Effect of short-term supplementation with ready-to-use therapeutic food or micronutrients for children after illness for prevention of malnutrition: a randomised controlled trial in Uganda

Summary of research¹

The potential for nutritional supplementation of sick children as a strategy for preventing malnutrition has not been adequately studied in developing country contexts. A recent Médecins Sans Frontières study investigated whether the incidence of malnutrition among sick children under five years of age could be reduced over a six-month period by providing either a lipid-based, fortified food product or micronutrients during their two-week convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; this paper reports on the trial that took place in Kaabong, a poor agro-pastoral region of Karamoja in east Uganda. Prevalence of acute malnutrition in Karamoja region in children aged 6-59 months ranges from 8.4 to 11.5% (2-3% severe acute malnutrition); more than half (58%) of the population in the district of Kaabong is considered food insecure.

Methods

This study investigated the effect of two types of nutritional supplementation on the incidence of malnutrition in sick children presenting at outpatient clinics during March 2011 to April 2012 in Kaabong. A three-armed, partially-blind, randomised controlled trial was conducted in children diagnosed with malaria, diarrhoea or lower respiratory tract infection (LRTI). All care and treatment for sickness followed current national medical protocols. Non-malnourished children aged six to 59 months were randomised to one of three arms: one sachet per day of ready-to-use therapeutic food (RUTF), two sachets per day of standard UN formulation micronutrient powder (MNP), or no supplement (control). The enrolled participants were followed up after the first 14 days and then monthly for six months.

All groups (including the control group) received health education, including the message that following an illness, a child should eat one extra, healthy meal per day for two weeks. Home visitors supported the study by reminding the caretakers to come to appointments, urging absentees to return, and reporting on deaths that occurred at home; any deaths were reviewed by a national doctor and the study team. Compliance was measured by questionnaires and asking the caretakers to return all sachets, empty or full. Three focus group discussions were held during the study period with caretakers who had completed the trial.

The primary outcome was the incidence of first negative nutritional outcome (NNO) during the six-month follow-up. NNO was a study-specific measure used to indicate progression to moderate or severe acute malnutrition; it was defined as weight-for-height z-score <−2, mid-upper arm circumference (MUAC) <115 mm, or oedema, according to whichever came first.

Findings

Of the 2,202 randomised participants, 51.2% were girls, and the mean age was 25.2 (±13.8) months; 148 (6.7%) participants were lost to follow-up, nine (0.4%) died, and 14 (0.6%) were admitted to hospital. The majority of participants (63.1%) had diarrhoea on enrolment, 29.8% had malaria and 34.5% had LRTI (more than one disease could be reported). After the onset of illness, caretakers waited an average 2.5 days before seeking help at the clinic.

The incidence of first NNO event during the six-month follow-up for the RUTF, MNP, and control groups were 0.143 (95% confidence interval [CI], 0.107-0.191), 0.185 (0.141-0.239), and 0.213 (0.167-0.272), respectively. The incidence rate ratio was 0.67 (95% CI, 0.46-0.98; p = 0.037) for RUTF versus control; a significant reduction of 33.3%. The incidence rate ratio was neither significant at 0.86 (0.61-1.23; p = 0.413) for MNP versus control (13.8% reduction) or at 0.77 for RUTF versus MNP (95% CI 0.52- 1.15; p = 0.200).

The incidence of NNO in the RUTF group was 39.3% lower compared with the control group (p =0.037) and 19.6% lower compared with the MNP group (p =0.394). The incidence in the MNP group was 23.8% lower than the control group (p=0.248).

The average numbers of study illnesses for the RUTF, MNP and control groups were 2.3 (95% CI, 2.2-2.4), 2.1 (2.0-2.3), and 2.3 (2.2-2.5), respectively. The proportions of children who died in the RUTF, MNP and control groups were 0%, 0.8%, and 0.4%.

A total of 166 participants developed moderate malnutrition; 44 (6.09%), 56 (7.7%) and 66 (9.14%), in the RUTF, MNP and control groups respectively. Sixteen participants developed severe malnutrition; 4 (0.55%), 9 (1.24%) and 3 (0.42%), in the RUTF, MNP and control groups, respectively.

The proportion of children having a newly diagnosed episode of diarrhoea or LRTI during the study was similar among the study groups. However, the MNP group had a lower average number of malaria episodes than the control group (p =0.001).

Sub-group analyses suggested that the effect of supplementation on the incidence of NNO was not modified by socioeconomic characteristics, season of enrolment, age, breastfeeding status or study disease at enrolment. Both the weight-gain rate and MUAC-gain rate were significantly higher for the supplementation groups compared with the control group. The change in both weight-for-age index and weight-for-height index was also higher for the supplementation groups than the control groups. The change in height and the change in height-for-age index were not different between the supplementation arms. In the first 14 days after the first supplementation, the RUTF and MNP groups showed a significantly higher weight-gain rate compared with the control group and a lower proportion of participants did not gain weight in the supplementation groups. The data shows that both RUTF and MNP improved the nutritional status of the children, but that RUTF was more effective in preventing children falling below the threshold of malnutrition.

Discussion

With the promising results with MNP alone and the clear effect of a high-quality food providing 500 kcal (RUTF), the authors suggest that a supplement with a lower energy content (at a lower cost than RUTF) might also be effective in reducing incidence of malnutrition, such as lipid-based supplements. From a cost-effectiveness perspective, the authors suggest that further research using these types of products with morbidity surveillance and treatment is warranted.

The findings apply to sick but not malnourished children and cannot be generalised to a wider population including children who are not necessarily sick or who are already malnourished. The companion study in Nigeria showed no reduction in the incidence of malnutrition with short-term supplementation of either RUTF of MNP compared with a control group and there was no impact on any of the anthropometric indices. The authors postulate that the high morbidity in Nigeria necessitates a higher dose or a longer duration of supplementation for effectiveness. The incidence of malnutrition in this population was remarkably low; this may be due to reduced conflict and improved security during the study period.

The effect of supplementation on further morbidity in sick children was mixed and inconclusive. The mortality data are difficult to interpret because of the low numbers and lack of data on the cause of death for those who died at home.

Conclusions

This study showed that a two-week nutrition supplementation programme with RUTF as part of routine primary medical care to non-malnourished children with malaria, LRTI or diarrhoea proved effective in preventing malnutrition in eastern Uganda. The low incidence of malnutrition in this population may warrant a more targeted intervention (such as sick children younger than three years old, or during the hunger season) to improve cost-effectiveness.

While supplementation with MNP showed a positive trend for several nutritional indicators, it appears that a certain level of macronutrients is needed to prevent malnutrition. The authors suggest that further research should focus on an appropriate balance between macro- and micronutrients to optimise the cost-effectiveness of supplementation with lipid-based fortified foods in preventing malnutrition in sick children.