Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase. In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2–5 days), which was similar between randomized groups (0.23 [95% CI −0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite. Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM. ClinicalTrials.gov NCT02246296.

Ready-to-use therapeutic food (RUTF) containing less dairy may be a lower-cost treatment option for severe acute malnutrition (SAM). The objective was to understand the effectiveness of RUTF containing alternative sources of protein (nondairy), or <50% of protein from dairy products, compared with standard RUTF in children with SAM. The Cochrane Library, MEDLINE, Embase, CINAHL, and Web of Science were searched using terms relating to RUTF. Studies were eligible if they included children with SAM and evaluated RUTF with <50% of protein from dairy products compared with standard RUTF. Meta-analysis and meta-regression were completed to assess the effectiveness of intervention RUTF on a range of child outcomes. The quality of the evidence across outcomes was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A total of 5868 studies were identified, of which 8 articles of 6 studies met the inclusion criteria evaluating 7 different intervention RUTF recipes. Nondairy or lower-dairy RUTF showed less weight gain (standardized mean difference: −0.20; 95% CI: −0.26, −0.15; P < 0.001), lower recovery (relative risk ratio: 0.93; 95% CI: 0.87, 1.00; P = 0.046), and lower weight-for-age z scores (WAZ) near program discharge (mean difference: −0.10; 95% CI: −0.20, 0.0; P = 0.047). Mortality, time to recovery, default (consecutive absences from outpatient therapeutic feeding program visits), nonresponse, and other anthropometric measures did not differ between groups. The certainty of evidence was high for weight gain and ranged from very low to moderate for other outcomes. RUTF with lower protein from dairy or dairy-free RUTF may not be as effective as standard RUTF for treatment of children with SAM based on weight gain, recovery, and WAZ evaluated using meta-analysis, although further research is required to explore the potential of alternative formulations. This review was registered at https://www.crd.york.ac.uk/prospero/ as CRD42020160762.

Background The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this recommendation. Specifically, the objective was to answer the question: "In children with severe acute malnutrition, does psychosocial stimulation improve child developmental, nutritional, or other outcomes?" Methods A review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2016: CRD42016036403). MEDLINE, Embase, CINAHL, and PsycINFO were searched with terms related to SAM and psychosocial stimulation. Studies were selected if they applied a stimulation intervention in children with SAM and child developmental and nutritional outcomes were assessed. Findings were presented within a narrative synthesis and a summary of findings table. Quality of the evidence was evaluated using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings Only two studies, both non-randomized controlled trials, met the selection criteria for this review. One was conducted in Jamaica (1975) with a follow-up period of 14 years; the other was done in Bangladesh (2002) with a six-month follow-up. At the individual study level, each of the included studies demonstrated significant differences in child development outcomes between intervention and control groups. Only the study conducted in Bangladesh demonstrated a clinically significant increase in weight-for-age z-scores in the intervention group compared to the control group. Conclusions The evidence supporting the recommendation of psychosocial stimulation for children with SAM is not only sparse, but also of very low quality across important outcomes. High-quality trials are needed to determine the effects of psychosocial stimulation interventions on outcomes in children with SAM.

Undernutrition remains a global struggle and is associated with almost 45% of deaths in children younger than 5 years. Despite advances in management of severe wasting (though less so for nutritional edema), full and sustained recovery remains elusive. Children with severe wasting and/or nutritional edema (also commonly referred to as severe acute malnutrition and part of the umbrella term “severe malnutrition”) continue to have a high mortality rate. This suggests a likely multifactorial etiology that may include micronutrient deficiency. Micronutrients are currently provided in therapeutic foods at levels based on expert opinion, with few supportive studies of high quality having been conducted. This narrative review looks at the knowledge base on micronutrient deficiencies in children aged 6–59 months who have severe wasting and/or nutritional edema, in addition to highlighting areas where further research is warranted (See “Future Directions” section).