|
Indian Pediatr 2010;47: 845-849 |
|
Effect of Oral Zinc Supplementation on the
Growth of Preterm Infants |
MN Islam, MAKA Chowdhury,* M Siddika,† SB Qurishi,$
MKJ Bhuiyan,** MM Hoque* and S Akhter
From the Department of Pediatrics, Mymensingh Medical
College Hospital; *Division of Neonatology, Bangladesh Institute of Child
Health, Dhaka Shishu Hospital; Department of Gynaecology and Obstetrics†
CBMCB, Mymensingh; $Chemistry Division, Atomic Energy Center,
Ramna, Dhaka; and **Department of Agricultural Statistics, Bangladesh
Agricultural University, Mymensingh, Bangladesh.
*Correspondence to: Dr Md Nazrul Islam, Assistant
Professor, Department of Paediatrics,
Mymensingh Medical College, Bangladesh.
Email: [email protected]
Received: July 7, 2009;
Initial review: August 7, 2009;
Accepted: November 5, 2009.
Published online: 2010
Jan 15.
PII: S097475590900473-1
|
Abstract
Objective: To compare the effect of oral zinc
supplementation on growth of preterm infants.
Design: Randomized controlled trial.
Setting: Dhaka Shisu Hospital (Tertiary care
hospital).
Subjects: 100 appropriate for date preterm
infants weighing between 1000 to 2500g were randomized to receive zinc
and multivitamin supplement (Group I; n=50) or only multivitamin
supplement (Group II).
Intervention: Zinc supplementation was given
2mg/kg/day for 6 weeks along with multivitamin in Group I and only
multivitamin to Group II.
Primary outcome variable: Increment of weight and
length.
Results: At enrollment, serum zinc (62.1±12.4µg/dL
in Group I and 63.1±14.6µg/dL in Group II) and hemoglobin levels
(14.9±2.4g/dL in Group I and 14.4±1.7g/dL in Group II) were almost
similar in both groups. Serum zinc levels were in lower limit of normal
range. After supplementation, serum zinc and hemoglobin levels were
significantly higher in Group I (105±16.5µg/dL) than Group II
(82.2±17.4µg/dL) (P<0.05). Weight, length and head circumference were
comparable in both groups at enrollment. Significant differences in
weight gain and increment in length were found in first and second
follow up between two groups but OFC increments were not significant
(P>0.05). Reduction of morbidity was apparent in zinc supplemented
group. No serious adverse effect was noted related to supplementation
therapy.
Conclusion: Zinc supplementation for preterm low
birth weight babies is found effective to enhance the growth in early
months of life.
Key words: Infants, Preterm, Supplementation,
Zinc.
Research No: BICH/2006/384
|
Z inc deficiency is common in young
infants in the developing world and is associated with reduced
immunocompetence and increased rates of serious diseases(1). Low zinc
concentrations have been observed in the cord blood of low birthweight (LBW)
newborn babies (<2500 g) and birthweight has been shown to be highly
correlated with cord zinc concentration in India(2,3). For several
reasons, preterm infants have relatively high zinc dietary requirements
and face special challenges to meet them. About 60% of fetal zinc is
acquired during the third trimester of pregnancy, when fetal weight
increases three-fold. Preterm infants (<37 weeks gestation) have lower
zinc reserves than term infants and because of immaturity, they may be
less efficient at absorbing and retaining zinc for growth(4). Zinc
deficiency has a negative effect on the endocrine system, leading to
growth failure, among other clinical manifestations. Zinc plays an
important role in gene transcription and is also one of the most prevalent
trace elements in the brain(5).
Zinc supplementation has been shown to reduce the rates
of diarrhea and pneumonia, and to enhance physical growth of young
infants(6). Several studies conducted in various parts of the world have
shown beneficial effect of zinc supplementation in early growth of preterm
babies (7,8). No study has been conducted in Bangladesh to evaluate the
effect of zinc on growth of preterm babies. We conducted this study to
evaluate the efficacy of oral zinc on growth of preterm infants.
Methods
This randomized controlled trial was conducted in the
Neonatal Special Care unit of Dhaka Shishu (Children) Hospital between
January 2006 and May 2007. According to the incidence of low birthweight,
the assumed targeted proportion was 0.03 (UNICEF, 2005)(9), the degree of
accuracy was 0.05 and with 5% level of significance, the targeted sample
size was 323 for population size equal or more than 10,000. However,
during the study period of 16 months, there were only 160 population
cases, and the estimated sample size was 107. As seven cases were not
enrolled due to their parent’s unwillingness to participate in the study,
100 cases were included and randomized to supplemented group (n=50)
and control group (n=50). Randomization was done by lottery method
of selection cards, which were equal in number for each group in sealed
opaque envelopes. Principal investigator and data analyzer were blinded to
the allocation of the treatment groups.
We included preterm infants below 37 weeks, weighing
1000 g to <2500 g and appropriate for gestational age. Those with major
birth defect or congenital deformities, unstable vital signs, or with
parents unwilling to participate, were excluded. The study protocol was
approved by ethical review committee of Dhaka Shishu Hospital. Informed
written consent was obtained from the parents before enrollment of the
patient in the study.
Immediately after registration of the patient, detailed
history was taken from mothers or relatives and physical examination was
performed. Gestational age was determined by maternal record and by New
Ballard Score system. Before intervention weight was measured by an
electronic weighing scale (Scale–Tronix Pediatric Scale, USA), which was
accurate to 5g and was calibrated before each measurement. Weighing was
carried out with the baby nude and before feeding. Occipito-frontal
circumference (OFC) was measured with a non-elastic standard plastic
measuring tape (1cm wide) to the nearest 1mm. Baseline serum zinc level
and hemoglobin estimation were done in both the groups, before giving
supplementation, within 7-21 days of postnatal age. Determination of serum
zinc concentration was carried out in the laboratory of chemistry division
of Atomic Energy Centre, Ramna, Dhaka, Bangladesh. Serum zinc level was
measured by flame atomic absorption spectrophotometry method. At the same
time, blood sample was sent for hemoglobin estimation and hemoglobin level
was assayed within half an hour of blood collection, using the
cyanmethemoglobin method.
When the neonates were 7 to 21 days old, before
discharge from the hospital, mother was given two bottles of supplement
containing zinc and instructed to feed her baby at a dose of 2 mg/kg/day
orally with other multivitamins for 6 weeks (Group I). Control group
(Group II) was instructed to take only the multivitamins (0.3mL daily,
each mL containing vitamin A 1500 IU, vitamin D 300 IU, thiamin
hydrochloride 0.48mg, riboflavin 0.3mg, pyridoxine hydrochloride 0.3mg,
nicotinamide 3mg, calcium D pantothenate 1.5mg and ascorbic acid 15mg) for
the same duration. Mothers were advised to attend the follow up clinic
after six weeks. Information was obtained about diarrhea, respiratory
illness, presence of fever or vomiting, pattern of feeding during these
six weeks. Anthropometric measurements were also recorded.
Blood samples for serum zinc and hemoglobin estimation
were obtained again from the babies of both the groups. Mothers of both
the groups were advised to visit again after six weeks. This time no zinc
supplementation was given but iron supplementation was added at a dose of
2.5 mg/kg/day along with multivitamin. During the second follow up,
anthropometric measurements and related history were obtained again.
Statistical analyses were done by SPSS. Independent
samples t test and Chi-square test were used to evaluate the
significance of differences between the groups and considered significant
at P<0.05.
Results
We enrolled 100 preterm appropriate for gestational age
neonates; 50 in zinc and multivitamin supplemented group (Group I) and 50
in multivitamin group (Group II). Seven infants were lost to follow-up in
Group I (3 at 1 st follow up and 4 at
2nd follow-up) and eight infants were lost to follow-up in Group II (3 at
1st follow-up and 5 at 2nd follow-up). These 15 infants were excluded from
analysis of growth. 43 infants in Group I and 42 infants in Group II
completed follow-up till 12 weeks of age for growth monitoring. The two
groups were comparable for age at enrollment, sex distribution, feeding
practices, maternal age, regularity of antenatal visits, and birth order.
Mean serum levels of zinc and hemoglobin are depicted in Table
I. Serum zinc level increased in both the groups after supplementation
but the increase was more marked in the zinc supplemented group.
Hemoglobin level decreased in both the groups.
Table I
Serum Zinc and Hemoglobin (Mean±SD) of the Study Infants At Enrollment and After Supplementation
|
Group I |
Group II |
P value |
|
n=50 |
n=50 |
|
Serum zinc (µg/dL) |
Baseline |
62.1±12.4 |
63.1±14.6 |
0.458 |
After supplementation |
105.8±16.5 |
82.2±17.4 |
0.001 |
Hemoglobin (g/dL) |
Baseline |
14.9±2.4 |
14.4±1.7 |
0.259 |
After supplementation |
10.2±1.4 |
11.6±1.8 |
0.403 |
Group I: Zinc supplementation group; Group II: Control group. |
Table II shows that weight, length and
OFC were almost similar in both the groups at enrollment. Gain in weight
and height were significantly more in zinc supplemented group both at
first and second follow up (P<0.05). There was no difference
between the groups for head circumference even after supplementation.
