Am J Perinatol
DOI: 10.1055/s-0043-1776762
Original Article

Zinc Supplementation in Very Low Birth Weight Infants: A Randomized Controlled Trial

Suzan Sahin
1   Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Izmir Demokrasi University, Izmir, Turkey
Fatma N. Sari
2   Division of Neonatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, Ankara, Turkey
Duygu Bidev
3   Division of Neonatology, Department of Pediatrics, Koru Sincan Hospital, Ankara, Turkey
4   Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
Evrim A. Dizdar
2   Division of Neonatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, Ankara, Turkey
Serife S. Oguz
2   Division of Neonatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, Ankara, Turkey
› Author Affiliations
Funding None.


Objective Preterm infants have high zinc (Zn) requirements and are generally believed to be in a negative Zn balance in the early period of life. In this study, we aimed to investigate the effect of high-dose Zn supplementation in very low birth weight (VLBW: infants with birth weight < 1.5 kg) infants on feeding intolerance and development of mortality and/or morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS).

Study Design This is a prospective randomized trial. VLBW preterm infants with gestational age of <32 weeks were randomly allocated on the seventh day of life to receive extra amount of supplemental Zn along with the enteral feedings (9 + 3 mg), besides regular low-dose supplementation (3 mg), from enrollment until discharge. Outcome measures were feeding intolerance, NEC (stage ≥ 2), LOS, and mortality.

Results A total of 195 infants (97 from study group and 98 from control group) were analyzed. A total of 46 (47.4%) infants in the study group and 64 (65.3%) infants in the control group ended up with feeding intolerance (p = 0.012). NEC was observed in 11 infants (11.2%) in the control group and only 1 infant (1%) in the study group (p = 0.003). There was a negative correlation between high-dose Zn supplementation and number of culture-proven LOS episodes (p = 0.041). This significance was also present for clinical sepsis, being higher in the control group (p = 0.029). No relationship between high-dose Zn supplementation and mortality and other morbidities (hemodynamically significant patent ductus arteriosus, bronchopulmonary dysplasia, retinopathy of prematurity, and severe intraventricular hemorrhage) was observed.

Conclusion Zn supplementation for VLBW infants is found to be effective to decrease feeding intolerance, NEC, and LOS episodes in this vulnerable population. Current data support the supplementation of VLBW infants with higher than regular dose of Zn.

Key Points

  • Higher dose of Zn supplementation is shown to be a beneficial intervention in VLBW infants.

  • Zn may decrease feeding intolerance, sepsis or NEC.

  • Higher than regular dose of Zn seems to be safe.


This study was conducted when all the authors were working in the Zekai Tahir Burak Maternity Teaching Hospital, Department of Neonatology.

Availability of Data and Material

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Authors' Contributions

S.S. conceptualized and designed the study, designed the data collection instruments, coordinated and supervised data collection, drafted the initial manuscript, and reviewed and revised the manuscript. F.N.S. conceptualized and designed the study, drafted the initial manuscript, performed the initial analyses, reviewed, and revised the manuscript. D.B. designed the data collection instruments, collected data, reviewed, and revised the manuscript. O.B. collected data, reviewed, and revised the manuscript. E.A.D. and S.S.O. conceptualized and designed the study, critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publication History

Received: 13 April 2023

Accepted: 17 October 2023

Article published online:
08 November 2023

© 2023. Thieme. All rights reserved.

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