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1112  Original article

Effect  of zinc supplementation on growth of preterm infants

Ghada M. El Mashada, Hanan M. El Sayeda, Amr M. Shawky Elghorabb
a
Department of Paediatrics, Faculty of
Medicine, Menoufiya University,bDepartment of
Paediatrics, General Hospital, Menoufiya, Egypt
Correspondence to Amr M. Shawky Elghorab,
MBBCh, Shebin El‑kom‑Batanoun, Menoufia,
32721, Egypt
Tel: +20 100 386 6455;
e-mail: amrshawky8@gmail.com
Received 24 March 2016
Accepted 22 May 2016
Menoufia Medical Journal 2016, 29:1112–1115
Objective
This work aimed to study the effect of zinc supplementation on growth of preterm infants.
Background
Preterm infants have impaired zinc status because of low body stores, as 60% of fetal zinc
is acquired during the third trimester of pregnancy. In addition, this can be attributed to their
limited capacity to absorb and retain micronutrients, coupled with increased endogenous
losses associated with organ immaturity.
Patients and methods
The present study was carried out on 60 healthy preterm infants below 37 weeks of age divided
into two groups: a zinc-supplemented group fed with breast milk and supplemented with zinc
(2 mg/kg/day) since the first day of life, and a non-zinc-supplemented group fed with breast
milk (without zinc supplementation). Both groups were followed up for 6 months for growth
and serum levels of zinc and hemoglobin at the age of 6 months.
Results
The zinc-supplemented group showed a significant increase (P<0.05) in both weight and
length at the age of 6 months. There was a highly significant increase in the serum zinc and
hemoglobin levels in the zinc-supplemented group compared with the non-zinc-supplemented
group, in addition to a significant positive correlation between zinc level and hemoglobin level
at day 1 and at 6 months.
Conclusion
Zinc supplementation for preterm low birth weight babies was found effective in enhancing the
growth in early months of life and has a positive effect on their linear growth.

Keywords:
6 months, growth, hemoglobin, preterm, zinc

Menoufia Med J 29:1112–1115

© 2017 Faculty of Medicine, Menoufia University
1110‑2098

Introduction
Preterm birth is often associated with nutritional
compromise and impaired growth performance. It
is believed that the relation between nutrition and
growth is mediated by changes in the hormone and
growth factor axis [1].
Zinc deficiency during infancy has a negative effect
on the endocrine system, leading to growth failure
among other clinical manifestations. Zinc is a key
component of cell architecture and function in the
organism. It is required for the production of over 200
enzymes, including phosphatases, metalloproteinases,
oxidoreductases, and transferases, which are involved
in protein synthesis, nucleic acid metabolism, and
immune functions. In addition, it is a structural
component of various proteins, hormones, and
nucleotides [2].
Preterm infants have a high risk for zinc, copper, and
other micronutrient deficiencies and are frequently
growth‑retarded. There are multiple contributing
factors that explain this. As a consequence of shorter
gestation and the immaturity of the gastrointestinal
tract, these infants have lower body stores. Premature
infants also have a high nutrient demand because
of rapid postnatal growth and an increased risk for
intercurrent diseases, which means that the intake of
nutrients may be inadequate during the first months
of life [4].
In an attempt to improve the growth of premature
infants, various controlled nutritional intervention
studies have been conducted. These studies have shown
that zinc supplementation has a positive influence on
linear growth, motor development  [5], and weight
gain, and a lower prevalence of diarrhea [6].

Zinc also plays an important role in gene transcription.

Zinc is one of the most prevalent trace elements in the
brain. Accordingly, there is evidence that zinc may be
essential for brain function as well as for growth of the
fetus and child [3].
This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as
long as the author is credited and the new creations are licensed under
the identical terms.

