Effect of a Complementary Food Supplement on Growth and Morbidity of Ghanaian Infants
Condition: Growth Disorders; Infant Malnutrition; Micronutrient Deficiency; Protein Malnutrition; Morbidity;Infant
MeSH terms: Malnutrition; Infant Nutrition Disorders; Kwashiorkor; Growth Disorders
Study type: Interventional

Summary: 
      Prevention of malnutrition in infants and children requires access and intake of nutritious
      food starting at birth with exclusive breastfeeding for the first 6 months of life,
      breastfeeding in combination with complementary foods from 6-24 months of age, access to
      clean drinking water and sanitation, access to preventive and curative health care (including
      prenatal).

      In Ghana, the Demographic and Health Survey of 2014 reports rates of stunting, wasting and
      underweight in children aged 0-59 months are 28%, 14% and 9% respectively. Furthermore,
      height for age starts dropping from age 4-6 months with children aged 6-23 months being more
      likely to be stunted (40%) than those below 6 months (4%). Infant and young child feeding
      data show that for breast-fed children ranging from 6 months through 35 months of age,
      cereals are predominantly the first foods introduced in the diet (6-8 months of age). As the
      child grows older, consumption of fruits rich in Vitamin A, other fruits and vegetables and
      meat, fish, poultry and eggs are reported by the mothers. The Demographic and Health Survey
      (DHS) found that the proportion of breast fed children aged 6-23 months who received a
      recommended variety of foods the minimum number of times per day increases with child's age
      from 28% in children 6-8 months to 50% in children aged 18-23 months.

      The study objective is to examine the effect of providing a macro- and micro-nutrient
      fortified complementary food supplement (KokoPlusTM) on growth and nutritional status of
      Ghanaian infants.
    

Detailed description: 
      The current study is a cluster randomized single blind intervention design study with three
      study arms that aimed to examine the effect of providing a macro- and micro-nutrient
      fortified complementary food supplement (KokoPlus) for a period of 12 months (starting at 6
      months of age) on growth and nutritional status of Ghanaian infants at 18 months of age.
      KokoPlus was formulated using linear programming methodology based on formative and market
      analysis research findings.

      The subjects in this cluster-randomized trial are from communities in three districts of the
      Central region in Ghana with high rates of moderate and severe acute malnutrition. A total of
      38 communities will be randomly assigned to one of three groups using block randomization and
      another 11 (randomly selected) will be followed cross sectionally as part of a fourth/non
      intervention group (growth monitoring).

      The total sample size is 1204. Sample size calculations were based on two outcome measures:
      expected reduction in diarrheal morbidity and growth (improvements in height-for-age). Sample
      size estimates for detecting a 0.5 cm change in height in children provided a caloric and non
      caloric micronutrient supplement using a design effect of 2, power of 0.80, alpha of 0.05 and
      assuming an attrition rate of 15%, the required sample size per group was 301.

      Mother-infant pairs will be recruited between infant age of 0 to 3 months to participate in
      monthly nutrition educations sessions and to encourage the women to continue exclusive breast
      feeding across all three groups. At 6 months of age, infants in each of the three groups were
      enrolled into the intervention study (upon receipt of informed consent). Data collection
      involves baseline, midline and endline measurements in the infants at 6, 12 and 18 months of
      age. In addition, participating mother-infant pairs will be visited weekly for delivery of
      the supplements and for morbidity monitoring and monthly for the measurement of
      anthropometry. Anthropometric measurements include: length (Infant/Child Shorr Height Board;
      Weigh and Measure, LLC ), weight (Seca 874 digital scale ), mid-upper arm circumference
      (MUAC) (Child MUAC Tape; Weigh and Measure, LLC), subscapular and triceps skinfolds (Holtain
      skinfold caliper ),head and chest circumference.

