
In conclusion, this study demonstrates that the distribution of RUTF to non-malnourished children 6 to 60 mo of age can be effective in limiting reductions in weight-for-height and reducing the incidence of wasting and severe wasting in the short-term. The effectiveness of any intervention to prevent malnutrition, however, will ultimately depend on its consideration of the underlying causes of malnutrition, integration with other broad-based strategies to improve public nutrition, and feasibility within the resource constraints of humanitarian and public health programming.