Prevention of Intrauterine Growth Retardation in Hounde District, Burkina Faso
Condition: Multiple Micronutrient Deficiencies During Pregnancy
MeSH terms: Fetal Growth Retardation
Study type: Interventional
Phase: Phase 4

Summary: 
      Intrauterine Growth Retardation 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 IUGR in DCs represents therefore a
      major public health problem. Maternal malnutrition is usually assumed to be a major
      determinant of the problem in these countries. An increasing amount of evidence points to the
      potential role played by micronutrient deficiencies during pregnancy. The adverse effect on
      birthweight of maternal iron deficiency anaemia, lack of zinc and lack of iodine have been
      documented. A similar effect is suspected for Vitamin A, Magnesium, Calcium, Copper,Thiamine,
      Pyridoxine and Folic acid. It seems that not one specific deficiency alone is responsible for
      this adverse effect, but rather a combination of them. Therefore, it is expected that
      covering needs of pregnant women by a multivitamin-mineral supplement will have an effect of
      public health importance on children's health.

      This study has the objective of improving children's health by preventing intrauterine growth
      retardation through the provision of multivitamin-mineral supplements during pregnancy.

      This research includes 2 constituents:

        1. a pilot phase during which socio-anthropological, nutritional and epidemiological
           aspects of IUGR will be assessed through qualitative and epidemiological methods.

        2. a double-blind, randomised, placebo-controlled trial, including 1215 pregnant women
           aimed at testing 3 hypotheses: supplementing pregnant women with a multivitamin-minerals
           mix will improve fetal growth; improved fetal growth will have a positive effect on
           health and growth during infancy; covering nutritional needs of lactating women with a
           multivitamin-minerals mix during 3 months after delivery will improve health and growth
           of infants.

      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 programmes with possible replication at the national
      level. The research lasts from June 2003 to October 2006.
    

Detailed description: 
      Low birthweight (LBW; birthweight<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 behavioural 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 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. It is therefore expected that providing multiple micronutrients (MMN), instead of
      iron and folic acid (IFA) as currently recommended by WHO, could have an effect of public
      health importance on fetal growth and its correlates. The UNICEF/WHO/UNU multiple
      micronutrient supplement for pregnancy and lactating women (UNIMMAP) was designed by experts
      and was proposed for field testing. A recent systematic review concluded that additional
      evidence was needed to establish the effects of maternal MMN supplements on infant and
      maternal health. The study described here is part of a series of efficacy studies on the
      effect of the UNIMMAP supplements on pregnancy outcomes.

      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. Twenty-five 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 double-blind, randomized controlled trial, with directly observed drug
      intake. Pregnant women are randomly assigned to receive either IFA (iron 60 mg and folic acid
      400µg) or 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)
      until 3 months after delivery. Intervention and control micronutrient tablets are identical
      in appearance and manufactured by Scanpharm (Copenhagen, Denmark) in containers with a letter
      code (A/B) for each intervention group. This code is kept secret from study participants and
      study personnel until data analysis. Micronutrients are kept in a cool room until allocation.
      Vitamin C levels, identified as the most labile component in the MMN, are monitored once a
      year and found remarkably constant through the trial. Participants are also randomly assigned
      to receive either malaria weekly chemoprophylaxis (chloroquine 300 mg) versus intermittent
      preventive treatment (sulphadoxine 1500 mg and pyrimethamine 75 mg once in the 2nd and 3rd
      trimester). 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): Multiple micronutrient supplements (MMN); IFA
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Iron and folic acid: iron 60 mg and folic acid 400µg; Iron and folic acid (IFA)(iron 60 mg and folic acid 400µg).
Intervention MeSH terms: Micronutrients; Trace Elements
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention