The Effects of Biscuits Containing Red Palm Oil on School Children With Vitamin A Deficiency in West and East Malaysia

Study Overview
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Brief Summary
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Based on recent nutrition survey (SEANUTS Malaysia) on a total of 3542 Malaysian Children aged between 6 months to 12 years old, 4.4% of the children had vitamin A deficiency. Rural areas recorded a higher prevalence of vitamin A deficiency (6.4%) compared with urban areas (3.8%). Besides, prevalence of iron deficiency due to low ferritin concentrations is 4.4% and anaemia based on low haemoglobin concentrations is 6.6%. It is proposed that a red palm oil intervention programme to be conducted in alliance with RMT in Malaysia to enhance the Vitamin A status of school children in underprivileged community in Malaysia.

Detailed Description
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Deficiency of vitamin A or retinol is a public health problem and listed as the most widespread nutritional deficiency worldwide (Sommer, 1995). According to the World Health Organization (WHO), about 190 million preschool children in underdeveloped countries especially in the region of Africa and South-East Asia are vitamin A deficient (2011, 2011). Infants and children have higher vitamin A requirements to promote rapid growth and better immunity to combat infections. Vitamin A deficiency in children causes visual impairment and blindness, risk of infection, stunting, anemia, respiratory diseases and mortality due to common childhood infections such as diarrhea and measles. On the basis on Cochrane meta-analysis on 194,795 children, vitamin A supplementation could reduce childhood mortality by 23% and incidences of illnesses (Imdad et al., 2010). According to WHO, an estimated 2.8 million preschool-age children are at risk of nutritional blindness or active xerophthalmia due to Vitamin A deficiency in low-income countries (Organization, 2010). Sadly, approximately 250 000 to 500 000 children suffering from vitamin A deficiency become blind yearly, and half of the number die within a year of losing their vision (Organization, 2010). The different eye signs of vitamin A deficiency (VAD) in children as graded by the WHO are night blindness, conjunctival xerosis, Bitot's spots, corneal xerosis, corneal ulcer/keratomalacia and corneal scarring (Sommer, 1995). Severe vitamin A deficiency distresses ocular tissue by reducing regeneration of visual pigment upon exposure to bright light or lasting damage on the epithelium of the cornea and conjunctiva. Classical ocular manifestation due to vitamin A deficiency may lead to less serious Bitot's spots and night blindness, or severe xerophthalmia and keratomalacia leading to blindness (Scrimshaw, 2000). Ocular manifestation of vitamin A deficiency still exists in underprivileged communities in Malaysia (Ngah et al., 2002). Vitamin A deficiency is prevalent in pre-school and primary school children of aborigines (Orang Asli) and those from rubber estates. 82.2% of Orang Asli children had ocular manifestations of vitamin A deficiency ranging from history of night blindness to corneal scars (Ngah et al., 2002). Based on recent nutrition survey (SEANUTS Malaysia) on a total of 3542 Malaysian Children aged between 6 months to 12 years old, 4.4% of the children had vitamin A deficiency. Rural areas recorded a higher prevalence of vitamin A deficiency (6.4%) compared with urban areas (3.8%) (Poh et al., 2013). There is significant association between iron deficiency and vitamin A deficiency represented by low serum retinol (Al-Mekhlafi et al., 2013). According to WHO, iron deficiency is the commonest and widespread nutritional deficiency in the world. Over 30% of the world's population are known to be anaemic due to iron deficiency, poor diet, or exposed to infectious diseases. Malaria, HIV/AIDS, hookworm infestation, schistosomiasis, and other infections such as tuberculosis are particularly important factors contributing to the high prevalence of anaemia in some areas. Iron deficiency may lead to impaired health, development and learning in children. Based on Malaysian SEANUTS survey, the overall prevalence of iron deficiency due to low ferritin concentrations is 4.4% and anaemia based on low haemoglobin concentrations is 6.6% (Poh et al., 2013). The occurrence of anaemia and iron deficiency among Orang Asli children is relatively high. The Orang Asli children aged 2-15 years old, living in eight villages in Selangor showed high episodes of anaemia 41.5% and 36.5% had iron deficiency anaemia. In another recent study, nearly half (48.5%) of the Orang Asli children from 18 villages in Pahang were found to be anaemic and the prevalence of iron deficiency was 34% (Al-Mekhlafi et al., 2013). In Malaysia, the school-feeding program is called Rancangan Makanan Tambahan (RMT) which literally means additional food plan. The RMT program is provided only to primary school children (aged 6 - 12 years) from poor families. It is not meant to replace food served at home, but to provide extra nourishment for children from poor families. The RMT program is managed by the School Division of the Ministry of Education, Malaysia. Food is served during recess time (10.30 a.m. for morning session, and 3.30pm for afternoon session) and provides 1/4 to 1/3 of daily requirements. It is proposed that a red palm oil intervention programme to be conducted in alliance with RMT in Malaysia to enhance the Vitamin A status of school children in underprivileged community in Malaysia.

