Short Stature
Conditions
Keywords
Zinc, Growth, Child, Dietary Supplements, Randomized Controlled Trial
Brief summary
The purpose of this study is to measure the effect of weekly zinc supplementation on schoolchildren with growth deficit or normal stature.
Detailed description
Zinc is an important micronutrient for humans. Trials with zinc have shown positive effects of supplementation on growth, but there is still a lack of results on schoolchildren population. This Randomized Double-Blind Controlled Trial was design to measure the effect of weekly zinc supplementation on schoolchildren with growth deficit and normal stature. Schoolchildren were allocated into two homogeneous groups named Growth Deficit (HAZ \< -1,5 Z-score), and Normal Stature (HAZ between -1,0 and ±1,0 Z-score) and were randomly assigned to compose two exposed and two control groups to receive a supplement of 30mg of zinc amino acid chelate or placebo individually once a week, during 12 weeks. Children's heights were measured at the end of supplementation period and again after 12 weeks.
Interventions
DIETARY_SUPPLEMENTZinc amino acid chelate
During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
OTHERPlacebo
During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student.
Sponsors
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 10 Years
Healthy volunteers
Yes
Inclusion criteria
* Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD). For the Normal Stature group(NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex.
Exclusion criteria
* Children of GD group were evaluated by a Pediatrician specialized in growth disorders with the objective of excluding any organic or genetic condition correlated with growth deficit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period. | Height-for-Age Z-score was measured at the End of Supplementation period and again at the End of Follow-up period, with a 12 weeks interval. | Schoolchildren were allocated into two homogeneous groups named Growth Deficit (HAZ \< -1,5 Z-score), and Normal Height (HAZ between -1,0 and ±1,0 Z-score), and were randomly assigned to compose two exposed groups to receive a supplement of 30mg of zinc amino acid chelate, and two control groups to receive placebo individually once a week, during 12 weeks. Children's heights were measured at the End of Supplementation period and again after 12 weeks (Follow-up period). In combination with sex and age we transformed stature to Height-for-Age, expressed in Z-score, which was calculated as a number of standard deviations or Z-scores below or above the reference mean or median value, according to the formula below: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population. We analyzed and discussed the change in HAZ (HAZ at the End of Follow-up period - HAZ at End of Supplementation). |
Participant flow
Recruitment details
From original database of 2.519 children, enrolled in the first and second grades of four State-run public basic schools, we selected this study sample using height for age indicator (HAZ). Meetings were held at school with parents/guardians to explain the objective and procedures of the study in order to obtain a written consent.
Pre-assignment details
From original database (n=2.519), we selected children with one and a half or more standard deviations below the mean height for age (HAZ) and gender of the reference population as Growth Deficit group. For the Normal Height group, HAZ was define as between -1 and +1 standard deviations from the mean height reference for age and sex (n=218).
Participants by arm
| Arm | Count |
|---|---|
| Growth Deficit+Zinc Amino Acid Chelate Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD).
During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student. | 50 |
| Growth Deficit + Placebo Children with one and a half or more standard deviations below the mean height for age and gender of the reference population (Z-score under -1.6) were included in the Growth Deficit group (GD).
During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student. | 50 |
| Normal Height+Zinc Amino Acid Chelate For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex.
During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup containing zinc amino acid chelate at 3%, i.e. the equivalent to 30mg of elemental zinc per ml, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student. | 49 |
| Normal Height + Placebo For the Normal Stature group (NS), HAZ was set up as being between -1 and +1 standard deviations from the mean height reference for age and sex.
During twelve weeks, children received weekly 1ml of lemon flavor caramel syrup, disposed into an individual amber glass, containing 20ml of syrup. The supplement administration was made individually with 1ml BD Plastipak disposable syringe, directly into the child's mouth, by the principal investigator. The chosen supplementation day was Tuesday. Therefore, the following weekdays were reserved to supplement any absent student. | 50 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up Period | transference or evasion of school | 13 | 20 | 15 | 12 |
| Supplementation Period | Adverse Event | 2 | 0 | 1 | 0 |
| Supplementation Period | less than 12 weeks supplementation | 0 | 3 | 1 | 2 |
| Supplementation Period | refused to receive supplement | 1 | 0 | 1 | 0 |
| Supplementation Period | transference or evasion of school | 7 | 9 | 7 | 6 |
Baseline characteristics
| Characteristic | Growth Deficit + Placebo | Normal Height+Zinc Amino Acid Chelate | Growth Deficit+Zinc Amino Acid Chelate | Normal Height + Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 50 Participants | 49 Participants | 50 Participants | 50 Participants | 199 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 7.64 years STANDARD_DEVIATION 0.71 | 7.63 years STANDARD_DEVIATION 0.66 | 7.63 years STANDARD_DEVIATION 0.66 | 7.64 years STANDARD_DEVIATION 0.71 | 7.63 years STANDARD_DEVIATION 0.68 |
| Region of Enrollment Brazil | 50 participants | 49 participants | 50 participants | 50 participants | 199 participants |
| Sex: Female, Male Female | 25 Participants | 24 Participants | 25 Participants | 25 Participants | 99 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 25 Participants | 25 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 50 | 0 / 50 | 1 / 49 | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 | 0 / 49 | 0 / 50 |
Outcome results
Primary
Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period.
Schoolchildren were allocated into two homogeneous groups named Growth Deficit (HAZ \< -1,5 Z-score), and Normal Height (HAZ between -1,0 and ±1,0 Z-score), and were randomly assigned to compose two exposed groups to receive a supplement of 30mg of zinc amino acid chelate, and two control groups to receive placebo individually once a week, during 12 weeks. Children's heights were measured at the End of Supplementation period and again after 12 weeks (Follow-up period). In combination with sex and age we transformed stature to Height-for-Age, expressed in Z-score, which was calculated as a number of standard deviations or Z-scores below or above the reference mean or median value, according to the formula below: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population. We analyzed and discussed the change in HAZ (HAZ at the End of Follow-up period - HAZ at End of Supplementation).
Time frame: Height-for-Age Z-score was measured at the End of Supplementation period and again at the End of Follow-up period, with a 12 weeks interval.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Deficit+Zinc Amino Acid Chelate | Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period. | 0.04 Z-Score | Standard Deviation 0.12 |
| Growth Deficit + Placebo | Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period. | -0.08 Z-Score | Standard Deviation 0.45 |
| Normal Height+Zinc Amino Acid Chelate | Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period. | 0.10 Z-Score | Standard Deviation 0.15 |
| Normal Height + Placebo | Change in Height-for-Age Z-score (HAZ) From End of Supplementation to End of Follow-up Period. | 0.02 Z-Score | Standard Deviation 0.26 |
Comparison: Null Hypothesis: There isn't difference in the HAZ mean difference between children with Growth Deficit who received zinc amino acid or placebo.~We attributed α=0.05, β=0.20, and power=0.80.p-value: <0.05t-test, 2 sided
Comparison: Null Hypothesis: There isn't difference in the HAZ mean difference between children with Normal Height who received zinc amino acid or placebo.~We attributed α=0.05, β=0.20, and power=0.80.p-value: <0.05t-test, 2 sided