Vitamin A Supplementation at Birth and Atopy in Childhood

The Effect of Vitamin A Supplementation at Birth on the Development of Atopy in Childhood: Long-term Follow-up of a Randomised Placebo-controlled Trial

INTRODUCTION Eight trials studying the effect of providing neonatal vitamin A supplementation (NVAS) have been reported, and another four are underway to test whether NVAS should become WHO policy. Three of the four African trials were conducted by the Bandim Health Project (BHP) in Guinea-Bissau. One of them was a two-by-two factorial trial among low-birth-weight children. From 2004-2008, the children were randomly allocated to 25,000 IU vitamin A or placebo at birth, and furthermore to BCG vaccination at birth or later as is local policy. In 2011, the investigators conducted a follow-up study. A remarkably strong harmful effect of NVAS on atopy and wheezing was found (manuscript under review).

Seen in the context that NVAS may soon become a WHO policy it is obviously worrying if NVAS is associated with a higher risk of atopy and wheezing. The investigators therefore aim to conduct a similar follow-up study of participants in the first NVAS trial conducted in Guinea-Bissau from 2002-2004, among normal-birth-weight infants, to test whether NVAS is associated with an increased risk of atopy and wheezing and other allergic symptoms as well as growth.

METHODS

Study population:

From 2002-2004 BHP conducted a randomised trial of NVAS. The investigators recruited newborns when they came for BCG vaccination. Provided parental consent, they received an oral supplement of 50,000 IU vitamin A or placebo.

Study design:

This study will be a follow-up study of the cohort of children randomised to NVAS (intervention) or placebo (current policy) together with BCG vaccine at birth.

Other exposures:

The investigators will also investigate the effect of receiving an additional dose of measles vaccine and the timing of DTP vaccine on the development of atopy.

Assessment of outcomes:

The investigators will visit all children at the last known address. Height, weight and mid upper arm circumference will be measured. BCG scar will be examined and vaccination card details recorded by the field assistant. Children will be excluded from skin prick testing (SPT) if they have a history suggestive of anaphylaxis or are currently using anti-histamine medication. SPT will be performed using aero-allergens, food allergens and positive histamine and negative saline control. The mother or guardian will be interviewed by a local assistant. Symptoms of eczema and asthma as well as food allergy will be assessed.

Statistical analysis:

Effect of randomisation group and other factors on outcomes will be analysed in multivariable regression models. All analyses will be adjusted for skin prick tester. All analyses will be conducted stratified by sex.

Study Overview

• Status: Unknown
• Conditions: Asthma; Eczema; Food Allergy; Atopy

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau Codex
    • Bissau, Bissau Codex, Guinea-Bissau, 1004
      • Bandim Health Project

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants in a previous neonatal vitamin A supplementation trial

Description

Inclusion Criteria:

• Enrolled at birth in NCT00168610

Exclusion Criteria:

• Children with history suggestive of anaphylaxis will be excluded from skin prick testing but included in the study population

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atopic sensitisation	Skin prick test positivity. A wheal >=3mm will be considered positive.	Single observation on day of recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of asthma	Questionnaire based on ISAAC survey for 6-7 year olds	Single observation on day of recruitment
Symptoms of eczema	Questionnaire based on ISAAC survey for 6-7 year olds	Single observation on day of recruitment
Symptoms of food allergy	Questionnaire based on Health Nuts survey	Single observation of day of recruitment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight		Single observation on day of recruitment
Height		Single observation on day of recruitment
Mid-upper arm circumference		Single observation on day of recruitment
Hospitalisations		Single observation on day of recruitment
Infectious diseases	History of chickenpox or measles	Single observation on day of recruitment

Collaborators and Investigators

• Sponsor: Bandim Health Project
• Investigators: Principal Investigator: Christine Benn, DMSc, Statens Serum Institut

Publications and helpful links

General Publications

• Aage S, Kiraly N, Da Costa K, Byberg S, Bjerregaard-Andersen M, Fisker AB, Aaby P, Benn CS. Neonatal vitamin A supplementation associated with increased atopy in girls. Allergy. 2015 Aug;70(8):985-94. doi: 10.1111/all.12641. Epub 2015 May 18.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Anticipated): February 1, 2014

Study Registration Dates

• First Submitted: January 28, 2013
• First Submitted That Met QC Criteria: January 28, 2013
• First Posted (Estimate): January 30, 2013

Study Record Updates

• Last Update Posted (Estimate): November 15, 2013
• Last Update Submitted That Met QC Criteria: November 14, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: atopy; Vitamin A supplementation; BCG vaccination; measles vaccination; diphtheria-tetanus-pertussis vaccination
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: 2013-VAS-Atopy