CURRICULUM

V I TA E

Prof. Dr. dr. DASRIL DAUD,

Sp.A(K)
EDUCATION

General Practitioner
FK.UNHAS
1978
Pediatrician
FK.UNHAS
1981
Hemato-Oncology of
Pediatric Consultant
FKUI/RSCM
1992
Doctoral
FK.UNHAS
201
ORGANIZATION
Head of Pediatric Dept, FK.UNHAS/RSWS Makassar
Head of Hemato-Oncology Division, Pediatrics Dept, FK.UNHAS/RSWS
Makassar
Head of Combine Degree Program, FK.UNHAS
Head of Ethic Commision, RSWS Makassar
Professor of Pediatric, Medical Faculty University of Hasannudin, Makassar

Dasril Daud

MPU, Makassar, 1-2 November 2014

The Importance of Iron in the Body

More than 100 chemical elements known
Only 24 different elements are
essential to the human body:

- The largest elemental components of the body:

Oxygen (65%), hydrogen (10%) and nitrogen (3%)
- The Other elements in the body:
calcium, phosphorus, iron and copper:
mineral elements and trace elements
Iron comprises only 0,008% of the bodys mass
We cannnot live without this important element

The Crucial Role of Iron in the Body

Iron is essential element for electron transport and is required for
the functioning of numerous proteins

Function

Compound

Oxygen transport

Hemoglobin
Myoglobin

Oxydative energy production

Cytochrome
Catalase
Peroxidase

Mitochondrial respiration

Succinate dehydrogenase

DNA synthesis Cell division)

Ribonucleotide reductase

ZAT BESI:
Proliferasi, diferensiasi, tumbuh & kembang
Zat besi sangat esensial:
- Hemoglobin
- Mioglobin
- Sitokrom

- Bagian integral dari berbagai enzim

- Sintesis DNA :
Proliferation and activation of sel B and T

Multifungsi

DEFISIENSI ZAT BESI: Gangguan Pertumbuhan

Defisiensi besi:
- gangguan pertumbuhan mukosa

DEFISIENSI ZAT BESI: Gangguan Pertumbuhan

Defisiensi besi:
Imunitas seluler & humoral menurun
Fagositosis terganggu
Mudah Infeksi

DEFISIENSI ZAT BESI:

Gangguan Perkembangan Fungsi Kognitif
Fungsi Kognitif:
- mengambil
- menyimpan
- menyajikan kembali

berbagai
bentuk ingatan

Zat besi: komponen esensial untuk

pertumbuhan dan perkembangan
otak & fungsi SSP

DEFISIENSI ZAT BESI:

Gangguan Perkembangan Fungsi Kognitif

Area otak untuk fungsi kognitif membutuhkan

zat besi lebih banyak
Pertumbuhan otak sangat sensitive thdp perubahan
status besi krn tumbuh & kembang otak sgt cepat
& terjadi dlm kurun waktu singkat.

Gangguan fgs kognitif

DEFISIENSI ZAT BESI:

Gangguan Perkembangan Fungsi Kognitif
Tiga proses utama pd defisiensi besi
dasar ggn fungsi kognitif:
1. Ggn pembentukan mielin
2. Ggn metabolisme neurotransmitter

3. Ggn metabolisme sel otak:

- perolehan 02 dan energi menurun
Area otak yang paling terpengaruh def. besi
fungsi kognitif tinggi: hipokampus

DEFISIENSI ZAT BESI:

Gangguan Perkembangan Fungsi Kognitif
Mielinisasi:
oligodendrosit
sel predominan dg zat besi

Def. besi transmisi lambat

Myelin

Makin dini & makin lama

def. besi makin sulit
memulihkan fgs kognitif

DEFISIENSI ZAT BESI:

Gangguan Perkembangan Fungsi Kognitif

Defisiensi besi gangguan

perkembangan psikomotor

DEFISIENSI ZAT BESI: Gangguan Pertumbuhan

Defisiensi besi:
- proliferasi sel otot menurun
- mioglobin berkurang

Otot atrofi
& lemah

Proliferation
Differentiation
Maturation

Iron

Enzymes
Cytochrom
Neurotransmitter

Hemoglobin

Growth
Development

Anemia def. besi (ADB/IDA):

WHO 39% penduduk dunia < usia 5 tahun
48% usia 5 -14 tahun
Indonesia :
40 45%
SKRT (2001) prevalensi ADB pada bayi 0-6 bulan
61,3%
Prevalensi tertinggi: usia tahun kedua
asupan besi rendah
pertumbuhan yg cepat pd tahun pertama

ADB masalah serius:

gangguan pertumbuhan & perkembangan
kualitas SDM

Prevalence of IDA in Indonesia

Study

Year -place

Incidence (%)

Dirjen Kesmas RI

2000

< 5 year : 40.5

School- age : 47.2
Adolescence (female) : 57.1

SKRT

2001

< 5 y.o : 48.1 %

< 1 y.o : 55%,
0-6 m.o : 61,3 %

Pusponegor HD, IDAI 2004 (1000 school-age in 20-25 %

11 province )
Susilowaty
(Puslitbangkes)

2004 in Bogor, Buleleng: 56,5 %

2-4 mo (317 infants)

Nelly R, Bidasari L
at.al

2008 in Medan

52 % (9-12 y.o )

Every age group of children are a susceptible for anemia

Hasil: sampel terdiri dari 55 bayi, 63,6% laki-laki, 58,2% berumur 812 bulan, dan 87,3% berasal dari keluarga dengan pendapatan per
kapita per bulan rendah. Sebagian besar berstatus gizi kurang (60%),
96,4%
cukup bulan,
3,6% bayi
dengan
berat
badan rendah
38,2%lahir
mengalami
anemia
danlahir
71,4%
bayi
anemia
pemberian ASI ekslusif 94,5%. Diantara 55 bayi 38,2% mengalami
tersebut
menderita anemia defisiensi besi. Prevalensi
anemia dan 71,4% bayi anemia tersebut menderita anemia defisiensi
anemia
defisiensi
besi
lebih besar
pada
bayi
8-12
besi. Prevalensi
anemia
defisiensi
besi lebih
besar
pada
bayibulan
8-12
daripada
bayibayi
yang
lebih
yaitu73,3%.
73,3%.
bulan daripada
yang
lebihmuda,
muda, yaitu

The prevalence of Hb<90 g/L was 13,4%, <100 g/dl, 37%, <110
g/L,71%. Normal birth weight infants (>2500 g) of anemic mothers
(<120 g/L had an odds ratio (OR) 1,81 [1,34 2,43] to have a low Hb
(<100 g/L) compared of with infants of nonanemic mothers with a
normal birth weight. Infants of nonanemic mothers but with low birth
weight had an OR of 1,15 [0,61 2,16], and those with low birth
weight and anemic mothers of 3,68 [1,69 8,02], anemic mothers
(Hb<120 g/L) had an odds ratio (OR) of 1,81 [1,34 2,43]

Risk factors of iron deficiency

Below 1 y.o
1 2 y.o
2 5 y.o
> 5 y.o
adolescence

Decrease of storage : preterm, LBW, growth,

breastfed > 6 mo
without iron supllementation, milk formula with
low iron contain
Inadequate Iron intake , only milk formula, rapid
growth
Increase requirement due to recurrent infection,
malabsorption
Decrease iron intake (especially heme iron ).
Increase requirement due to recurrent infection, blood
lost
Blood lost due to parasit infection, polyposis

Menstruation >>

Weinberg 1974
Free iron is essential for the multiplication of bacteria including
species of Candida, Escherichia, Mycobacterium, Pasteurella,
Shigella and Staphylococcus.

Smith et al. 1989

Parenteral iron treatment is associated with exacerbation of certain
infections in particular malaria and respiratory diseases in infants in
popu lations where malaria is endemic.

Oppenheimer, 1989
Parenteral iron is also associated with increased risk of serious
Esche richia coli sepsis in neonates

Brunser et al. 1993

Daily feeding of iron-enriched milk for 6 mo was associated with an
increased frequency of watery diarrhea and persistent diarrhea