Table II
Weight Gain, Length and Occipito-Frontal Circumference (Mean±SD) of the Study Infants
|
|
Group I |
Group II |
P value |
|
|
n=50 |
n=50 |
|
Weight (g) |
Baseline |
1736.4±446.7 |
1632.8±321.7 |
0.19 |
|
1st follow-up |
2343.8±540.3 |
2060.2±396.3 |
<0.001 |
|
2nd follow-up |
2779.0±638.7 |
2474.6±441.8 |
<0.001 |
Length (cm) |
Baseline |
42.1±3.3 |
41.9±2.6 |
0.06 |
|
1st follow-up |
46.9±2.6 |
44.1±2.8 |
<0.001 |
|
2nd follow-up |
50.3±2.8 |
47.4±3.2 |
<0.001 |
OFC (cm) |
Baseline |
30.0±1.2 |
30.1±1.5 |
0.78 |
|
1st follow-up |
32.5±1.7 |
32.2±1.4 |
0.40 |
|
2nd follow-up |
34.4±1.1 |
34.1±1.5 |
0.42 |
1st Follow-up: After 6 weeks of supplementation, 2nd follow-up: 6 weeks after 1st follow-up;OFC: Occipeto-frontal circumference.
|
During the follow-up, only two children (4%) in zinc
supplemented group had diarrhea as compared to 8 (16%) in multivitamin
group. Thus, the incidence of diarrhea was significantly less in the zinc
group. However, there was no significant difference in children developing
ARI in the zinc (n=1) and vitamin (n=3) groups. There was no
statistically significant difference between the two groups in terms of
side effects. Vomiting and loose stools were noted in 6 and 4 children in
zinc group, 5 children each in multivitamin group, respectively.
Discussion
Zinc supplementation to preterm babies for 6 weeks
resulted in improved weight gain and linear growth and also helped in
reducing incidence of diarrhea. There were no significant side effects of
the supplements. These findings could have important implications for
child health survival program in developing countries with high incidence
of preterm low birth infants.
The strengths of this study included its randomized,
double-blind design and minor differences in initial anthropometric
status. The groups were similar at baseline, thus any differences in study
outcomes were likely due to the supplements that were provided. Follow-up
was given by highly trained observers and no significant differential loss
to follow-up between the groups was observed. Compliance with
supplementation was good. Limitations of the study included: single center
study, supplementation was given for shorter duration, surveillance was
not conducted daily and long term follow-up was not done due to difficulty
in communication, and fund limitation.
Baseline serum zinc levels and hemoglobin levels were
seen in both the groups. Altigani, et al.(10) reported serum zinc
concentration approximately 65µg/dL in low birth weight babies in their
study. Itabashi, et al.(11) found mean serum zinc
concentration 54±14.4µg/dL in their study. A similar serum zinc level
(62.4 ± 27.5µg/dL) was found in Bangladeshi preterm babies(12). Our
findings corro-borated the findings of these studies(10-12). Baseline
hemoglobin levels were within normal level but gradually hemoglobin level
reduced. Reduction of hemoglobin was due to prematu-rity(13). Lind, et
al.(14) found similar result in their study. We provided 2mg/kg/day
elemental zinc to the patients. Significant improvements were noted in
serum zinc values in the zinc supplemented group and not in the control
group. This indicated that zinc supplementation was successful in
improving the zinc status of these infants (P<0.001). Other studies
found similar results(8,15,16).
There were no significant difference in weight, length
and OFC at enrollment but a significant difference were found at 6 weeks
and 12 weeks follow up (P<0.05). This is understandable as zinc has
profound role on cellular growth and proliferation and performs various
metabolic functions. Castillo- Duran, et al. demonstrated improved
growth of low birthweight babies in their study, significantly greater
weight for age and length for age were found in the zinc supplemented
group(17). Lira, et al.(18) found that growth was enhanced in low
birthweight babies by giving 5 mg/day zinc. Sur, et al.(1) showed
improved weight gain of low birth weight baby after long time
supplementation of zinc. Osendarp, et al.(8) found similar results,
but others found no significant weight gain after zinc supplementation to
preterm babies in their studies(15,16). OFC was increased in both the
groups after supplementation at 1 st
and 2nd follow-up. The difference was not statistically significant. This
result was consistent with the results of Lind, et al.(14) and
Diaz-Gomez, et al.(16).
Morbidity pattern of both the groups were observed in
this study and significant difference in morbidity was found between two
groups. Osendarp, et al.(8) observed significant reduction of
morbidity after zinc supplementation among young infants who were zinc
deficient at baseline. Sur, et al.(1) demonstrated that zinc
supplementation was effective in reducing diarrhea incidence in their
study. Our find-ings are comparable with these studies. Thus, zinc
supplementation can be recommended along with other vitamins and minerals
to preterm low birth weight infants for their growth and developments.
