Advances in Food and Nutrition Research: 69

All data were entered twice and inconsistencies resolved. The primary response variable was change in height, expressed in centimeters or HAZ. We utilized adjusted estimates of linear growth when available. If only the baseline and endline values were reported, we calculated the crude mean change in height by subtracting baseline mean from the endline mean. In studies with multiple intervention groups and a single control group, the sample size of the control group was divided equally by the number of intervention groups while retaining the same value for the change in linear growth and its SD to avoid multiple counting of the control group.

A sensitivity analysis to assess the effect of assumptions regarding correlation between growth measures pre- and postintervention was conducted by using the following: Effect sizes for each individual study were computed by dividing the mean change in the intervention and control groups by the pooled SD.

Data were consolidated by using an inverse variance method. I 2 statistics were used to measure the heterogeneity of the studies. We visually assessed funnel plots to investigate potential publication bias 9. Data were analyzed by using RevMan version 5. The literature search yielded references Figure 1 , of which were excluded on the basis of title and abstract, and studies were excluded following full review.

An additional 19 articles were identified from reference lists. A total of 69 articles were included in the systematic review and meta-analysis. The baseline characteristics for single-micronutrient and other nutrition-based interventions are reported in Tables 1 and 2 , respectively. Using the Jadad test, 37 studies were classified as high quality, 19 were of medium quality, and 13 were of low quality. Symmetric funnel plots suggested a low chance of publication bias in zinc, iodine, and food-based analysis. Asymmetrical funnel plots for iron, calcium, vitamin A, MMs, and protein suggest potential publication bias Supplemental Figure 1.

The key effects of nutritional interventions administered after age 24 mo on linear growth are summarized in Table 3. A total of 14 studies were included in the meta-analysis.

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The number of subjects in each study ranged from 41 to , with mean ages ranging from 34 to mo. One study 21 did not have extractable baseline height data. In 2 studies, the daily dose of iron could not be determined because administration of the mineral was based on body weight 10 , The duration of supplementation lasted from 1 to 12 mo.

The overall standard mean effect was not statistically significant 0. Sensitivity analyses excluding studies in which no children were stunted 0. Data derived from systematic literature review of nutrient interventions administered after age 2 y. Fixed, fixed-effects model; IV, inverse variance; random, random-effects model; std. We identified 17 studies that examined the effect of zinc on height. The number of subjects in each study ranged from 18 to , with mean ages of subjects ranging from 27 to mo.

Each point represents one study estimate. HAZ, height-for-age z score. A total of 12 studies contributed 16 data sets. The remaining studies were conducted in high-income countries, including 2 in the United States, 4 in Australia, 2 in Switzerland, and 1 in France. The number of subjects in each study ranged from 31 to , with mean ages of subjects ranging from 33 to mo.

Four studies enrolled both boys and girls, 6 studies enrolled only girls, and 2 enrolled only boys.

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There was insufficient data to calculate baseline HAZ in the study by Courteix et al. Two studies that examined the impact of iodine supplementation on linear growth were identified. One study contributing 2 data sets was included in the meta-analysis. The number of subjects was and , with mean ages and mo, respectively. Supplemental iodine was delivered as iodized oil in one large bolus mg or 2 smaller doses mg every 3 mo.

The duration of both studies was 6 mo. Because of limited data, effect modification by baseline HAZ, age, and study length was not examined. We identified 5 studies that assessed the effect of vitamin A on linear growth. The studies contributed 16 datasets for analysis. The studies were conducted in Sudan 53 , Tanzania 19 , China 55 , 56 , and Indonesia The study in Sudan 53 was stratified by age group and sex, the study in Tanzania 19 had 2 treatment groups, and the study in Indonesia 54 was stratified by breastfeeding status.

The number of subjects in each study ranged from 63 to , with mean ages of subjects ranging from 2 to 12 y. The study by Fawzi et al. The dose of vitamin A ranged from to , international units, and duration of supplementation lasted from 3 to 17 mo. One dataset by Mwanri et al.

The overall standardized mean effect was statistically significant with 0. Seventeen trials were identified. All studies were conducted primarily in LMICs: The number of subjects in each study ranged from 25 to , with mean ages of subjects ranging from 29 to mo. MM interventions were administered as either supplements e. The composition and dose of the MM supplements varied among studies.

All interventions contained iron, whereas the inclusion of zinc The duration of supplementation ranged from 3 to 20 mo. The studies by Zadik et al. The overall weighted mean effect was 0.

Excluding studies in which no children were stunted at baseline did not alter these conclusions 0. Fixed, fixed-effects model; IV, inverse variance; MM, multiple micronutrient; random, random-effects model; std. Each point represents 1 study estimate. A total of 7 protein-based intervention trials that provided data to calculate an effect on linear growth were identified. Five studies contained multiple treatment groups, each providing either 2 69 , 73 , 75 or 3 data sets The number of subjects in each study ranged from 35 to , with mean ages of subjects ranging from 33 to mo.

Protein supplements were administered as either meat 69 , cow milk liquid or powder 69 , 71 — 73 , amino acid—supplemented rice or wheat 74 , 75 , casein 72 , whey 72 , or high-protein diets The duration of supplementation ranged from 0. The data sets extracted from Lampl et al. Excluding studies in which no children were stunted at baseline did not alter the conclusions 1.

Sufficient data were available from 6 data sets from 5 studies 69 , 73 , 76 — 78 for calculation of the effect of food-based supplementation on height. The number of subjects in each study ranged from 57 to , with mean ages of subjects ranging from 49 to mo. Food-based supplements were delivered in many forms including Pediasure Abbott Laboratories 76 , fat 69 , ready-to-use therapeutic food 77 , additional meals 73 , or the addition of sorghum to the diet The overall weighted mean effect was not statistically significant 0.

Furthermore, excluding studies in which no children were stunted at baseline did not alter the conclusions 0. A few notable observations may have programmatic implications. Specifically, interventions containing iron, calcium, or iodine or those providing food do not improve linear growth, whereas interventions containing zinc 0. A range of sensitivity analyses with the use of different assumptions for the SD for the change in height did not alter these conclusions Supplemental Table 1.

Several observational studies have reported associations between iron-deficiency anemia and impaired linear growth that may stem from impaired immunity, appetite, and thyroid hormone metabolism 18 , 79 , As such, the impact of iron supplementation on linear growth has been the subject of a number of systematic reviews and meta-analyses 81 — The review by Ramakrishnan et al.

Despite methodological differences, our findings were consistent with those of earlier reviews. When we excluded studies with normal hemoglobin, the effect size increased 0. Our study further contributes to the growing body of evidence suggesting that iron is ineffective at promoting linear growth. Zinc is an essential transition metal that plays a critical role in normal linear growth via mechanisms involving growth-hormone release, insulin-like growth factor I, chondrogenesis, collagen synthesis, osteoblast function, and calcification of bone Close mobile search navigation Article navigation.

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