Early and late Iron supplementation for low birth weight infants: a meta-analysis
Jin et al. Italian Journal of Pediatrics
Early and late Iron supplementation for low birth weight infants: a meta-analysis
Hong-Xing Jin 0
Rong-Shan Wang 0
Shu-Jun Chen 0
Ai-Ping Wang 0
Xi-Yong Liu 0
0 Yiwu Maternity and Child Care Hospital , No.320 Nanmen Street, Yiwu 32200Zhejiang , China
Background: Iron deficiency in infancy is associated with a range of clinical and developmentally important issues. Currently, it is unclear what is the optimal timing to administer prophylactic enteral iron supplementation in preterm and very low birth weight infants. The objective of this meta-analysis was to evaluate early compared with late iron supplementation in low birth weight infants. Methods: PubMed and Cochrane Library databases were searched up to May 10, 2014 for studies that compared the benefit of early and late iron supplementation in infants of low birth weight. Sensitivity analysis was carried out using the leave one-out approach and the quality of the included data was assessed. Results: The data base search and detailed review identified four studies that were included in the meta-analysis. The number of included patients was 246 (n = 121 for early supplementation and n = 125 for late supplementation) and the majority were premature infants. Across studies, early supplementation ranged from as early as enteral feeding was tolerated to 3 weeks, and late supplementation ranged from 4 weeks to about 60 days. Early treatment was associated with significantly smaller decreases in serum ferritin and hemoglobin levels (P < 0.001). In addition, the rate of blood transfusions was lower with early compared with late iron supplementation (P = 0.022). There was no difference between early and late supplementation in the number of patients with nectorizing enteroclitis (>bell stage 2) (P = 0.646). Sensitivity analysis indicated no one study overly influenced the findings and that the data was reliable. Conclusion: In conclusion, early iron supplementation resulted in less a decrease in serum ferritin and hemoglobin levels in infants with low birth rate. However, caution should be used when treating infants with iron so as not to result in iron overload and possibly negative long-term effects on neurodevelopment.
Iron; Supplementation; Low birth weight; Infant; Meta-analysis
Iron is an essential nutrient and plays a key role in many
processes including growth and development. Iron
deficiency in infancy is associated with a range of clinical
and developmentally important issues including
neurodevelopmental deficits, delayed maturation of the
auditory brainstem response, and abnormalities of memory
and behavior [1,2]. Iron deficiency is estimated to range
between 25% and 80% in preterms during infancy [3,4].
Low birth weight infants are particularly susceptible to
developing iron deficiency anemia since they typically
have small iron stores at birth and a greater need for
iron due to the rapid increase in red cell mass [5-7].
Other factors that may impact development of iron
deficiency anemia in low birth weight infants are preterm
birth, maternal conditions (such as diabetes mellitus,
hypertension, smoking, etc.) increased hemolysis,
reduced red blood cell life span, low circulating
erythropoietin levels, blood sampling, and loss of blood due to
A number of studies have found that iron
supplementation increases the levels of hematologic indicators or
iron status and reduces the frequency of anemia or iron
deficiency in low birth weight or premature infants [8,9].
One concern with iron supplementation is that free
ferrous iron may increase oxidative stress via the production
of free radicals . Hence, it is important to prevent not
only iron deficiency but also iron overload. Currently, it is
unclear at what time to administer prophylactic iron
supplementation in preterm very low birth weight infants
. In fact, the different international associations
recommend different timings for initiation of iron
supplementation for these babies . European Society for
Paediatric Gastroenterology, Hepatology, and Nutrition
Committee on Nutrition recommends prophylactic
enteral iron supplementation (given as a separate iron
supplement, in preterm formula or in fortified human milk)
should be started at 2 to 6 weeks of age (2–4 weeks in
extremely-low-birth weight infants) . The Canadian
Pediatric Society suggests for infants with low birth
weight (<1000 g) they should receive a total intake of
3–4 mg/kg per day starting at 6–8 weeks after birth
. The American Academy of Pediatric recommend
that that a preterm infant who is fed milk should receive
a supplement of elemental iron at 2 mg/kg per day
starting by 1 month of age and extending through
12 months of age . The objective was to gain insight
into the importance of timing of iron supplementation
by evaluating early compared with late iron
supplementation in low birth weight infants.