Iron Balance in the Neonate

Carissa Cheng and Sandra Juul
Neoreviews 2011;12;e148
Consequences of Iron Excess: Preterm Infants
Providing excess iron might be particularly harmful to preterm infants, who are at increased
risk for oxidative injury for several reasons, including immature antioxidant defense systems.
(39) Neonates tend to have low TIBC; high saturation of circulating transferrin; and low
concentrations of ceruloplasmin, unbound transferrin, and albumin, all of which bind free
iron. (40) Although no direct link has been shown between iron excess and disease in
preterm infants, concerns have been raised about the potential for iron to cause increased
oxidative stress, which may contribute to complications of prematurity such as retinopathy of
prematurity
(41) studies
or bronchopulmonary
dysplasia.
(42) Short-term
studies
indicatestress,
that iron
Short-term
indicate that
iron does
not induce
oxidative
does not induce oxidative stress, as measured by isoprostanes and antioxidant status, when
as measured
by isoprostanes
and
antioxidant
status,from
when
provided
to stable, growing
low-birthweight
infants
at doses ranging
2 toprovided
12 mg/kg per
toorstable,
growing
low-birthweight
infants at doses ranging from 2 to
day
at a twice-daily
dose
of 9 mg per day. (43)(44)

12 mg/kg per day or at a twice-daily dose of 9 mg per day.

IRON REGULATION

The body regulates iron:

- to make use of iron as efficiently as
adequate iron status.
- to pacify (rander safe) iron meticulously
prevent iron free

IRON REGULATION
Hepatocyte
Enterocyte

Fe2+

Macrophage
P

Fe2+
FPN

FPN

P
Absorption

Hepcidin

Fe2+

FPN
Recycling

Hepcidin (LEAP-1):
Powerful negative regulator of iron
Inhibits:
Dietary iron absorption
The efflux of recycled iron (macrophage)
Release of iron from stroge in hepatocyte
Hepcidin controls the entry of iron into plasma by regulating ferroportin

IRON REGULATION

The regulation of iron

metabolism involves the
interaction of a number of
specific proteins.
Hepcidin controls
dietary iron absorption.

Mucosal block"
Mucosal intelligence

PHYSIOLOGY AND MOLECULAR BIOLOGY OF

DIETARY IRON ABSORPTION.
Silvia Miret, Robert J. Simpson, and Andrew T. McKie
Annu. Rev. Nutr. 2003. 23:283301

In man the normal diet should contain 1318 mg of iron per day of which
only 1 mg is absorbed. Even in iron deciency, absorption is only 24 mg
and in iron overload it is reduced to 0.5 mg.

Review Articles

Iron supplementation in early childhood: health

benefits and risks
Lora L Iannotti, James M Tielsch, Maureen M Black, and Robert E Black

We reviewed 26 randomized controlled trials of preventive, oral iron supplementation

in young children (aged 059 mo) living in developing countries to ascertain the associated
health benefits and risks. The outcomes investigated were anemia, development, growth,
morbidity, and mortality. Initial hemoglobin concentrations and iron status were considered
as effect modifiers, although few studies included such subgroup analyses. Among irondeficient or anemic children, hemoglobin concentrations were improved with iron
supplementation. Reductions in cognitive and motor development deficits were observed in
iron-deficient or anemic children, particularly with longer-duration, lower-dose regimens.
With iron supplementation, weight gains were adversely affected in iron-replete children; the
effects
height were
inconclusive.
foundalthough
no effect on
morbidity,
although few
Mostonstudies
found
no effectMost
on studies
morbidity,
few
had sample
had sample sizes or study designs that were adequate for drawing conclusions. In a
sizes or study
designs
that were
adequate
for drawing
malaria-endemic
population
of Zanzibar,
significant
increases
in seriousconclusions
adverse events
were associated with iron supplementation, whereas, in Nepal, no effects on mortality in
young children were found. More research is needed in populations affected by HIV and
tuberculosis. Iron supplementation in preventive programs may need to be targeted through
identification of iron-deficient children. Am J Clin Nutr 2006;84:126176.

Long-Term Oral Supplementation with Iron Is

Not Harmful for Young Children in a Poor
Community of Bangladesh.
Amal K. Mitra, Syed M. Akramuzzaman, George J. Fuchs, Mohammad
M. Rahman and Dilip Mahalanabis.
ABSTRACT The effect of long-term oral iron supplementation on morbidity due to diarrhea, dysentery and
respiratory infections in 349 children, aged 248 mo, living in a poor community of Bangladesh, was
evaluated in this double-blind study. The treatment group received 125 mg of ferrous gluconate (15 mg
elemental iron) plus multivitamins and the controls received only multivitamins, daily for 15 mo. House-tohouse visits were made onalternate days by trained community health workers for recording symptoms
and duration of illnesses and for monitoring medicine intake. Seventy-six percent of the children continued
the syrup for over 1 y. No untoward effects were noticed in either treatment group. The attack rates for
diarrhea, dysentery and acute respiratory tract infections (ARI) were 3, 3 and 5 episodes per child per
year, respectively. Each episode of diarrhea lasted a mean of 3 d, and those of dysentery and ARI, 5 d.
The two treatment groups did not differ in the number of episodes, mean duration of each episode, or total
days of illnesses
due to diarrhea,
dysentery
andsuggest
ARI. However,
a 49%
greater number
of episodes of
The results
of this
study
that
long-term
oral
dysentery was observed with iron supplementation in a subset of the study children who were less than
supplementation
not harmful
for
older
children is not
12 mo oldiron
(P 0.03).
The results of this studyissuggest
that long-term
oral
iron supplementation
harmful for
children
in a poor community. Further studies are needed to demonstrate the safety and
inolder
a poor
community.
efficacy of iron administration in young infants. J. Nutr. 127: 14511455, 1997.

