ABSTRACT
Objectives: To determine the frequency of
iron deficiency anemia and thalassemia trait among children attending the Pediatric
Department at Prince Rashed Bin Al-Hassan Military Hospital in the North of
Jordan.
Methods: This hospital based study was conducted in the year
2008 on 1,012 children aged 6 months to 14 years who attended the Pediatric
Department at Prince Rashed Bin Al-Hassan Military Hospital in North of Jordan using fully automated blood cell
counter for of the mean corpuscular volume, serum ferritin level and high
performance liquid chromography, or genotyping. None of
the subjects included in the study had been on any hematinic in the previous
six months, had infection in the past one month or had a chronic disease. The
diagnosis of iron
deficiency anemia was defined as mean corpuscular volume ≤ mean – 1 standard deviation corrected for age, with
a ferritin level < 7 ng/ml of the serum (normal reference range 7 – 140
ng/ml). The diagnosis of thalassemia trait, for subjects
with normal or high serum ferritin and those whose mean corpuscular volume was non-compliant to iron therapy, was obtained by high
performance liquid chromography or polymerase chain reaction, which was performed
at Princess Eman Research and Laboratory Science Center.
Results: The
frequency of iron
deficiency anemia and thalassemia trait was 13.3% and 5.8% respectively. They were equally
frequent among males and females. The age specific-rate was as follows: 6
months to 2 years 7.4% iron deficiency anemia and 1.3% thalassemia trait,
2 - 6 years 3.1% iron
deficiency anemia and 2.5% thalassemia trait, 6 - 12 years 1.6% iron deficiency anemia and 1.2% thalassemia trait
and 12-14 years 1.3% iron deficiency anemia and 0.9% thalassemia trait.
Conclusion: The frequency of iron deficiency anemia (13.3%) and thalassemia trait (5.8%) among
children in North of Jordan was estimated by statistical measurement of mean corpuscular volume fL. It is a strong cost effective predictor in the
majority of cases. The red-blood indices complemented with serum ferritin and high
performance liquid or polymerase chain reaction are of value for precise
diagnosis.
Key
words: Children, Frequency,
Iron deficiency anemia, North of Jordan, Thalassemia Trait
JRMS
March 2011; 18(1): 39-44
Introduction
Anemia is a major pediatric health problem and iron
deficiency anemia (IDA) is the most common cause of anemia,(1-3)
it is usually due to nutritional imbalances
in children among vulnerable groups of population in Jordan, and it is an important
public health problem worldwide.(4-8)
Iron deficiency is not normally present in hereditary
anemias like thalassemias,(9) but it is one of the causes of
microcytic hypochromic anemia. Moreover, in many parts of the world, thalassemia
trait (TT) as a cause of microcytic anemia is only less prevalent than IDA and is
sometimes confused with it, since it is characterized by microcytosis and
sometimes mild anemia. The use of mean corpuscular volume (MCV) to classify
anemias as microcytic, normocytic or macrocytic is a standard diagnostic
approach.(4,9) On other hand the red-cell distribution width coefficient variation
percentage (RDW-CV%) has been reported to be of value in the discrimination of
IDA from TT.(10-12) It is an index of the variation in the size of
red cells and can be used to detect subtle degrees of anisocytosis.(13)
Therefore, an elevated RDW-CV% appears to be the earliest hematolological
manifestation of IDA.(14-16)
The serum ferritin concentration is particularly
informative in estimating the amount of iron storage and provides direct
information about any deficit in the iron nutritional status. Moreover, it is
the first in line to drop if the individual suffers any iron deficiency from
diet as seen in IDA.(17-19) On other hand, the serum ferritin
level, which is usually conducted in conjunction with MCV, can indirectly help
understand iron metabolism as MCV measures how large the red blood cells are.
When a deficiency in iron occurs, not enough hemoglobin is made. This leads to
a reduced rate of red blood cell production and the red blood cells become
smaller (microcytic) and paler (hypochromic) than normal.(3,20,21)
The measurement of hemoglobin A2 (HbA2)
and hemoglobin F (HbF) by High performance liquid chromography (HPLC) is rapid,
reproducible and an appropriate method for screening ß-thalassemia carriers,(22)
which have been characterized by microcytosis, hypochromia and HbA2
above 3.5%.(23) On the other hand, the polymerase chain
reaction (PCR) is used for the diagnosis of a few number of α-thalassemia trait
subjects that should be considered in all children of high risk family origins
with a blood picture suggestive of ß-thalassemia trait but in whom the level of
HbA2 and HbF are within normal limits.(4)
The aim of this study was to determine the frequency
of IDA and TT among children attending the Pediatric Department at Prince Rashed
Bin Al-Hassan
Military Hospital
in the North of Jordan based on MCV, serum ferritin level and HPLC or PCR.
