Effects of Multiple-micronutrients Supplementation on Growth and Iron Status of Indigenous Children in Malaysia
Condition: Underweight; Stunted Growth; Wasting; Anemia
MeSH terms: Thinness; Growth Disorders
Study type: Interventional

Summary: 
      Child undernutrition is largely attributed to inadequate nutrition including micronutrient
      deficiency. Undernutrition is prevalent among indigenous children as compared to the general
      population. This cluster randomized controlled trial aimed to determine the effect of
      multiple-micronutrients supplement (MMS) on growth and iron status of Orang Asli (indigenous
      group in Peninsular Malaysia) young children (6 to 24 months) in Selangor. MMS is a blend of
      15 micronutrients in powder form that can be used for home fortification of foods for young
      children. A total of 98 children recruited in this study with 49 children randomly assigned
      for each intervention (IG) and control group (CG). At baseline, all children were normal in
      weight-for-age (WAZ>-2SD), length-for-age (LAZ>-2SD), weight-for-length (WLZ>-2SD) and blood
      haemoglobin (>11g/dL). IG was supplemented with three sachets of MMS each week i.e. every
      other day for 12 months and received health and nutrition advice. CG only received health and
      nutrition advice. Both groups were assessed for body weight, length and dietary intake at
      baseline, month 3, 6, 9, 12 of intervention, and 3 months post intervention. Blood
      haemoglobin was assessed at baseline, month-12 of intervention and 3 months post
      intervention. Compliance to MMS was measured in IG. The primary outcomes were weight, length,
      WAZ, LAZ, WLZ and haemoglobin, while the secondary outcome was dietary intake. The
      independence sample t-test and the chi-square test were used to determine the difference in
      the baseline variables between the groups. ANOVA using General Linear Model (GLM) for
      repeated measures was performed to determine the difference in the growth measures z scores,
      haemoglobin, energy, nutrients and food group within and between the groups over the period
      of the study. Per protocol analysis was performed. This study hypothesized that there were
      significant differences in the changes (before and after MMS intervention) related to growth
      [(weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ)]; iron status
      (haemoglobin concentration); and dietary intake (energy, nutrients and food group intakes)
      between intervention and control groups.
    

Detailed description: 
      1. Study Objectives This study was undertaken to determine the effect of Multiple
           micronutrients supplement (MMS) on the nutritional status of Orang Asli (indigenous
           people in Peninsular Malaysia) children (6 to 24 months) in Selangor. This study
           assessed growth (weight, length, WAZ, LAZ, WLZ) and iron status (haemoglobin
           concentration) of children as primary outcomes, while the secondary outcome included
           dietary intake (energy, nutrients and food groups) of children.

        2. Study Location This study was conducted in Orang Asli (OA) communities in Selangor,
           Peninsular Malaysia. The specific communities were identified with the assistance of
           Department of Orang Asli Development Selangor (JAKOA). The majority of residents are
           Temuan (78%), followed by Mah Meri (15%), Semai (2%) and mixed (5%). This study included
           only the Temuan tribe as study population.

        3. Study Design This was a cluster randomized controlled trial. Villages as clusters were
           randomly allocated into either intervention or control group. All households in each
           cluster were included in the trial.

        4. Sample Size A formula for mean difference between two groups was used for sample size
           calculation. The sample size was calculated to have 80% chance of detecting a mean
           difference in length of 0.56 cm or more with an estimated standard deviation of 0.31. An
           additional 50% was applied to the calculation of sample size to account for withdrawal
           and non-compliance. Hence, the total number of respondents per group was 49.

        5. Sampling Procedure There were 74 OA clusters (villages) in Selangor. Screening of
           clusters were conducted according to inclusion and exclusion criteria of clusters. Upon
           screening, 17 non-Temuan clusters and 6 Temuan clusters were excluded from this study.
           Temuan cluster is defined as having at least 80% of the households in the village are of
           Temuan ethnicity. The remaining 51 Temuan clusters were then randomly assigned either to
           the intervention or control group by considering the distance and geographical locality
           of the clusters. A total of 22 clusters were randomly allocated to the intervention
           group, while 29 clusters randomly allocated to the control group. There were 7 small
           clusters in the control group which grouped into 2 clusters as the small clusters have a
           small number of young children.

