Does nutritional supplementation for two weeks prevent malnutrition in ill children?
Summary of research1
Location: DRC, Uganda and Nigeria
What we know: Ill children are at increased risk of malnutrition due to the infection-malnutrition cycle.
What this article adds: Three randomised controlled trials (RCTs) were conducted to test the effect of 14 days of nutritional supplementation for ill children on incidence of malnutrition during one to six months of follow-up. In DRC, 180 non-malnourished children with malaria were given ready-to-use therapeutic food (RUTF) or no supplementation (control). Children in the RUTF group had higher weight gain at 14 days but similar weight gain at 28 days compared to control. In Uganda (n=2,202) and Nigeria (n=2,213) children with malaria, lower-respiratory tract infection (LRTI) or diarrhoea received RUTF, micronutrient powder (MNP) or no supplementation (control). In Uganda, RUTF reduced incidence of acute malnutrition by one third; no reduction was found in Nigeria. No MNP groups showed reduction in malnutrition incidence. One third of MAM cases (only enrolled in Nigeria) developed SAM during follow-up. Combined Uganda/Nigeria analysis showed no significant association between supplementation and reduction of malnutrition, a strong association between incidence of malnutrition and diarrhoea, and a mixed association between incidence of malnutrition and malaria (this may be related to country differences in malaria incidence, testing and treatment approach). Effectiveness of supplementation is context-specific. Supplementation alone is unlikely to be sufficient to prevent acute malnutrition in sick children; a combination of preventive and curative health and nutrition interventions is key.
Background
It is well recognised that ill children are at increased risk of malnutrition through the infection-malnutrition cycle. To prevent malnutrition after infection, the World Health Organisation (WHO) recommends that children are given additional healthy food daily for two weeks following the onset of illness (WHO, 1994). However, this strategy may not be possible in resource-poor settings with constrained food availability. A more effective strategy may be to provide ill children with a high-quality nutritional supplement during convalescence. The aim of this study was to assess the effectiveness of nutritional supplementation to ill children on the incidence of malnutrition in order to inform future nutritional strategies.
Médecins Sans Frontières (MSF) conducted three randomised controlled trials (RCTs) primarily to investigate whether supplementation for 14 days with ready-to-use therapeutic food (RUTF) reduced incidence of acute malnutrition during six-months follow-up among non-malnourished children aged 6-59 months with malaria and/or lower respiratory tract infection (LRTI) and/or diarrhoea at recruitment, compared to a control group. The secondary objective of the studies was to investigate the effect of multi-micronutrient powder (MNP) versus RUTF. Other objectives were to determine whether the effectiveness of supplementation on malnutrition differed within groups, such as moderately malnourished versus non-malnourished children on recruitment, and effects of supplementation on other anthropometric measurements, morbidity and mortality. A pilot RCT was carried out in the Democratic Republic of Congo (DRC) (Box 1), followed by two larger studies in Uganda and Nigeria (Boxes 2 and 3). The results were then analysed together to draw conclusions.
Box 1: Summary of published results of pilot RCT in Dubié, Katanga region, Democratic Republic of the Congo (DRC)
Dubié is situated in Katanga Province, a forest region of DRC. At the time of the study, a recent conflict had been resolved and food was accessible. An RCT was undertaken on children aged 6-59 months with confirmed malaria who attended an MSF-supported outpatient clinic and received malaria treatment. Children with severe acute malnutrition (SAM) were excluded. Children were randomly assigned to either an RUTF group, receiving daily RUTF for 14 days, or a control group, receiving no supplemental food. Children were weighed at baseline and on days 14 and 28.
A total of 180 children participated in the study; 93 received RUTF and 87 no food supplementation. At day 14, the RUTF group had a significantly higher mean weight gain of 353g compared with 189g in the control group (difference 164 [95%CI 52–277], p?=?0.005). However, at day 28 there was no statistically significant difference (539g versus 414g, respectively [p?=?0.053]). Similarly, rate of weight gain per kg bodyweight per day was significantly higher at day 14 in the RUTF group (2.4 g/kg per day versus 1.3g/kg per day, p?=?0.005) but at day 28 was not (1.9g/kg per day in the RUTF group versus 1.5g/kg per day in the control group (p?=?0.076)).
There were no significant differences between study groups in the proportion of children reporting fever, diarrhoea or vomiting; however at 14 days the proportion of children with cough was significantly lower in the RUTF group compared to the control (18.2% vs 37.2%; p=0.006). A significantly smaller proportion of children from the RUTF group also reported reduced appetite by day 14 compared to the control group; however these differences disappeared by 28 days.
Children receiving RUTF for 14 days after effective treatment for an uncomplicated malaria episode had faster weight gain than children not given supplementation, reducing the period of risk of malnutrition. By day 28 there was no difference between the groups. The positive catch-up in the control group could be due to the relatively stable food security situation at the time and a good overall nutritional situation.