Methods
This study was conducted in the period between January
and December 2008, on all children who were seen at the out patient clinic of
the Pediatric Department of Prince Rashed Bin Al-Hassan Military Hospital in
the North of Jordan. The study subjects included those whom aged is between 6
months to 14-years-old, not on any hematinic in the previous six months, had no
infection in the past one month and had no chronic diseases. The Jordanian
Royal Medical Services Ethics Committee approved the study. All subjects had a
complete blood count and RBC indices performed at the first visit during the
study period.
The cutoff value for the diagnosis of microcytic
anemia was arbitrarily set at MCV ≤ mean – 1 standard deviation (1SD) of the corresponding
age group. If a subject was found to have an MCV below the cutoff value, serum
ferritin level was estimated and if it was found < 7 ng/ml (normal reference
range 7 - 140 ng/ml) a provisional diagnosis of IDA was made and iron
replacement therapy was started. RBC indices were repeated monthly and after 3
months of iron replacement therapy if the MCV improved and became above the
cutoff value, the diagnosis of IDA was considered confirmed. If the MCV did not
improve and remained below the cutoff value, HPLC was done to confirm or
exclude β-thalassemia. If β-thalassemia was excluded, PCR was performed to
confirm or exclude α-thalassemia.
If serum ferritin level was within the normal range, a
diagnosis of "possible thalassemia" was made and HPLC was done to confirm or exclude β-thalassemia. If β-thalassemia
was excluded, PCR was done to confirm or exclude α-thalassemia. HPLC and PCR for all subjects
in this study were performed at Princess
Eman Research and Laboratory
Science Center.
Demographic data included the age, and gender in
addition to RBC indices, serum ferritin, and the results of HPLC and/or PCR
were recorded and analyzed using Statistical Package of Social Science (SPSS)
software. Fisher exact test was used to compare the level of serum ferritin and
RBC indices between males and females, RBC indices between different age
categories and to compare serum ferritin level and RBC indices between
non-anemic, IDA, and TT subjects. Descriptive
statistics and cross-tabulation were used to find the frequencies of IDA and TT corrected for age, and the overall frequency of IDA and TT. The Mann-Whitney U test was used to compare between males and females in the rates of IDA and TT, and to see if IDA and TT show sex predilection compared to the non-anemic reference group.
Table I. Comparison of the RBC indices (n = 1012) and serum
ferritin (n = 227) between males and females
|
Parameter
|
Males
|
Females
|
P-Value
|
|
Hematocrit or PCV (%)
|
34.6 ± 3.9
|
34.3 ± 3.8
|
0.540
|
|
MCV fL
|
74.5 ± 6.5
|
75.4 ± 6.8
|
0.051
|
|
MCH
pg
|
23.9 ± 2.7
|
24.2 ± 2.9
|
0.057
|
|
RDW-CV%
|
14.5 ± 2.3
|
14.2 ± 2.4
|
0.077
|
|
RBC
x 1012/L
|
4.68 ± 0.59
|
4.63 ± 0.51
|
0.140
|
|
Serum
ferritin
|
12.9 ± 14.5
|
13.1 ± 15.2
|
0.891
|
Table II. Age-Specific RBC indices
|
Age
group
|
No.
