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Pemaparan bahan aktif yang mempengaruhi tumbuh
kembang anak
Aznan Lelo, Datten Bangun
Dep. Farmakologi & Terapeutik,
Fakultas Kedokteran
Universitas Sumatera Utara
Novmber 2008, KBK-GDS, FK USU1
Anak
• Anak merupakan suatu amanah dari Allah YMK,
• setiap orang tua menginginkan anak-anaknya tumbuh menjadi anak yang soleh, cerdas, sehat dan masa depan yang cerah
• Tumbuh kembang anak harus ditangani dengan seksama
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Kecacatan bayi
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Pemaparan bahan aktif yang mempengaruhi
tumbuh kembang anak
� Bahan aktif pada ibu hamil dan menyusui
� Paparan pada janin
� Paparan pada ASI
� Bahan aktif yang ditambahkan pada obat-obatan untuk anak
� Bahan aktif yang ditambahkan pada susu tambahan
� Bahan aktif yang ada di lingkungan anak
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Bahan aktif pada ibu hamil dan
menyusuiPaparan pada janin & Paparan pada ASI
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Homocysteine
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Kadar homocysteine
�Kadar homocysteine
meningkat menurut
usia
�Kadar homocysteine
berbeda menurut
gender
o Hormon
o Otot
o Gaya hidup
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Homocystinurias
Mostly due to inborn error of metabolism;
= transmitted as autosomal recessive traits
= can be diagnosed in the foetus by assaying
appropriate enzymes in cultured amniotic
cells
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Homocysteine metabolism
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Homocysteine dan ….
� Makin tinggi kadar homocysteine makin jelek rangking di sekolah (Borjel A, dkk.)�Increasing homocysteine levels were strongly
associated with reducing grades (p=0.004).
� Makin tinggi kadar homocysteine makin depresi (Ingvar dkk.)�homocysteine level above 15 µmol/L confers a 2
fold risk for depression.
� Makin tinggi kadar homocysteine makin nyata gejala tanda gila schizopreni (Levine J dkk.)�schizophrenic patients (16.3 µM) compared with
in healthy subjects (10.6 µM). 9
Kecacatan jiwa yang berkaitan dengan peningkatan kadar homocysteine
� Alcoholism� Age-related memory decline� Alzheimer’s disease� Autism� Dementia� Depression, severe (especially in women)� Down’s syndrome (children low, mothers high)� Epilepsy in children and adults� Mental retardation� Migraine headaches� Parkinson’s disease� Schizophrenia
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Kecacatan jasmani yang berkaitan dengan
peningkatan kadar homocysteine
� Penyakit pembuluh darah otak
� Penyakit pembuluh darah jantung
� Penyakit pembuluh darah tepi
� Trombosis vena dalaman
� Dementia/pelupa
� Patah tulang (paha/pinggul)-----osteoporosis
� Neurotoxicity (> 14 µmol/L
� Dislocated lenses
� Sering keguguran
� KECACATAN BAYI11 12
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Bahan aktif yang TIDAK BOLEH ditambahkan
untuk / dikonsumsi IBU
• Teratogenic
– Thalidomide
• Fetal death
– NSAID (in particular COXIB) at late semester or in
delivery time
• Early closing ductus arteriosus
• Mother intoxication
– Alcohol
– Psychotropic (XTC, cocaine, morphine, etc)
– Smoking 13
Importance of Micronutrient
Balance During Pregnancy
• Examples : vitamin A, vitamin D, folic acid, iron, calcium, zinc
• Folic acid and iron deficiency are risk factors for preterm birth, anemia, and infant mortality– Folic acid and iron supplementation are the most widely used
nutritional interventions during pregnancy
• Omega-3 fatty acid supplementation ensures appropriate fetal and neonatal development – Brain growth and central nervous systems (CNS) maturation
• Deficiency can be especially dangerous to mother and fetus – Impaired maternal/fetal immunity, vision disturbance,
osteoporosis, hypertension– Stillbirth, birth defects, decreased cognitive development
1. Bartley KA et al. Am J Clin Nutr. 2005;81:1188S-1198S.2. Holick MF. South Med J. 2005;98:1024-1027.3. Lips P. Prog Biophys Mol Biol. 2006;92:4-8. 14
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Importance of Macronutrient Balance
During Pregnancy
• Fats, protein, carbohydrates, water
• Adequate intake essential to healthy pregnancy
• Excessive intake may cause maternal obesity and associated morbidity– Hypertension, gestational diabetes
• Maternal obesity also linked to birth defects1
– NTDs, congenital heart disease, intestinal malformations
Bartley KA et al. Am J Clin Nutr. 2005;81:1188S-1198S.NTDs=neural tube defects
“Eating for 2” does NOT mean doubling intake
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Dose-Response Relationship Between
Folic Acid and Reduced Incidence of NTDs
-100
-80
-60
-40
-20
0
0 0,2 0,4 0,8 1,0 4,0 5,0
Increase in Daily Folic Acid Intake (mg)
Ris
k r
ed
ucti
on
(%
)
23%
36%
57%
82%85%
Wald NJ et al. Lancet. 2001;358:2069-2073.