Official Title
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The Effect of Biscuits Containing Red Palm Oil on School Children With Vitamin A Deficiency in West and East Malaysia

Conditions
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Vitamin A Deficiency in Children

Intervention / Treatment
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* Dietary Supplement: red palm shortening group
* Dietary Supplement: palm shortening group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 7-11 years old Vitamin A deficient children defined as concentration of serum retinol <0.70 µmol/L and suspected vitamin A deficiency defined as concentration of serum retinol 0.70 - 1.04 µmol/L. Not physically handicapped Exclusion Criteria: - Children with malaria, oedema including severe acute malnutrition, nephritic syndrome, or gastrointestinal disorders Children allergic to wheat- and/or gluten-containing foods Children who are studying Primary Six

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In this study, the subjects will be randomly assigned to two groups: a group receiving biscuits with red palm oil and a control group receiving biscuits with palm shortening with corresponding fatty acids.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: red palm shortening group<br>A group receiving the supplementation of red palm shortening biscuits. The subjects are expected to receive 630 µg RE of vitamin A/day by consuming the biscuits four days a week. | Dietary Supplement: red palm shortening group<br>* Biscuits made of red palm shortening will be distributed to the subjects given four days a week on schooling days for a duration of 6 months. The biscuits for each subject will contain  200 kcal with 10 g of red palm shortening/day (630 µg RE/day). This biscuit would be given four days a week on schooling days for a duration of 6 months. On average in a week, subject is expected to receive 630 µg RE of vitamin A/day. This would fulfill  70% of the RNI of vitamin A for children aged 7-11 years old.<br>|
| Placebo Comparator: palm shortening group<br>A group receiving supplementation of palm shortening biscuits with corresponding fatty acids as red palm shortening group. | Dietary Supplement: palm shortening group<br>* Biscuits made of palm shortening (control group) will be distributed to the subjects given four days a week on schooling days for a duration of 6 months. The palm shortening biscuits contain corresponding fatty acids as red palm shortening group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinol level | Vitamin A deficiency is defined as concentration of serum retinol <0.70 µmol/L and suspected vitamin A deficiency is defined as concentration of serum retinol 0.70 - 1.04 µmol/L. | During screening, after 6 months of dietary intervention period and post 200 days after the intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum beta carotene, alpha carotene, vitamin E levels | Serum beta carotene, alpha carotene, vitamin E levels are lower in Vitamin A deficiency kids | During screening, after 6 months of dietary intervention period and post 200 days after the intervention. | 
| Retinol binding protein levels | Retinol is transported in a 1-to-1 complex with retinol-binding protein. The cutoff od equimolar RBP is able to predict vitamin A deficiency | During screening, after 6 months of dietary intervention period and post 200 days after the intervention. | 
| Hemoglobin and ferritin level | vitamin A is essential for normal haematopoiesis. The occurrence of anaemia is indicated by haemoglobin concentration lower than 115 g/L. The occurrence of iron deficiency is indicated by the serum ferritin concentration lower than 15 μg/L. | During screening, after 6 months of dietary intervention period and post 200 days after the intervention. | 
| Ocular signs | Eyes examined at optimal light for conjuctival xerosis, Bitot's spots, corneal xerosis, and corneal ulceration or keratomalacia. The eye assessments include visual acuity assessment via a Snellen chart, examination with a portable slit lamp for signs of xerophthalmia, fundus photography with portable non mydriatic camera and questionnaire on night blindness symptoms. | During screening, after 6 months of dietary intervention period and post 200 days after the intervention. | 
| Inflammatory/infection status | high sensitivity C-reactive protein (hsCRP), fibrinogen, haematology tests | During screening, after 6 months of dietary intervention period and post 200 days after the intervention. | 
| Gut Microbiota | As malnutrition is generally associated with the changes in gut microbiota [14], it is important to study the effects of red palm oil-fortified biscuit supplementation to gut microbiota of VAD children. | at the baseline, 3 months after intervention, after 6-months intervention. | 
| Soil-transmitted helminths | Malnutrition can weaken immune responses and increase the susceptibility to bacterial and parasitic infections. Therefore, the supplementation of vitamin A to VAD children has the potential to boost their immunity against bacterial and parasitic infections. | at the baseline, 3 months after intervention, after 6-months intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin A Deficiency, Iron Deficiency, Parasite, Gut Microbiota, Red palm oil