|
PCV
|
MCV
|
MCH
|
RDW-CV
|
RBC
|
|
6
mo to< 2 yr
|
403
|
33.4 ± 3.5
|
72.8 ± 6.2
|
22.9 ± 2.6
|
15.2 ± 2.6
|
4.69 ± 0.49
|
|
2
to< 6 yrs
|
329
|
34.3 ± 3.3
|
75.2 ± 6.2
|
24.3 ± 2.6
|
14.1 ± 2.0
|
4.62 ± 0.64
|
|
6
to< 12 yrs
|
201
|
35.8 ± 4.2
|
78.0 ± 5.8
|
25.5 ± 2.4
|
13.4 ± 1.6
|
4.59 ± 0.48
|
|
12-14
yrs
|
79
|
36.7 ± 4.6
|
76.8 ± 8.6
|
24.6 ± 3.6
|
14.1 ± 2.4
|
4.79 ± 0.61
|
|
Overall
|
1012
|
34.4 ± 3.8
|
74.9 ± 6.6
|
24.0 ± 2.8
|
14.4 ± 2.3
|
4.66 ± 0.56
|
Table
III. Age-specific frequency of IDA and
TT
|
Age
group
|
Non-anemic
No. (%)
|
IDA
No (%)
|
TT
No (%)
|
|
6 mo - < 2 yr
|
315 (31.1)
|
75 (7.4)
|
13 (1.3)
|
|
2 - < 6 yrs
|
273 (27.0)
|
31 (3.1)
|
25 (2.5)
|
|
6 - <12 yrs
|
173 (17.1)
|
16 (1.6)
|
12 (1.2)
|
|
12 - <14 yrs
|
57 (5.6)
|
13 (1.3)
|
9 (0.9)
|
|
Total
|
818 (80.8)
|
135 (13.3)
|
59 (5.8)
|
Table
IV. Gender-specific frequency of IDA
and TT
|
Age
|
Non-anemic
No (%)
|
IDA
No (%)
|
TT
No (%)
|
|
Males
|
436 (43.1)
|
83 (8.2)
|
35 (3.6)
|
|
Females
|
382 (37.7)
|
52 (5.1)
|
24 (2.4)
|
|
Total
|
818 (80.8)
|
135 (13.3)
|
59 (5.8)
|
|
P-value
|
|
0.054
|
0.520
|
Table
V. Comparison of the serum ferritin (n
= 227) and RBC indices (n = 1012) between IDA, and TT
|
Parameter
|
Non-anemic
|
IDA
|
TT
|
P-value
|
|
Serum ferritin ng/ml
|
15.9 ± 3.9
|
4.3 ± 1.9
|
28.6 ± 18.6
|
< 0.0001
|
|
Hematocrit or PCV (%)
|
34.9 ± 3.4
|
32.2 ± 4.8
|
31.9 ± 3.5
|
0.721
|
|
MCV fL
|
76.9 ± 4.6
|
67.9 ± 6.9
|
62.4 ± 4.7
|
< 0.0001
|
|
MCH
pg
|
24.9 ± 1.9
|
20.6 ± 3.0
|
19.3 ± 1.9
|
0.003
|
|
RDW
CV%
|
13.6 ± 1.3
|
18.5 ± 2.4
|
16.3 ± 2.4
|
< 0.0001
|
|
RBC
x 1012/L
|
4.56 ± 0.46
|
4.97 ± 0.69
|
5.22 ± 0.74
|
< 0.023 |
Results
During the study period, 1,012 children fulfilled the
inclusion criteria. They were 554 males
and 458 females. Of these, 227 (22.43% of the total sample) had an MCV below
the cutoff value for this study. They were 135 (59.5%) males, 92 (40.5%)
females. 33 out of the microcytic subjects come for follow up appointment and
the MCV was somewhat improved, they included in a non-anemic group because of
normal serum ferritin, in addition HPLC and PCR excluded any evidence of a β or
α-thalassemia. The remaining 194 microcytic subjects in this study presented as
either IDA or TT.
There were no statistically significant differences in
RBC indices and serum ferritin level between males and females (P-value >
0.05), as shown in Table I.
Table II, shows the PCV percentage, MCV (fL) and MCH (pg)
to be directly related to the age of the subjects (increased with increasing
age), while RDW-CV% was indirectly related to the age of subjects (decreased as
age increased).
The overall frequency of IDA
and TT among children in the current study was 135 (13.3%) and 59 (5.8%)
respectively. Of the 59 thalassemic subjects 57 (96.6%) were β-thalassemic and 2 (3.4%) were α-thalassemic. It is interesting however
that the 2 α-thalassemic subjects had
concomitant iron deficiency proven by low serum ferritin level.
The frequency of IDA and TT among different age groups
was as follows: 6 months to < 2 years (7.4% IDA and 1.3% TT), 2 to < 6
years (3.1% IDA and 2.5% TT), 6 to < 12 years (1.6% IDA and 1.2% TT) and
12-14 years (1.3% IDA and 0.9% TT). The highest rate of IDA was in the age
group 6 months – < 2 years as demonstrated in Table III.
