Vitamin A Status and Risk of Excessive Vitamin A Intake Among Urban Filipino Children (GloVitAS-P)

Vitamin A Status and Risk of Excessive Vitamin A Intake Among Urban Filipino Children Exposed to Multiple Vitamin A Intervention Programs

The goal of this study is to assess whether children 12-18 months of age who are exposed to multiple large-scale vitamin A programs, and who are likely to have vitamin A intakes above the tolerable upper intake level (UL), have higher total body vitamin A stores and biomarkers of excessive vitamin A status, compared to children 12-18 months of age who have adequate vitamin A intake.

Study Overview

• Status: Completed
• Conditions: Vitamin A Status
• Intervention / Treatment: Other: High VA intake, recent VAS; Other: High VA intake; Other: Low/adequate VA intake

Detailed Description

This is an observational study with 3 groups, which are identified using a screening tool to obtain information on exposure to vitamin A programs and consumption of vitamin A-rich foods and supplements. Children and their mothers are studied over the course of one month to determine 1) child total body vitamin A stores, using the 13C retinol isotope dilution method, 2) the child's vitamin A intake, using multiple dietary assessment methods, 3) total breast milk intake (among breastfeeding children), using the dose-to-mother deuterium dilution method, and 4) potential biomarkers of excessive vitamin A status, including markers of bone and liver health. Blood collection is structured in a "Super-Child" design, to construct plasma retinol kinetic curves. Other indicators related to vitamin A nutrition among children will be measured, in addition to the vitamin A intake and breast milk vitamin A concentration (for breastfeeding mothers) of the mother.

• Study Type: Observational
• Enrollment (Actual): 123

Contacts and Locations

Study Locations

• Philippines
  • National Capital Region
    • Mandaluyong, National Capital Region, Philippines
      • Block 37 Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children 12-18 months of age and their mothers in selected neighborhoods in the National Capital Region of the Philippines

Description

Inclusion Criteria:

• Children 12-18 months of age, and their mothers (18-49 years of age)
• Living in selected communities in the National Capital Region of the Philippines
• The mother and child must plan to stay in the study area for the duration of the study.
• Child's estimated vitamin A intake and exposure to vitamin A programs must meet eligibility criteria for one of three groups, based on a screening questionnaire administered by an interviewer to the child's mother.

Eligibility criteria for children in Group 1: 1) consumed MNP or a multi-vitamin preparation that contains vitamin A in the previous 7 days, 2) consumed at least one fortified staple food (oil or wheat flour) in the previous 7 days, 3) consumed breast milk or fortified milk in the past 24 hours, 4) received a high-dose VA capsule during the previous month, and 5) received a screening tool 'score' suggesting VA intake above 600 µg retinol/d.

Eligibility criteria for children in Group 2: will include children who: 1) consumed MNP or a multi-vitamin A preparation that contains vitamin A in the previous 7 days, 2) consumed at least one fortified staple food (oil or wheat flour) in the previous 7 days, 3) consumed breast milk or fortified milk in the past 24 hours, 4) received a high-dose VA capsule in the previous 3-6 months, and 5) received a screening tool 'score' suggesting VA intake above 600 µg retinol/d.

Eligibility criteria for children in Group 3: will include children who: 1) received a high dose VA capsule during the previous 3-6 months, and 2) received a screening tool 'score' suggesting VA intake 200-500 µg/d.

Exclusion Criteria:

• The child did not receive a high-dose VA capsule during the most recent national campaign
• The mother or child has chronic disease
• The child has moderate or severe anemia (Hb <10 g/dL)
• The mother or child has signs or symptoms of vitamin A deficiency (Bitot's spots, conjunctival xerosis, nightblindness)
• The child has weight for length < -2 z-scores of the median of the WHO growth standards
• The mother is breastfeeding more than one child