           Screening assessment of children then were conducted in clusters (that obtained consent
           from head of villages) based on the lists of children aged between 6 to 24 months given
           by the head of villages. All listed children were screened according to inclusion and
           exclusion criteria of children. Upon screening, 68 children in four clusters of
           intervention group, and 102 children in seven clusters of control group were excluded as
           not meeting the inclusion criteria of children. Based on the screening assessment, the
           total number of children recruited initially was 98 children, with 49 children in each
           of the two groups.

        6. Selection of Clusters (Villages) and Children Approval by JAKOA was obtained prior to
           the selection of clusters (villages). OA villages were visited by investigator and a
           research assistant to conduct the selection of clusters based on inclusion and exclusion
           criteria. Head of villages were interviewed to obtain information on majority of
           households' ethnicity and availability of child/children aged between 6 to 24 months.
           For Temuan cluster that has at least one child aged between 6 to 24 months old, the head
           of villages were given an invitation letter, letter of study approval by JAKOA and
           information of the study. The head of villages were briefed about the purpose, benefits
           and potential risks of the study to the children. They were given the opportunity to ask
           for further details if they were not clear about the given explanation. Consent from the
           head of villages were obtained after the briefing. List of households with children aged
           between 6 to 24 months was then given to the investigator by the head of villages for
           the selection of children.

        7. Treatments The intervention group was supplemented with three sachets of MMS in powder
           form each week for every other day for a period of 12 months. Each sachet containing 1 g
           consisting of ten vitamins and five minerals. The amount of each micronutrient provided
           by MMS was mostly ≥ 42% of the Malaysian Recommended Nutrient Intake, (RNI). This was
           adequate to meet the daily nutrient requirement of children in addition to nutrients
           provided by daily complementary foods. The MMS was manufactured by DSM Singapore
           Industrial Pte. Ltd. It was in powder form and to be sprinkled over a cooked meal or
           dissolved in a drink for the child. The intervention group was visited weekly in first 2
           months and two-weekly in the following months to distribute and monitor the
           supplementation of MMS. Written instruction for using and storing the MMS in simple
           language with visuals was given prior to the supplementation. The intervention group
           also received health and nutrition advice delivered by investigator at 3, 6 and 9 months
           after supplementation begins. The control group received health and nutrition advice
           that were similar to intervention group and delivered at 3, 6 and 9 months after the
           study began.

        8. Measurements 8.1 Demographic and Socioeconomic Information Demographic and socioeconomic
           information were obtained through face-to-face interview with parents/ caregivers using
           a pre-tested questionnaire and assistance from a local translator. Age of children was
           calculated from childbirth date that obtained from birth certificate or child health
           record. Data were collected prior to the intervention as baseline data.

           8.2 Anthropometry Birth weight and length of children were obtained from child health
           record. Body weight and length of children were measured at baseline, 3, 6, 9, 12 and 15
           months after supplementation begins. Weight and length of children were measured using
           Tanita Digital Weighing Scale HD 325 (to the nearest 0.1 kg) and Recumbent Measuring
           Board (to the nearest 0.1cm), respectively using standard procedures. All measurements
           were taken twice, and the average value were used as final data. Age, weight and length
           of the children were translated into three indices of weight-for-age, length-for-age and
           weight-for-length. WHO Anthro program version 3.2.2 was used to estimate the Z scores
           for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ). Z score was
           used to distinguish between normal and underweight (WAZ <-2), stunted (LAZ <-2) and
           wasted (WLZ <-2) children according to WHO classifications.

           8.3 Haemoglobin Haemoglobin level was assessed using finger-prick blood method. A staff
           nurse conducted the assessment using a portable HemoCue®201+ Analyzer. Haemoglobin
           assessment was performed at baseline, 12 and 15 months of study.

