ArticlePDF Available

Abstract

Chronic anemia has a negative effect on linear growth during all stages of growth (infancy, childhood and adolescence). In addition, infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. The mechanisms of defective growth in IDA includes defective IGF-I secretion. Correction of anemia is associated with an improvement of catch-up growth and a signifi cant increase in IGF-I secretion.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
Indian Journal of Endocrinology and Metabolism / 2014 / Vol 18 | Supplement 1 S1
IJEM_453_14R1
INTRODUCTION
Anemia in childhood is de ned as a hemoglobin (Hb)
concentration below cut off levels established by the
World Health Organization: <11 g/dl in children aged
6–59 months, <11.5 g/dl in children aged 5–11 years and
12 g/dl in older children (aged 12–14).[1]
The likely cause of childhood anemia varies in different
regions, with iron de ciency anemia (IDA) being the most
common cause. In the developing world, infectious diseases
such as malaria, helminth infections, HIV and tuberculosis
are other important causes of anemia.[2] Inherited forms
of anemia are occasionally encountered in certain racial
groups. Sickle cell disease is more common in people of
Central African origin while β-thalassaemias are more
common in Mediterranean, Middle Eastern and Southeast
Asian populations.[3,4]
In infants and young children, severe chronic anemia
may lead to delayed growth and long term effects on
neurodevelopment and behavior, mediated by changes in
neurotransmitter myelination, monoamine metabolism
in striatum, functioning of the hippocampus and energy
metabolism. Growth and pubertal delay are common
complications of thalassemia major.[5-7]
Iron is essential for all tissues in a young child’s developing
body. Iron is reversibly stored within the liver as ferritin
and hemosiderin and is transported between different
compartments in the body by transferrin. Ferritin is the
stored form of iron used by the cells, and a better measure
of available iron levels than serum iron. Fe performs
vital functions including carrying of oxygen from lung
to tissues, transport of electrons within cells, acting as
co-factor for essential enzymatic reactions, including
synthesis of steroid hormones and neurotransmission.
Mitochondria supply cells with adenosine triphosphate,
heme, and iron-sulfur clusters (ISC), and mitochondrial
energy metabolism involves both heme-and ISC-dependent
enzymes. Mitochondrial iron supply and function require
iron regulatory proteins that control messenger RNA
translation and stability and iron is positively correlated
with mitochondrial oxidative capacity.[8-10]
EFFECT OF IRON SUPPLEMENTATION ON
GROWTH OF NORMAL CHILDREN
Many authors have reviewed the effect of routine iron
supplementation on growth in children. A systematic
review analyzed 25 randomized controlled trials (RCTs) that
evaluated the effect of iron supplementation on physical
growth in children (interventions included oral or parenteral
iron supplementation, or iron-forti ed formula milk or
cereals). The pooled estimates (random effects model) did
not document a statistically signi cant (P > 0.05) positive
effect of iron supplementation on any anthropometric
variable (Weight [Wt]-for-age, Wt-for-height [Ht],
Ht-for-age, mid-arm circumference [MAC], skinfold
thickness, HA). However, greater Wt-for-age in
supplemented children in malaria hyper-endemic regions
and greater Wt-for-Ht for children above 5 years of age
were noted, along with a negative effect on linear growth
in developed countries and with supplementation for
6 months or longer.[11] Two other meta-analysis of 21 RCTs
examining iron (supplementation) interventions in children
aged <18 years found that the iron-supplementation had
no signi cant effect on growth.[12]
AQ2
Corresponding Author: Prof. Ashraf T. Soliman, Department of Pediatrics, Hamad General Hospital, P. O. Box 3050, Doha, Qatar.
E-mail: atsoliman@yahoo.com
Anemia and growth
Ashraf T. Soliman, Vincenzo De Sanctis1, Sanjay Kalra2
Department of Pediatrics, Hamad Medical Centre, Doha, Qatar, 1???, Pediatric and Adolescent Outpatient Clinic, Private Accredited Quisisana
Hospital, Italy, 2???, Indian Journal Endocrinology and Metabolism, Journal of Social Health in Diabetes, Bharti Hospital and B.R.I.D.E.,
Karnal 132001, Haryana, India
AQ1
Editorial
Access this article online
Quick Response Code:
Website:
www.ijem.in
DOI:
*****
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
Soliman, et al.: Anemia and growth
Indian Journal of Endocrinology and Metabolism / 2014 / Vol 18 | Supplement 1
S2
The second meta-analysis included iron-forti ed foods,
iron-forti ed formula, or iron supplements and evaluated
Ht, Wt, MAC, head circumference (HC), birth weight, or
length of gestation in infants, children, and adolescents,
and seven studies conducted in pregnant women.[13]
The overall pooled result (random-effects model) showed
no signi cant effects of iron intervention on any of
the parameters measured. When results were strati ed
according to dose of iron, duration of intervention,
age, and baseline iron status, only doses of 40–66 mg of
supplemental iron and intervention in children 6 years of
age showed a slight but signi cant association with weight
and MAC.[13]
Effect of antenatal and infant anemia on growth
Early ID appears to have speci c effects on the central
nervous system. In the rat, a brief period of ID during
the brain growth spurt (10–28 days) causes a lasting
de cit in brain iron, which persists into adulthood despite
correction of the anemia. Altered neurotransmitter
function is present in the brains of iron-de cient rats.
The activity of monoamine oxidase and aldehyde oxidase
are reversibly diminished, as is the functional activity
of dopamine Dd2 receptors. Many dopamine-mediated
behaviors are modi ed.[14-16] Pregnant rats on Fe restricted
diet produced litters with a signi cant reduction in the
physical growth indexes (body weight, body length, tail
length, and head length) compared with the control group.
These results suggest that adequate Fe is essential during
both intrauterine and neonatal life.[17]
In human, both brain and body growth, especially during
the phase of rapid infantile growth, requires relatively high
energy supply and metabolism. Cellular energy metabolism
is dependent on oxygen. Fe de ciency decreases oxygen
dependent cellular energy metabolism due to decreased
heme and Hb synthesis, decreased red blood cells (RBC)
synthesis, and decreased RBC survival due to increased
oxidative stress in RBC, Hb autoxidation, generation of
toxic oxygen radicles scrambling and increased removal
by macrophage. Consequently, IDA leads to impaired
cognitive abilities and defective linear growth.[18-23]
Effect of anemia and iron supplementation, on growth in
anemic children
Only few controlled studies have investigated the effect
of IDA, and the effect of treatment with iron, on growth
in children with IDA. Aukett et al., showed that treatment
of IDA with oral iron for 2 months was associated with a
signi cantly greater increase in weight velocity compared
to the placebo group.[24] Other studies have con rmed
these observations, and also suggest that the correction
of anemia is associated with a reduction in the increased
morbidity (fever, respiratory tract infections, diarrhea) seen
in children with IDA.[21,22] Bandhu et al., studied the effects
of IDA, and its correction with Fe, in school going children
on anthropometric parameters. Pre-supplementation values
of IDA children were signi cantly lower for MAC and
HC in girls and for Ht and MAC in boys, when compared
to the control group. Iron supplementation-induced
improvement in hematological parameters was associated
with signi cant improvement of Ht, Wt and MAC. Post
therapy, the anemic girls and boys grew faster than their
respective control groups.[25]
Soliman et al. measured growth and parameters in 40
children (aged 17.2 ± 12.4 months) with IDA before
and for 6 months after iron therapy in comparison with
normal controls. Before treatment children with IDA were
signi cantly shorter and had slower growth compared
with age-matched controls. After treatment, their growth
velocity (GV), length standard deviation scores (SDS) and
body mass index (BMI) increased signi cantly (signi cant
catch-up of growth). Their GV was correlated signi cantly
with mean Hb concentration.[26] Similarly, Bhatia et al.
assessed the growth status of 117 anemic (Hb 7–10 g/dl)
and 53 normal (11 g/dl) children (3–5 years). The anemic
children had signi cantly lower body weight, height and
weight for age. Iron treatment (40 mg elemental iron/day)
for both groups of children for 6 months produced a
signi cant increase in Hb levels of both groups (1.6 g/dl in
the anemic and 0.8 g/dl in the non-anemic) compared to their
respective controls who received sugar placebos.[27] Growth
performance of anemic children supplemented with iron
was superior to that of anemic placebo-treated children as
indicated by a better weight gain and a signi cantly higher
weight for height.[28] In summary, IDA in children, especially
during the rst 2 years of life signi cantly impairs growth
that can be corrected by adequate iron therapy.
Effect of iron de ciency anemia and iron treatment on
growth hormone-insulin-like growth factor-I axis
Novel endocrine pathways have been proposed to explain the
effect of IDA on growth. Anemia imposes a hypoxic condition
on hepatocytes. Hepatic protein synthesis is inhibited by
hypoxia. In vitro, low oxygen conditions inhibit insulin-like
growth factor-I (IGF-I) action by increasing IGF binding
protein -1 (IGFBP-1), especially phosphorylated IGFBP-1,
which inhibits IGF-I action. In addition, IGF-I-induced cell
proliferation is also inhibited in low oxygen conditions.[27,29,30]
Transferrin (Tf) is the major circulating iron binding protein.
In addition to its function as the Fe3+-carrier protein in
serum has a unique ability to bind IGFs and to interact with
IGFBP-3. Tf can abolish IGFBP-3-induced cell proliferation
and apoptosis in different cell lines. On the other hand, the
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
Soliman, et al.: Anemia and growth
Indian Journal of Endocrinology and Metabolism / 2014 / Vol 18 | Supplement 1 S3
Fe3 ± Tf complex might facilitate the transport of IGFs
across the capillary wall by receptor-mediated transcytosis.
Therefore, increased Tf during IDA may adversely affect
the integrity of IGF-I system.[31]
Animal studies
In Wistar rats, dietary ID decreased hematocrit and Hb
concentrations, IGF-I, 1,25-dihydroxycholecalciferol,
IGF-I, and osteocalcin concentrations and bone mineral
density of the femur and vertebrae compared with control
rats. Bone histomorphometric parameters showed that the
bone formation rate and osteoclast surface in the lumbar
vertebra were signi cantly reduced in the ID group compared
with the control group.[32-34] Calves with IDA were found to
have low plasma IGF-I concentrations. After recombinant
growth hormone (GH) administration, increments in
IGF-I in IDA calves were reduced despite high plasma
GH levels. This suggested decreased sensitivity (partial
resistance) to GH during anemia.[35] Gestational ID in rats
attenuates postnatal hippocampal IGF signaling and results
in markedly suppressed hippocampal IGF activation and
protein kinase B signaling. Early postnatal iron treatment
of gestational ID reactivates the IGF system and promotes
neurogenesis and differentiation in the hippocampus.[36]
Human studies
In 40 infants and young children with IDA
(Hb = 8.2 ± 1.2 g/dl) treated for 6 months with iron
therapy, circulating IGF-I increased signi cantly, along with
acceleration of GV and increased length SDS and BMI.[37]
Isguven et al., studied 25 prepubertal children with IDA
and 25 healthy controls. IGF-I, Ghrelin, and insulin levels
were signi cantly lower in the ID group.[38] They suggested
that low ghrelin and insulin levels might be the cause of
the appetite loss in IDA. In addition, low Ghrelin (a GH
secretagogue) may decrease GH and subsequently IGF-I
secretion. They related growth delay both to low IGF-I
secretion and appetite loss.[39]
In adolescents, Choi and Kim reported significant
correlation between Hb concentration and serum iron on
the one hand and IGF-I concentration on the other hand.[40]
In a large adult cohort (n = 1,093) the association of
IGF-1 with Hb concentration was studied. Anemic
adults exhibited signi cantly lower IGF-1 compared with
non-anemic controls.[41]
Effect of thalassemia on growth and growth
hormone-insulin-like growth factor-I axis
Thalassemia and growth are linked by different,
multifactorial mechanisms. Growth retardation occurs
almost invariably in homozygous β-thalassemia. Signi cant
size retardation is observed in stature, sitting height, weight,
biacromial (shoulder), and bicristal (iliac crest) breadths.
After the age of 4 years, the longitudinal growth patterns
display rates consistently behind those of normal controls.
Growth retardation becomes markedly severe with the failure
of the pubertal growth spurt.[38,42-44] With the introduction
of high transfusion regimes and ef cient iron chelation
in thalassemia management, prepubertal linear growth
has improved markedly.[44,45] However, abnormal growth
is still observed in the majority of patients during late
childhood and adolescence.[46] Hemosiderosis (secondary
to repeated packed cell transfusion) induced damage of
the endocrine glands (pituitary, thyroid, gonads, pancreas),
liver, and growth plate, is a major cause of growth failure.[44]
However, other important factors also contribute to this
growth delay [Table 1].[45-51]
Many studies done on children with thalassemia have
shown a variable prevalence of defective GH secretion
in response to different stimuli (clonidine, glucagon,
Insulin hypoglycemia, GrowthGH-releasing hormone).
Some of the short thalassemic children with normal
GH secretion, have neurosecretory dysfunction of GH
secretion.[44,47,49] In addition, IGF-I concentrations have
been shown to be low in the majority of children and
adults with thalassemia, with or without GH de ciency.