Large scale multicenteric studies are required to confirm our results.
Contributors: All authors contributed to the study
design, collection of data, analysis and drafting the manuscript.
Funding: Partial funding by Bangladesh
Medical Research Council (BMRC). Orion laboratories, Bangladesh supplied
zinc syrup.
Competing interests: None stated.
What Is Already Known?
• Zinc supplementation reduces rates of diarrhea
and pneumonia in young infants.
What This Study Adds?
• Zinc supplementation to preterm low birthweight babies enhances
their growth.
|
References
1. Sur D, Gupta DN, Mondal SK, Ghosh S, Manna B,
Rajendran K, et al. Impact of zinc supplementation on diarrhoeal
morbidity and growth pattern of low birth weight infants in Kolkata,
India: A randomized, double-blind, placebo-controlled, community-based
study. Pediatrics 2003; 112: 1327-1332.
2. Gupta AP, Bhandari B, Gupta A. Serum copper, zinc,
magnesium and calcium in neonates. Indian Pediatr 1984; 21:
569-573.
3. Jeswani RM, Vani SN. A study of serum zinc levels in
cord blood of neonates and their mothers.Indian J Pediatr 1991; 58:
683-686.
4. Hambidge KM, Krebs NF. Zinc in the fetus and
neonate. In: Polin R, Fox W, Abman SH, editors. Fetal and Neonatal
Physiology. 3rd edn. Philadephia: Elsevier Science; 2004. p. 324-346.
5. Black M. Zinc deficiency and childhood development.
Am J Clin Nutr 1998; 68: 4-9.
6. Penny ME, Marin RM, Duran A, Peerson JM, Lanata CF,
Lonnerdal D, et al. Randomized controlled trial of the effect of
daily supplementation with zinc or multiple micronutrients on the
morbidity, growth and micronutrient status of young Peruvian children. Am
J Clin Nutr 2004; 79: 457-465.
7. Osendarp SJM, Van Raaij JMA, Arifeen SE, Wahed MA,
Baqui AH, Fuchs GJ. A randomized, placebo-controlled trial of the effect
of zinc supplementation during pregnancy and pregnancy out come in
Bangladeshi urban poor. Am J Clin Nutr 2000; 71: 114-119.
8. Osendarp SJM, Santosham M, Black RE, Wahed MA, Van
Raaij JMA Fuchs GJ. Effect of zinc supplementation between 1 and 6 mo of
life on growth and morbidity of Bangladeshi infants in urban slums. Am J
Clin Nutr 2002; 76: 114-119.
9. UNICEF. The State of the World’s Children 2005. New
York: UNICEF 2005. p. 110-134.
10. Altigani M, Murphy JF, Gray OP. Plasma zinc
concentration and catch up growth in preterm infants. Acta Paediatr Scand
1989; 357: 20-33.
11. Itabashi K, Saito T, Ogawa Y, Uteni Y. Incidence
and predicting factors of hypozincemia in very low birth weight infants at
near term postmenstrual age. Biol Neonate 2003; 83: 235-240.
12. Bagum NA. Comparison of zinc levels in blood, urine
of preterm and term baby and their relationship with zinc levels in
maternal blood and breast milk. Division of Neonatology, Department of
Paediatrics BSMMU, Dhaka; 2004. p. 37-40.
13. Roberts IAG, Murray NA. Hematology. In:
Textbook of Neonatology. 4th edn. Rennie JM. Edinburgh: Churchill
Livingstone; 2005. p.739-772.
14. Lind T, Lonnerdal B, Stenlund H, Gamaynti IL,
Ismail D, Seswandhana R, et al. A community based randomized
controlled trial of iron and zinc supplementation in Indonesian infants;
interactions between iron and zinc. Am J Clin Nutr 2003; 77: 883-890.
15. Friel JK, Andrews WL, Matthew JD, Long DR, Cornel
AM, Cox M, et al. Zinc supplementation in very low birth weight
infants. J Pediatr Gastroenterol Nutr 1993; 17: 97-104.
16. Díaz-Gómez NM, Domenech E, Barroso F, Castells S,
Cortabarria C, Jimenez A. The effect of zinc supplementation on linear
growth, body composition and growth factors in preterm infants. Pediatrics
2003; 111: 1002-1009.
17. Castillo-Duran C, Rodriguez A, Venegas GV, Alvarez
P, Icaza P. Zinc supplementation and growth of infants born small for
gestational age. J Pediatr 1995; 127: 206-211.
18. Lira PI, Ashworth A, Morris, SS. Effect of zinc
supplementation on the morbidity, immune function and growth of low birth
weight, full term infants in northeast Brazil. Am J Clin Nutr 1998;
68: 418-423.
|
|
|
|