      Data collection at baseline, midline and endline included one venous sample (3ml) from the
      infant, HemoCue (Model 301) measurement to assess severe anemia (7 <g/dl) with appropriate
      referrals as mentioned earlier. Ethylenediaminetetracetic acid (EDTA) Vacutainers (BD ;
      catalog number 368841) for whole blood and plasma analyses and Trace Element Serum Separator
      Tube Vacutainers (BD; catalog number 368380) for serum analyses will be used for the sample
      collection with butterfly needles (21 or 23 gauge). Samples will be immediately placed in a
      super cooler tube rack and transported back to the lab within five hours where they were
      processed immediately. Questionnaires will be administered to assess socio-economic status,
      infant and young child feeding practices, morbidity (past week), household food security
      along with a 24 hour diet recall. Data was uploaded daily through cellular network, stored on
      Formhub and then Ona organization servers.

      The primary outcome of the study is the change in length for age Z-score from 6 to 18 months
      of age in infants in the KokoPlus group versus Micronutrient powder group and the Nutrition
      Education group. Data calculations included estimating anthropometric indices using the WHO
      (World Health Organization) 2006 growth reference charts using the WHO macro in STATA (18),
      computing the USAID Food and Nutrition Technical Assistance (FANTA) household insecurity
      access scores (HFIAS) (19) maternal body mass index (BMI), dietary diversity scores (20), and
      re-coding variables as required to binary and accounting for missing. Infant anthropometric
      indices calculated include length for age (LAZ) Z- score, weight for age Z-score (WAZ) and
      weight for length (WLZ score).

      All analyses are intent to treat. Descriptive statistics (means, medians, standard deviations
      and standard errors) were computed. To verify the randomization assumption, any differences
      in mean values at baseline across three groups were tested using linear mixed effects
      regression analyses accounting for clustering. The effect of the supplement (KokoPlus,
      Micronutrients and Nutrition Education group) on different dependent variables across the
      intervention period will be tested using mixed effects regression analyses accounting for
      clustering and repeated measures. The dependent variables tested included change in LAZ
      between baseline and endline (primary outcome), change in LAZ on a monthly basis (primary
      outcome 2), change in WAZ, WLZ, serum hemoglobin (unadjusted and adjusted for inflammation),
      serum ferritin (unadjusted and adjusted for inflammation), serum zinc, serum cortisol, serum
      insulin growth factor-1 (IGF-1), serum retinol binding protein, C-reactive protein and alpha
      glycoprotein, prevalence of acute and chronic infection.

      A cross-sectional assessment (anthropometry) will be conducted at baseline, midline and
      endline in 301 infants that are randomly selected from another set of communities (to be
      identified based on the same community selection criteria). These infants will not be
      followed longitudinally and the only measurements to be collected include weights and
      heights. Informed consent procedures will be similar to the three intervention arms. This
      group is a reference group only and cannot be included in any comparative analysis.

      Monitoring of groups that receive a supplement will happen weekly. Compliance will be defined
      based on the number of supplement packets that are consumed per week. To assure that the
      mothers are compliant in using the supplement, they will be asked to return the empty
      supplement packages at the end of the week. Optimal compliance will be defined as consumption
      of at least 50% of the weekly samples. Supplements will be provided in plastic or paper bags
      with a clearly labelled household ID (identity number). Compliance and dose response to
      compliance will be reviewed in existing studies to determine minimum compliance required.
    

Intervention name(s): Macro-micronutrient complementary food supplement; A micronutrient powder; Nutrition education
Intervention type(s): Dietary Supplement; Dietary Supplement; Behavioral
Intervention description(s): This intervention provided a 15 g complementary food supplement called KokoPlus with nutrition education; This intervention provided a 1 g micronutrient powder with nutrition education; This intervention provided nutrition education sessions
Intervention MeSH terms: Micronutrients; Trace Elements
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study has three intervention arms and one cross sectional growth monitoring follow up group.
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Complementary food supplement; Protein quality and linear growth; Intervention targeting complementary foods and growth