Table IV, illustrated that the rates of IDA and TT were
similar among males and females (P-value > 0.05), as follows: males (8.2%
IDA and 3.6% TT) and females (5.1% IDA and 2.4% TT).
The MCV fL, MCH pg and RDW-CV% were significantly
higher among IDA subjects than TT subjects, 67.9 ± 6.9fL versus 62.4 ± 4.7 fL, 20.6
± 3.0 pg versus 19.3 ± 1.9 pg and 18.5 ± 2.4% versus 16.3 ± 2.4%, respectively.
while serum ferritin and red blood cell count were significantly higher among
TT subjects than IDA subjects, 28.6 ± 18.6 versus 4.3 ± 1.9 ng/ml and 5.22 ±
0.74 versus 4.97 ± 0.69, respectively (P-value < 0.05). Hematocrit on the
other hand was not statistically significantly different between the two groups
(32.2 ± 4.8 % for IDA and 31.9 ± 3.5% for TT) (P-value = 0.721) as shown in
Table V.
Discussion
In this study, 22.43% of children who were seen in the
Pediatric Department of Prince Rashed Bin Al-Hassan Military Hospital in the
North of Jordan had microcytic anemia. Of these, the overall rate of IDA and TT
was identified as 13.3% and 5.8% respectively. Previous studies demonstrated a
prevalence of 5.4% of IDA among schoolchildren in north-eastern Badia in Jordan,(24)
other studies reported a prevalence of ß-thalassemia trait and α-thalassemia
trait in the north of Jordan of 3.1% and 1% respectively.(23,25)
On the other hand, the prevalence of IDA in the United States has been reported
to range from 3% to 10% and may be as high as 30% in low-income population.(4,26)
The current study showed that the highest rate of IDA was
in the age group of 6 months to <2 years which is consistent with a study that
reported the prevalence
of
IDA among Kelantanese children
aged
8 -26 months in Malaysia
as high as 31.6%. This could be attributed to prolonged breastfeeding beyond
six months of age and failure to introduce formula milk at later infancy.(27)
In this study, infants below the age of 6 months were
excluded because at this age they have high stores of iron, which are unlikely
to be depleted, although breast milk is low in iron content.(26)
Therefore, iron supplementation or fortification of food is recommended.(28,29)
The current study showed that the rate of IDA and TT was
not related to the sex of the patient. These findings are consistent with those
of studies that reported the prevalence of IDA among schoolchildren of
different socio-economic status in urban Turkey(30) and in
children aged 6-60 months in Thail and(31) Thalassemia trait
on the other hand is a group of autosomal-recessive inherited human disorders,
resulting from defects in hemoglobin synthesis and is known to affect males and
females equally.(23,32-35)
This study also revealed that the MCV (fL) was lower
among TT patients and the RDW-CV% was higher among IDA patients. This could be attributed
to the fact that RDW-CV% is a measure of the degree of variation in red cell
size. Some causes of microcytic anemia, most notably IDA, are characterized by
an increased RDW-CV%. The thalassemias in contrast, tend to produce a uniform
microcytic red cell population without a concomitant increase in RDW-CV%.(11,3-16,26,36-38)
Limitations of the present study include the restricted
sampling of children who attended the department where the study was conducted
and therefore may not represent the whole population. Moreover, we did not
study the socio-economic, demographic variables, feeding practices and racial
differences attributed to underlying cause of microcytic anemia. The investigations
by serum ferritin and hemoglobin electrophoresis or PCR were performed for
children with blood picture of microcytosis. Therefore, it is not possible to
detect all subjects with TT by screening on the basis of the full blood count
as some subjects have normal RBC indices (silent TT). We did not use the
hemoglobin level to define the severity of IDA. However, our study was carried
out for the purpose of the best estimation for the frequency of IDA, and TT in
limited samples North of Jordan regardless of the types of TT and severity of
IDA, and it must have detected the great majority of cases.
Conclusion
The frequency of IDA (13.3%) and TT (5.8%) among children in North of Jordan was
estimated by statistical measurement of MCV fL, is a cost effective predictor in
the majority of cases. The red-blood indices complemented with serum ferritin
and HPLC or PCR are of value for precise diagnosis.
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