Multiple Micronutrient Deficiencies During Pregnancy Clinical Trial
Official title:
Prevention of Intrauterine Growth Retardation in Hounde District, Burkina Faso
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention