Anemia
Conditions
Keywords
anemia, iron supplementation, sub-clinical inflammation, adolescents
Brief summary
Anemia and vitamin A deficiency (VAD) are major nutritional problems in the world and also in Myanmar. Both nutrient deficiencies result from interaction of several causal factors, and a better understanding of the etiology to interpret the prevalence and to formulate appropriate measures to reduce these deficiencies is necessary. There is a growing concern on the role of sub-clinical inflammation on the nutritional status indicators during the nutritional status assessment. However, there is lack of information on the role of inflammation on the iron supplementation. The adolescent period is a window of opportunity to improve the preconceptional iron status of the girls and recently gained much attention. The purpose of the study is to understand the role of inflammation on iron and vitamin A status during iron and vitamin A supplementation. The findings will show the extent to which iron supplementation has been hampered by inflammation and to formulate the necessary measures to overcome the interference.
Interventions
DIETARY_SUPPLEMENTIron group
Ferrous fumarate, 60 mg, weekly dose
DIETARY_SUPPLEMENTVitamin A group
Retinol, weekly dose, 15,000 IU
DIETARY_SUPPLEMENTIron and vitamin A group
Ferrous fumarate, Retinol combination group, weekly dose
DIETARY_SUPPLEMENTPlacebo group
folic acid only as placebo group
Sponsors
Department of Medical Research, Lower Myanmar
Indonesia University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 19 Years
Healthy volunteers
Yes
Inclusion criteria
* adolescent girls (age 12-19 years) * already experienced menarche * anemic girls (Hb\<120 g/L) * no known illness (apparently healthy) * free from haemoglobinopathy * No regular consumption of iron and vitamin A supplement during the last 3 months
Exclusion criteria
* subjects with chronic illness * subjects with severe anaemia * who do not give the consents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Haemoglobin Level | at week 0, week 6 and week12 | Haemoglobin level (g/L) measured by cyanmethaemoglobin method |
| Status of Tissue Iron Store | at week 0, week 6 and week12 | Tissue iron store was measured by serum ferritin |
| Status of Cellular Iron Deficiency | at week 0, week 6 and week12 | Cellular Iron deficiency status is also measured by serum transferrin receptor |
Countries
Burma
Participant flow
Recruitment details
Screening for the study subjects was conducted in July, 2010 among the adolescent schoolgirls in Nyaung Done Township, Irrawaddy Division. It included assessment of Hb status using the Coulter Counter. Information on the general characteristics and menarche status of the girls are obtained.
Pre-assignment details
Deworming with 400 mg Albendazole was done one week before the baseline data collection.
Participants by arm
| Arm | Count |
|---|---|
| Iron Group Iron group received 60 mg elemental iron, 2.5 mg folic acid with vitamin A placebo weekly | 98 |
| Vitamin A Group Vitamin A group received 15,000 IU Vitamin A + Iron placebo with 2.5 mg folic acid weekly | 102 |
| Iron and Vitamin A Group Iron and Vitamin A group received 60 mg elemental iron, 2.5 mg folic acid +15,000 IU Vitamin A weekly | 100 |
| Placebo Group Placebo group received iron placebo containing 2.5 mg folic acid weekly | 102 |
| Total | 402 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Resigned from schools | 4 | 1 | 1 | 4 |
Baseline characteristics
| Characteristic | Vitamin A Group | Iron and Vitamin A Group | Iron Group | Placebo Group | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 102 Participants | 100 Participants | 98 Participants | 102 Participants | 402 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 | 16.1 years STANDARD_DEVIATION 1.2 | 16.1 years STANDARD_DEVIATION 1.2 | 15.9 years STANDARD_DEVIATION 1.2 | 15.8 years STANDARD_DEVIATION 1.1 | 16.0 years STANDARD_DEVIATION 1.2 |
| Region of Enrollment Myanmar | 102 participants | 100 participants | 98 participants | 102 participants | 402 participants |
| Sex: Female, Male Female | 102 Participants | 100 Participants | 98 Participants | 102 Participants | 402 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 / 98 | 0 / 102 | 0 / 100 | 0 / 102 |
| serious Total, serious adverse events | 0 / 98 | 0 / 102 | 0 / 100 | 0 / 102 |
Outcome results
Primary
Haemoglobin Level
Haemoglobin level (g/L) measured by cyanmethaemoglobin method
Time frame: at week 0, week 6 and week12
Population: Per Protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Group | Haemoglobin Level | Hb week 0 (Baseline) | 88.3 g/L | Standard Deviation 11.2 |
| Iron Group | Haemoglobin Level | Hb week 12 (Endline) | 110.8 g/L | Standard Deviation 9.8 |
| Iron Group | Haemoglobin Level | Hb week 6 (Midline) | 98.1 g/L | Standard Deviation 10.6 |
| Vitamin A Group | Haemoglobin Level | Hb week 0 (Baseline) | 89.2 g/L | Standard Deviation 11.5 |
| Vitamin A Group | Haemoglobin Level | Hb week 12 (Endline) | 109.0 g/L | Standard Deviation 9.1 |
| Vitamin A Group | Haemoglobin Level | Hb week 6 (Midline) | 98.7 g/L | Standard Deviation 9.6 |
| Iron and Vitamin A Group | Haemoglobin Level | Hb week 6 (Midline) | 99.2 g/L | Standard Deviation 10 |
| Iron and Vitamin A Group | Haemoglobin Level | Hb week 0 (Baseline) | 88.4 g/L | Standard Deviation 12.1 |
| Iron and Vitamin A Group | Haemoglobin Level | Hb week 12 (Endline) | 111.4 g/L | Standard Deviation 9 |
| Placebo Group | Haemoglobin Level | Hb week 0 (Baseline) | 89.6 g/L | Standard Deviation 12.7 |
| Placebo Group | Haemoglobin Level | Hb week 12 (Endline) | 109.7 g/L | Standard Deviation 8.4 |
| Placebo Group | Haemoglobin Level | Hb week 6 (Midline) | 98.3 g/L | Standard Deviation 10.7 |
Comparison: Null Hypothesis~1. Haemoglobin level was not influenced by sub-clinical inflammation during iron supplementation in the anaemic adolescent school girls~2. Vitamin A does not improve the haemoglobin level of the anaemic schoolgirls during iron supplementation in the presence of inflammation.p-value: <0.05GLM for repeated measures
Primary
Status of Cellular Iron Deficiency
Cellular Iron deficiency status is also measured by serum transferrin receptor
Time frame: at week 0, week 6 and week12
Population: Per Protocol analysis
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Midline) | 6.69 mg/L | Standard Deviation 1.51 |
| Iron Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Endline) | 6.44 mg/L | Standard Deviation 1.55 |
| Iron Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Baseline) | 7.09 mg/L | Standard Deviation 1.52 |
| Vitamin A Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Endline) | 6.27 mg/L | Standard Deviation 1.44 |
| Vitamin A Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Midline) | 6.39 mg/L | Standard Deviation 1.41 |
| Vitamin A Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Baseline) | 6.56 mg/L | Standard Deviation 1.42 |
| Iron and Vitamin A Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Endline) | 6.24 mg/L | Standard Deviation 1.43 |
| Iron and Vitamin A Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Baseline) | 7.16 mg/L | Standard Deviation 1.59 |
| Iron and Vitamin A Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Midline) | 6.73 mg/L | Standard Deviation 1.53 |
| Placebo Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Baseline) | 6.74 mg/L | Standard Deviation 1.5 |
| Placebo Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Midline) | 6.59 mg/L | Standard Deviation 1.53 |
| Placebo Group | Status of Cellular Iron Deficiency | serum transferrin receptor (Endline) | 6.61 mg/L | Standard Deviation 1.54 |
Comparison: Null Hypothesis~1. iron status indicator (sTfR) was not influenced by sub-clinical inflammation during iron supplementation in the anaemic adolescent school girls~2. Vitamin A does not improve iron status indicator (sTfR) of the anaemic schoolgirls during iron supplementation in the presence of inflammation.p-value: <0.05GLM for repeated measures ANOVA
Primary
Status of Tissue Iron Store
Tissue iron store was measured by serum ferritin
Time frame: at week 0, week 6 and week12
Population: Per Protocol analysis
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Group | Status of Tissue Iron Store | serum ferritin (Baseline) | 32.1 µg/L | Standard Deviation 2.5 |
| Iron Group | Status of Tissue Iron Store | serum ferritin (Midline) | 34.5 µg/L | Standard Deviation 1.9 |
| Iron Group | Status of Tissue Iron Store | serum ferritin (Endline) | 39.6 µg/L | Standard Deviation 2.1 |
| Vitamin A Group | Status of Tissue Iron Store | serum ferritin (Baseline) | 34.4 µg/L | Standard Deviation 2.6 |
| Vitamin A Group | Status of Tissue Iron Store | serum ferritin (Endline) | 35.0 µg/L | Standard Deviation 2.5 |
| Vitamin A Group | Status of Tissue Iron Store | serum ferritin (Midline) | 32.1 µg/L | Standard Deviation 2.3 |
| Iron and Vitamin A Group | Status of Tissue Iron Store | serum ferritin (Endline) | 35.4 µg/L | Standard Deviation 2.4 |
| Iron and Vitamin A Group | Status of Tissue Iron Store | serum ferritin (Midline) | 32.3 µg/L | Standard Deviation 2.1 |
| Iron and Vitamin A Group | Status of Tissue Iron Store | serum ferritin (Baseline) | 25.9 µg/L | Standard Deviation 3.1 |
| Placebo Group | Status of Tissue Iron Store | serum ferritin (Endline) | 28.2 µg/L | Standard Deviation 2.5 |
| Placebo Group | Status of Tissue Iron Store | serum ferritin (Midline) | 26.5 µg/L | Standard Deviation 2.3 |
| Placebo Group | Status of Tissue Iron Store | serum ferritin (Baseline) | 31.1 µg/L | Standard Deviation 2.5 |
Comparison: Null hypothesis~1. Iron status indicator (serum ferritin) was not influenced by sub-clinical inflammation during iron supplementation in the anaemic adolescent school girls~2. Vitamin A does not improve the iron status indicator (serum ferritin) concentration of the anaemic schoolgirls during iron supplementation in the presence of inflammation.p-value: <0.05GLM for repeated measures ANOVA