Making Maternal Post-partum Vitamin A Supplementation Effective: The Role of Timing and Inflammation

This study has been completed.
Sponsor:
Collaborators:
Thrasher Research Fund
University of Copenhagen
National Institute of Nutrition, Hanoi, Vietnam (implementation)
Information provided by (Responsible Party):
Frank Wieringa, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00952640
First received: August 3, 2009
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

Background:

Vitamin A is of utmost importance for health and survival of children. A recent series in The Lancet on maternal and child health put vitamin A deficiency at the top of most important micronutrient deficiencies, responsible for more than 600.000 child deaths/year worldwide. Vitamin A status of mothers and infants is closely linked. Hence, a mother with vitamin A deficiency cannot give enough vitamin A to her fetus to build stores during the last months of pregnancy, and will also have insufficient amounts of vitamin A in her breast milk, resulting in a high risk for vitamin A deficiency in her newborn infant. The World Health Organization (WHO) has implemented several strategies to fight vitamin A deficiency in mothers and children. One of these is to give women after delivery a high dose vitamin A supplement, to improve vitamin A status of mother and, via breast milk, her infant. Surprisingly however, several recent studies investigating the effect of a high dose vitamin A supplement for mothers directly after birth found no effect on vitamin A status in infants 6 months of age. In contrast, earlier studies in Bangladesh and Indonesia, in which women received a high dose vitamin A supplement somewhere in the first 6 weeks after delivery, reported a large impact on vitamin A status in the infants at 6 mo of age. The WHO recommendation on post-partum vitamin A supplementation was based on these earlier studies from Bangladesh and Indonesia. The more recent studies suggest however that this intervention is not effective, and that millions of women currently receive a high dose vitamin A supplement without clear benefits for vitamin A status in either the women or their children.

The human body reacts to infection or injury with an inflammatory response, which kicks off with the acute phase response. The acute phase response helps the body to fight the infection. It is characterized by many altered physiological processes, including changed availability of vitamins and minerals. Recently, we found that delivery in itself causes a major acute phase response. We have formed the hypothesis that the acute phase response initiated by delivery prevents the high dose vitamin A supplement given to the mother directly after delivery from being absorbed and from being available for breast milk. If this is true, the current WHO recommendation to give the vitamin A within the first 6 weeks post-partum should be changed to giving the vitamin A 4 - 6 weeks post-partum instead, to allow the acute phase response induced by delivery to fade.

Objective(s) and Hypothesis(es):

The main objective is to improve the effectiveness of the current WHO policy of vitamin A supplementation after delivery to improve vitamin A status and health of mothers and their infants.

Methodology:

In a randomized, placebo-controlled, double-blind trial, 400 women will receive a high dose of vitamin A (200.000 IU) within 6 weeks of delivery, as recommended by WHO. Half of the women will receive the vitamin A directly after delivery (within 3 days, current practice), whereas the other women will receive the vitamin A 6 weeks after delivery. To guarantee blinding, women will receive a placebo capsule if they are not receiving a vitamin A capsule.

Main outcomes will be maternal and infant vitamin A status 6 months post-partum and the time-course of the acute phase response, to establish the optimal time after delivery for the initiation of the vitamin A supplementation.

Secondary outcomes will be the morbidity of the infants during the first 6 months of life and growth performance of the infants at 6 mo of age.

Potential Impact:

The results of this study will enable WHO to improve the effectiveness of the current WHO recommendations concerning post-partum vitamin A supplementation. If our hypothesis is true, postponing the timing of the post-partum vitamin A supplement from directly after delivery to 6 week post-partum, will significantly increased the availability of the supplement for the mother. This will increase the vitamin A status of both mother and infant. Moreover, there are several significant implications for global health policies, with important consequences for infant survival worldwide by reducing morbidity and mortality from infectious diseases during the first 6 months of life. Results of the study will also have important consequences for other micronutrient health programs, such as vitamin A supplementation for children above 6 months of age and iron supplementation in areas with endemic malaria, as these are also subject to the effects of the acute phase response


Condition Intervention
Healthy Women Giving Birth to Singleton Infants
Dietary Supplement: vitamin A

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Making Maternal Post-partum Vitamin A Supplementation Effective: The Role of Timing and Inflammation.

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • vitamin A status of lactating women 6 mo post-partum vitamin A status of infants 6 mo of age acute phase proteins concentrations (CRP, AGP) at several time-points during the first 6 mo post-partum [ Time Frame: several times points during the first 6 mo post-partum (different time points for different indicators) ] [ Designated as safety issue: No ]
  • plasma retinol 6 mo post-partum (women and infants), breast milk retinol (6 weeks, 4 mo and 6 mo post-partum), liver retinol stores of infants 6 mo post-partum acute phase proteins, at 2 weeks, 6 weeks, 4 mo and 6 mo post-partum (women) [ Time Frame: 2 and 6 weeks, 4 mo and 6 mo post-partum ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • morbidity infants during the first 6 mo of life anthropometry at 6 mo post-partum [ Time Frame: 6 mo of age ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: June 2010
Study Completion Date: October 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: vitamin A directly post-partum
200.000 IU of vitamin A within 3 days of delivery
Dietary Supplement: vitamin A
high dose vitamin A, 200.000 IU
Experimental: vitamin A delayed
200.000 IU vitamin A 6 weeks post-partum
Dietary Supplement: vitamin A
high dose vitamin A, 200.000 IU

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Criteria

Inclusion Criteria:

  • Healthy women giving birth to a singleton infant.

Exclusion Criteria:

  • Women giving birth to infants weighing < 1500 gram (very low birth weight infant) will be excluded.
  • Also excluded will be twin pregnancy, because of different growth patterns of the infants and congenital abnormalities interfering with normal growth.
  • Furthermore, women indicating that they are planning not to breast feed their baby will be excluded, as well as women who experience delivery complications which result in prolonged (> 3 days) hospital stay.
  • Complications such as eclampsia or excessive blood loss will be registered, but will not be a reason for exclusion per se.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00952640

Locations
Vietnam
National Institute of Nutrition
Hanoi, Vietnam
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Thrasher Research Fund
University of Copenhagen
National Institute of Nutrition, Hanoi, Vietnam (implementation)
  More Information

Publications:
Responsible Party: Frank Wieringa, Senior Rechercher, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT00952640     History of Changes
Other Study ID Numbers: VitA_PP
Study First Received: August 3, 2009
Last Updated: October 9, 2012
Health Authority: France: Institut de Recherche pour le Developpement, Montpellier
Denmark: Department of Human Nutrition, Copenhagen University, Copenhagen
Vietnam: National Institute of Nutrition, Hanoi

Keywords provided by Institut de Recherche pour le Developpement:
vitamin A
post-partum
infant
acute phase response

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Vitamin A
Vitamins
Retinol palmitate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014