Fortified lipid-based spreads, containing different concentrations of micronutrients, are broadly categorized as lipid-based nutrient supplements (LNSs). Several formulations of LNSs exist, including ready-to-use therapeutic food (RUTFs) and ready-to-use supplementary foods (RUSFs). RUTF has proven effective in the nutritional rehabilitation of children with severe acute malnutrition [4]–[8], leading the World Health Organization (WHO) to recommend the use of RUTF within the framework of community-based management of severe acute malnutrition without medical complications [8]–[10].

Based on this success, both RUTF and RUSF have been used in targeted supplementation to complement the dietary intake of moderately malnourished children or children at risk of malnutrition [11],[12]. Recent studies have assessed the effectiveness of provision of RUTF and RUSF in preventing malnutrition in non-wasted children in settings of permanent or seasonal food insecurity [13]–[15]. However, questions have been raised as to whether such practices are universally effective and cost-effective [16].

In emergency settings, “general food distributions” are implemented by international organizations to provide basic food support to affected populations. While there is a clear need for such interventions, it remains unclear whether such programs are effective in preventing child wasting, as rations are targeted at the household level. In addition, it has been suggested that targeting nutrition interventions to prevent child undernutrition might be more effective than curative treatment to reduce child undernutrition [17].

Compared to baseline values, mean WHZ for both arms was slightly higher at end point, while mean HAZ was slightly lower. We found no difference in the incidence of wasting (incidence rate ratio: 0.86; 95% CI: 0.67, 1.11; p=0.25) or mean change in WHZ (−0.002 WHZ/mo; 95% CI: −0.032, 0.028; p=0.89) between the arms. The difference in weight increase between arms was 0.02 kg/mo (95% CI: −0.01, 0.04; p=0.10). Children in the intervention group had a significantly higher linear growth velocity of 0.03 HAZ-score/mo (95% CI: 0.02, 0.05; p<0.001) compared to the control group (Table 3). This observed difference was equivalent to a small difference in height gain of 0.09 cm/mo (95% CI: 0.04, 0.14; p<0.001). Identical ponderal growth in control and intervention group was confirmed by a lack of difference in MUAC growth. Age at inclusion was not found to modify the intervention effects on child anthropometric measurements. Observed intervention effects did not noticeably change when missing outcome data were imputed using the last value carried forward method (data not shown).

After adjustment for age, sex, SES, and morbidity status at inclusion, we found that children from the RUSF group had lower risk of self-reported diarrhea by 29.3% (95% CI: 20.5, 37.2; p<0.001) and fever by 22.5% (95% CI: 14.0, 30.2; p<0.001), compared to the control group (Table 4). Effects on morbidity did not appreciably change when missing data were imputed.

RUSF significantly increased mean hemoglobin concentration at end point by 3.8 g/l (95% CI: 0.6, 7.0; p=0.02), resulting in significantly lower odds of anemia (OR: 0.52; 95% CI: 0.34, 0.82; p=0.004) for children in the intervention group (Table 5).

The absence of an effect on wasting incidence could have multiple explanations. First, the energy contribution of RUSF may have been “diluted” by the general food distribution, which mainly provided a supplement of energy and protein. We did not systematically monitor whether or not children received food rations. However, post-distribution monitoring surveys carried out 2 wk after each distribution reported that more than 70% of children under 5 y had three meals or more per day in both arms (ACF-France, unpublished data). Furthermore, a previous study noted that energy-dense spreads have little effect on children's habitual diet and breast milk intake [35],[36], although additional dietary assessment studies investigating the impact of RUSF on diet substitution are warranted. Second, the energy dose of 46 g (≈247 kcal) daily RUSF and the duration of the supplementation could have been insufficient to support ponderal growth, particularly for the older children in the cohort. However, no significant triple interactions were found between age at baseline, intervention, and follow-up time on wasting incidence and mean ponderal growth. Furthermore, it is possible that the RUSF may have been shared with other children in the household. However, if this were done to a large extent, we may not have seen the observed intervention effects on secondary outcomes like HAZ and hemoglobin concentration. Also, program staff emphasized during distribution sessions that RUSF was intended only for the targeted child and that the family food rations could serve to feed other children. Finally, caution should be exercised when interpreting the reported difference in wasting incidence between arms, as the study is clearly underpowered to assess such small differences.