PubMed and Cochrane Library databases were searched
up to May 10, 2014 for studies that compared the
benefit of early and late iron supplementation in infants of
low birth weight. Search terms included premature birth,
preterm birth, premature infant, preterm infant, low
birth weight infant, iron supplementation, early, and late.
The search also included: (premature birth OR preterm
birth OR low birth weight) AND (iron deficiency OR
iron supplement OR iron). Included studies were
randomized controlled prospective trials whose patient
population were low birth weight infants (<2500 g) or
premature infants (gestational age <37 weeks). Eligible
studies used an intervention that involved iron
supplementation (any kind), and had to compare the effect of
early and late iron supplementation. Early
supplementation was considered between 2–3 weeks postnatal age
and late supplementation was defined as >4 weeks
postnatal age. Studies were included if they evaluated infants
who could tolerate enteral feeding (usually >2 weeks of
age). Studies were excluded if they were single arm and
did not evaluate serum ferritin and hemoglobin levels.
Studies were also excluded if the intervention was
combined with erythropoietin treatment, andif they were
non-English, case reports, letters, or comments.
The following data was extracted: author’s first name,
study design, inclusion criteria, iron source, early or late
supplementation, dosing route, number of subjects,
gestational age, birth weight, gender, and time of evaluation.
Also the level of serum ferritin (ng/mL) and hemoglobin
before and after treatment was extracted as was the
percent of subjects requiring blood transfusions and
necrotizing enterocolitis (>bell stage 2). Two reviewers
extracted the studies, and a third reviewer was consulted
to resolve any disagreements.
Quality assessment of the included studies was based on
Cochrane handbook version 5.1.0 Chapter 8 “Assessing
risk of bias in included studies” table for validity
assessment of eligible trials .
The changes in serum ferritin and hemoglobin levels,
blood transfusion rate, and necrotizing enterocolitis rate
were compared between participants who received early
supplementation and participants who received late
supplementation. For the continuous data, changes in serum
ferritin levels and hemoglobin levels, the data were
represented as mean ± standard deviation (SD) or mean (range:
min, max) for a given group in each study. The effect size
was calculated as difference in means of outcomes after
iron supplementation between early and late groups with
estimated 95% confidence intervals (95% CI) and
corresponding P values. For those data with mean (range), the
SD was utilized according to the equation SD = Range/
4before analysis . The difference in means of outcomes
greater than 0 indicated the late group was favored. The
difference in means of outcomes lower than 0 indicated
the early group was favored. If the means difference was
zero than both the early and late groups had similar
change in outcomes. For blood transfusion and
necrotizing enterocolitis rates, data were represented as events/
total participants for a given group in each study.
The effect size was calculated as odd ratio (OR) of
outcomes after iron supplementation with estimated 95% CI
between early and late groups and corresponding P values.
OR >1 indicates late group had higher rate than early
group; OR <1 indicates late group had lower rate than
early group; OR = 0 indicated both groups had similar rate.
A χ2 based test of homogeneity was performed using
Cochran’s Q statistic and I2. I2 indicates the percentage of
the total variability in effect estimates among trials due to
heterogeneity rather than chance. Random-effects model
of analysis (DerSimonian–Laird method) was used if
heterogeneity was detected (I2 >50% or P-value <0.05).
Otherwise, fixed-effects model (Mantel-Haenszel method) was
used. For evaluation, a combined difference in mean with
95% CI for continuous outcomes and OR (95% CI) for
categorical variables were calculated for the pooled study
results. A two-sided P value <.05 was taken to indicate
statistical significance for one comparison group over the
other. Sensitivity analysis was carried out for the outcomes
using the leave-one-out approach. Publication bias was
not performed because more than five studies are required
to detect funnel plot asymmetry . All analyses were
performed using Comprehensive Meta-Analysis statistical
software, version 2.0 (Biostat, Englewood, NJ).
