Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review

Abstract

Context: In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios.

Objectives: The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting.

Data sources: Twelve databases, trial repositories, and article references with no publication limitations.

Data extraction: Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included.

Data analysis: Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008).

Conclusion: Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes.

Systematic review registration: PROSPERO registration no. CRD42022303694.

Keywords: docosahexaenoic acid; fatty acids; malnutrition; neurodevelopment; ready-to-use therapeutic foods; severe acute; wasting.

Figure 1

Flow diagram of the literature search process.

Figure 2

Risk-of-bias assessment of the included studies.

Figure 3

Meta-analysis of plasma phospholipid eicosapentaenoic acid content in the percentage of total fatty acids. DHA-HO-RUTF: high-oleic-acid RUTF; Lower n-6:n-3 ratio RUTF, added HO peanuts, perilla oil, linseed oil, combination soy, maize, sorghum, flaxseed oil, canola oil, HO soybeans; RUTF with n-3 LCPUFA, added fish-oil capsules, fish paste from dried fish. Abbreviations: CI, confidence interval; DHA, docosahexaenoic acid; HO, high-oleic-acid; IV, inverse variance; LCPUFA, long-chain polyunsaturated fatty acid; RUTF, ready-to-eat food; SD, standard deviation

Figure 4

Meta-analysis of plasma phospholipid DHA content in the percentage of total fatty acids. DHA-HO-RUTF: high-oleic-acid RUTF; Lower n-6:n-3 ratio RUTF, added HO peanuts, perilla oil, linseed oil, combination soy, maize, sorghum, flaxseed oil, canola oil, HO soybeans; Higher n-6:n-3 ratio RUTF, added soy; RUTF with n-3 LCPUFA, added fish-oil capsules, fish paste from dried fish. Abbreviations: CI, confidence interval; DHA, docosahexaenoic acid; HO, high-oleic-acid; IV, inverse variance; LCPUFA, long-chain polyunsaturated fatty acid; RUTF, ready-to-eat food; SD, standard deviation

Figure 5

Meta-analysis of the rate of weight gain in grams per kilogram body weight per day. DHA-HO-RUTF: high-oleic-acid RUTF; Lower n-6:n-3 ratio RUTF, added HO peanuts, perilla oil, linseed oil, combination soy, maize, sorghum, flaxseed oil, canola oil, HO soybeans; RUTF with n-3 LCPUFA, added fish-oil capsules, fish paste from dried fish. Abbreviations: CI, confidence interval; DHA, docosahexaenoic acid; HO, high-oleic-acid; IV, inverse variance; LCPUFA, long-chain polyunsaturated fatty acid; RUTF, ready-to-eat food; SD, standard deviation

Figure 6

Summary of the findings of systematic review. Abbreviations: DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FA, fatty acid; LCPUFA, long-chain polyunsaturated fatty acid; MDAT, Malawi Developmental Assessment Tool; PUFA, polyunsaturated fatty acid; RUTF, ready-to-use-therapeutic food; SAM, severe acute malnutrition; WHZ, weight-for-height z score.