Effect of milk protein and whey permeate in large quantity lipid-based nutrient supplement on linear growth and body composition among stunted children: A randomized 2 × 2 factorial trial in Uganda

Abstract

Background Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. Methods and findings We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) −3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p Conclusions Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered. Trial registration ISRCTN13093195 In a randomized trial Benedikte Grenov and colleagues investigate the effects of milk protein and whey permeate on catch-up growth among 1-5 year-old Ugandan children affected by growth stunting. Author summary Why was this study done? Stunting affects 149 million children below 5 years and is associated with increased morbidity and mortality, delayed cognitive development and later risk of chronic diseases. There are concerns that catch-up growth beyond 2 years may not be possible and that supplementation of already stunted children may lead to fat mass accretion. But no trials have evaluated the effect of lipid-based nutrient supplement (LNS) among children already stunted. Milk may support growth and fat-free mass accretion. However, it is expensive and individual effects of milk protein (MP) and whey permeate (WP) are unknown. We aimed to assess the effects of MP and WP in large quantity LNS among 1- to 5-year-old children that were already stunted. What did the researchers do and find? MAGNUS was a randomized 2 × 2 factorial trial with an unsupplemented control group among 750 stunted 1- to 5-year-old children. The effect of large quantity LNS with MP and/or WP on linear growth (primary outcome) and body composition (secondary outcome) was assessed. There were no effects of MP or WP on linear growth or body composition. During the 12-week study, height-for-age z-score (HAZ) declined in unsupplemented children, and relative to their height, these children accumulated fat mass and lost fat-free mass. In contrast, children receiving LNS—irrespective of milk ingredients—increased in HAZ and fat-free mass, however, not fat mass. There was no difference in catch-up growth between children below and above 2 years. What do these findings mean? Since children on a growth-faltering trajectory gain fat at the expense of fat-free mass, programs using LNS to treat stunting should be considered.