One-day-IGF-I generation tests have shown lower IGF-I
generation in thalassemic children compared with normal
short children and those with GHD. Defective GH
secretion and hepatic siderosis are major causes of low
IGF-I secretion.[49-51] Acute correction of anemia, by
packed cell transfusion, signi cantly increases the serum
concentration of IGF-I but does not affect GH secretion
or IGF-I in response to GH stimulation. Increasing
caloric intake and improving nutrition has been shown
to increase IGF-I and growth in these patients. Some
acceleration of linear growth can be achieved by GH
therapy; however this growth response appears inferior
to the response of non-thalassemic children with GH
de ciency.[45,46,51]
SUMMARY
Chronic anemia has a negative effect on linear growth
during all stages of growth (infancy, childhood and
adolescence). In addition, infants with chronic IDA have
delayed cognitive, motor, and affective development that
may be long-lasting. The mechanisms of defective growth
in IDA includes defective IGF-I secretion. Correction of
anemia is associated with an improvement of catch-up
growth and a signi cant increase in IGF-I secretion.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
Soliman, et al.: Anemia and growth
Indian Journal of Endocrinology and Metabolism / 2014 / Vol 18 | Supplement 1
S4
In view of the signi cant impact of IDA on growth,
endocrinologists should advocate primary prevention and
screening for ID. Although the use of iron supplemented
formulas offers an easy method of primary prevention
of IDA, evidence now indicates that routine iron
supplementation appears useful only in areas with high
prevalence of IDA, including malaria-endemic areas, and
may present some risks for those with normal Hb. Hence,
universal iron supplementation cannot be supported.
In thalassemia, adequate packed cell transfusion
(hypertransfusion) and proper iron chelation, sound
nutrition, early diagnosis and management of dysfunction
of growth and pubertal axes can improve the nal outcome
of these children.
REFERENCES
1. World Health Organization. Haemoglobin concentrations for the
diagnosis of anaemia and assessment of severity. ???: ???; 2011.
2. Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N,
Lozano R, et al. A systematic analysis of global anemia burden from
1990 to 2010. Blood 2014;123:615-24.
3. Williams TN, Weatherall DJ. World distribution, population genetics,
and health burden of the hemoglobinopathies. Cold Spring Harb
Perspect Med 2012;2:a011692.
4. Weatherall DJ. The inherited diseases of hemoglobin are an emerging
global health burden. Blood 2010;115:4331-6.
5. Lozoff B. Iron deficiency and child development. Food Nutr Bull
2007;28:S560-71.
6. Shafir T, Angulo-Barroso R, Calatroni A, Jimenez E, Lozoff B. Effects
AQ3
of iron deficiency in infancy on patterns of motor development over
time. Hum Mov Sci 2006;25:821-38.
7. Waugh EJ, Polivy J, Ridout R, Hawker GA. A prospective
investigation of the relations among cognitive dietary restraint,
subclinical ovulatory disturbances, physical activity, and bone mass
in healthy young women. Am J Clin Nutr 2007;86:1791-801.
8. Rouault TA. The role of iron regulatory proteins in mammalian iron
homeostasis and disease. Nat Chem Biol 2006;2:406-14.
9. Galy B, Ferring-Appel D, Sauer SW, Kaden S, Lyoumi S, Puy H,
et al. Iron regulatory proteins secure mitochondrial iron sufficiency
and function. Cell Metab 2010;12:194-201.
10. Zhang DL, Ghosh MC, Rouault TA. The physiological functions
of iron regulatory proteins in iron homeostasis – An update. Front
Pharmacol 2014;5:124.
11. Sachdev H, Gera T, Nestel P. Effect of iron supplementation on
physical growth in children: Systematic review of randomised
controlled trials. Public Health Nutr 2006;9:904-20.
12. Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient
interventions but not vitamin a or iron interventions alone improve
child growth: Results of 3 meta-analyses. J Nutr 2004;134:2592-602.
13. 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.
14. Callahan LS, Thibert KA, Wobken JD, Georgieff MK. Early-life iron
deficiency anemia alters the development and long-term expression
of parvalbumin and perineuronal nets in the rat hippocampus. Dev
Neurosci 2013;35:427-36.
15. Hubbard AC, Bandyopadhyay S, Wojczyk BS, Spitalnik SL, Hod EA,
Prestia KA. Effect of dietary iron on fetal growth in pregnant mice.
Comp Med 2013;63:127-35.
16. Guidi GC, Lechi Santonastaso C. Advancements in anemias related
to chronic conditions. Clin Chem Lab Med 2010;48:1217-26.
17. Woodall SM, Johnston BM, Breier BH, Gluckman PD. Chronic
Table 1: Effect of iron de ciency anemia versus chronic hemolytic anemia on and thalassemia on growth and
endocrine glands
Chronic hemolytic anemia on repeated RBC transfusion Iron de ciency anemia
Early brain growth and
metabolism
No effect In-utero and early life leads to altered
neurotransmission and monoamine oxidase
and other enzyme metabolism
Psychomotor
development
No effect Defective psychomotor development that may
persist later
In-utero and early infantile
postnatal linear growth
No effect Defective intrauterine and early postnatal
growth
Childhood linear growth Marked effect Marked effect
Pubertal growth spurt Marked effect because of delayed and/or failure of puberty and
defective GH-IGF-I axis
Less signifi cant effect
GH secretion Signifi cant decrease in variable number of patients (pituitary iron
overload)
No effect
IGF-I secretion Marked decrease of IGF-I secretion Hepatic siderosis) Decreases IGF-I secretion
Effect on appetite and
weight gain
Decreases appetite and many have low BMI (correction of nutrition
increases IGF-I and weight gain)
Decreases appetite and is associated with
underweight in many children and adolescents
Effect on other endocrine
glands
Hypothyroidism
Hypogonadotropic hypogonadism and diabetes mellitus (iron overload)
are common complications
No effect (in adults thyroid dysfunction may
occur)
Effect on liver Liver fi brosis, cirrhosis and failure may occur secondary to iron
overload (siderosis)
No effect on hepatic function
Effect on heart Arrhythmia and heart failure still occur secondary to iron overload
and hypoxia
Heart failure is rare and occurs in severe
prolonged cases
Effect of treatment of
anemia
Adequate blood transfusion and iron chelation improves IGF-I
secretion, weight gain and linear growth but short stature is still
common complication
Fe therapy; 1 increases IGF-I, weight gain and
linear growth (complete catch-up growth)
GH: Growth hormone, RBC: Red blood cell, IGF-I: Insulin-like growth factor I
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
Soliman, et al.: Anemia and growth
Indian Journal of Endocrinology and Metabolism / 2014 / Vol 18 | Supplement 1 S5
maternal undernutrition in the rat leads to delayed postnatal
growth and elevated blood pressure of offspring. Pediatr Res
1996;40:438-43.
