Effectiveness of Fortification With Folic Acid and Vitamin B12 Among Teenage Girls

NCT06100146 | Completed

• 1 other identifier: ONZ-2023-0137-C
• Study Type: interventional
• Target: 472
• Locations: 1 country
• Sites: 2

Brief Summary

Folic acid and vitamin B12 play an interdependent role in key cellular processes, namely deoxyribonucleic acid synthesis, cell division, red blood cell formation, and nervous system myelination. A deficiency of either vitamin will predispose teenagers to many diseases, which persist across their lifespan. Fortification of food with micronutrients has been promoted to reduce micronutrient deficiencies. A large segment of vulnerable populations in low- and middle-income countries (LMICs) resides in rural settings and has limited access to large-scale commercialized fortified foods. In such operational constraints, the use of locally (small-scale) fortified cereals could be an alternative intervention. The study aims to evaluate the effectiveness of small scale folic acid and vitamin B12 fortified cereals in improving folate and vitamin B12 status, growth velocity, puberty status, anaemia, cognitive development and mental health among teenage girls, in rural rift valley of Ethiopia.

Conditions

Folate Deficiency; Vitamin B 12 Deficiency; Anemia, Megaloblastic; Cognitive Development; Depressive Symptoms

Keywords

Small scale fortification; Folic acid; Vitamin B12; Anemia; Cognitive development; Teenage girls

Outcome Measures

Primary Outcomes (8)

• Serum folic acid concentrations

  Serum folate levels ng/ml (nmol/l)

  Assessed at 6 months

• Erythrocyte (RBC) folic acid concentrations

  RBC folate level ng/ml (nmol/l)

  Assessed at 6 months

• General cognitive ability

  Raven Progressive Matrices (RPM) tests, a measure of nonverbal intelligence.

  Assessed at 6 months

• Working memory

  Digit Span (Forward, Backward, and Sequencing) is a standardized test that assesses the working memory of participants.

  Assessed at 6 months

• Depression

  Depressive symptoms will be assessed by Patient Health Questionnaire (PHQ) 9 modified for adolescents (PHQ-9A), a self-report instrument comprised of 9-items. Items are rated on a four-point ordinal scale.

  Assessed at 6 months

• Serum vitamin B12 concentrations

  Serum vitamin B12 level (pmol/L)

  Assessed at 6 months

• Fat-free mass

  An index of adiposity will be measured to evaluate girls' body composition, in %

  Assessed at 6 months

• Fat mass

  An index of adiposity will be measured to evaluate girls' body composition, in kg

  Assessed at 6 months

Secondary Outcomes (9)

• RBC structure (megaloblastic anaemia)

  Assessed at 6 months

• Plasma homocysteine concentrations

  Assessed at 6 months

• Weight

  Assessed at 3 and 6 months

• Adherence to the intervention/fortification

  Assessed weekly for the whole period of intervention (until 6 months)

• Haemoglobin concentration

  Assessed at 6 months

Study Arms (2)

Control group

PLACEBO COMPARATOR

Teenage girls randomly assigned to the control group will receive a standard bag of unfortified cereal flours every week for six months.

Other: Unfortified cereal flour

folic acid & vit B12 fortified flour

EXPERIMENTAL

Teenage girls randomly assigned to the control group will receive a standard bag of cereal flours fortified with folic acid and Vit B12 every week for six months.

Dietary Supplement: Folic acid and vitamin B12 fortified flour

Interventions

Folic acid and vitamin B12 fortified flour DIETARY_SUPPLEMENT

Standard bags of fortified cereal-based flours will be prepared at local mills from the common staple cereal food in the area. The dose of vitamins will be added to the flour of the intervention group and mixed with batch mixing technique. The concentration of folic acid and vitamin B12 per 1kg of flour will be 2mg and 0.02mg, respectively. Participants will be supplied with 6 kg bags of flour, which will be enough for 30 days, and 1.5kg bags of flour will be delivered to their home on a weekly basis and lasting for 6 months. Instructions on the preparation of meals and frequency of intake with a weekly compliance sheet will be provided for monitoring the intervention.

