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

NCT ID: NCT06100146

Last Updated: 2023-12-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 474 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-06
• Study Completion Date: 2025-12-31

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.

Detailed Description

Folic acid (FA) 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. Teenagers are the future mothers. Hence their health and nutritional status have long term consequences on future pregnancies and birth outcomes. Neural Tube Defects (NTDs) are a group of fatal or severely disabling birth defects known to be mainly a consequence of severe folate deficiency in early pregnancy. The policy of advising women to take iron & FA (IFA) supplements during pregnancy has not been successful in preventing NTDs because of the low adherence to antenatal care services including IFA, the large proportion of unplanned pregnancies, the timing at which IFA supplementation starts, and the logistical limitation that makes the access to IFA limited. The evidence is strong on the importance of food fortification in the promotion of maternal and child health mainly through reducing micronutrient deficiencies. A large segment of vulnerable populations in developing countries resides in rural settings and has limited access to fortified foods in the market. In such operational constraints, using locally fortified cereals could be an alternative intervention. However, there is a paucity of evidence regarding effectiveness of small-scale cereal-based fortification; in Ethiopia, the evidence is inexistent. Moreover, teenage girls are an under-studied group and do not constitute a target population from different nutritional intervention programs.

The overall objective of this study is 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 rural teenage girls (13-19 years of age).

This study will be conducted in Arba Minch Health and Demographic Surveillance Sites (AM-HDSS), Southern Ethiopia from October 2023 to April 2024. Effectiveness of intake of folic acid and vitamin B12 fortified meals will be evaluated in a randomized, double-blind controlled trial among 474 teenage girls between 13 and 19 years of age who are residing in and attending one of the schools at AM-HDSS.

Data on the following variables, except for demographic characteristics of teenage girls and their respective parents and/or household heads will be collected at the start and end point of the 6 months intervention. Data collection will be carried out at schools and at respective girls' home.

• Demographic characteristics of the teenage girls, morbidity status, helminthic infections, dietary intake, anthropometry, puberty status, presence of depressive symptoms, biochemical samples and cognitive development will be assessed in teenage girls directly at schools.
• Socio-demographic characteristics of the parents or the head of the household if different from parents, family wealth status, food security, health care services and environmental characteristics will be collected in recruited teenage girls' households within the one week following the enrolment and at the end of the intervention.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Control group

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

Group Type: PLACEBO_COMPARATOR

Unfortified cereal flour

Intervention Type: 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.

folic acid & vit B12 fortified flour

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.

Group Type: EXPERIMENTAL

Folic acid and vitamin B12 fortified flour

Intervention Type: 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.

Interventions

Folic acid and vitamin B12 fortified flour

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.

Intervention Type: DIETARY_SUPPLEMENT

Unfortified cereal flour

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.

Intervention Type: OTHER

Other Intervention Names

Intervention group; Control group

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Arba Minch University

OTHER

Sponsor Role: collaborator

Institut de Recherche en Sciences de la Sante, Burkina Faso

OTHER_GOV

Sponsor Role: collaborator

Addis Ababa University

OTHER

Sponsor Role: collaborator

University Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefaan De Henauw, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Locations

Arba Minch Health and Demographic Surveillance System sites

Arba Minch, , Ethiopia

Site Status: RECRUITING

Arba Minch University

Arba Minch, , Ethiopia

Site Status: NOT_YET_RECRUITING

Countries

Ethiopia

Central Contacts

Souheila Abbeddou, MSc, PHD

Role: CONTACT

Phone: +32467630892

Email: Souheila.Abbeddou@UGent.be

Eshetu Tariku, MPH

Role: CONTACT

Phone: +251917835302

Email: eshetuzerihun.tariku@ugent.be

Facility Contacts

Eshetu Zerihun Tariku

Role: primary

Eshetu Tariku Zerihun, MPH

Role: primary

Muluken Bekele Sorrie, MPH

Role: backup

References

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.

Reference Type: BACKGROUND

PMID: 33083093 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35942520 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23848243 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31257574 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25898711 (View on PubMed)

Other Identifiers

ONZ-2023-0137-C

Identifier Type: -

Identifier Source: org_study_id