Conclusion:
- iron supplementation increases the levels of hematologic indicators
- reduces the prevalence of IDA/ID in low birth weight/premature infants.
- There is insufficient evidence to make a definitive statement regarding
the effects of Iron supplementation on growth,neurodevelopment, or
the occurrence of adverse effects in low birth weight/premature infants.

BBLR, perlu suplementasi besi

Kebutuhan
besi sesuai
massa sdm
dibanding
aterm
Hemolisis,
Rendahnya
kadar EPO

Sedikit
cadangan besi
saat lahir

ANEMIA

Risk of iron supplementation in early childhood

Extensive studies and review
have looked at oxidative
damage to DNA protein, and
lipid .
(Kadiiska et al, 1995,
Aust SD 1985 )

Potential neurologic
dysfunction associated with
dietary iron overload early in
life (animal study ) in human is
less clear. Srigiridhar,1998

Excess iron may be

detrimental to cognitive, motor,
and behavioral development (
limited to case of genetically
susceptible) .
Hayflick SJ et al, 2003

Iron supplementation can

result in generation of free
radicals.
Kadiiska et all, 1995

RATIONAL IRON SUPPLEMENTATION

Timing, dosis, duration, and monitoring

We need Iron supplementation

in Early Childhood
In adequate iron store
Low birthweight and
prematurity
- smaller iron store
- greater iron req
- increase hemolysis
- low EPO level

More than 1.6

billion people
worldwide are
anemic

Iron deficiency generally develops

slowly and is not clinically apparent
until anemia is severe even though
functional consequences already
exist

Iron def is
thought to be
commonenst
cause

Blood sampling,
blood loss with
medical procedure

before
anemia ID
iassociated
with many
adveerse effect

The cognitive
performance,
behaviour, and
physical growth of
infants, preschool
and school-aged
children
The immune
status and
morbidity
from
infections of
all age
groups

The use of energy

source by muscle
,,,,the physical
capacity and work
performance

We need Iron supplementation

in Early Childhood
In adequate iron store
Low birthweight and
prematurity
- smaller iron store
- greater iron req
- increase hemolysis
- low EPO level

More than 1.6

billion people
worldwide are
anemic

Iron deficiency generally develops

slowly and is not clinically apparent
until anemia is severe even though
functional consequences already
exist

Iron def is
thought to be
commonenst
cause

Blood sampling,
blood loss with
medical procedure

ID generally
develops slowly
and is not clinically
apparent until
anemia eventhough
functional
consequencies
aleeady exist

Need
Iron
supplemen
tation

The cognitive
performance,
behaviour, and
physical growth of
infants, preschool
and school-aged
children
The immune
status and
morbidity
from
infections of
all age
groups

The use of energy

source by muscle
,,,,the physical
capacity and work
performance

Rationale
Tepat Diagnosis
Tepat Terapi
Tepat dosis
Tepat Indikasi
Waspada efek samping

Iron supplementation for anemia control

recommendations must balance safety and efficacy

The Cochrane Library 2012, Issue 5

Kesimpulan
Bayi yang mendapat supplementasi besi :
- terjadi peningkatan kadar Hb
- Peningkatkan cadangan besi , menurunkan risiko akan ADB
- Belum jelas ada hub antara suplementasi besi pada preterm dan BBLR
terhadap neurodevelopmental , dan pertumbuhan dikemudian hari .
- Dosis standar Fe : 2-3 mg/kgbb/hari
- Supplementasi dimulai usia 2 bulan dilajutkan hingga usia 12 bulan

