Abstract

Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included. Meta-analyses showed improvement in several key birth outcomes, such as preterm birth, small-for-gestational age (SGA) and low birthweight with MMN supplementation, compared to IFA. MMN also improved child outcomes, including diarrhea incidence and retinol concentration, which are findings not previously reported. Across all comparisons, micronutrient supplementation had little to no effect on mortality (maternal, neonatal, perinatal, and infant) outcomes, which is consistent with other systematic reviews. IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities. For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc). These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit. In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs.

Highlights

  • Subgroup analyses were conducted for the following comparisons: zinc vs. placebo, iron vs. placebo, and multiple micronutrient (MMN) vs. iron and folic acid (IFA) supplementation

  • This review indicated little to no improvement in low birthweight as a result of calcium supplementation compared to placebo; a recent systematic review found a 15% reduction in the risk of low birthweight infants [41]

  • Micronutrient and vitamin supplementation is a key intervention to promote maternal and child nutrition, health and well-being, and implementation should be continued, especially during pregnancy amongst mothers living in low- and middle-income countries (LMICs) regardless of maternal nutritional status

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Summary

Introduction

Micronutrient deficiencies are a key contributing factor to poor health and suboptimal development outcomes, and they especially affect women and children who reside in low- and middle-income countries (LMICs) [1,2]. Micronutrient deficiencies are defined as insufficient amounts of essential vitamins and minerals, which are obtained from the diet, to meet recommended daily allowances for proper health, growth and development [3]. They often result from diets that chronically lack diversity or proper and sufficient nutrients, and in some cases, from infections and/or chronic disease that inhibit proper nutrient absorption [4]. Micronutrient deficiencies are of particular concern as they will threaten the survival and well-being of women of reproductive age (WRA) and their infants, and may put subsequent generations of children at risk due to the intergenerational transfer of malnutrition [5,7]

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