18. Ramesh J, Shaik MI, Srivalli J. Impact of Iron indices, mitochondrial
oxidative capacity, oxidative stress and inflammatory markers on
insulin resistance and secretion: A pathophysiologic perspective.
J Diabetes Metab 2012;3:9.
19. De-Regil LM, Jefferds ME, Sylvetsky AC, Dowswell T. Intermittent
iron supplementation for improving nutrition and development
in children under 12 years of age. Cochrane Database Syst Rev
2011;CD009085.
20. Agriculture and Consumer. Protection. Human Nutrition in the
Developing World. Available from: http://www.fao.org/docrep/
w0073e/w0073e05.htm#P3355_389439.
21. Angeles IT, Schultink WJ, Matulssi P, Gross R, Sastroamidjoj S.
Increased rate of stunting among anaemic Indonesian pre-school
children through iron supplementation. Am J Clin Nutr
1993;58:339-42.
22. Chowang L, Soemantri AG, Pollitt E. Iron supplementation and
physical growth or rural Indonsian children. Am J Clin Nutr
1988;47:496-501.
23. Beard JL. Iron biology in immune function, muscle metabolism and
neuronal functioning. J Nutr 2001;131:568S-79.
24. Aukett MA, Parks YA, Scott PH, Wharton BA. Treatment with iron
increases weight gain and psychomotor development. Arch Dis Child
1986;61:849-57.
25. Bandhu R, Shankar N, Tandon OP. Effect of iron on growth in iron
deficient anemic school going children. Indian J Physiol Pharmacol
2003;47:59-66.
26. Soliman AT, Al Dabbagh MM, Habboub AH, Adel A, Humaidy NA,
Abushahin A. Linear growth in children with iron deficiency anemia
before and after treatment. J Trop Pediatr 2009;55:324-7.
27. Preedy VR, Smith DM, Sugden PH. The effects of 6 hours of hypoxia
on protein synthesis in rat tissues in vivo and in vitro. Biochem J
1985;228:179-85.
28. Bhatia D, Seshadri S. Growth performance in anemia and following
iron supplementation. Indian Pediatr 1993;30:195-200.
29. Tsunawaki T, Sakai K, Momomura M, Wachi Y, Matsuzawa Y,
Iwashita M. Hypoxia alters phosphorylation status of insulin-like
growth factor (IGF)-binding protein-1 and attenuates biological
activities of IGF-I in HepG2 cell cultures. J Obstet Gynaecol Res
2013;39:1367-73.
30. Kajimura S, Aida K, Duan C. Insulin-like growth factor-binding
protein-1 (IGFBP-1) mediates hypoxia-induced embryonic
growth and developmental retardation. Proc Natl Acad Sci U S A
2005;102:1240-5.
31. Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, et al.
Transferrin binds insulin-like growth factors and affects binding
properties of insulin-like growth factor binding protein-3. FEBS Lett
2001;509:395-8.
32. Katsumata S, Katsumata-Tsuboi R, Uehara M, Suzuki K. Severe iron
deficiency decreases both bone formation and bone resorption in
rats. J Nutr 2009;139:238-43.
33. Medeiros DM, Stoecker B, Plattner A, Jennings D, Haub M.
Iron deficiency negatively affects vertebrae and femurs of
rats independently of energy intake and body weight. J Nutr
2004;134:3061-7.
34. Katsumata S, Tsuboi R, Uehara M, Suzuki K. Dietary iron deficiency
decreases serum osteocalcin concentration and bone mineral density
in rats. Biosci Biotechnol Biochem 2006;70:2547-50.
35. Ceppi A, Blum JW. Effects of growth hormone on growth
AQ4
performance, haematology, metabolites and hormones in
iron-deficient veal calves. Zentralbl Veterinarmed A 1994;41:443-58.
36. Tran PV, Fretham SJ, Wobken J, Miller BS, Georgieff MK.
Gestational-neonatal iron deficiency suppresses and iron treatment
reactivates IGF signaling in developing rat hippocampus. Am J
Physiol Endocrinol Metab 2012;302:E316-24.
37. Soliman AT, Eldabbagh M, Adel A, Sabt A. Linear growth and
circulating IGF-I concentrations in children with Iron deficiency
anemia after treatment. Arch Dis Child 2012;97:A220.
38. De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C,
Angastiniotis M, et al. Growth and endocrine disorders in
thalassemia: The international network on endocrine complications
in thalassemia (I-CET) position statement and guidelines. Indian J
Endocrinol Metab 2013;17:8-18.
39. Isguven P, Arslanoglu I, Erol M, Yildiz M, Adal E, Erguven M. Serum
levels of ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones
and cortisol in prepubertal children with iron deficiency. Endocr J
2007;54:985-90.
40. Choi JW, Kim SK. Association of serum insulin-like growth factor-I
and erythropoiesis in relation to body iron status. Ann Clin Lab Sci
2004;34:324-8.
41. Succurro E, Ar turi F, Caruso V, Rudi S, Sciacqua A, Andreozzi F, et al.
Low insulin-like growth factor-1 levels are associated with anaemia
in adult non-diabetic subjects. Thromb Haemost 2011;105:365-70.
42. De Sanctis V, Katz M, Vullo C, Bagni B, Ughi M, Wonke B. Effect
of different treatment regimes on linear growth and final height in
beta-thalassaemia major. Clin Endocrinol (Oxf) 1994;40:791-8.
43. De Sanctis V. Growth and puberty and its management in
thalassaemia. Horm Res 2002;58 Suppl 1:72-9.
44. Kyriakou A, Skordis N. Thalassaemia and aberrations of growth and
puberty. Mediterr J Hematol Infect Dis 2009;1:e2009003.
45. Soliman AT, Abushahin A, Abohezeima K, Khalafallah H, Adel A,
Elawwa A, et al. Age related IGF-I changes and IGF-I generation in
thalassemia major. Pediatr Endocrinol Rev 2011;8 Suppl 2:278-83.
46. Soliman AT, Khalafallah H, Ashour R. Growth and factors affecting
it in thalassemia major. Hemoglobin 2009;33 Suppl 1:S116-26.
47. Soliman AT, El Banna N, Ansari BM. GH response to provocation
and circulating IGF-I and IGF-binding protein-3 concentrations, the
IGF-I generation test and clinical response to GH therapy in children
with beta-thalassaemia. Eur J Endocrinol 1998;138:394-400.
48. Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM.
Bone mineral density in prepubertal children with beta-thalassemia:
Correlation with growth and hormonal data. Metabolism
1998;47:541-8.
49. Soliman AT, elZalabany MM, Mazloum Y, Bedair SM, Ragab MS,
Rogol AD, et al. Spontaneous and provoked growth hormone (GH)
secretion and insulin-like growth factor I (IGF-I) concentration in
patients with beta thalassaemia and delayed growth. J Trop Pediatr
1999;45:327-37.