Wald NJ. N Engl J Med. 2004;350:101-103.NTDs=neural tube defects 16
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The Role of Omega-3 Fatty Acids• Vital to human development and health
– Necessary components of cell membranes and tissues
– Involved in human reproductive, brain, and visual function
• Cannot be synthesized by the body
• Maternal fatty acid levels tend to fall– Supplementation during pregnancy is important for maternal
health, fetal development, and early childhood development
• Conversion of ALA is minimal and variable
• Only 0.2%-15% of ALA is converted
to DHA– DHA is a major fat of CNS, important to brain, heart, eye health,
but the body’s conversion is inefficient
– ALA conversion to EPA is better, but still not sufficient to maintain adequate recommended levels
Hornstra G. Am J Clin Nutr. 2000;71(suppl):1262S-1269S.Kris-Etherton PM et al. Arterioscler Thromb Vasc Biol. 2003;23:1-11.
ALA = alpha-linolenic acid; EPA = eicosapentaenoic acid;
DHA= docosahexaenoic acid 17
EPA dan DHA
• omega-3 fatty acids
– EPA (eicosapentaenoic acid) and
– DHA (docosahexaenoic acid)
• are important for child growth and development and associated with a lower risk of heart disease later in life
• ALA's dietary recommendations for children aged 2 years and older stress a diet that primarily relies on fish, fruits and vegetables, whole grains, low- fat dairy products, beans and lean meat
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Maternal Omega-3 Supplementation Augments
Children’s Mental Processing
105103
109
106102
99
106102
80
90
100
110
120
130
Mental Processing Composite Sequential Processing Simultaneous Processing Nonverbal Abilities
Omega-3s (DHA, EPA) Omega-6s
P=0.049P=0.098 P=0.11 P=0.17
K-A
BC
sco
res (
me
an
[SD
])
Helland M et al. Pediatrics. 2003;111:e39-e44.19
Bahan aktif yang ditambahkan pada
obat-obatan untuk anak
2
Sweeteners
Flavors
Dangerous agents
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Bahan aktif yang ditambahkan pada obat-
obatan untuk anak
• Obat racikan
– Saccharum lactis
• Obat jadi
• Syrup
– Flavors
– Alkohol
• Tablet kunyah
– Flavors
– Pemanis rasa 21
Dangerous agents added to medicines
• Alcohol, as a solvent
• Fluoride
• Thimerosal in vaccinations
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Halogenated organic compounds and child's growth:
a growing public health problem
• Halogenated organic compounds (HOCs) such
as – polychlorinated biphenyls (PCBs) and
dichlorodiphenyl dichloroethylene (DDE) may
– interfere with normal hormonal function and,
thereby, affect growth and maturation. • two outcomes, easily observed and frequently linked to
HOCs, are birth size and post-natal height and growth.