The search of the databases identified 330 studies of
with 312 were excluded as not being relevant (Figure 1).
Eighteen studies were evaluated in detail and 13 were
excluded due to being a single arm study (n = 2), did not
compare early versus late iron supplementation (n = 10),
or did not report an outcome of interest (n = 1). Five
studies were identified and their data extracted [17-20]
However, the study of Franz et al.  was not included
in the meta-analysis due to lack of detail in sample size
for the outcomes evaluated. Hence, only four studies
were used for the meta-analysis [17-20].
All the studies included babiess with low birth weight
with premature babies being the most common (Table 1).
The mean gestational age of participants (ranged from
26.7 to 32.4 weeks) was similar between studies and
between groups within studies. The source of iron included
colloidal iron, iron trivalent (III)-hydroxide polymaltose
complex, ferrous sulfate, and ferrous succinate. The
number of participants in each study ranged from 15 to
105 (n = 226) for the early supplementation group and
from 13 to 99 (n = 224) for the late supplementation
group. About 50% of the infants were male and the time of
evaluation ranged from 1–2 days to 6 months. Early
treatment ranged from as early as enteral feeding was tolerated
 to 2 [17-19] or 3 weeks . Late supplementation
ranged from 4 weeks  to about 60 days [18,20,21].
Generally, across all studies serum ferritin and hemoglobin
numerically decreased following either early or late iron
supplementation (Table 2). In the different studies the serum
ferritin was measured by enzyme immunoassay and the
method sensitivity ranged from 1–2.5 ng/ml and
specificity of about 100%. Hemoglobin was estimated by Coulter
LH 750 analyzer and the specificity and sensitivity for this
assay are not reported. The percent of patients requiring
blood transfusions was numerically higher for those
receiving late iron supplementation compared to those
receiving early supplementation. Necrotizing enterocolitis
was similar between early and late iron supplementation.
Overall the studies were of high quality. In three of the
studies the participants and personnel were not blinded
to treatment (Table 3). The remaining two studies did
not describe blinding. Jansson et al.  did not describe
if allocation was concealed or if outcome assessments
were blinded. Only three of the studies describe that
they included an intention-to-treat analysis.
Serum ferritin level
Four studies with serum ferritin data were included in the
analysis [14-17]. A random effects analysis was applied
because there was evidence of heterogeneity among the
studies (Q statistic = 11.108, I2 = 72.99%, P = .011). The
summarized difference in means of change of serum
ferritin levels after iron supplementation significantly
favored the early iron supplementary group (difference in
means = −14.54, 95% CI = −22.14 to −6.94, P <.001)
(Figure 2A). The magnitude of fall in serum ferritin
level was smaller in the early compared with the late
iron supplementation group.
Three studies had complete hemoglobin data and were
included in the analysis A fixed effects analysis was
applied because there was no evidence of heterogeneity
among the studies (Q statistic = 0.817, I2 = 0%, P = .665).
Similar to ferritin levels, the summarized difference in
Figure 1 Flow diagram of study selection.
Preterm VLBW (<1500 g) infants who
reached at least 100 mL/kg/day of oral
feeds by day 14
All infants with a gestational age of
32 weeks who were fed human milk and
reached enteral intake of 100 mL/kg/d
Jansson  RCT
LBW infants with a birth weight ≦2000 g
and/or a gestational age of ≦35 weeks
Gestational age and birth weight were presented as mean ± SD.
*mean (range); †median (range).
na, not available; PO, per os;RCT, randomized clinical trial; VLBW, very low birth weight.
Table 1 Summary of basic characteristics of selected studies
Intramural preterm (<37 weeks gestational colloidal ferric early
age) VLBW infants (birth weight 1000–1500 g) hydroxide
who reached full enteral feeds of 180 mL/kg/
day by 2 weeks postnatal age
Group Route ; dose
of subject age (weeks)
(male/female) time point
1.248 (0.859, 1.960)† 18/12
1.072 (0.830, 2.173)† 14/16
26.9 (23, 35)*
0.872 (0.370, 1.300)*
All: 34 (29–37)* 1.855 ± 0.430
ferrous sulfate early
26.7 (23, 33)*
0.868 (0.380, 1.300)* na
Sankar  early
Arnon  early
Jansson  early
na, not available.