50. Soliman A, De Sanctis V, Elsedfy H, Yassin M, Skordis N, Karimi M,
et al. Growth hormone deficiency in adults with thalassemia: An
overview and the I-CET recommendations. Georgian Med News
2013;79-88.
51. Soliman AT, El-Matary W, Fattah MM, Nasr IS, El Alaily RK,
Thabet MA. The effect of high-calorie diet on nutritional parameters
of children with beta-thalassaemia major. Clin Nutr 2004;23:1153-8.
Author Queries???
AQ1: Kindly provide departments.
AQ2: Kinldy provide expansion
Cite this article as: Citation will be included before issue gets online***.
Source of Support: Nil, Con ict of Interest: No.
AQ3: Kindly provide publisher details.
AQ4: Kindly provide last accessed details.
... Effects of anemia throughout life stages[25][26][27]. ...
Article
Full-text available
Iron deficiency anemia (IDA) has a long-term impact on each life stage and remains worldwide a major public health problem. Eleven experts were invited to participate in a virtual meeting to discuss the present situation and the available intervention to prevent iron deficiency anemia in Indonesia. The experts consisted of obstetric gynecologists, pediatricians, nutritionists, midwives, a clinical psychologist, and an education expert. Existing interventions focus attention on preconception and early childhood stages. Considering the inter-generational effects of IDA, we call attention to expanding strategies to all life stages through integrating political, educational, and nutritional interventions. The experts agreed that health education and nutritional intervention should be started since adolescence. Further research to explore the effectiveness of these interventions would be important for many regions in the world. The outcome of this Indonesian consensus is applicable worldwide.
Article
Hemoglobin (Hb) is an iron-containing metalloprotein present in red blood cells that carries and transports oxygen from the lungs to the tissues. Hb is an essential clinical parameter to evaluate since its insufficiency is recognised to be the major cause of anaemia. In general, the Hb measuring procedure necessitates a complex and costly laboratory setup staffed by highly experienced specialists. In underdeveloped nations, especially in rural and distant places, such a complex setup and knowledge is difficult to construct. As a result, a quick and portable Hb diagnostic test is urgently needed to improve test accessibility in these places, with the added benefit of offering point-of-care diagnostic tests (POCT) at the patient's door and in the field for mass screening at lower costs. Aspen Hb meter, developed by Aspen Laboratories Pvt. Ltd and available on the market, is one such instrument. Aspen Hb meter has 94 % accuracy, 93.3 % sensitivity and 94.8% specificity when compared to an automated haematology analyzer (Serachem SC-60+). As a result, the Aspen Hb meter was shown to be an acceptable POCT device for Hb monitoring in clinical and field settings.
Article
Full-text available
Undernutrition is a major global health problem. Various types of animal milk are used for feeding children at early ages; however, associations of camel milk (CaM) and bovine milk (BM) with the nutritional status of children have not been explored. A comparative community-based cross-sectional study was conducted among pre-schoolers in rural pastoral districts of Somali, Ethiopia. Children were selected from households with lactating camels or cows. Anthropometric measurements followed standard procedures for height-for-age, weight-for-age and weight-for-height scores. Independent sample t -tests identified significant differences in anthropometric indices based on the type of milk consumed. Multivariable logistic regression was used to examine associations between milk consumption and other predictors of growth failures. The prevalence of stunting was 24⋅1 % [95 % confidence interval (CI) 20⋅5, 28⋅3] of pre-schoolers, 34⋅8 % (95 % CI 29⋅9, 39⋅6) were wasted and 34⋅7 % (95 % CI 30⋅1, 39⋅9) were underweight. Higher proportions of BM-fed children were severely stunted, wasted and underweight compared with CaM consumers. Using logistic regression models, children who consumed BM [adjusted odds ratio (AOR): 2⋅10; 95 % CI 1⋅22, 3⋅61] and who were anaemic (AOR: 4⋅22; 95 % CI 2⋅23, 7⋅98) were more likely to be stunted than their counterparts, while girls were less likely to be stunted than boys (AOR: 0⋅57; 95 % CI 0⋅34, 0⋅94). Similarly, children who consumed BM (AOR: 1⋅97; 95 % CI 1⋅20, 3⋅24), who were anaemic (AOR: 2⋅27; 95 % CI 1⋅38, 3⋅72) and who drank unsafe water (AOR: 1⋅91; 95 % CI 1⋅19, 3⋅07) were more likely to be underweight than their counterparts. In conclusion, CaM consumption was associated with lower prevalence of stunting and underweight than BM. Promoting CaM in pastoralist areas may help to curb the high level of undernutrition.
Article
Full-text available
Thalassemia is the most common hematological transfusion-dependent disease in Thailand. Even though prenatal diagnosis (PND) can detect the condition, many new cases are diagnosed in pediatric practice. This study assessed the clinical outcome of patients with thalassemia who did PND. One hundred and six participants (53 female, 50%), with a median age of 8.5 years (Interquartile range [IQR] 8.00), were enrolled in the study. Twenty-one participants (19.8%) were prenatally diagnosed with thalassemia, with a median age of 8 years (IQR 9.00), 16 were diagnosed with transfusion-dependence thalassemia (TDT), and 5 participants were diagnosed with non-TDT. Another 80.2% did not prenatally diagnose, with a median age of 9 years (IQR 8.00). The PND group found early diagnosis compared with a non-PND group, at a median age of 6 months versus 15 months. There was a significant early diagnosis ( P < .001). Furthermore, the participants’ height for age z-score was significantly superior in the PND group ( P = .018). Even though the result of PND was abnormal, the parents still willing to continue with the pregnancy. The reason was they wanted to have a child. However, their child may require lifelong transfusion therapy.
Article
Background: Crucial gaps persist in knowledge, attitude, and practice (KAP) of adolescent girls that affect anemia and linear growth failure. Objective: To understand the role of KAP as a risk factor of anemia and linear growth problem in adolescent girls. Methods: We conducted a cross-sectional survey of 335 adolescent girls selected by clustered random sampling. The KAP questionnaire had 18 variables consisting of 9 knowledge, 3 attitude, and 6 practice components. Twelve variables addressed nutrition, dietary diversity, and health environments related to both anemia and stunting. The questionnaire was adapted from the 2014 Food and Agriculture Organization nutrition-related KAP guidelines for anemia. Dietary practice was evaluated from 2-day 24-hour recalls and a semi-quantitative food-frequency questionnaire. Associations between KAP and anemia, and height-for-age z-score (HAZ), were analyzed using multivariate logistic and linear regression models, respectively. Results: The mean hemoglobin (Hb) level was 119.7 g/L, with 44% of the adolescent girls being anemic (Hb < 120 g/L) and mean height was 151.0 cm with 25% being stunted (HAZ < -2 standard deviation [SD]). The median KAP score was 7 and ranged from 3 to 10. Low to moderate KAP scores were not significantly associated with being anemic (adjusted odds ratio [AOR] = 1.26; P = .43), however 1-point KAP score increment was associated with an increase of HAZ by 0.037 SD (P = .012). Conclusions: The KAP related to diet and healthy environments was not associated with anemia prevalence, but was positively associated with increased HAZ among adolescent girls. Strategy to reduce anemia risk in this population should combine KAP improvement with other known effective nutrition interventions.
