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Randomized Controlled Trial
. 2022 May 1;115(5):1322-1333.
doi: 10.1093/ajcn/nqab363.

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial

Kevin Stephenson  1 , Meghan Callaghan-Gillespie  2 , Kenneth Maleta  3 , Minyanga Nkhoma  3 , Matthews George  3 , Hui Gyu Park  4 , Reginald Lee  2 , Iona Humphries-Cuff  5 , R J Scott Lacombe  4 , Donna R Wegner  2 , Richard L Canfield  4 , J Thomas Brenna  4   6 , Mark J Manary  2   3   7
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Randomized Controlled Trial

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial

Kevin Stephenson et al. Am J Clin Nutr. .

Erratum in

Abstract

Background: There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for the treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery.

Objectives: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high-oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), improves cognition when compared with standard RUTF (S-RUTF).

Methods: A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF, and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem-solving assessment (PSA) intention score for 3 standardized problems, measured 6 mo and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, plasma fatty acid content, anthropometry, and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF.

Results: Among the 2565 SAM children enrolled, mean global MDAT z-scores were -0.69 ± 1.19 and -0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI: 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (OR: 0.92, 95% CI: 0.67, 1.26 for DHA-HO-RUTF). After 4 wk of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared with S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF (P < 0.001).

Conclusions: Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit 6 mo after completing diet therapy. This treatment should be explored in operational settings. This trial was registered at clinicaltrials.gov as NCT03094247.

Keywords: DHA; MDAT; PUFA; cognition; ready-to-use therapeutic food; severe acute malnutrition.

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Figures

Graphical Abstract
Graphical Abstract
FIGURE 1
FIGURE 1
CONSORT diagram of study participation. DHA-HO-RUTF, high-oleic acid RUTF with added DHA; HO-RUTF, high-oleic acid RUTF; MAM, moderate acute malnutrition; MDAT, Malawi Developmental Assessment Tool; PSA, problem-solving assessment; RUTF, ready-to-use therapeutic food; SAM, severe acute malnutrition; S-RUTF, standard RUTF. 1For the PSA, beginning in February 2018, children aged <2 y at time of SAM outcome were invited to undergo neurocognitive testing within 4 wk of SAM outcome. For the MDAT, beginning in March 2018, children aged <30 mo at time of SAM outcome were invited to return 5–7 mo after their SAM outcome to undergo neurocognitive testing.
FIGURE 2
FIGURE 2
Probability density plots of Malawi Developmental Assessment Tool global and domain z-scores of children receiving RUTF made with high-oleic acid peanuts with added DHA (DHA-HO-RUTF), RUTF made with high-oleic acid peanuts but without added DHA (HO-RUTF), or standard RUTF (S-RUTF). Probability densities were constructed using kernel density estimation. Global nDHA-HO-RUTF = 332, nHO-RUTF = 312, nS-RUTF = 342. Gross motor domain nDHA-HO-RUTF = 331, nHO-RUTF = 312, nS-RUTF = 342. Fine motor nDHA-HO-RUTF = 323, nHO-RUTF = 306, nS-RUTF = 337. Language nDHA-HO-RUTF = 331, nHO-RUTF = 312, nS-RUTF = 342, nDHA-HO-RUTF = 332, nHO-RUTF = 311, nS-RUTF = 342. RUTF, ready-to-use therapeutic food.
FIGURE 3
FIGURE 3
Problem-solving assessment intention scores of children receiving RUTF made with high-oleic acid peanuts with added DHA (DHA-HO-RUTF), RUTF made with high-oleic acid peanuts but without added DHA (HO-RUTF), or standard RUTF (S-RUTF). Percentages of children in each intervention group with each score are shown. Overall, children in each study food had similar intention scores in all 3 problems; the differences between food groups were not significant. The lowest and highest scores possible in each problem were the most common results among children with scores. Children with “No Score” were unable to engage in the task. RUTF, ready-to-use therapeutic food.
FIGURE 4
FIGURE 4
Box and whisker plots of plasma fatty acid content of 6 selected fatty acids in severely malnourished children receiving RUTF made with high-oleic acid peanuts with added DHA (DHA-HO-RUTF), RUTF made with high-oleic acid peanuts (HO-RUTF), or standard RUTF (S-RUTF). The boxes represent the IQR of the distribution with a heavy midline median value. The whiskers extend to 1.5 times the IQR, values outside of these designations are plotted as points. The statistical comparisons were made using a Wilcoxon Rank Sum test. The number of participants sampled in each group were nDHA-HO-RUTF = 208, nHO-RUTF = 189, and nS-RUTF = 162. AA, arachidonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; RUTF, ready-to-use therapeutic food.
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