Children receiving RUSF supplementation showed a modest, but statistically significant, increase in mean linear growth (as indicated by HAZ). This finding is in line with a program using a 6-mo supplementation with RUSF in 6- to 36-mo-old Nigerians [15]. Although this effect was small, it is noteworthy because the supplementation lasted only 4 mo. This finding is also consistent with other previous studies. A significant reduction in severe stunting was reported among 6- to 28-mo-old Malawians after a 12-mo intervention [37]. Significant length gains were reported among 6- to 36-mo-old Nigerians after a 6-mo intervention with RUTF [14], in 6- to 12-mo-old Ghanaians after a 6-mo intervention with the LNS Nutributter [38], in 6- to 17-mo-old underweight Malawian infants after 12 wk of supplementation with milk-based fortified spreads [39], and in 3- to 6-y-old Algerians after a 6-mo intervention with a spread fortified with vitamins and minerals [40].

The group receiving RUSF had a significantly lower risk of diarrhea and fever compared to the control group. These findings are not confirmed by previous studies using RUTF or RUSF, except in the study by Ciliberto et al., which found a lower prevalence of diarrhea, fever, and cough in a group of moderately malnourished children given RUTF compared to a group that received standard therapy [4].

Significant positive intervention effects were also found on mean hemoglobin concentration and the prevalence of anemia. A 46-g daily dose of RUSF provided not only an average of 9 mg of iron per day but also addressed deficiencies in folic acid, vitamin B12, vitamin A, and riboflavin, which are known to limit erythropoiesis [41]. Similar results were found for Nutributter and Nutritabs in Ghana [42] and for milk-based fortified spreads in Malawi [39]. Lopriore et al. also showed that supplementation with a nutrient-dense fat-based spread fortified with vitamins and minerals produced a 2-fold higher increase in hemoglobin concentration after 6 mo of intervention compared to the 6-mo difference in a control group of 3- to 6-y-old children [40].

The absence of an effect on ponderal growth, but modest effects on morbidity, linear growth, and, most of all, hemoglobin could suggest that a MMN effect is at play. For example, zinc, one of the micronutrients added to RUSF, is currently recommended as adjunct therapy by the United Nations Children's Fund and WHO for the treatment of diarrhea [43]. A number of studies support its therapeutic and prophylactic role [44]–[48]. In addition, two systematic reviews concluded that MMN supplementation in young children improved micronutrient status and had modest effects on linear growth [49],[50]. Golden proposed that providing empty calories to children with MMN deficiencies would lead to ponderal growth without any effect on linear growth [50]. The author argues that MMNs, along with protein and energy, are essential building blocks necessary to make skeletal tissue to sustain linear growth. In that respect, we could regard MMNs as essential cofactors for linear growth, responsible for the observed effect on growth [51].

These observations could lead to the speculative hypothesis that supplementation with MMN supplements like powders or tablets might result in the same effects as RUSF if basic food rations were provided. Very few studies have compared RUSF to other MMN formulations to support child nutritional status. An interesting study by Adu-Afarwuah et al. compared three MMN supplements: Sprinkles, crushable Nutritabs, and 20 g of Nutributter. In addition to greater weight gain, children in the Nutributter group also experienced a greater gain in length compared to children given Nutritabs (p<0.05) and Sprinkles (p>0.05) [38].

One important additional benefit that lipid-based nutrient supplements offer is the lipid component. In addition to providing a small amount of essential fatty acids, which hold a potential to support child growth [52], the lipid component serves as an essential matrix that ensures that fat-soluble vitamins like vitamin A, D, and E are properly absorbed [53]. Particularly when the child's diet is poor in fat, this would provide leverage to increase the efficacy of supplemented fat-soluble vitamins [54]. Therefore, more mechanistic studies are required to elucidate the additional contribution to the efficacy of the MMNs by the functional fat fraction of the RUSF.

The study has a number of limitations, which need to be addressed. First, the projected sample size was not attained, limiting the study's statistical power. The main reason for this was the unpredictable security situation, which obliged field staff to restrict their field activities during the screening period. In addition, ACF-France decided to restrict the target sample population to households with high dependency ratio, which resulted in difficulties in achieving the anticipated sample size. It is noteworthy to mention nonetheless that the post hoc calculated intra-cluster correlation coefficient of 0.0075 showed a lower value than the anticipated value of 0.01 used for the sample size calculation. Second, the study participants were not blinded with respect to the intervention assignment because of the type of supplement (paste) provided to children. We opted for a cluster-randomized design to minimize the effects of contamination (RUSF sharing); however, clusters were not always geographically separated from each other. Significantly fewer children from the control group were present at follow-up sessions; this was likely due to the following factors. The monthly food rations for both control and intervention participants were distributed to mothers/caretakers regardless of whether their child was present at the anthropometry sessions. Conversely, the RUSF was given only if the child was present at the anthropometry sessions. This factor, while limiting follow-up observations of children in the control group, also ensured that households received monthly food rations regardless of their participation in the study, thereby sustaining their exposure to the control treatment. Finally, child morbidity was recorded through caretaker recall, which could have resulted in underestimation.

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