Acknowledging the gap: a systematic review of micronutrient supplementation in infants under six months of age

Background: Micronutrient deficiencies remain common worldwide, but the consequences to growth and development in early infancy (under six months of age) are not fully understood. We present a systematic review of micronutrient interventions in term infants under six months of age, with a specific focus on iron supplementation. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) from January 1980 through December 2019. Interventions included iron or multiple micronutrients (MMNs). Results: Of 11,109 records identified, 33 publications from 24 trials were included (19 iron and five MMN supplementation trials). All but one trial (evaluating only morbidity and mortality) evaluated the effect of supplementation on biochemical outcomes, ten reported on growth, 15 on morbidity and/or mortality and six on neuro-behavioural development. Low- and middle- income countries made up 88% (22/25) of the total trial locations. Meta-analysis was not possible due to extensive heterogeneity in both exposure and outcome measures.  However, these trials indicated that infants less than six months of age benefit biochemically from early supplementation with iron, but the effect of additional nutrients or MMNs, along with the impacts on growth, morbidity and/or mortality, and neuro-behavioural outcomes remain unclear. Conclusions: Infants less than six months of age appear to benefit biochemically from micronutrient supplementation. However, well-powered randomised controlled trials are required to determine whether routine supplementation with iron or MMNs containing iron should commence before six months of life in exclusively breast-fed infants in low-resource settings.