Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
Condition: Intrauterine Growth Retardation; Low Birth Weight
MeSH terms: Fetal Growth Retardation; Birth Weight
Study type: Interventional
Phase: Phase 4

Summary: 
      Low birth weight (LBW; birth weight<2,500g) is the most important determinant of mortality
      and morbidity in the neonatal period. It is also a very important factor in predicting
      nutritional status, health and development in childhood. It even influences health in adult
      life, contributing to the vicious cycle of disease and poverty. The high rate LBW in DCs
      represents therefore a major public health problem. Maternal chronic energy deficiency is
      assumed to be a major determinant of the problem in these countries along with prenatal
      micronutrient deficiencies. A large body of recent evidence points out that multiple
      micronutrient supplementation as such has only a modest beneficial effect on fetal growth.
      Therefore, it is expected that providing these multiple micronutrients in a food supplement
      covering energy requirement needs of pregnant women will have an effect of public health
      importance on children's health.

      This study has the objective of improving children's health by improving birth outcome and
      fetal growth through the provision of a food supplement enriched in multimicronutrients
      during pregnancy.

      This research includes 2 constituents:

        1. a pilot phase during which dietary behavior of pregnant women is assessed as a component
           for optimal fetal growth

        2. a randomized, placebo-controlled trial, including 1300 pregnant women aimed at testing 2
           hypotheses: supplementing pregnant women with a food supplement containing a
           multivitamin-minerals mix will improve fetal growth; improved fetal growth will have a
           positive effect on health and growth during infancy.

      The trial is planned in Hounde District, Burkina Faso, in collaboration with Centre Muraz,
      which plays a leader role in research and services providing at the district level and in
      policy recommendations at the national level. This will ensure that the study findings are
      incorporated into on-going district programs with possible replication at the national level.
      The research lasts from February 2006 to August 2009.
    

Detailed description: 
      Low birth weight (LBW; birth weight<2500g) is an important predictor of mortality and
      morbidity in the neonatal period of early postnatal growth and growth during childhood. It is
      also associated with cognitive and behavioral development in the first years of life, health
      status during childhood, and adult health and human capital. As much as 16 % of all live
      births worldwide present a LBW, more than 90% being in low-income countries. Rates are
      particularly high in Asia and sub-Saharan countries. In Burkina Faso, it is estimated that 19
      % of all live births in 1999-2005 were LBW.

      In developing countries, most cases of LBW are attributed to intrauterine growth retardation
      (IUGR) rather than to preterm delivery. Factors interacting with fetal development are
      numerous. Among them maternal malnutrition, particularly energy and micronutrient
      deficiencies, and malaria during pregnancy are assumed to be major determinants of IUGR.
      Dietary surveys have consistently shown that multiple micronutrient deficiencies, rather than
      single deficiencies, are common. However, a number of randomized clinical trials in various
      countries have shown only a modest beneficial effect on fetal growth when providing multiple
      micronutrient supplements during pregnancy compared to folic acid and iron supplementation.
      It is expected that chronic energy deficiency during pregnancy could be hampering the full
      potential of the effect of multiple micronutrient supplementation. Therefore it is expected
      that incorporating multiple micronutrients in a food supplement (FS), that provides
      supplementary energy and protein, instead of multiple micronutrients (UNIMMAP), could have an
      effect of public health importance on fetal growth and its correlates. The UNIMMAP supplement
      composition, incorporated in the FS or given in the form of a tablet, was proposed by an
      expert committee organized by UNICEF, WHO and UNU for pregnancy and lactating women.

      The study takes place in the health district of Houndé (south-west of Burkina Faso) in the
      surroundings of 2 health centers (12,000 inhabitants) from June 2003 to October 2006. Houndé
      is situated in a Sudano-Sahelian climate belt. The diet is essentially cereal-based. In 2004
      and 2006, food consumption surveys estimated the average caloric intake during pregnancy at
      8.6 MJ and 8.1 MJ during the postharvest and pre-harvest season respectively. Malaria
      transmission is permanent with seasonal variations. In 2002, the HIV prevalence among
      consulting pregnant women in the district was estimated at 2 %. The incidence of LBW in term
      infants was around 17% at the District Hospital in 2000-2001.

