ArticlesEffects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial
Introduction
A third of global deaths happen in children younger than 5 years,1 most in the neonatal period.2 Low birthweight (<2500 g, irrespective of gestation) underlies many of these deaths. 25 million low-birthweight infants are born every year, and associations with neonatal mortality have been well described.3, 4, 5, 6 Low birthweight is also associated with diminished childhood growth,7 morbidity,8 compromised cognitive and behavioural development,9, 10 and disease in adulthood.11 It is, however, rather a blunt indicator of fetal history and infant health: low-birthweight infants can be small for gestational age, preterm, or both. Most birthweight data from poor countries do not discriminate between these factors, a dilemma that has led to several approaches to classification and uncertainty about disease burden.12, 13 Although the epidemiology and associations of low birthweight have been examined closely,14 approaches to alleviate the burden have met with limited success.15, 16
Maternal nutritional status is linked with fetal weight, particularly small-for-gestational-age birth, as a result of presumptive intrauterine growth restriction. Increases in macronutrient consumption during pregnancy do lead to increased birthweight,17, 18 but control of fetal growth is complex,19 and the effectiveness of interventions remains patchy.20, 21 The possibility that improvements in vitamin and mineral status might lead to reductions in low birthweight is attractive in terms of policy planning. A wealth of descriptive epidemiology has drawn links between deficiencies of such micronutrients—particularly several at the same time22—and birth outcomes.23 Many women in wealthy and poor countries already take multiple micronutrient supplements before and during pregnancy, and iron and folic acid supplements are generally recommended. If multiple micronutrient supplement tablets were shown to be helpful, only minor adjustments to policy would be needed.
Repletion might improve birth outcomes,24 a proposal lent support by findings of a study of infants of women infected with HIV.25 An expert group has formulated a combination of ten vitamins and five minerals at levels of about one recommended daily allowance for this reason.26 However, the evidence base for policy change is insufficient.27, 28 We undertook a trial with the aim of establishing whether second and third trimester supplementation with a multiple micronutrient regimen at one recommended daily allowance would increase birthweight and prolong gestational duration.
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Study location and population
Nepal is a south Asian country challenged by geography, poverty, and a violent insurrection. The most recent estimates of neonatal and perinatal mortality rates are 39 per 1000 livebirths and 47 per 1000 births, respectively.29 More than half of women cannot read.30 About a third have low body-mass index (<18·5 kg/m2)31 and a quarter report limiting their own food consumption to provide food for their children;32 half of children have stunted growth.31 Deficiencies of several micronutrients
Results
The first participant joined the trial on Aug 11, 2002, and the last on Oct 22, 2003; all women had exited the trial by July, 2004. The figure shows the trial profile. Most exclusions from enrolment were for gestations of more than 20 weeks. Maternal illnesses that led to exclusion were: recently treated recurrent cysticercosis (1); need for chlorpromazine (1) or anticoagulant (1) drugs with changing doses; and symptomatic mitral stenosis (1) or multivalvular heart disease (1). Fetal exclusions
Discussion
We have shown that antenatal supplementation with a multiple micronutrient preparation was associated with increased birthweight when compared with a standard iron and folic acid preparation. Gestational duration was not affected by supplementation. We achieved high retention rates, and imprecision was restricted to tolerances implied by use of electronic scales for weighing, a 72-h window for measurement of birthweight, and ultrasound biometry for gestational assessment.
A trial of this type
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