112 ± 5 at 2
weeks of age
113 ± 6 at 2
weeks of age
55.7 ± 12.1 at
59.0 ± 12.1 at
94 ± 27 at 2
weeks of age
90 ± 21 at 2
weeks of age
102 (34–220)*at 1–2
days of age
30 ± 12 at 8
weeks of age
at 8–10 weeks
of age 26 (18–45)*
at 6 months of age
1-2 days: 100 72 (21–170)* at
(45–200)*at 1–2 days 8–10 weeks of age 28
of age (10–115)* at 6 months
Table 2 Summary of outcomes of selected studies
Group number of
Serum ferritin (ng/mL)
10.3 ± 1.0 at 8–10 weeks of age; na
11.5 ± 0.7 at 6 monthsof age
9.7 ± 1.0 at 8–10 weeks of age
11.5 ± 0.5at 6 months of age
9.0 ± 1 at 8 weeks of age
7.4 ± 0.7 at 8 weeks of age
Blood transfusion (%) Necrotizing enterocolitis
(>bell stage 2)
Table 3 Quality assessment
Sankar  Y
Arnon  Y
Jansson  Y
Allocation Blinding of
concealment participants and
NA: not available; N: no;Y: yes.
means of change of hemoglobin levels after iron
supplementation favored the early iron supplementation group
(difference in means = −1.07, 95% CI = −1.29 to −0.85, P < .001)
(Figure 2B). The decrease in hemoglobin levels was smaller
in the early compared with the late iron supplementation
Three studies were included in the analysis since they had
complete data for the frequency of blood transfusions. A
fixed effects analysis was used because there was no evidence
of heterogeneity among the studies (Q statistic = 1.625,
I2 = 0%, P = .444). The summarized OR = 0.287 with a
95% CI = 0.099 to 0.834 indicating that early iron
supplementation lowered the frequency of blood
transfusion rate compared with late supplementation (P = .022)
Necrotizing enterocolitis (> bell stage 2)
Three studies that had complete necrotizing enterocolitis
data were included in the analysis. A fixed effects analysis
was applied as there was no evidence of heterogeneity
among the studies (Q statistic = 1.242, I2 = 0%, P = .537).
The summarized OR = 0.755 with a 95% CI = 0.227 to
2.506 indicated there was no difference between early and
late supplementation in the frequency of necrotizing
enterocolitis(P = .646) (Figure 2D).
We performed sensitivity analysis where the data was
reevaluated after each study was removed in turn. The
direction and magnitude of the combined estimates did
not change markedly for ferritin levels (Figure 3A),
hemoglobin levels (Figure 3B), frequency of blood
transfusions (Figure 3C), and the rate of developing
necrotizing enterocolitis (Figure 3D) when any one study was
removed. These findings indicate that the meta-analysis
had good reliability and that no one study overly
influenced the results.
Our analysis investigated the relative benefit of early
versus late iron supplementation in low birth weight infants
outcome data reporting
including premature infants. Early treatment was
associated with significantly smaller decreases in serum ferritin
and hemoglobin levels (P <.001). In addition, the rate of
blood transfusions was lower with early compared with
late iron supplementation (P = .022). There was no
difference between early and late supplementation in the
number of patients with nectorizing enteroclitis (P = .646).
Sensitivity analysis indicated no one study overly
influenced the findings and that the data was reliable.