      The recruitment of participants is community-based. During a preliminary census, houses in
      the study area are mapped and numbered and a unique identification code allocated to every
      woman of child-bearing age. Thirty locally trained home-visitors visit monthly every compound
      for early detection of pregnancy and referral to the health center for pregnancy test. Once
      the pregnancy is confirmed and after extensive explanation of the study purposes and
      procedures in Bwamu, Moré or Dioula, participants are asked to provide signed consent or
      thumbprints. There are no exclusion criteria other than planning to leave the area within the
      next 2 years.

      This study is a randomized controlled trial, with directly observed supplement intake.
      Pregnant women are randomly assigned to receive daily either UNIMMAP tablet ( vitamin A
      800µg, vitamin E 10 mg, vitamin D 5 µg, vitamin B1 1.4 mg, vitamin B2 1.4 mg, niacin 18 mg,
      vitamin B6 1.9 mg, vitamin B12 2.6 µg, folic acid 400 µg, vitamin C 70 mg, iron 30 mg, zinc
      15 mg, copper 2 mg, selenium 65 µg, and iodine 150 µg) until delivery, or either a food
      supplement containing the UNIMMAP. The food supplement consists of 33% peanut butter, 32%
      heat-treated soy flour, 15% vegetable oil, 20% plain sugar and the UNIMMAP micronutrient
      cocktail in powdered form. Each participant allocated to the FS study group will receive 72g
      of FS daily which provides 1.56 MJ (372 kcal) of energy and 14.7g protein. The supplement is
      produced by a local women's association in collaboration with a food technologist, the
      micronutrients in the FS are dosed by a laboratory technician. UNIMMAP micronutrient tablets
      are manufactured by Scanpharm (Copenhagen, Denmark). A randomization scheme is generated by a
      computer program in permuted blocks of 4. Randomization numbers are sealed in opaque
      envelopes by administrative staff. At each inclusion, the consulting physician in the field
      opens the next sealed envelope and transmits the randomization number in case of MMN to a
      pharmacist managing for the packaging of drugs in individual plastic zip sachets containing
      31 tablets. In case the randomization number shows allocation to the FS group, the
      responsible of the FS production site together with project staff, prepares a plastic bag
      containing 31 FS sachets.

      Participants are also randomly assigned randomized to receive intermittent malaria
      prophylaxis by either two doses or more than two doses of combined sulfadoxine-pyrimethamine
      (a single dose represented 1500 mg sulfadoxine and 75mg pyrimethamine). The malaria component
      will be analysed separately.

      In case of maternal illness, appropriate treatments are provided according to national
      guidelines. Severely anemic women (hemoglobin < 70 g/L, without dyspnea) receive ferrous
      sulphate (200 mg) + folic acid (0.25 mg) twice daily, during 3 months whatever their
      allocation group. All participants also receive Albendazole 400 mg in the second and third
      trimester. In case of malaria episode despite the preventative treatment, quinine (300 mg, 3
      times a day) is given during 5 days. Vitamin A (200.000 IU) is given to all women after
      delivery, in conformity with the national recommendations.
    

Intervention name(s): UNIMMAP - multiple micronutrients; Food supplement enriched with multiple micronutrients
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Daily supplementation of one UNIMMAP tablet
multiple micronutrient supplements (MMN): UNIMMAP: vitamin A 800µg, vitamin E 10 mg, vitamin D 5 µg, vitamin B1 1.4 mg, vitamin B2 1.4 mg, niacin 18 mg, vitamin B6 1.9 mg, vitamin B12 2.6 µg, folic acid 400 µg, vitamin C 70 mg, iron 30 mg, zinc 15 mg, copper 2 mg, selenium 65 µg, and iodine 150 µg; One dose of 72g per day during whole pregnancy
Recipe of food supplement: 33% peanut butter, 32% soy flour, 15% vegetable oil, 20% sugar, UNIMMAP in powdered form Nutritional composition (per dose of 72g) Energy 1.56 MJ, protein 14.7 g, vitamin A 881 µg, vitamin E 13 mg, vitamin D 5 µg, vitamin B1 1.4 mg, vitamin B2 1.4 mg, niacin 21 mg, vitamin B6 1.9 mg, vitamin B12 2.6 µg, folic acid 461 µg, vitamin C 70 mg, iron 30 mg, zinc 15 mg, copper 2 mg, selenium 65 µg, and iodine 150 µg
Other intervention name(s): Lipid based nutritional supplement (LNS)
Intervention MeSH terms: Micronutrients; Trace Elements
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: multiple micronutrients; energy deficiency