1110-2098 © 2017 Faculty of Medicine, Menoufia University DOI: 10.4103/1110-2098.20249

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Zinc supplementation on growth  of preterm infants El Mashad et al.  1113
Preterm infants are at an increased risk for death;
acute and long‑term morbidities are often associated
with nutritional compromise and impaired growth.
With about 13 million preterm babies born each
year worldwide, the burden is disproportionately
concentrated in Africa and Asia, where about 85% of
all preterm births occur (31 and 54%, respectively) [7].
Patients and methods
This study was carried out on 60 preterm infants (male
and female with weight between 1800 and 2500  g)
admitted in the NICU at Tala Hospital, Menoufia
Governate. The infants were divided into two groups.
Group  I included preterm infants who received
zinc supplementation at a dose of 2  mg/kg/day
orally for 6  months. Group  II  (the control group)
included preterm infants who did not receive zinc
supplementation.
Consent
Written consent was obtained from their parents
before enrollment in the study.
Privacy
All participants’ names were hidden and replaced with
code numbers to maintain privacy of the participants.
Both groups fulfilled the same inclusion and exclusion
criteria.
The inclusion criteria were as follows: Gestational age
(GA) between 32 and 36 weeks, birth weight between
1800 and 2500  g, appropriate for GA  (birth weight
between the 10th and the 90th percentile for GA), and
in a stable clinical condition without any evidence of
disease likely to influence growth.
The exclusion criteria were as follows: term
neonates (>37 weeks of gestation), intrauterine growth
restriction, congenital malformations, chromosomal
abnormalities, suspected inborn errors of metabolism,
multiple gestations, congenital heart disease, and
perinatal asphyxia (Apgar <3, longer than 5 min).
All candidates were subjected to a thorough
clinical examination, immediately after birth, and
anthropometric measurements  (weight, length, and
head circumference) were recorded. Blood samples
were drawn for serum hemoglobin  (Hb%) and zinc
level determination on the first day. At the age of
6  months, anthropometric measurements  (weight,
length, and head circumference) for all infants were
recorded again. Blood samples were drawn for serum
zinc level and Hb% level determination at the age of
6 months.
Approval
Oral informed consent was obtained from the parents
of the preterm infants studied. The ethics committee
of Faculty of Medicine, Menoufia University, approved
the study.
Data management and statistical analysis
This phase included the following: coding of collected
data and data entry into the computer, and statistical
analysis of the collected data. The collected data were
entered into the computer using the Statistical Package
for Social Sciences  (SPSS; SPSS Inc., Chicago,
Illinois, USA) program for statistical analysis. Two
types of statistical analyses were carried out: descriptive
statistics  [e.g.  n  (%), mean and SD] and analytical
statistics  (e.g.  Student’s t‑test, Mann–Whitney
test, χ2‑test, paired  t‑test, and Pearson’s correlation
coefficient). A P value of less than 0.05 was considered
statistically significant.
Results
The 60 healthy exclusively breastfed preterm infants
were divided equally into two groups: the zinc
supplemented group and the non‑zinc‑supplemented
group.
In the present study, on comparison between the two
groups for anthropometry, it was observed that there
was a significant increase in weight and length at
6  months in the zinc‑supplemented group compared
with the non‑zinc‑supplemented group.
Our study also found a highly significant increase in
the serum zinc levels of the zinc‑supplemented group
compared with the non‑zinc‑supplemented group
at the age of 6  months, in addition to a significant
positive correlation between zinc level and Hb% at day
1 and at 6 months. In the present study, on comparing
the two groups in terms of Hb% and serum zinc levels,
it was found that the supplemented group acquired
significantly higher levels compared with the other
group at the age of 6 months.
Discussion
Zinc is a nutrient essential for maintaining the structure
and functions of several enzymes, including those that
are involved in the production of growth hormones
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1114  Menoufia Medical Journal, Volume 29 | Number 4 | October-December 2016