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1: High VA intake, recent VAS; Children who are exposed to multiple vitamin A (VA) programs, have received a high-dose VA supplement (VAS; 200,000 IU) in the past month, and are identified as being likely to have chronic excessive dietary VA intake	Other: High VA intake, recent VAS; Children who are exposed to multiple VA programs, have received a high-dose VA supplement (VAS; 200,000 IU) in the past month, and are identified as being likely to have chronic excessive dietary VA intake.
Group 2: High VA intake; Children who are exposed to multiple vitamin A (VA) programs, have received a high-dose VA supplement (200,000 IU) in the past 3-6 months, and are identified as being likely to have chronic excessive dietary VA intake.	Other: High VA intake; Children who are exposed to multiple VA programs, have received a high-dose VA supplement (200,000 IU) in the past 3-6 months, and are identified as being likely to have chronic excessive dietary VA intake.
Group 3: Low/adequate VA intake; Children who are not exposed to multiple vitamin A (VA) programs, have received a high-dose VA supplement in the past 3-6 months, and are identified as being likely to have chronic low to adequate dietary VA intake.	Other: Low/adequate VA intake; Children who are not exposed to multiple VA programs, have received a high-dose VA supplement in the past 3-6 months, and are identified as being likely to have chronic low to adequate dietary VA intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total body vitamin A stores among children 12-18 mo of age	Estimated using the 13C-retinol dilution method	28-day study period
Total dietary vitamin A intake among children 12-18 mo of age	Estimated using 24-hour dietary recalls, observed weighed food records, food and supplement frequency questionnaire, breast milk vitamin A concentration, and total breast milk intake (measured by the dose-to-mother deuterium dilution technique)	28-day study period
Total breast milk intake (among breastfeeding children 12-18 mo of age)	Estimating using the dose-to-mother deuterium dilution technique.	15-day study period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma or serum retinol among children 12-18 mo of age		28-day study period
Plasma or serum retinol-binding protein among children 12-18 mo of age		28-day study period
Ratio of retinol to retinol-binding protein among children 12-18 mo of age		28-day study period
Retinol metabolites among children 12-18 mo of age		28-day study period
Transthyretin among children 12-18 mo of age		28-day study period
Bone health markers among children 12-18 mo of age		28-day study period
Liver function markers among children 12-18 mo of age		28-day study period
Consumption of fortifiable foods among women	Estimated by combining data from 24-hour recalls, observed weighed food records, food frequency questionnaires, and the Fortification Assessment Coverage Tool	28 day study period
Consumption of fortifiable foods among children	Estimated by combining data from 24-hour recalls, observed weighed food records, food frequency questionnaires, and the Fortification Assessment Coverage Tool	28 day study period
Total vitamin A intake among women	Estimated using 24-hour dietary recalls and food frequency questionnaires	28-day study period
Breast milk vitamin A concentration among lactating women		28-day study period

Other Outcome Measures

Outcome Measure	Time Frame
Total food and nutrient intakes among women	28-day study period and 30 days prior to study period
Total food and nutrient intakes among children	28-day study period and 30 days prior to study period
Infant weight-for-length z score	At recruitment
Infant length-for-age z score	At recruitment
Systemic inflammation among children	28-day study period
Iron status among children	28-day study period
Zinc status among children	28-day study period
Hepatitis infection among children	28-day study period
Genetic markers related to vitamin A metabolism among children	28-day study period
Infant hemoglobin concentration	At enrollment
Infant morbidity symptoms	28-day study period and previous 7 days

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Bill and Melinda Gates Foundation; Penn State University; Newcastle University; Helen Keller International; International Atomic Energy Agency; Food and Nutrition Research Institute, Philippines; Global Alliance for Improved Nutrition
• Investigators: Study Director: Georg Lietz, Newcastle University

Publications and helpful links

General Publications

• Engle-Stone R, Miller JC, Reario MFD, Arnold CD, Stormer A, Lafuente E, Oxley A, Capanzana MV, Cabanilla CVD, Ford JL, Clark A, Velavan TP, Brown KH, Lietz G, Haskell MJ. Filipino Children with High Usual Vitamin A Intakes and Exposure to Multiple Sources of Vitamin A Have Elevated Total Body Stores of Vitamin A But Do Not Show Clear Evidence of Vitamin A Toxicity. Curr Dev Nutr. 2022 Jul 25;6(8):nzac115. doi: 10.1093/cdn/nzac115. eCollection 2022 Aug.
• Oxley A, Engle-Stone R, Miller JC, Reario MFD, Stormer A, Capanzana MV, Cabanilla CVD, Haskell MJ, Lietz G. Determination of Vitamin A Total Body Stores in Children from Dried Serum Spots: Application in a Low- and Middle-Income Country Community Setting. J Nutr. 2021 May 11;151(5):1341-1346. doi: 10.1093/jn/nxaa446.
• Ford JL, Green JB, Haskell MJ, Ahmad SM, Mazariegos Cordero DI, Oxley A, Engle-Stone R, Lietz G, Green MH. Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries. J Nutr. 2020 Feb 1;150(2):411-418. doi: 10.1093/jn/nxz225.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: January 17, 2017
• First Submitted That Met QC Criteria: January 20, 2017
• First Posted (Estimate): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: infant; Vitamin A status; dietary assessment; retinol isotope dilution; breast milk intake
• Other Study ID Numbers: 903681; OPP1115464 (Other Grant/Funding Number: Other)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: To be determined.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No