Also known as: Intervention group

folic acid & vit B12 fortified flour

Unfortified cereal flour OTHER

Standard bags of unfortified cereal-based flours will be prepared at local mills from the common staple cereal food in the area. Participants will be supplied with 6 kg bags of flour, which will be enough for 30 days, and 1.5kg bags of flour will be delivered to their home on a weekly basis and lasting for 6 months. Instructions on the preparation of meals and frequency of intake with a weekly compliance sheet will be provided for monitoring the intervention.

Also known as: Control group

Control group

Eligibility Criteria

• Age: 13 Years - 19 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Teenage girls between 13 and 19 years of age who live in households at Arba Minch Health and Demographic Surveillance Sites (AM-HDSS) are eligible to participate in the study if:
• One or both of their parents signed an informed consent form and the girl's agreement.
• Their parents and the girl planned to stay in the study area during the period of the study (minimum 6 months) in the kebele.
• Both parents and girls accept the intervention packages including blood draws and home visits.

You may not qualify if:

• Chronically ill girls diagnosed with diabetes and asthma;
• Severely undernourished girls (defined as body mass index z score \< -3 standard deviations of the median World Health Organization reference population);
• Severely anaemic girls (Hb concentration \<80g/L);
• Teenage girls who are pregnant, lactating or taking IFA/B12 supplements;
• Diagnosed hemoglobinopathy (sickle cell or thalassemia);
• Diagnosed liver diseases like acute hepatitis, cirrhosis, hepatocellular carcinoma, and metastatic liver disease

Sponsors & Collaborators

• Addis Ababa University: collaborator
• University Ghent: lead
• Arba Minch University: collaborator
• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator

Study Sites (2)

Arba Minch Health and Demographic Surveillance System sites

Arba Minch, 21, Ethiopia

Location

Arba Minch University

Arba Minch, Ethiopia

Location

Related Publications (5)

• Oumer M, Taye M, Aragie H, Tazebew A. Prevalence of Spina Bifida among Newborns in Africa: A Systematic Review and Meta-Analysis. Scientifica (Cairo). 2020 Oct 6;2020:4273510. doi: 10.1155/2020/4273510. eCollection 2020.

  PMID: 33083093 BACKGROUND

• Wald NJ. Postscript to 'Folic acid and neural tube defects: Discovery, debate and the need for policy change'. J Med Screen. 2022 Sep;29(3):147. doi: 10.1177/09691413221117464. Epub 2022 Aug 8. No abstract available.

  PMID: 35942520 BACKGROUND

• Ardila A. Development of metacognitive and emotional executive functions in children. Appl Neuropsychol Child. 2013;2(2):82-7. doi: 10.1080/21622965.2013.748388. Epub 2013 Jan 28.

  PMID: 23848243 BACKGROUND

• Centeno Tablante E, Pachon H, Guetterman HM, Finkelstein JL. Fortification of wheat and maize flour with folic acid for population health outcomes. Cochrane Database Syst Rev. 2019 Jul 1;7(7):CD012150. doi: 10.1002/14651858.CD012150.pub2.

  PMID: 31257574 BACKGROUND

• Mildon A, Klaas N, O'Leary M, Yiannakis M. Can fortification be implemented in rural African communities where micronutrient deficiencies are greatest? Lessons from projects in Malawi, Tanzania, and Senegal. Food Nutr Bull. 2015 Mar;36(1):3-13. doi: 10.1177/156482651503600101.

  PMID: 25898711 BACKGROUND

MeSH Terms

Conditions

Folic Acid Deficiency; Vitamin B 12 Deficiency; Anemia, Megaloblastic; Depression; Anemia

Interventions

Folic Acid; Control Groups

Condition Hierarchy (Ancestors)

Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Anemia, Macrocytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Stefaan De Henauw, MD,PHD

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Flours will be indistinguishable in appearance except for the vitamins added to the flours of the intervention group. An independent trained person will be assigned to monitor the fortification process and the two products will be packed immediately and coded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In randomized control trial, eligible teenage girls attending one of the schools in AM-HDSS will be randomly assigned to: 1. An intervention group receiving a standard bag of cereal flours fortified with folic acid and Vitamin B12 at local mills every week for six months. 2. A placebo group receiving a standard bag of unfortified cereal flours every week for six months. Participants in all the treatment groups remain eligible to benefit from the standard health care and nutrition programs provided at school, such as deworming at the beginning of the school year.

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 25, 2023
• Study Start: September 6, 2023
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ET (2)