           8.4 Dietary Intake Dietary intake was assessed using a standard 24-hour diet recall
           questionnaire at baseline, 3, 6, 9, 12 and 15 months. This assessment involved
           face-to-face interview with parents/ caregivers to obtain information on time, types and
           amount of foods and beverages consumed by children during the 24 hours prior to the
           interview. Household measurements (e.g. cups, teaspoons, plates, bowls) were used to
           assist parents/ caregivers in estimation of portion sizes of consumed foods and
           beverages. Dietary intake data was analysed using a computerized dietary analysis
           program, Nutritionist Pro. The USDA Food Database was used in this software for dietary
           analysis.

           8.5 Child Vaccination, Infection and Household Sanitation and Hygiene History of child
           vaccination, infection and household sanitation and hygiene were assessed using a
           standard questionnaire at 12 months of study (end of the intervention). History of child
           vaccination was obtained from child health record. Assessments of child infection
           history involved face-to-face interview with parents/ caregivers to obtain information
           on common infections in children in the preceding two weeks. Interview with parents/
           caregivers were conducted as well to obtain information on household sanitation and
           hygiene.

           8.6 Compliance to MMS Every week, parents/ caregivers in intervention group were given a
           pack which contains 3 sachets of MMS to be taken by their children in a week. After a
           week, the parents/ caregivers were required to return the empty sachets (including
           unused or half used) to the investigator. Compliance to MMS was measured by dividing the
           total number of empty sachets with a total number of distributed sachets for the 3, 6, 9
           and 12-months periods.

           8.7 Adverse effect of MMS Any adverse effect was assessed during a weekly visit. The
           information was obtained through a weekly face-to-face interview with the parents/
           caregivers.

        9. Study Withdrawal Children who withdrew the study were visited several times and attempts
           were made to persuade the parents/ caregivers to continue with the study. Withdrawals
           were recorded in Case Report Form to determine percentage of the participants who
           withdrew for reasons related to the intervention or those who missed at random.

       10. Ethics Approval and Funding The study protocol was approved by the Ethics Committee for
           Research Involving Human Subjects (JKEUPM) of Universiti Putra Malaysia. Permission to
           conduct the study in Orang Asli communities was obtained from the Department of Orang
           Asli Development (JAKOA). Written informed consent was obtained from parents /caregivers
           who agree to participate in the study. This study was funded by a research grant from
           Universiti Putra Malaysia (GP-IPS/2016/9514200).

       11. Data Analysis Data were analyzed using 'Statistical Package for Social Sciences'
           programme for Windows version 22.0. Categorical data were described using count and
           percentage. All numerical data were tested for normality of distribution and were
           presented as mean and standard deviation. Non-parametric tests were used whenever the
           assumptions of normality and/ or homogeneity of variances were not met. Logarithmic
           conversion was performed for data not normally distributed. Per protocol analysis was
           performed, and children who withdrew from the study, noncompliant, and has missing
           outcomes were excluded from analysis.

      The independence sample t-test was used to determine the difference in the mean of continuous
      variables between the intervention and control groups, while for categorical variables the
      Pearson's chi-square test was used. Paired t-test was conducted to assess changes in outcomes
      variables within each group (intervention and control) between baseline and 12 months as well
      as 15 months follow-up. ANCOVA using General Linear Model for repeated measures was performed
      to determine the effects of intervention between the groups on main and specific outcomes.
      Demographic and socioeconomic characteristics of both groups such as gender of children, age
      of children at selected time points, education of mothers and baseline measures were
      controlled in the analysis. Differences between groups were considered statistically
      significant at p<0.05 using two-tailed tests.
    

Intervention name(s): Multiple-micronutrients supplement
Intervention type(s): Dietary Supplement
Intervention description(s): Multiple-micronutrients supplement with 15 micronutrients
Intervention MeSH terms: Micronutrients; Trace Elements
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: micronutrients supplementation; child underweight; stunted; wasted; anemia