Zinc supplementation in premature infants: an overview of current recommendations and scientific findings

Czech version

Authors: J. Dušek ^1,2
Authors‘ workplace: Neonatologické oddělení Nemocnice České Budějovice, a. s. ¹; Zdravotně sociální fakulta Jihočeské univerzity v Českých Budějovicích ²
Published in: Čes-slov Neonat 2025; 31 (2): 93-96.
Category: Original Paper

Overview

Zinc is a key trace element essential for growth, neurodevelopment, and immune function. Preterm infants are at risk of zinc deficiency due to insufficient intrauterine storage, increased postnatal needs, and higher losses. This article summarizes current recommendations for zinc supplementation in preterm infants, including ESPGHAN guidelines, and describes the role of zinc in growth, development, and immunity. It also discusses the risks of deficiency and over-supplementation, the relationship between zinc deficiency and neurodevelopmental disorders, and provides an overview of available clinical studies. Zinc supplementation is a key component of nutritional care in this vulnerable population.

Keywords:

supplementation – Immunity – Zinc – Neurodevelopment – growth – preterm infants – ESPGHAN

Sources

1. Brion LP, Heyne R, Lair CS. Role of zinc in neonatal growth and
brain growth: Review and scoping review. Pediatr Res 2021; 89
(7): 1627–1640.

2. Terrin G, Berni Canani R, Di Chiara M, Pietravalle A, Aleandri
V, Conte F, et al. Zinc in early life: A key element in the fetus and
preterm neonate. Nutrients 2015; 7(12): 10427–10446.

3. Chasapis CT, Ntoupa PA, Spiliopoulou CA, Stefanidou ME.
Recent aspects of the effects of zinc on human health. Arch
Toxicol 2020; 94 (5): 1443–1460.

4. Skalny AV, Aschner M, Tinkov AA. Zinc. Adv Food Nutr Res
2021; 96 : 251–310.

5. Kambe T, Tsuji T, Hashimoto A, Itsumura N. The physiological,
biochemical, and molecular roles of zinc transporters in zinc ho-
meostasis and metabolism. Physiol Rev 2015; 95 (3): 749–784.

6. Wessels I, Fischer HJ, Rink L. Dietary and physiological effects
of zinc on the immune system. Annu Rev Nutr 2021; 41 : 133–
175.

7. Livingstone C. Zinc: Physiology, deficiency, and parenteral
nutrition. Nutr Clin Pract 2015; 30 (3): 371–382.

8. Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status
is associated with inflammation, oxidative stress, lipid, and glu-
cose metabolism. J Physiol Sci 2018; 68 (1): 19–31.

9. Tamura Y. The role of zinc homeostasis in the prevention of
diabetes mellitus and cardiovascular diseases. J Atheroscler
Thromb 2021; 28 (11): 1109–1122.

10. Berezin AE, Berezin AA, Lichtenauer M. Emerging role of
adipocyte dysfunction in inducing heart failure among obese
patients with prediabetes and known diabetes mellitus. Front
Cardiovasc Med 2020; 7 : 583175.

11. Vela G, Stark P, Socha M, Sauer AK, Hagmeyer S, Grabrucker
AM. Zinc in gut-brain interaction in autism and neurological
disorders. Neural Plast 2015; 2015 : 972791.

12. Sanctuary MR, Kain JN, Angkustsiri K, German JB. Dietary
considerations in autism spectrum disorders: The potential role
of protein digestion and microbial putrefaction in the gut-brain
axis. Front Nutr 2018; 5 : 40.

13. Sinha B, Dudeja N, Chowdhury R, Choudhary TS, Upadhyay
RP, Rongsen-Chandola T, et al. Enteral zinc supplementation
in preterm or low birth weight infants: A systematic review and
meta-analysis. Pediatrics 2022; 150 (Suppl 1).

14. Jeon KI, Jeong JY, Jue DM. Thiol-reactive metal compounds
inhibit NF-kappa B activation by blocking I kappa B kinase. J Im-
munol 2000; 164 (11): 5981–5989.

15. Lassi ZS, Haider BA, Bhutta ZA. Zinc supplementation for
the prevention of pneumonia in children aged 2 months to 59
months. Cochrane Database Syst Rev 2010 (12): Cd005978.

