Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda.
PLoS Med. 2023 May 23;20(5):e1004227. doi: 10.1371/journal.pmed.1004227. eCollection 2023 May.
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.
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 < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration.
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.
ISRCTN13093195.
尽管牛奶对生长可能有益，但对于营养不良的儿童来说，在食物中添加牛奶是昂贵的。此外，不同牛奶成分、乳蛋白（MP）和乳清渗透物（WP）的相对效果尚不清楚。我们旨在评估 MP 和 WP 在基于脂质的营养补充剂（LNS）中的作用，以及 LNS 本身对生长迟缓儿童的线性生长和身体成分的影响。
我们在乌干达对 12 至 59 个月大的生长迟缓儿童进行了一项随机、双盲、2×2 析因试验。儿童被随机分配到含有 MP 或大豆蛋白分离物和 WP 或麦芽糊精的 4 种 LNS 配方（每天 100 g，持续 12 周）或不补充。研究者和结果评估者被设盲；然而，只有参与者对 LNS 的成分是盲的。根据意向治疗（ITT）进行数据分析，采用线性混合效应模型，根据年龄、性别、季节和地点进行调整。主要结局是身高和膝高的变化，次要结局包括生物电阻抗分析（ISRCTN13093195）的身体成分。2020 年 2 月至 9 月期间，我们招募了 750 名中位数年龄为 30 岁（四分位间距 23 至 41）的生长迟缓儿童，平均（±标准差）身高年龄 z 评分（HAZ）为-3.02 ± 0.74，12.7%（95）为母乳喂养。这 750 名儿童被随机分配到 LNS（n=600），有或没有 MP（n=299 与 n=301）和 WP（n=301 与 n=299），或不补充（n=150）；736（98.1%）名儿童均匀分布在各组，完成了 12 周的随访。10 名（1.3%）儿童发生了 11 例严重不良事件，主要为疟疾和贫血住院，均被认为与干预无关。未补充的儿童 HAZ 下降了 0.06（95%置信区间，0.02 至 0.10；p=0.015），脂肪量指数（FMI）增加了 0.29（95%置信区间，0.20 至 0.39；p<0.001），但脂肪无机组分指数（FFMI）下降了 0.06（95%置信区间，-0.002 至 0.12；p=0.057）。MP 和 WP 之间没有相互作用。MP 的主要作用是身高增加 0.03（95%置信区间，-0.10 至 0.16；p=0.662）cm 和膝高增加 0.2（95%置信区间，-0.3 至 0.7；p=0.389）mm。WP 的主要作用是身高下降 0.08（95%置信区间，-0.21 至 0.05；p=220）cm 和膝高下降 0.2（95%置信区间，-0.7 至 0.3；p=403）mm。WP 与母乳喂养之间存在交互作用，影响线性生长（p<0.02），这是由于母乳喂养儿童的效果为正，而非母乳喂养儿童的效果为负。总体而言，LNS 使身高增加了 0.56（95%置信区间，0.42 至 0.70；p<0.001）cm，相当于 HAZ 增加了 0.17（95%置信区间，0.13 至 0.21；p<0.001），体重增加了 0.21（95%置信区间，0.14 至 0.28；p<0.001），其中 76.5%（95%置信区间，61.9%至 91.1%）为无脂体重。使用身高调整指标，LNS 增加了 FFMI（0.07 kg/m2，95%置信区间，0.0001 至 0.13；p=0.049），但不增加 FMI（0.01 kg/m2，95%置信区间，-0.10 至 0.12；p=0.800）。主要限制因素是缺乏对护理人员的盲法和研究时间短。
在 12 至 59 个月大的生长迟缓儿童中，在 LNS 中添加牛奶对线性生长或身体成分没有额外影响。然而，补充 LNS，无论是否添加牛奶，都支持线性追赶生长和脂肪无机组分的积累，但不支持脂肪的积累。如果不进行治疗，已经处于生长迟缓轨迹的儿童会以脂肪取代脂肪无机组分的方式增加体重，因此应考虑针对此类儿童的营养治疗方案。
ISRCTN13093195。