Van der Kam S, Swarthout T, Niragira O, Froud A, Sompwe ME, Mills C et al. (2012) Ready-to-use therapeutic food for catch-up growth in children after an episode of plasmodium falciparum malaria: An open randomised controlled trial. PLoS One. 2012; 7(4). http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035006
Box 2: Summary of published results of RCT in Kaabong, eastern Uganda
The population of the Kaabong in Karamoja region, eastern Uganda, is semi-pastoral, with low wealth indicators and high food insecurity (58%). An RCT was conducted among non-malnourished children aged 6 to 59 months diagnosed with malaria, diarrhoea, or lower respiratory tract infection (LRTI) presenting at outpatient clinics from March 2011 to April 2012. Children were excluded when they presented with SAM or moderate acute malnutrition (MAM), were exclusively breastfed, had a severe disease, had a sibling enrolled in the study, or were offspring of study staff. Children with signs of severe disease were referred to hospital.
Children were randomised to one of three arms: RUTF, MNP or no supplement (control) for 14 days for each illness and followed up over six months. The primary outcome was the incidence of a first negative nutritional outcome (NNO) during the six-months follow-up. NNO was a study-specific measure used to indicate MAM or SAM, defined as weight-for-height z score (WHZ) <-2 or MUAC <115mm, or oedema. 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, 9 (0.4%) died, and 14 (0.6%) were admitted to hospital.
The incidence rates of NNO 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 reduction of 33.3%. The incidence rate ratio was 0.86 (0.61-1.23; p = 0.413) for MNP versus control and 0.77 for RUTF versus MNP (95% CI 0.52-1.15; p = 0.200). 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). The proportions of children who died in the RUTF, MNP, and control groups were 0%, 0.8%, and 0.4%.
A two-week nutrition supplementation programme with RUTF as part of routine primary medical care to non-malnourished children with malaria, diarrhoea or LRTI proved effective in preventing malnutrition. MNP, however, was not effective.
For a longer summary see: 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. Field Exchange 52, June 2016. p22. www.ennonline.net/fex/52/supplementationchildrenfood
Van der Kam S, Rolls S, Swarthout T, Edvegu-Otelu G, Matsumoto A, Kasujja FX et al. (2016) 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. PLoS Med. 2016; 13 (2): e1001951. https://www.ncbi.nlm.nih.gov/pubmed/26859481
Box 3: Summary of published results of RCT in Goronyo, northwest Nigeria
Goronyo is situated in northwest Nigeria; the economy is based on agriculture and trade. The area is less poor than Kaabong in Uganda but has higher rates of morbidity and malnutrition. An RCT was conducted in children aged 6 to 59 months with malaria, diarrhoea or LRTI presenting at an outpatient clinic from February to September 2012. The same criteria for exclusion were used as in the Kaabong study (Box 2), but children with MAM on enrolment were included. Children were randomised to one of three arms: RUTF, MNP or no supplement (control) for 14 days for each illness over six months. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the six-month follow-up. Of the 2,213 randomised participants, 50.0% were female and the mean age was 20.2 (standard deviation 11.2) months; 160 (7.2%) were lost to follow-up, 54 (2.4%) were admitted to hospital and 29 (1.3%) died.
The incidence rates of NNO for the RUTF, MNP, and control groups were 0.522 (95% confidence interval (95% CI), 0.442–0.617), 0.495 (0.415–0.589), and 0.566 (0.479–0.668) first events/y, respectively. The incidence rate ratio was 0.92 (95% CI, 0.74–1.15; p = 0.471) for RUTF versus control; 0.87 (0.70–1.10; p = 0.242) for MNP versus control and 1.06 (0.84–1.33, p = 0.642) for RUTF versus MNP. A sub-group analysis showed no interaction, confounding or difference in effectiveness of supplementation among children who were moderately malnourished compared with non-malnourished at enrolment. The average number of study illnesses for the RUTF, MNP and control groups was 4.2 (95% CI, 4.0–4.3), 3.4 (3.2–3.6), and 3.6 (3.4–3.7). The proportion of children who died in the RUTF, MNP and control groups was 0.8% (95% CI, 0.3–1.8), 1.8% (1.0–3.3), and 1.4% (0.7–2.8).
One quarter of the participants who were moderately malnourished on enrolment improved to non-malnourishment without showing any difference between the supplementation groups (RUTF, MNP and control groups: 25.4%, 25.0% and 27.3%). The incidence of first NNO for children who were moderately malnourished on enrolment (i.e. those who declined to severe malnutrition) was 0.695, 0.705 and 0.711 respectively for RUTF, MNP and control groups, with no significant reduction in the RUTF or MNP groups.
A two-week supplementation with RUTF or MNP to ill children did not reduce the incidence of malnutrition in this context. The lack of effect may be due to a high frequency of morbidity in the area, which may increase the impact of the illness-malnutrition cycle.