16. Jarosz M, Olbert M, Wyszogrodzka G, Młyniec K, Librowski
T. Antioxidant and anti-inflammatory effects of zinc. Zinc-de-
pendent NF-κB signaling. Inflammopharmacology 2017; 25 (1):
11–24.

17. Richter M, Bonneau R, Girard MA, Beaulieu C, Larivée P. Zinc
status modulates bronchopulmonary eosinophil infiltration
in a murine model of allergic inflammation. Chest 2003; 123(3
Suppl): 446.

18. Zalewski PD, Truong-Tran AQ, Grosser D, Jayaram L, Murgia
C, Ruffin RE. Zinc metabolism in airway epithelium and airway
inflammation: Basic mechanisms and clinical targets: A review.
Pharmacol Ther 2005; 105 (2): 127–149.

19. Morgan CI, Ledford JR, Zhou P, Page K. Zinc supplementation
alters airway inflammation and airway hyperresponsiveness to
a common allergen. J Inflamm 2011; 8 : 36.

20. Chvapil M, Stankova L, Zukoski Ct, Zukoski C. Inhibition of
some functions of polymorphonuclear leukocytes by in vitro
zinc. J Lab Clin Med 1977; 89 (1): 135–146.

21. Chvapil M, Weldy PL, Stankova L, Clark DS, Zukoski CF. Inhi-
bitory effect of zinc ions on platelet aggregation and serotonin
release reaction. Life Sci 1975; 16 (4): 561–571.

22. Rao KM, Schwartz SA, Good RA. Age-dependent effects of
zinc on the transformation response of human lymphocytes to
mitogens. Cell Immunol 1979; 42(2): 270–278.

23. Boyle MD, Langone JJ, Borsos T. Studies on the terminal
stages of immune hemolysis. IV. Effect of metal salts. J Immunol
1979; 122 (4): 1209–1213.

24. Chen X, Jiang Y, Wang Z, Chen Y, Tang S, Wang S, et al. Altera-
tion in gut microbiota associated with zinc deficiency in school-
-age children. Nutrients 2022; 14(14).

25. Fischer Walker C, Black RE. Zinc and the risk for infectious
disease. Annu Rev Nutr 2004; 24 : 255–275.

26. Alshaikh B, Abo Zeed M, Yusuf K, Guin M, Fenton T. Effect of
enteral zinc supplementation on growth and neurodevelop-
ment of preterm infants: A systematic review and meta-analysis.
J Perinatol 2022; 42 (4): 430–439.

27. Klein CJ. Nutrient requirements for preterm infant formulas.
J Nutr 2002; 132 (6 Suppl 1): 1395s–1577s.

28. Embleton ND, Jennifer Moltu S, Lapillonne A, van den Akker
CHP, Carnielli V, Fusch C, et al. Enteral nutrition in preterm in-
fants (2022): A position paper from the ESPGHAN committee on
nutrition and invited experts. J Pediatr Gastroenterol Nutr 2023;
76 (2): 248–268.

29. Wulf K, Wilhelm A, Spielmann M, Wirth S, Jenke AC. Frequen-
cy of symptomatic zinc deficiency in very low birth weight in-
fants. Klin Padiatr 2013; 225 (1): 13–17.

30. Aumeistere L, Ciproviča I, Zavadska D, Bavrins K, Borisova
A. Zinc content in breast milk and its association with maternal
diet. Nutrients 2018; 10(10).

31. de Figueiredo CS, Palhares DB, Melnikov P, Moura AJ, dos
Santos SC. Zinc and copper concentrations in human preterm
milk. Biol Trace Elem Res 2010; 136(1): 1–7.

32. Krebs NF, Reidinger CJ, Hartley S, Robertson AD, Hambidge
KM. Zinc supplementation during lactation: Effects on maternal
status and milk zinc concentrations. Am J Clin Nutr 1995; 61 (5):
1030–1036.

33. Staub E, Evers K, Askie LM. Enteral zinc supplementation for
prevention of morbidity and mortality in preterm neonates.
Cochrane Database Syst Rev 2021; 3(3): Cd012797.

34. Sahin S, Sari FN, Bidev D, Bozkurt O, Dizdar EA, Oguz SS. Zinc
supplementation in very low birth weight infants: A randomi-
zed controlled trial. Am J Perinatol 2024; 41 (S 01): e3107–14.