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.