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      Tracing Zinc’s Role in Preterm Infants’ Health: A Narrative Review

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          Abstract

          Zinc (Zn) is a trace element involved in numerous physiological processes, including enzyme function, gene transcription, and cell signaling. Its importance is especially pronounced in preterm infants, who are at high risk of Zn deficiency due to disrupted transplacental transfer, high nutrient demands, and medical complications. The inherent risk of Zn deficiency in this population is further increased by poor Zn dietary intake. Human milk from preterm mothers contains low concentrations of Zn, although it is highly bioavailable. Additionally, the Zn content steadily declines from colostrum (first few days postpartum) to mature milk (>10–14 d postpartum). Formula milk contains higher Zn concentrations to compensate for nutrient losses during production and storage, and lower bioavailability compared with human milk, which is further decreased in case of high phytate content, such as in soy milk-based formulas. Zn supplements may prove useful in meeting the preterm infant’s needs, although caution is warranted regarding potential interactions with other nutrients within multinutrient supplements. Early detection of Zn deficiency is challenging due to the lack of reliable Zn status biomarkers, necessitating a high index of suspicion. Clinical signs of Zn deficiency can range from mild, nonspecific symptoms to severe, multisystem involvement. Chronic deficiency may lead to failure to thrive. Zn supplementation can support growth and mitigate comorbidities in preterm infants, although variability across studies complicates efforts to establish optimal dosing, and define safety and long-term effects. Although rare, Zn toxicity in preterm infants should not be overlooked, especially in infants on long-term parenteral nutrition. This narrative review aimed to consolidate existing knowledge and identify research gaps, highlighting the critical role of Zn in supporting preterm infants’ health. Further research is needed to establish evidence-based practices to improve health outcomes in this vulnerable population.

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          Most cited references133

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          Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

          The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.
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            The role of zinc in growth and cell proliferation.

            The inhibition of growth is a cardinal symptom of zinc deficiency. In animals fed a zinc-inadequate diet, both food intake and growth are reduced within 4-5 d. Despite the concomitant reduction in food intake and growth, reduced energy intake is not the limiting factor in growth, because force-feeding a zinc-inadequate diet to animals fails to maintain growth. Hence, food intake and growth appear to be regulated by zinc through independent, although well coordinated, mechanisms. Despite the long-term study of zinc metabolism, the first limiting role of zinc in cell proliferation remains undefined. Zinc participates in the regulation of cell proliferation in several ways; it is essential to enzyme systems that influence cell division and proliferation. Removing zinc from the extracellular milieu results in decreased activity of deoxythymidine kinase and reduced levels of adenosine(5')tetraphosphate(5')-adenosine. Hence, zinc may directly regulate DNA synthesis through these systems. Zinc also influences hormonal regulation of cell division. Specifically, the pituitary growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis is responsive to zinc status. Both increased and decreased circulating concentrations of GH have been observed in zinc deficiency, although circulating IGF-I concentrations are consistently decreased. However, growth failure is not reversed by maintaining either GH or IGF-I levels through exogenous administration, which suggests the defect occurs in hormone signaling. Zinc appears to be essential for IGF-I induction of cell proliferation; the site of regulation is postreceptor binding. Overall, the evidence suggests that reduced zinc availability affects membrane signaling systems and intracellular second messengers that coordinate cell proliferation in response to IGF-I.
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              Biomarkers of Nutrition for Development (BOND)-Zinc Review.

              Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or DNA damage.

                Author and article information

                Contributors
                Journal
                Adv Nutr
                Adv Nutr
                Advances in Nutrition
                American Society for Nutrition
                2161-8313
                2156-5376
                08 November 2024
                December 2024
                08 November 2024
                : 15
                : 12
                : 100295
                Affiliations
                [1 ]Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023–2027, University of Milan, Milan, Italy
                [2 ]Pediatric Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
                [3 ]Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
                [4 ]NICU, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
                Author notes
                [* ]Corresponding author. carlo.agostoni@ 123456unimi.it
                Article
                S2161-8313(24)00129-7 100295
                10.1016/j.advnut.2024.100295
                11705620
                39675840
                21e2da51-96e1-4c07-a327-f1c99be2973b
                © 2024 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 28 June 2024
                : 30 August 2024
                : 3 September 2024
                Categories
                Review

                zinc,preterm infants,micronutrients,parenteral nutrition,human milk,supplements

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