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Zinc Supplementation for Improving Outcome in Neonatal Sepsis: A Systematic Review

Akhil Deepak Vatvani1, Prio Wibisono1, Andry Juliansen2

1Facultyof Medicine, Pelita Harapan University, Tangerang, Indonesia
2Department of Pediatrics, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia

Background Discussion
Despite the advancement of neonatal care, the mortality rate of neonatal • The study by Metha et al did not show any significant difference in
sepsis is still high. Various factors contribute to increased susceptibility of mortality rates and hospital stay maybe due to the insufficient dose
infection in neonates, one of which is the immature immune system. Zinc and short duration of therapy. The study by Banupriya et al
has been known to play a role in the immune system as it is crucial for showed significant reduction of mortality rates in the zinc group
immune cell maturation. compared to the control group maybe due to the high dose and
longer duration. This may suggest that zinc supplementation is
Objectives dose-dependent for improving outcome in neonatal sepsis.
This study aims to review the effect of zinc supplementation for • Therefore, future studies are needed with a detailed stratification
improving outcome in neonatal sepsis. to see the effect of different doses in neonatal sepsis and find the
optimum dose. Also, other outcomes such as morbidity rates and
adverse effect of zinc in various doses should also be taken into
Methods account.
• The PRISMA model guided this systematic literature search.
• PubMed, EBSCOhost, Cochrane and ScienceDirect journals were
searched for articles published between 2000 to 2018.
• Search terms included neonatal, neonate, newborn, premature, low Zinc supplementation at a higher dose (3mg/kg twice a day) maybe
birth weight, infant, sepsis and zinc. beneficial in reducing mortality rate, but not length of hospital stay.
• The primary outcome was mortality. However, further research is needed to confirm this result.
• The secondary outcome was length of hospital stay.
• This study also used suggested risk of bias criteria for Cochrane
EPOC reviews (Table 1). References
1. Banupriya N, Bhat B, Benet B, Catherine C, Sridhar M, Parija S. Short Term Oral Zinc Supplementation
among Babies with Neonatal Sepsis for Reducing Mortality and Improving Outcome – A Double-Blind
Randomized Controlled Trial. The Indian Journal of Pediatrics. 2017;85(1):5-9.
Results 2. Mehta K, Bhatta N, Majhi S, Shrivastava M, Singh R. Oral zinc supplementation for reducing mortality in probable
neonatal sepsis: A double blind randomized placebo controlled trial. Indian Pediatrics. 2013;50(4):390-393.
• The search yielded a total of 93 articles, out of which two met criteria. 3. Terrin G, Berni Canani R, Passariello A, Messina F, Conti M, Caoci S et al. Zinc supplementation reduces morbidity
and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an
• Both studies are randomized controlled trials (Table 2). industrialized country. The American Journal of Clinical Nutrition. 2013;98(6):1468-1474.
• The first study consisted of 614 neonates that were given 1mg/kg/day Table 2. Summary of Included Studies
zinc did not show significant difference in mortality rates between zinc Author(s) Year Patient(s) Outcome Assessed Dose of Zinc Comparison Main Findings
and control group. K Mehta et al 2012 614 (Drug group 1.Mortality 1 mg/kg/day; mean Placebo group 1. 30 neonates in the zinc group and 24 in the placebo group
• The second study consisted of 150 neonates that were given 3mg/kg = 307 ; Placebo 2.Hospital Stay (hours) duration of treatment (no zinc given) expired (P = 0.393).
zinc twice a day showed significant difference in mortality rates group = 307) 3.Use of 2/3 line antibiotics is 145 hours 2. 142.85 ± 69.41 hours in the zinc group as compared to 147.99 ±
between zinc and control group (6.6% vs. 17.3%; P < 0.04). 73.13 hours in the placebo group (P = 0.841).
• Both studies did not show significant difference in length of hospital 3. 41 neonates in the zinc group as compared to 37 in the placebo
stay between two groups. group required higher lines of antibiotic therapy (P = 0.628).
Knowledge of the allocated interventions

Newton 2017 150 (Treatment 1.Mortality 3 mg/kg of Zinc sulfate Control group 1. 5 neonates in the zinc group and 13 neonates in the control
Baseline outcome measurements similar

adequately prevented during the study

Random Sequence Generation

Protection against contamination

Baseline characteristics similar

Selective outcome reporting

Banupriya et al group = 75 ; 2.Hospital stay in NICU (days) monohydrate twice a (no zinc given) group expired (P < 0.04).
Incomplete outcome data

Control group = 3.Serum zinc (after 10 days) day orally for 10 days 2. 15 (11 – 46) days in the zinc group compared to 15 (10 – 46) in
Allocation concealment

75) the control group expired (P = 0.83)

3. In zinc’ group, serum zinc level was considerably increased
compared to ‘no zinc’ group after 10 days (P < 0.03).

= Low Risk

K Mehta et al = High Risk

= Unclear Risk
Newton Banupriya et al Akhil Vatvani akhilvatvani@gmail.com
Table 1. Assessment of Bias