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A brief history of iron metabolism | SpringerLink

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A brief history of iron metabolism

Tissue iron stores are consumed quickly in premature infants demonstrating rapid growth. Interestingly, iron status at birth has no effect on the postnatal growth rate. With the increases in blood volume and Hb mass, the high rate of postnatal catch-up growth needs extra iron supplementation Rao and Georgieff, The iron concentration in human breast milk is about 0.

Iron Studies (part 1: Iron Absorption)

Although iron absorption rate of human breast milk is better than neonate formula, it is obtained only 0. Although ID is more common in preterm neonates, other factors that cause iron overload should be considered. Although IDA has been considered to be an issue in growing premature neonates, the impact of iron overload has not been thoroughly investigated. As an invasive test, liver biopsy is the gold standard for diagnosing iron excess, while serum ferritin level, which is a helpful biochemical assay, is usually utilized as a surrogate indicator to assess and guide treatment of iron excess in older children Fleming and Ponka, This is the main factor resulting in iron overload in preterm infants.

Section outline

Premature neonates that receive more erythrocyte transfusions not only could replace phlebotomy losses but also maintain certain level of Hb concentrations. This poses several risks, including iron overload Park and Kim, , because excess iron is not able to be eliminated by physiological pathways, even though the iron released after degradation of the transfused red blood cells increases body iron storage.

Significant sex differences in iron overload have been observed during infancy. In general, iatrogenic factors are responsible for excess iron accumulation in premature neonates, but other risk factors such as medical iron supplementation and infant formula containing a higher level of iron should not be ignored Figure 1 , middle bottom. Screening the iron status of mothers, neonates, and children is necessary to avoid long-term adverse health impacts for mothers and children, especially neurodevelopment abnormalities in the child caused by ID.

In view of the current lack of sufficient evidence, the standard for describing iron status clinically for healthy preterm infants is still unknown. As summarized above, iron imbalance including both deficiency and overload has severe impacts on brain development, and thus it seems essential to establish the association between potential indicators such as non-TBI and neurological outcomes in infants.


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Hb and ferritin are used as indicators of iron status in infants. Because most physiological changes in iron status and erythrocyte morphology occur during early development, age-specific cutoffs indicators of iron status should be utilized for preterm neonates with LBW Table 1. In these clinical indicators for iron status, we could see that the thresholds appear to decrease slightly with advancing postnatal age, with the exception of the 2-month value for example, Hb. Table 1. Clinical indicators for iron imbalance in LBW preterm infants at different ages.

However, because ID is highly prevalent throughout the world, the indicators for detecting iron status are initially focused on identifying whether ID occurs. The present clinical indicators and proposed tests for monitoring ID include hematologic and non-hematologic measurements Table 2.

These indicators are changing gradually before individuals become more iron-deficient. However, to protect the developing brain, the two main points in this process are worthy to be noted. As summarized by Georgieff , first, none of the markers directly index iron levels in brain tissue. In addition, it is unclear whether the brain is lacking iron in this process from sufficient to anemia unless it occurs prior to obvious anemia. Neurobehavioral tests are attractive candidates as bio-indicators of brain iron status because it reflects iron-specific brain functions Georgieff, Thus, none of the proper neurobehavioral tests can be used as a direct iron-specific indicator for indexing brain functions.

Table 2. Clinical indicators for monitoring iron deficiency and iron deficiency anemia. The physiological iron requirements for growth vary in different stages during infancy and childhood Hider and Kong, ; Figure 2 , bottom part. Thus, proper iron supplementation is crucial, especially for preterm infants who are at high risk of iron imbalance.

Premature neonates will get about 1. Despite the use of iron-containing formulas, some preterm infants develop ID during the first year of life. Thus, some formula-fed premature neonates might require an extra iron supplement; nevertheless, there is insufficient evidence to confirm this as a common recommendation at this time. Even if iron-fortified follow-on formulas should be supplemented, determining the optimal level of iron in follow-on formulas still lacks sufficient evidence.

Preterm infants are at high risk of iron imbalance, and ID and iron overload are important nutritional issues in preterm infants. The potential risk for neurodevelopmental abnormalities caused by ID requires regular screening and preventive measures.

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It is also beneficial and safe for preterm infants to be given iron supplementation. On the other side, iron overload is another significant concern in preterm infants; however, the management of premature infants who have excess iron has not been well investigated. Because iron levels in premature neonates vary greatly, we should monitor its status carefully during neonatal and post-discharge periods.

The gestational age-specific clinical indicators for evaluating iron status and the neurobehavioral examinations reflecting iron-specific brain function are necessary to be developed. In the previous iron status and iron supplementation studies, most of them were conducted before the period of increased survival of high-risk premature neonates.


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Thus, randomized and well-controlled trials are required to establish iron supplement guidelines for these preterm infants. CZ devised the review. XW and CZ substantially contributed to the literature review and the writing of this manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Agostoni, C. Enteral nutrient supply for preterm infants: commentary from the European society of paediatric gastroenterology, hepatology and nutrition committee on nutrition.

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