Our study is consistent with findings that suggest early
compared with later iron supplementation may benefit
infants with low birth weights. The study of Lundstrom
et al.  found that in low birth weight infants (1,000 to
2,000 gm) (N = 117) that those infants who did not
receive iron supplementation (2 mg of iron/kg/day starting
at 2 weeks of age) had a higher tendency (about 80% of
infants by 6 months) to develop iron deficiency
compared to those infants who did receive iron
supplementation (about 5-10% by 6 months) . Hall et al. 
performed a randomized controlled study that compared
iron nutritional status in premature infants with birth
weight <1800 g (N = 20) who received iron (1.7 mg/L,
3 mg/L or 15 mg/L) added to premature formula that
was fed to the infants during initial hospitalization. They
found that the higher iron supplementation (3 mg/L and
15 mg/L) added at this early timepoint resulted in a
reduced frequency of anemia and low transferrin
saturation compared with the infants who were given the
1.7 mg/L iron supplementation . A study by Miller
at al.  found that there was no difference in
conventional measures of iron status in preterm babies (24–32
weeks of gestation) who either did or did not receive
iron supplementation (3–12 mg/kg/day) when the
supplementation occurred relatively late (ie, 7- to 60-days
Iron deficiency in infancy is associated with growth
and neurodevelopmental deficits. Steinmacher et al. 
in a follow-up study of a prior randomized trial
examined whether early compared with late iron
supplementation improved neurocognitive and motor development
in preterm infants (<1301 gm) . The original study
found that early enteral iron supplementation (as early
at enteral feeding was possible) compared with late
Figure 2 Forest plot evaluating the serum ferritin level (A), hemoglobin level (B), blood transfusion rate (C) and necrotizing enterocolitis
rate (D) of participants receiving iron supplementation were represented. Abbreviations: CI, confidence interval; Lower limit, lower bound of
the 95% CI; Upper limit, upper bound of the 95% CI.
supplementation (Day 61 of life) reduced the frequency
of blood transfusions and the incidence of iron
deficiency in low birth weight infants . In the follow-up
study, they used the Kaufmann Assessment Battery for
Children and the Gross Motor Function Classification
Scale to evaluate neurocognitive and psychomotor
development in children at 5.3 years’ corrected age who had
been treated with early or late iron supplementation in
the original study. The Kaufman Assessment Battery for
Children is a standardized test that assesses intelligence
and achievement in children aged two years, six months
to 12 years, six months. The Gross Motor Function
Classification Scale is a scale from 0 to 5 that classifies
the severity of motor involvement of children on the
basis of their functional abilities and their need for
assistive technology. Steinmacher et al. found that early
Figure 3 Sensitivity analysis of the influence of each study on the pooled estimate for serum ferritin level (A), hemoglobin level (B), blood
transfusion rate (C) and necrotizing enterocolitis rate (D) of participants receiving iron supplementation were represented. The leave-one-out
approach was used. Abbreviations: CI, confidence interval; Lower limit, lower bound of the 95% CI; Upper limit, upper bound of the 95% CI.
enteral iron supplementation compared with late
supplementation was associated with a trend for better
longterm neurocognitive and psychomotor development;
about 19% of the early and 35% of the late
supplementation group had abnormal neurological development and
approximately 66% and 54%, respectively, were without
disability. Gross Motor Function Classification Scale
score >1 was found in 2% of patients for the early and
7% of patients in the late iron supplementation group. A
limitation of the study was that the original study was
not powered to evaluate neurocognitive development.
Two other studies also evaluated the use of iron
supplementation in low birth weight infants on cognitive
and neurodevelopment outcomes [25,26]. Friel et al. 
investigated the effect of increased iron intake on
hematologic and cognitive status in infants with low
birth rate (N = 58). They evaluated two levels of iron
supplementation: 13.4 mg iron/L and 20.7 mg iron/L.
They found that hemoglobin and Griffith’s Developmental
Assessment were not different between treatment groups
(P values <.05). They did find that the number of
respiratory tract infections was higher in the high compared with
low iron groups, possibly indicating a detriment for
administering high levels of iron. These findings suggest
there is no advantage to administering elevated iron to
infants with low birth weights.
Ohls et al.  assessed the effect of supplementing
erythropoietin and iron compared with iron alone on
long-term developmental outcomes in extremely low
birth weight infants (≤1000-gm birth weight) (N = 172).
