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

NCT00952640 | Completed

• 1 other identifier: VitA_PP
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Women Giving Birth to Singleton Infants

Keywords

vitamin A; post-partum; infant; acute phase response

Outcome Measures

Primary Outcomes (2)

• 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

  several times points during the first 6 mo post-partum (different time points for different indicators)

• 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)

  2 and 6 weeks, 4 mo and 6 mo post-partum

Secondary Outcomes (1)

• morbidity infants during the first 6 mo of life anthropometry at 6 mo post-partum

  6 mo of age

Study Arms (2)

vitamin A directly post-partum

ACTIVE COMPARATOR

200.000 IU of vitamin A within 3 days of delivery

Dietary Supplement: vitamin A

vitamin A delayed

EXPERIMENTAL

200.000 IU vitamin A 6 weeks post-partum

Dietary Supplement: vitamin A

Interventions

vitamin A DIETARY_SUPPLEMENT

high dose vitamin A, 200.000 IU

vitamin A delayed; vitamin A directly post-partum

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy women giving birth to a singleton infant.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherche pour le Developpement: lead
• Thrasher Research Fund: collaborator
• University of Copenhagen: collaborator
• National Institute of Nutrition, Vietnam: collaborator

Study Sites (1)

National Institute of Nutrition

Hanoi, Vietnam

Location

Related Publications (4)

• Friis H, Range N, Braendgaard Kristensen C, Kaestel P, Changalucha J, Malenganisho W, Krarup H, Magnussen P, Bengaard Andersen A. Acute- phase response and iron status markers among pulmonary tuberculosis patients: a cross-sectional study in Mwanza, Tanzania. Br J Nutr. 2009 Jul;102(2):310-7. doi: 10.1017/S0007114508162122. Epub 2009 Jan 28.

  PMID: 19175946 BACKGROUND

• Ayah RA, Mwaniki DL, Magnussen P, Tedstone AE, Marshall T, Alusala D, Luoba A, Kaestel P, Michaelsen KF, Friis H. The effects of maternal and infant vitamin A supplementation on vitamin A status: a randomised trial in Kenya. Br J Nutr. 2007 Aug;98(2):422-30. doi: 10.1017/S0007114507705019. Epub 2007 Mar 29.

  PMID: 17391562 BACKGROUND

• Wieringa FT, Dijkhuizen MA, van der Meer JW. Maternal micronutrient supplementation and child survival. Lancet. 2008 May 24;371(9626):1751-2. doi: 10.1016/S0140-6736(08)60758-8. No abstract available.

  PMID: 18502294 BACKGROUND

• Dijkhuizen MA, Wieringa FT, West CE, Muhilal. Zinc plus beta-carotene supplementation of pregnant women is superior to beta-carotene supplementation alone in improving vitamin A status in both mothers and infants. Am J Clin Nutr. 2004 Nov;80(5):1299-307. doi: 10.1093/ajcn/80.5.1299.

  PMID: 15531679 BACKGROUND

MeSH Terms

Conditions

Acute-Phase Reaction

Interventions

Vitamin A

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Rechercher

Study Record Dates

• First Submitted: August 3, 2009
• First Posted: August 6, 2009
• Study Start: June 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 11, 2012

Record last verified: 2012-10

Locations

VN (1)