Article
Full-text available
ABSTRAK Latar Belakang : Underweight masih menjadi salah satu masalah gizi di Indonesia. Balita merupakan kelompok usia yang rentan mengalami masalah gizi khususnya underweight. Salah satu penyebab langsung terjadinya underweight adalah asupan zat gizi. Asupan zat gizi makro (energi, protein, lemak dan karbohidrat) dan zat gizi mikro seperti zink dan zat besi yang rendah dapat menyebabkan pemanfaatan zat gizi didalam tubuh tidak optimal sehingga menyebabkan masalah gizi dan rentan mengalami penyakit infeksi.Tujuan: Tujuan dari penelitian ini adalah menganalisis hubungan asupan energi, protein, lemak, karbohidrat, zink dan fe dengan underweight pada ibu dan balita.Metode: Penelitian ini menggunakan desain studi case control dengan jumlah sampel 30 ibu dan 30 balita yang tinggal di wilayah Desa Suwari Bawean Gresik. Pengumpulan data dilakukan dengan wawancara menggunakan kuesioner terkait karakteristik keluarga, karakteristik ibu dan balita, form food recall 3x24 jam, form frequency questionere, form keragaman pangan, dan pengukuran antropometri seperti berat badan dan tinggi badan. Data dianalisis menggunakan uji chi square.Hasil: Hasil dari penelitian ini menunjukkan ibu dan balita underweight 50% dan ibu dan balita dengan status gizi normal 50%. Sebagian besar ibu memiliki tingkat asupan energi, lemak, karbohidrat, zink dan zat besi yang kurang, sedangkan sebagian besar balita memiliki tingkat asupan karbohidrat dan zink yang kurang. Terdapat hubungan antara asupan zink dengan underweight pada ibu (p=0,031) dan juga terdapat hubungan antara zat besi dengan underweight pada balita (p=0,032).Kesimpulan: Ibu dan balita dengan status gizi underweight memiliki tingkat kecukupan asupan energi, lemak, karbohidrat, zink dan zat besi lebih rendah dibandingkan dengan ibu dengan status gizi baik. Perlu meningkatkan asupan bahan makanan sumber energi, lemak, karbohidrat, zink dan zat besi pada ibu dan meningkatkan asupan bahan makanan sumber karbohidrat dan zink pada balita serta konsumsi makanan bervariasi agar masalah gizi underweight tidak memburuk.
Article
Full-text available
Background In Ethiopia, 38% of children less than 5 years of age are stunted and 57% are anaemic. Both have a negative impact later in life on physical growth and cognitive development and often coexist. There are few studies in Ethiopia that assessed co-morbid anaemia and stunting (CAS) and context-specific factors associated with it. Objective The objective of this study was to assess the prevalence of CAS, and factors associated with CAS among children aged 2 to 5 years, in southern Ethiopia. Methods A community-based cross-sectional survey was conducted among 331 randomly selected children in 2017. Mothers were interviewed using a structured questionnaire to obtain child and household information. Anthropometric measurements and blood samples for haemoglobin were collected. Stunting was defined as height-for-age Z-scores (HAZ) less than −2 SDs and anaemia was defined as altitude-adjusted haemoglobin levels less than 11.0 g/dL. CAS was defined when a child was both stunted and anaemic. Crude and adjusted multinomial logistic regression analyses were used to identify factors associated with CAS. Results Out of 331 children studied, 17.8% (95% CI 13.87% to 22.4%) had CAS. Factors found significantly linked with higher odds of CAS were increased child age (adjusted OR (AOR) 1.0 (1.0 to 1.1)) and no iron supplementation during the last pregnancy (AOR (95% CI) 2.9 (1.3 to 6.2)). One factor found significantly linked to lower odds of CAS was food secured households (AOR (95% CI) 0.3 (0.1 to 0.9)). Conclusions Co-morbid anaemia and stunting among children in the study area is of concern; it is associated with household food security, iron supplementation during pregnancy and child age. Therefore, comprehensive interventions focusing on improving household food security and promoting iron supplementation for pregnant women are suggested.
Article
Iron is a vital micronutrient required for growth and development at all stages of human life. Its deficiency is the primary cause of anemia that poses a significant global health problem and challenge for developing countries. Various risks are involved during iron deficiency anemia (IDA), such as premature delivery, low birth weight, etc. Further, it affects children's cognitive functioning, delays motor development, hampers physical performance and quality of life. It also speeds up the morbidity and mortality rate among women. The major reasons accountable are elevated iron demand in diet, socio-economic status, and disease condition. Various strategies have been adopted to reduce the IDA occurrence, such as iron supplementation, iron fortificants salts, agronomic practices, dietary diversification, biofortification, disease control measures, and nutritional education. Usually, the staple food groups for fortification are considered, but the selection of food fortificants and their combination must be safe for the consumers and not alter the finished product's stability and acceptability. Genetically modified breeding practices also increase the micronutrient levels of cereal crops. Therefore, multiple strategies could be relied on to combat IDA.
Article
Full-text available
This study evaluates the influence on body development of doing rhythmic gymnastics in girls from 10 to 17 years of age, the results of certain strength and flexibility abilities, and the trace element status (Ca, Fe, Zn, Cu, Mn, Cr, and Ni). The subjects were divided into three groups: (a) girls who practiced rhythmic gymnastics at a competition level (competition group); (b) girls who practiced this sport at a non-competitive level (training group); and (c) girls who do not practice any sport and with a low level of physical activity (control or sedentary group). Trace element status was determined in hair and urine samples. Results showed that doing rhythmic gymnastics does not alter the normal physical development of muscle mass, and even leads to a decrease in body fat content. Furthermore, better scores in the strength and flexibility test were obtained by the participants of this sports discipline. Statistically significant differences in urine Fe, Cu, and Mn values (p < 0.05) and in hair Cr, Cu, and Mn values (p < 0.05) were found between the two rhythmic gymnastics groups and the control group, and were higher in the competition and training groups. A principal component analysis model was performed to evaluate the possibility of cluster formation among the girls. The PCA results revealed a separation between the different groups although the separation was not perfect. PLS-DA was attempted in order to verify whether it was possible to discriminate between the groups included in this study. It was clear that the competition and control ones were very well classified (around 95% of correct predictions) but 20% of the girls belonging to the training group were misclassified as belonging to the competition one.