Dose and schedules of iron supplementation to prevent ADB

(WHO, 2001
Age groups

Indication for supplementation

Dosage schedule

Duration

Low birth-weight infants

Universal supplementation

Iron : 2mg/kg body weight/day

From 2 months of age up to 23

months of age

Children from 6 to 23 months of

Where the diet does not include

age

food foertified with iron or where

Iron : 2mg/kg body weight/day

From 6 months of age up to 23

months of age

anaemia prevalence is above 40%

Children from 24 to 59 months of

Where anaemia prevalence is

Iron : 2mg/kg body weight/day up

age

above 40%

to 30 mg

School-aged children (above 60

Where anaemia prevalence is

Iron : 30 mg/day

months)

above 40%

Folic acid: 250 g/day

Women of childbearing age

Where anaemia prevalence is

Iron : 60 mg/day

above 40%

Folic acid: 440 g/day

Universal supplementation

Iron : 60 mg/day

AS soon as posible after gestation

Folic acid: 400 g/day

starts- no later than the 3rd month-

Pregnant women

3 months

3 months

3 months

and continuing for the rest of

pregnancy
Lactating woman

Where anaemia prevalence is

Iron : 60 mg/day

above 40%

Folic acid: 400 g/day

3 months post partum

39

Dose and Duration of Iron supplementation , IDAI, 2011

Usia (tahun)

Dosis besi elemental

Lama pemberian

Bayi* : BBLR (< 2.500g)

3 mg/kgBB/hari

Usia 1 bulan sampai 2 tahun

2 mg/kgBB/hari

Usia 4 bulan sampai 2 tahun

1 mg/kgBB/hari

2x/ minggu selama 3 bulan berturut-turut

Cukup bulan
2-5 (balita)

setiap tahun
>5-12 (usia sekolah)

1 mg/kgBB/hari

2x/ minggu selama 3 bulan berturut-turut

setiap tahun

12-18 (remaja)

60 mg/hari*

2x/ minggu selama 3 bulan berturut-turut

setiap tahun

Keterangan :* Dosis maksimum untuk bayi: 15 mg/hari, dosis tunggal

*Khusus remaja perempuan ditambah 400 g asam folat
40

Iron supplementation

Percentage and amount of elemental iron

Preparation

Iron

Percent

Elemental Iron (mg)

compound

(%)

per tablet

(mg) per tablet Of Iron

Ferrous fumarate

200

33

66

Ferrous glukonat

300

12

36

Ferrous sulfate (7H2O)

300

20

60

Ferrous sulfate anhydrous

200

37

74

Ferrous sulfate, exsiccated 200

30

60

(1H2O)
International Nutritional Anemia Consultative Group (INACG). Guidelines for the use of iron supplements to prevent and treat iron
deficiency anemia. Washington, D. C.: ILSI PRESS; 1998.

 Suplementasi besi 2 mg/KgBB/hari : usia 6 minggu-6 bulan :

menurunkan resiko secara efektif tanpa efek yang
merugikan pada morbiditas dan pertumbuhan

RCT : Ferro sulfat dosis tunggal dan 3 kali/hari pada bayi

usia 6-24 bulan :
- feritin dan efek samping minimal terjadi sama pada
kedua kelompok
- Memperbaiki pertumbuhan dan perkembangan
psikomotor secara signifikan

CMAJ 2013. DOI:10.1503

efek pemberian suplementasi besi pada anak sekolah dasar usia

5-12 tahun : - Aman efek hematologi dan non hematologi

Kesimpulan. Insidens deplesi besi, defisiensi besi, ADB paling tinggi

pada bayi berusia 0 bulan. Suplementasi zat besi elemental dengan
dosis 1 mg/kg/hari hendaknya diberikan pada semua bayi aterm
sejak lahir. (Sari Pediatri 2008;10(3):163-70).

Positive Response to Therapy

- 3-5 days:

1. Reticulocyte increase
2. Increased appetite

- 5 -10 days 3. Decreased irritability

4. Improved well being

5. Increase in HB level > 0,1 gr/ dl

per day from 5th day
- 60 days

: Hb concentration virtually becomes normal

- 90-180 days: Repletion of iron states

KESIMPULAN

Setiap kelompok umur pada anak

rentan mengalami anemia ADB
Suplementasi zat besi hendaknya diberikan
pada semua bayi dan anak secara rasional.
Suplementasi zat besi pada bayi dan anak
diperlukan untuk mencapai pertumbuhan dan
perkembangan optimal.