• toxicants were termed endocrine disruptors
• Halogenated organic compounds (HOCs) such
as – polychlorinated biphenyls (PCBs) and
dichlorodiphenyl dichloroethylene (DDE) may
– interfere with normal hormonal function and,
thereby, affect growth and maturation. • two outcomes, easily observed and frequently linked to
HOCs, are birth size and post-natal height and growth.
• toxicants were termed endocrine disruptors
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BahanBahan aktifaktif yang yang ditambahkanditambahkan padapada
susususu tambahantambahan
Nutrient
Supplement
Food additives
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Bahan aktif yang ditambahkan pada susu
tambahan
�Calcium
�Vitamin D
�EPA dan DHA
�Food additives– Excitotoxins → MSG
Aspartame
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Neurotransmitters: Excitation and Inhibition
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Excitotoxin• Substances that cause an excess of excitatory
neurotransmission in the brain. – If inhibitory neurotransmission is lacking, the
excess excitation may lead to neuronal death.
– Neuronal death leads to chronic inflammation in
the brain.
• Excitotoxins → MSG
Aspartame
• Eksitotoksisitas →→→→ proses patologi dimana
neuron menjadi rusak atau mati akibat
stimulasi berlebihan 27
MSG = monosodium glutamate
• It is believed to cause headaches, vomiting,
severe bleeding, loss of consciousness and
convulsions, inflammation to the womb, and
eventually death.
• Some items are believed to enter the breast
milk and cause diarrhea and fever in the baby.
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Kerusakan otak akibat penggunaan MSG, area putih
pada gambar kanan adalah neuron yang telah mati
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The link between MSG and obesity
• Potato chips and others aren't health foods
• They're made with
– fried fats,
– hidden toxic chemicals (acrylamides), and
– monosodium glutamate (MSG).
• This is basically a recipe for obesity.
• How does MSG cause obesity?
• Like aspartame, MSG is an excitotoxin, a substance that overexcites neurons to the point of cell damage and, eventually, cell death. 30
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The link between MSG and obesity
• Humans lack a blood-brain barrier in the
hypothalamus, which allows excitotoxins to enter
the brain and cause damage
• MSG creates a lesion in the hypothalamus that
correlates with abnormal development, including
– obesity,
– short stature and
– sexual reproduction problems
• One characteristic of the obesity induced by
excitotoxins is that it doesn't appear to depend on
food intake.31
Bahan aktif yang ada di
lingkungan anak
4
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Bahan aktif yang ada di lingkungan anak
• Di badan
– Pewangi yang ada di bedak, pakaian
• Di kamar
– Semprotan pestisida obat nyamuk (organofosfat)
• Di rumah
– Gas buangan kenderaan bermotor (carbon monoxide)
– Makanan yang tidak sehat (MSG)
– Obat-obatan
– Bahan keperluan lain seperti LEM
• Di sekolah
– Pewangi aceton (pencyclidin) yang ada pada penghapus, pinsil, dsb
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We’re SurroundedIt is in the air• Coal-fired power plants spew
sulfates, nitrates and mercury into the air—linked to >20,000
premature deaths each year
• 10% of women carry mercury
concentrations high enough for fetal damage
• Manufacturing, transportation, electricity generation and other human
activities are taking its toll on our health and environment
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Home Sweet Womb
Even before we’re born
�Mother exposed = Fetus at risk
�Average newborn has 200 different
industrial chemicals, pollutants & pesticides
in blood
�Carcinogens
�Toxic to brain & nervous system
�Abnormal development
�Urban air pollution linked to chromosomal
abnormalities in infants35
Exposed to the Elements
• Environmental metals: – Cadmium, Copper, Cobalt, Nickel, Lead, Mercury, Tin & Chromium
linked to breast cancer
• Cadmium & Mercury found in breast milk of nursingmothers
• Cause of early puberty and altered mammary glanddevelopment in animals
• Fluoride– Fluorinated drinking water linked to Osteosarcoma &
Hypothyroidism
• Vaccinations– Thimerosal causes autism in children
• Radiation– Increased radiation exposure contributed to rising incidence of
breast cancer between 1950 & 1991 36