Article
Full-text available
Background: Pediatric anemia has a high prevalence in developing countries such as Pakistan. It is common knowledge among hospital specialties but little is done to manage this condition by hospitalists. The issue is compounded with a poor primary care infrastructure nationally. The aim of this study is to bring to light the high prevalence of anemic children in neurosurgery and to describe the difficulties in managing their anemia in a tertiary hospital setting. A literature review is presented highlighting the socioeconomic difficulties that contribute to this widespread comorbidity and the difficulty in managing it from a hospital specialty point of view. Methods: A prospective descriptive case series was carried out between March 2020 and September 2020. All patients under the age of 13 who presented to our department for traumatic brain injury (TBI) meeting our inclusion and exclusion criteria were enrolled and assessed for the presence and severity of anemia. Demographic data were collected. Following discharge, patients were referred to our hospital’s pediatrics’ anemia clinic which was before their first neurosurgery follow-up 2 weeks following discharge and attendance to follow up was documented. Results: The prevalence of anemia was 78.9%. Over 95% of patients attended their neurosurgery follow-up but only 28% of patients attended their referral to the anemia clinic. Conclusion: Anemia is highly prevalent in children presenting to neurosurgery for TBI and its longitudinal management has difficulties with lost to follow up in a tertiary hospital setting. There is a need for national initiatives to reduce the prevalence of anemia but concurrently better strategies need to be devised to manage anemic children in a hospital setting.
Article
Full-text available
Objective To assess linear growth of patients with Fe deficiency anemia (IDA) before and after in relation to their hematologic parameters and IGF-I concentration before and after treatment with iron. Methods Forty children (aged 17.2 +/– 12.4) months with iron deficiency anemia were studied with 40 healthy normal age-matched children (controls). Patients were treated with iron syrup or drops to supply 6 mg/kg/day. Growth (weight, length and head-circumference) and hematological parameters were measured and IGF-I concentrations measured before and 3 and 6 months after treatment. Results Growth parameters (weight, length and head-circumference) and hematological parameters were studied for 6 months after iron therapy. At presentation, patients with IDA had low Hb (8.2 +/– 1.2 g/dl), hematocrit (29 +/– 2.8), MCV (61.5 +/– 8.1), and MCH (19 +/– 3.2) which improved significantly after treatment to (11.2 +/– 1 g/dl, 70.6 +/– 6.8, 23.4 +/– 2.9 and 18.9 +/– 5 respectively). Before treatment children with iron deficiency they had length standard deviation score (LSDS) = – 1.2 +/– 1, annualized growth velocity (GV) = 7.5 +/– 2.2, GV SDS = –1.42 +/– 0.6 and BMI = 13.5 +/– 1.2. After 6 months their LSDS = –0.6 +/– –0.9, annualized GV=13.2 +/– 4.4 cm/year, GVSDS = 1.7 +/– 0.5, and BMI = 14.2 +/– 1.1). Circulating IGF-I increased significantly after treatment (52 +/– 18.8 ng/ml) vs before treatment (26.5 +/– 4.2 ng/ml).
Article
Full-text available
Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism by binding to RNA stem-loop structures known as iron responsive elements (IREs) in target mRNAs. IRP binding inhibits the translation of mRNAs that contain an IRE in the 5'untranslated region of the transcripts, and increases the stability of mRNAs that contain IREs in the 3'untranslated region of transcripts. By these mechanisms, IRPs increase cellular iron absorption and decrease storage and export of iron to maintain an optimal intracellular iron balance. There are two members of the mammalian IRP protein family, IRP1 and IRP2, and they have redundant functions as evidenced by the embryonic lethality of the mice that completely lack IRP expression (Irp1 (-/-)/Irp2(-/-) mice), which contrasts with the fact that Irp1 (-/-) and Irp2 (-/-) mice are viable. In addition, Irp2 (-/-) mice also display neurodegenerative symptoms and microcytic hypochromic anemia, suggesting that IRP2 function predominates in the nervous system and erythropoietic homeostasis. Though the physiological significance of IRP1 had been unclear since Irp1 (-/-) animals were first assessed in the early 1990s, recent studies indicate that IRP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis. Additionally, Irp1 (-/-) mice develop pulmonary hypertension, and they experience sudden death when maintained on an iron-deficient diet, indicating that IRP1 has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress that has been made in understanding the physiological roles of IRP1 and IRP2, and further discusses the implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension, and neurodegeneration.
Article
Full-text available
Before treatment children with IDA had length standard deviation score (LSDS) = - 1.2 +/- 1, annualized growth velocity (GV) = 7.5 +/- 2.2/y, GVSDS = -1.42 +/- 0.6 and BMI = 13.5 +/- 1.2. After 6 months their LSDS, annualized GV, GVSDS, and BMI. Circulating IGF-I increased significantly after therapy.
Article
Full-text available
Previous studies of anemia epidemiology have been geographically limited with little detail about severity or etiology. Using publicly available data, we estimated mild, moderate, and severe anemia from 1990 to 2010 for 187 countries, both sexes, and 20 age groups. We then performed cause-specific attribution to 17 conditions using data from the Global Burden of Diseases, Injuries and Risk Factors (GBD) 2010 Study. Global anemia prevalence in 2010 was 32.9%, causing 68.36 (95% uncertainty interval [UI], 40.98 to 107.54) million years lived with disability (8.8% of total for all conditions [95% UI, 6.3% to 11.7%]). Prevalence dropped for both sexes from 1990 to 2010, although more for males. Prevalence in females was higher in most regions and age groups. South Asia and Central, West, and East sub-Saharan Africa had the highest burden, while East, Southeast, and South Asia saw the greatest reductions. Iron-deficiency anemia was the top cause globally, although 10 different conditions were among the top 3 in regional rankings. Malaria, schistosomiasis, and chronic kidney disease-related anemia were the only conditions to increase in prevalence. Hemoglobinopathies made significant contributions in most populations. Burden was highest in children under age 5, the only age groups with negative trends from 1990 to 2010.
Article
Full-text available
This review paper provides a summary of the current state of knowledge regarding GHD provides recommendations for the diagnosis and treatment of GHD in adult patients with thalassaemia major (TM). The reported prevalence of adult GHD and /or IGF-I deficiency in TM patients varies from 8% to 44 % in different centers. Because GH treatment requires analysis of many factors, including the effect of treatment on cardiac functions, metabolic parameters and psychosocial functioning, along with safety, ethical considerations, financial cost and other burdens of therapy, stringent diagnostic criteria are needed. The authors report the diagnostic recommendations of the International Study Group of Endocrine Complications in Thalassemia (I-CET) for adult TM patients.The pros and cons of GH treatment must be discussed with each patient, after which GH doses should be individualized and titrated to maximum efficacy with minimal side effects. Prospective studies to monitor potential benefits versus possible side-effects will enable endocrinologists to define recommendations on dosage and the long term effects, particularly on cardiovascular and bone status of GH therapy in adult TM patients.