and in transcribing and translating deoxyribonucleic
acid and thereby cell division [4].
In the present study, there were statistically significant
differences between the two groups as regards weight
and length at the age of 6 months. This demonstrates
the high bioavailability of oral zinc on raising the
serum zinc levels, with subsequent positive effect on
weight and length.
In agreement with our study, Islam and colleagues (2010)
have found that zinc supplementation for preterm
low birth weight babies is effective in enhancing the
growth in early months of life. Weight, length, and
head circumference were comparable in both groups at
enrollment. Significant differences in weight gain and
increment in length were found during the first and the
second follow‑up between the two groups. Reduction
in morbidity was apparent in the zinc‑supplemented
group. No serious adverse effect was noted related to
supplementation therapy [8].
Moreover, Díaz‑Gómez et al. [9] found in their study
on the effect of zinc supplementation on linear growth,
body composition, and growth factors in preterm
infants that zinc supplementation has a positive effect
on linear growth in premature infants.
Moreover, O El-Farghali 2015 [10]   conducted a study
on early zinc supplementation and enhanced growth
of the low‑birth‑weight neonate. They concluded
that early start of oral zinc supplementation in
low‑birth‑weight neonates assists catch‑up growth,
probably through the rise in insulin‑like growth
factor‑1 [10].
Aminul et al. (2009) in their large study on 200 preterm
neonates (between 1200 and 2300 g) divided the cases
into two groups: group I, which received 5 mg Zn, and
group II, which received placebo. After following up of
their weight for 1 month, they found that the weight of
infants in the zinc‑supplemented group was significantly
higher than that in the placebo group  (P  <  0.001),
demonstrating that zinc supplementation in preterm
babies enhanced more weight gain and that such
babies experienced fewer problems such as infection,
convulsion, and jaundice. There was no adverse effect in
the zinc‑supplemented group [11].
However, there are other contradictory studies such
as that of Gulani et al. [12], who viewed that there is
no convincing evidence recommending routine zinc
supplementation for preterm newborns in developing
countries, and Mazariegos et  al.  [13], who in their
study on their study on growth of preterm infants
showed that no effect on linear growth was observed
with dietary phytate reduction, zinc supplementation,
or their combination. This contradiction could be
explained as the lack of growth response and may be
attributed to other micronutrient deficiencies that
coexist in this population, limiting the response to
zinc. Moreover, this may be due to the difference in the
number of studied cases.
In our study, we found a highly significant increase
in serum zinc levels in the zinc‑supplemented group
compared with the non‑zinc‑supplemented group at
the age of 6 months. Moreover, we found a significant
positive correlation between zinc level and both weight
and length.
In agreement with our study, Islam et al. [8] found that,
after supplementation, serum zinc was significantly
higher in group I (the zinc‑supplemented group) than
in group II (the non‑zinc‑supplemented group).

Table 1 Comparison between the studied groups as regards Apgar, gestational age, HC, length, and weight
Zinc‑supplemented (N=30) Non‑zinc‑supplemented (N=30) t‑test P‑value
Apgar score at 1 min 6.3±0.84 6.1±0.77 0.81 0.42
Apgar score at 5 min 8.60±0.49 8.62±0.49 0.88 0.38
Gestational age 35.1±0.83 35±0.85 0.3059 0.76
Head circumference at day 1 32.1±1.1 32.4±1.32 0.159 0.87
Head circumference at 6 months 41.3±0.89 41.25±0.63 0.8076 0.422
Length at day 1 45±1.32 44.8±2.41 0.4976 0.62
Length at 6 months 61.4±1.02 60.5±1.81 2.336 0.02
Weight at day 1 2380±268.33 2426.7±283.93 0.6524 0.52
Weight at 6 months 6730 ± 279.35 6566.7 ± 292.83 2.211 0.03
HC: Head circumference

Table 2 Comparison between the studied groups as regards zinc and hemoglobin
Zinc‑supplemented (N=30) Non‑zinc‑supplemented (N=30) t‑test P‑value
Hb at day 1 15.7±1.16 15.8±1.19 0.2307 0.82
Hb at 6 months 12.6±0.88 10.9±0.49 8.808 <0.001
Zinc at day 1 63±5.44 63.9±5.10 0.8796 0.38
Zinc at 6 months 99.1 ± 7.22 76.6 ± 4.61 14.37 <0.001
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Zinc supplementation on growth  of preterm infants El Mashad et al.  1115
In our study, we noted a highly significant increase in
Hb% levels in the zinc‑supplemented group (P < 0.001)
at the age of 6  months compared with the
non‑zinc‑supplemented group at the age of 6 months.
This is in agreement with the findings of, Díaz‑Gómez
et  al.  [9], O El-Farghali 2015 [10], and Osendarp
et al. [14] (Table 1 and 2).
Conclusion
Zinc supplementation for preterm low birth weight
babies is found effective in enhancing the growth in
early months of life and has a positive effect on their
linear growth. Zinc supplementation had a beneficial
effect on increasing serum zinc and hemoglobin level
of preterm infants.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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