Approximately 5 mg/kg of iron was included in both
treatment groups. The study evaluated the need for
transfusions, anthropometric measurements,
postdischarge events, and developmental outcomes at 18 to
22 months’ corrected age. They found no significant
difference in weight, length, or head circumferance
between the erythropoietin plus iron compared with iron
alone groups. There was also no difference between
groups in rate or rehospitalization, transfusions after
discharge, the percentage of patients with Bayley-II
Mental Developmental Index <70 (34% for
erythropoietin plus iron and 36% for iron alone) or other
neurodevelopmental and cognitive functions. The authors
conclude that early treatment with erythropoietin plus
iron was not of greater developmental benefit than iron
Our meta-analysis only included four studies and the
studies were heterogenous with respect to dosage and
timing of iron supplementation. For example, the
definition of “early” and “late” supplementation varied across
studies. Heterogeneity in studies investigating the effect
of iron supplementation in low birth infants has been
noted before  and indicates the need for more
consistent designs among studies that investigate this issue. In
addition, the iron sources used across the studies
differed and had different oral absorption and
gastrointestinal tolerance , which may have confounded our
findings. We also did not evaluate the effect of early
versus late iron supplementation on neurodevelopment,
cognitive function, or growth. Further studies are
required to address these important medical questions.
Our findings showed that the early group had a better
iron status than late group, which suggest that the
prevalence of iron deficiency and iron deficiency anemia
may be lower in early supplement group. However, only
one included study  evaluated iron deficiency, hence,
we were not able to analyze this directly. In addition, we
did not assess how dose and a more precise evaluation
of timing affected the results. This was not possible as
the doses across the studies overlapped and the timing
was variables. Moreover, only five studies were included
in the analysis making it not practical to do subgroup
In conclusion, early iron supplementation improved
serum ferritin and hemoglobin levels in infants with low
birth rate. However, caution should be used when
treating infants with iron so as not to result in iron overload
and possibly negative long-term effects on
The authors declare that they have no competing interests.
HXJ is the guarantor of integrity of the entire study, RSW helped in editing
the manuscript, SJC performed the literature search, APW extracted the data,
and XYL performed the statistical analysis. All authors read and approved the
1. Rao R , Georgieff MK . Iron in fetal and neonatal nutrition . Semin Fetal Neonatal Med . 2007 ; 12 : 54 - 63 .
2. Makrides M , Anderson A , Gibson RA , Collins CT . Improving the neurodevelopmental outcomes of low-birthweight infants . Nestle Nutr Inst workshop Ser . 2013 ; 74 : 211 - 21 .
3. Ferri C , Procianoy RS , Silveira RC . Prevalence and risk factors for iron-deficiency anemia in very-low-birth-weight preterm infants at 1 year of corrected age . J Trop Pediatr . 2014 ; 60 : 53 - 60 .
4. Vucic V , Berti C , Vollhardt C , Fekete K , Cetin I , Koletzko B , et al. Effect of iron intervention on growth during gestation, infancy, childhood, and adolescence: a systematic review with meta-analysis . Nutr Rev . 2013 ; 71 : 386 - 401 .
5. Lundstrom U , Siimes MA , Dallman PR . At what age does iron supplementation become necessary in low-birth-weight infants ? J Pediatr . 1977 ; 91 : 878 - 83 .
6. Rao R , Georgieff MK . Iron therapy for preterm infants . ClinPperinatol . 2009 ; 36 : 27 - 42 .
7. Gorten MK , Cross ER . Iron Metabolism in Premature Infants . Ii. Prevention of Iron Deficiency. J Pediatr . 1964 ; 64 : 509 - 20 .
8. Long H , Yi JM , Hu PL , Li ZB , Qiu WY , Wang F , et al. Benefits of iron supplementation for low birth weight infants: a systematic review . BMC Pediatr . 2012 ; 12 : 99 .
9. Mills RJ , Davies MW . Enteral iron supplementation in preterm and low birth weight infants . Cochrane Database Syst Rev . 2012 ; 3 : CD005095 .