Article
Full-text available
Insulin-like growth factor (IGF)-I is known to stimulate fetal growth. One of the IGF-binding proteins, IGFBP-1, suppresses IGF-I activity, and thereby inhibits fetal growth. Because hypoxic stress in the uterus is known to cause fetal growth restriction, we examined the effects of hypoxia on IGFBP-1 production and phosphorylation status. Because liver is a main IGFBP-1 production site in the fetus, we used a hepatoma cell line, HepG2 cells, that secrete a large amount of IGFBP-1, express IGF-I receptors and model fetal liver metabolism in vitro. IGFBP-1 was analyzed by sodium dodecylsulfate polyacrylamide gel electrophoresis (PAGE) following immunoblotting, and IGFBP-1 phosphorylation status was analyzed by native PAGE following immunoblotting. Total concentrations of IGFBP-1 in media were higher and the highly phosphorylated isoforms were dominant in low oxygen conditions. Phosphorylation of IGF-I receptor by IGF-I was attenuated in low oxygen conditions. IGF-I-induced phosphorylation of insulin receptor substrate-1 (IRS-1) was attenuated in low oxygen conditions as well. However, attenuated phosphorylation of IGF-I receptor and IRS-1 were not observed in low oxygen conditions if the cells were stimulated with LR(3) IGF-I that has a similar binding affinity to IGF-I receptor but much less binding affinity to IGFBP-1 compared to those of native IGF-I. While IGF-I-induced cell proliferation was also inhibited in low oxygen conditions, LR(3) IGF-I-stimulated cell proliferation was not inhibited. These findings indicate that low oxygen conditions inhibit IGF-I action by increasing IGFBP-1, especially phosphorylated IGFBP-1, which inhibits IGF-I action. This study has indicated that hypoxia-induced IGFBP-1 production in the fetus may be a conserved physiological mechanism for restricting IGF-I-stimulated fetal growth.
Article
Full-text available
The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patient's care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.
Article
Early-life iron deficiency anemia (IDA) alters the expression of critical genes involved in neuronal dendritic structural plasticity of the hippocampus, thus contributing to delayed maturation of electrophysiology, and learning and memory behavior in rats. Structural maturity in multiple cortical regions is characterized by the appearance of parvalbumin-positive (PV(+)) GABAergic interneurons and perineuronal nets (PNNs). Appearance of PV(+) interneurons and PNNs can serve as cellular markers for the beginning and end of a critical developmental period, respectively. During this period, the system progresses from an immature yet highly plastic condition, to a more mature and efficient state that is however less flexible and may exhibit poorer potential for recovery from injury. To test if fetal-neonatal IDA alters parvalbumin (PV) mRNA expression, protein levels, and the number of PV(+) interneurons and PNNs in the male rat hippocampus, pregnant dams were given an iron-deficient (ID) diet (3 mg iron/kg chow) from gestational day 2 to postnatal day (P) 7 and then placed on an iron-sufficient (IS) diet (198 mg/kg) for the remainder of the experiment. On this regimen, formerly ID animals become fully iron-replete by P56. Minimal levels of PV (mRNA and protein), PV(+) interneurons, and PNNs were found in IS and ID P7 rats. By P15, and continuing through P30 and P65, ID rats had reduced PV mRNA expression and protein levels compared to IS controls. While there were no differences in the number of PV(+) neurons at either P30 or P65, the percentage of PV(+) cells surrounded by PNNs was slightly greater in ID rats as compared to IS controls. The lower levels of these acknowledged critical period biomarkers in the ID group are consistent with studies that demonstrate later maturation of the acutely ID hippocampus and lower plasticity in the adult formerly ID hippocampus. The findings provide additional potential cellular bases for previously described electrophysiologic and behavioral abnormalities found during and following early-life IDA. © 2013 S. Karger AG, Basel.
Article
Background Anaemia is associated with increased maternal and neonatal mortality, with young children most at risk of developing long-term ramifications. Most previous studies have been geographically limited with little detail about severity or aetiology. In this analysis, we completed the most comprehensive survey of anaemia burden to date.Methods Using publicly available data, we estimated mild, moderate, and severe anaemia in 1990 and 2010 for 187 countries, both sexes, and 20 age groups. We then performed cause-specific attribution to 17 conditions using data and resources of the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2010.FindingsGlobal anaemia prevalence in 2010 was 32·9%, causing 68·36 million years lived with disability (95% CI 40·98–107·54 million; 8·8% of the total for all conditions, 95% CI 6·3–11·7). Prevalence dropped for both sexes from 1990 to 2010, though more so for males. Females' prevalence was higher in most regions and age groups. South Asia and central, west, and east sub-Saharan Africa had the highest burden, while east, southeast, and south Asia saw the greatest reductions. Ten different conditions were among the top three in prevalence, depending on the region. Malaria, schistosomiasis, and chronic kidney disease-related anaemia were the only conditions to increase in prevalence. Haemoglobinopathies made significant contributions to the anaemia burden in both sexes, most regions, and all time periods. Burden was highest in children under 5 years old, the only age groups with negative trends from 1990 to 2010.InterpretationAnaemia is a heterogeneous and complex condition. Despite significant progress, many challenges remain. Regional differences remain stark, some conditions are growing as a proportion of overall anaemia, the gender gap is widening, and the total disease burden remains high. Worryingly, young children, the most vulnerable group, appear to be doing worse over the past 20 years. Targeted surveillance and intervention in high-risk populations should be a greater priority.FundingFunding for GBD 2010 was provided by the Bill & Melinda Gates Foundation.
Article
To evaluate the effect of iron intervention on physical growth in fetuses, infants, children, and adolescents up to 18 years of age, a systematic review with meta-analysis of randomized controlled trials (RCTs) was conducted. Structured electronic searches were conducted to February 2010 using MEDLINE, Embase, and the Cochrane Library databases. RCTs that included iron-fortified foods, iron-fortified formula, or iron supplements and in which height, weight, mid-arm circumference (MAC), head circumference, birth weight, or length of gestation was evaluated were analyzed for inclusion. In total, 21 RCTs in infants, children, and adolescents and 7 studies in pregnant women met the inclusion criteria. The overall pooled result (random-effects model) showed no significant effects of iron intervention on any of the parameters measured. To accommodate wide heterogeneity, studies were stratified according to dose of iron, duration of intervention, age, and baseline iron status. However, only doses of 40-66 mg of supplemental iron and intervention in children ≥6 years of age showed a slight but significant association with weight and MAC.