Iron Deficiency and Iron Homeostasis in Low Birth Weight Preterm Infants: A Systematic Review

Abstract

Iron is an essential micronutrient that is involved in many functions in humans, as it plays a critical role in the growth and development of the central nervous system, among others. Premature and low birth weight infants have higher iron requirements due to increased postnatal growth compared to that of term infants and are, therefore, susceptible to a higher risk of developing iron deficiency or iron deficiency anemia. Notwithstanding, excess iron could affect organ development during the postnatal period, particularly in premature infants that have an immature and undeveloped antioxidant system. It is important, therefore, to perform a review and analyze the effects of iron status on the growth of premature infants. This is a transversal descriptive study of retrieved reports in the scientific literature by a systematic technique. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were adapted for the review strategy. The inclusion criteria for the studies were made using the PICO (population, intervention, comparison, outcome) model. Consequently, the systematic reviews that included studies published between 2008–2018 were evaluated based on the impact of iron status on parameters of growth and development in preterm infants.

Iron Homeostasis Disruption and Oxidative Stress in Preterm Newborns

“…Iron is an essential micronutrient that plays a pivotal role in early development, being involved in hemoglobin synthesis, oxygen delivery, electron transfer, energy metabolism, and cell differentiation [1]. Nowadays, there is consistent evidence about the relationship between in utero iron supply and subsequent cognitive and neurobehavioral outcomes [2,3].…”

“…Low iron reserves and increased iron requirement explain why preterm infants are at high risk of ID/IDA and need iron supplementation [1,14]. It is estimated that between 25% and 85% of premature newborns develop iron deficiency, usually in the first six months of life [16].…”

“…On the other hand, premature infants are vulnerable to oxidative stress caused by non-transferrin-bound iron (NTBI) overload due to the immature antioxidant system and the high transferrin saturation [1,6,19,20]. NTBI can derive from high doses of oral or parental iron supplementation and recurrent erythrocyte transfusions [14].…”

“…The same toxic reaction can be produced when the iron is delocalized from its binding protein, as it happens in the setting of hypoxia [6,23]. As a result, the sickest premature neonates are prone to develop complications that may share the same etiology, grouped under the expression coined by Saugstad, "the oxygen radical disease of neonatology" [24]: bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and punctate white matter lesions (PWM) [1,21,25].…”

“…Conversely, anemia, hypoxia, and low iron levels are associated with reduced hepcidin expression, leading to the increased activity of ferroportin and the mobilization of iron reserves [ 4 , 6 ]. Iron deficiency (ID) is a relevant public health problem and is the most common single-element deficiency worldwide, affecting around 2 billion people globally [ 1 , 8 ]. Both pre-existing anemia and increased iron requirements during pregnancy make pregnant women particularly vulnerable to develop iron deficiency anemia (IDA) [ 2 ].…”