10. Anabrees J. Early Enteral Prophylactic iron Supplementation May be Preferred in Preterm Very Low Birth Weight Infants . J Clin Neonatol . 2014 ; 3 : 14 - 5 .
11. Agostoni C , Buonocore G , Carnielli VP , De Curtis M , Darmaun D , Decsi T , et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition . J Pediatr Gastroenterol Nutr . 2010 ; 50 ( 1 ): 85 - 91 .
12. Nutrition Committee , Canadian Pediatric Society. Nutrient needs and feeding of premature infants . Nutrition Committee, Canadian Paediatric Society. CMAJ . 1995 ; 152 ( 11 ): 1765 - 85 . http://www.cmaj.ca/content/152/11/ 1765.reprint.
13. Baker RD , Greer FR , Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age) . Pediatrics . 2010 ; 126 ( 5 ): 1040 - 50 .
14. Higgins JP , Thompson SG . Quantifying heterogeneity in a meta-analysis . Stat Med . 2002 ; 21 : 1539 - 58 .
15. Hozo SP , Djulbegovic B , Hozo I. Estimating the mean and variance from the median, range, and the size of a sample . BMC Med Res Methodol . 2005 ; 5 : 13 .
16. Sutton AJ , Duval SJ , Tweedie RL , Abrams KR , Jones DR . Empirical assessment of effect of publication bias on meta-analyses . BMJ . 2000 ; 320 : 1574 - 7 .
17. Joy R , Krishnamurthy S , Bethou A , Rajappa M , Ananthanarayanan PH , Bhat BV . Early versus late enteral prophylactic iron supplementation in preterm very low birth weight infants: a randomised controlled trial . Arch Dis Child Fetal Neonatal Ed . 2014 ; 99 : F105 - 109 .
18. Sankar MJ , Saxena R , Mani K , Agarwal R , Deorari AK , Paul VK. Early iron supplementation in very low birth weight infants-a randomized controlled trial . Acta Paediatr . 2009 ; 98 : 953 - 8 .
19. Arnon S , Shiff Y , Litmanovitz I , Regev RH , Bauer S , Shainkin-Kestenbaum R , et al. The efficacy and safety of early supplementation of iron polymaltose complex in preterm infants . Am J Perinatol . 2007 ; 24 : 95 - 100 .
20. Jansson L , Holmberg L , Ekman R. Medicinal iron to low birth weight infants . Acta Paediatr Scand . 1979 ; 68 : 705 - 8 .
21. Franz AR , Mihatsch WA , Sander S , Kron M , Pohlandt F. Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams . Pediatrics . 2000 ; 106 : 700 - 6 .
22. Hall RT , Wheeler RE , Benson J , Harris G , Rippetoe L. Feeding iron-fortified premature formula during initial hospitalization to infants less than 1800 grams birth weight . Pediatrics . 1993 ; 92 ( 3 ): 409 - 414 .24.
23. Miller SM , McPherson RJ , Juul SE . Iron sulfate supplementation decreases zinc protoporphyrin to heme ratio in premature infants . J Pediatr . 2006 ; 148 ( 1 ): 44 - 8 .
24. Steinmacher J , Pohlandt F , Bode H , Sander S , Kron M , Franz AR . Randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams: neurocognitive development at 5.3 years' corrected age . Pediatrics . 2007 ; 120 : 538 - 46 .
25. Ohls RK , Ehrenkranz RA , Das A , Dusick AM , Yolton K , Romano E , et al. Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron . Pediatrics . 2004 ; 114 : 1287 - 91 .
26. Friel JK , Andrews WL , Aziz K , Kwa PG , Lepage G , L'Abbe MR . A randomized trial of two levels of iron supplementation and developmental outcome in low birth weight infants . J Pediatr . 2001 ; 139 : 254 - 60 .
27. Patil SS , Khanwelkar CC , Patil SK . Conventional and newer oral iron preparations . Int J Med Pharm Sci . 2012 ; 2 : 16 - 22 .