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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

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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

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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