Van der Kam S, Salse-Ubach N, Rol, S, Swarthou, T, Gayton-Toyoshima S, Jiya NM et al. (2016) Supplementation with ready-to-use therapeutic food or micronutrients for children after illness for prevention of malnutrition: A randomised controlled trial in Nigeria. PLoS Med. 2016;13(2):e1001952.
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001952
Comparative and merged analysis
The studies showed different results. In Kaabong, RUTF supplementation for two weeks decreased incidence of malnutrition by more than 30%, yet this effect was not seen in Goronyo. As the methodology of the Kaabong and Goronyo RCTs were almost identical, data from both were combined to increase the power of the analysis (n=3,765). In the combined dataset, incidences of first NNO in the RUTF, MNP and control groups were 0.287 (95%CI 0.245-0.337), 0.298 (95%CI 0.254-349) and 0.345 (95%CI 0.297-0.400) respectively. No significant association was found between supplementation and NNO; nor was there a dose-response relationship between number of supplements and incidence of NNO. The merged data did not therefore show effectiveness of supplementation of ill, non-malnourished children for 14 days with RUTF or MNP after an illness in prevention of malnutrition; effectiveness of RUTF in preventing malnutrition found in Kaabong (Box 2) should be interpreted with caution.
A multivariate regression analysis found positive associations between incidence of malnutrition and the study site, total number of allocations (including medical monitoring, treatment of illness and allocations of supplements), having MUAC <125mm, being younger than 24 months, number of diarrhoea episodes, and caregiver occupation. In Kaabong number of malaria events was associated with higher incidence of malnutrition but in Goronyo number of malaria events was associated with a lower incidence of malnutrition. Being breastfed on enrolment was associated with a significantly higher incidence of malnutrition in Goronyo; however closer examination found increased risk of malnutrition only for children who ceased breastfeeding during the study period. Continuous breastfeeding throughout the follow-up period did not increase the risk of malnutrition compared to non-breastfed children on enrolment.
In the group of participants with MAM on enrolment, the overall incidence of first NNO (equals the incidence of SAM) was 0.685 (95% CI 0.578-0.012) (n=544), with no difference between the supplementation groups. The combined MAM mortality rate for the RUTF, MNP and control groups respectively was 5.7, 27.4 and 15.9 deaths per 1,000/year. The difference in the mortality rate between the RUTF and MNP group was significant at 21.7 deaths/1,000/year and an incidence ratio of 0.210 (p=0.007).
Discussion
Effectiveness of supplementation appears to be dependent on context, including incidence of morbidity, access to healthcare and food and nutrition security. The fragile food security situation in Kaabong meant supply of nutrients was limited and supplementation with RUTF was effective; the lack of effectiveness in Goronyo was likely due to high incidence of morbidity, which limited potential for recovery; more than 70% of participants reported at least one new diarrhoea episode, more than 50% a new LRTI episode and more than 50% a new malaria episode. In some circumstances, prevention of morbidity may be more effective in preventing malnutrition than short-term supplementation with RUTF or MNP to all ill children. Prevention of diarrhoea is a priority, involving water, sanitation and hygiene (WASH) programmes. Results regarding malaria were conflicting. In Goronyo the association between higher frequency of malaria events and decreased incidence of acute malnutrition contrasted with Kaabong, where malaria events were associated with increased NNO incidence. One explanation may be the higher frequency of malaria testing and treatment in Garonyo, which in essence resembled seasonal malaria chemoprophylaxis, which may be effective in reducing malnutrition. More research is needed.
The incidence rate of severe malnutrition among participants who were moderately malnourished on enrolment in Gorongo was high: a third developed severe malnutrition in the study period. The lack of effect of RUTF in MAM cases was likely because the duration and quantity of RUTF were too low to prevent deterioration to SAM and high morbidity prevalence. Supplementation with RUTF showed a trend of decreasing mortality, which requires more investigation with a systematic review of available research. In Goronyo, stopping breastfeeding – rather than the act of breastfeeding – increased malnutrition. This highlights both the protective role of breastfeeding and the need for skilled support to mothers to help sustain breastfeeding in sick children during the complementary feeding period.
The author concludes that convalescence and weight gain after an illness is a multi-factor process and relevant factors in this process should be addressed in combination, such as adequate nutrition, reduction of diarrhoea and malaria, provision of accessible, preventative and curative healthcare, and complementary feeding support.
Footnotes
1Van der Kam S. (2017) Does a short term nutritional supplementation prevent malnutrition in ill children? Effectiveness of nutritional supplementation (ready-to-use therapeutic food and multi micronutrients) of 2 weeks in preventing malnutrition in children 6-59 months with infection (malaria, pneumonia, diarrhoea). PhD Dissertation. Ecole de Santé Publique – Université Libre de Bruxelles.
2Children with MAM on enrolment were excluded from the Goronyo dataset for the combined analysis to match the Kabbong data set. Defaulters were also excluded.
References
WHO (1994) Food, Water and Family Health?: A Manual for Community Educators. Geneva: