Zinc in extremely low-birthweight infants

With the increasing survival of extremely low-birthweight (ELBW) or very preterm infants, it is becoming increasingly important to understand micronutrient needs. Zinc is among the most abundant trace elements in the human body. It is involved in protein structure and function, and it is also important in gene expression, neurotransmission, and apoptosis. Moreover, zinc has a role in the inflammatory response.
Approximately 60% of fetal accretion of zinc occurs in the third trimester. This high amount of zinc accumulation occurs particularly in the liver, which is used later as a storage site to prevent zinc deficiency during infancy. Clearly, this can be a problem in ELBW infants born preterm before they have adequate hepatic stores of zinc,  putting these babies at risk of clinical deficiency.
For what concerns monitoring, the use of serum or plasma zinc concentrations as a marker of zinc status presents serious difficulties, including uncertainty about normal variations and different reference ranges. Given that serum zinc is only a small percentage of total body zinc and that exchange in preterm infants is understood only imperfectly, the importance of changes in serum zinc concentrations is unclear, which makes management decisions based solely on zinc concentrations in the absence of clinical features extremely difficult. However, some evidence can guide requirements to avoid deficiency.
Deficiency of zinc is associated with characteristic erosive skin changes in the anogenital area and over the head, face, fingers, and trunk. Other conditions associated to zinc deficiency are alopecia, occasional diarrhea, failure to thrive, oral candidiasis, and irritability. However, babies responds quickly to zinc supplementation, often within 2 or 3 days. The supplemented infants showed a significant improvement in serum zinc concentrations and are more resistant to infections and to other adverse clinical outcomes. Standard treatment of clinical deficiency has been 1 to 2 mg/kg per day of zinc (1 mg zinc ion is equivalent to 4.5 mg zinc sulfate). Occasionally the dose needs to be increased to 2 to 4 mg/kg per day.
Term infants have been estimated to have a zinc requirement of 780 mcg/d at 1 month of age, decreasing to 480 mcg/d by 5 months of age. VLBW infants, allowing for some use of hepatic zinc stores and an estimated absorption of zinc, may have a requirement of 2 mg/kg per day. In ELBW infants, recommended values can be mainly extrapolated for studies in term or, at best, VLBWI and are therefore controversial. Given the known importance of zinc in physiology and the potential for deficiency in early postnatal life, inadequate zinc supplementation may result in suboptimal growth in some of these infants, who may be at increased risk of infections and potentially have worse developmental outcomes. However, it should emphasize that, at present, the usefulness of routine monitoring of serum zinc concentrations is uncertain, and the concentration at which to treat with supplemental zinc in the absence of clinical signs of zinc deficiency is not known. Despite this, given the lack of reports of zinc toxicity, it seems prudent to err on the generous side when providing zinc to ELBW infants.

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