Anemia in Child GROWTH AND DEVELOPMENT ✓ oxygen transportation ✓ dendritic growth ✓ Oligodendrocytes : myelination ✓ enzymes activity : tryptophan & thyrosine hydroxilase ✓ neurotransmitter : serotonin, dopamine, epinephrine ✓ density and affinity of dopamine D2 receptors, ✓ neural metabolites in the hippocampus ✓ activity of proteins in energy metabolism (cytochrome C oxidase and cytochrome c), Gordon N. Iron deficiency and the intelect. Brain & Development 2003 ; 25: 3 – 8. 2 Title of Presentation | DD.MM.YYYY ▪ Iron in oligodendrocytes is required for proper myelination of the neurons ▪ sensory systems (visual, auditory), ▪ learning ▪ interacting behaviors ▪ Neuronal metabolism in the hippocampus and prefrontal projections : → memory processing ▪ Joyce C McCann JC, Ames BN. Am J Clin Nutr 2007;85:931– 45 ▪ Lannotti LL, Tielsch JM, Black MM, and Black RE. Am J Clin Nutr 2006;84:1261–76 3 Title of Presentation | DD.MM.YYYY ▪ cofactor for enzymes that synthesize neurotransmitters ▪ tryptophan hydroxylase (serotonin) ▪ tyrosine hydroxylase (norepinephrine, dopamine) ▪ dopaminergic neurotransmitter systems related to behavioral development ▪ inhibition, ▪ affect, ▪ attention processing, ▪ extraneous motor movements 4 Title of Presentation | DD.MM.YYYY Joyce C McCann JC, Ames BN. Am J Clin Nutr 2007;85:931 Lannotti LL, Tielsch JM, Black MM, and Black RE. Am J Clin Nutr 2006;84:1261–76 Fetus Baby Hampir semua syaraf terletak pada otak Lapisan luar otak biasanya masih belum matang Kebanyakan proses pembentukan syaraf terjadi sejak lahir 6 months Infant 12 months Pembentukan sinapis terjadi puncaknya pada usia 12 bln Pembentukan syaraf otak sangat cepat hingga usia 2 tahun Toddler 24 months Childhood & adolescence Semua saluran utama akan berkembang hingga 3 tahun Volume area abu – abu berkembang pada usia 4 tahun Johnson MH. Nat Rev Neurosci 2001;2:475–483 5 Title of Presentation | DD.MM.YYYY Fetus Baby Periode tercepat pada saat perkembangan syaraf 1 6 months Infant 12 months Toddler 24 months Childhood & adolescence 1. Beard JL. J Nutr 2008;138:2534–2536 2. Lozoff B et al. Nutr Rev 2006;64:S34–S91 Resiko Tinggi mengalami “Iron Deficiency “ 1 Efek jangka panjang dari “Iron Deficiency dari usia dini dlm perkembangan otak 2 Besi : perkembangan metabolik dan struktural Vitamin B12: Pembentukan syaraf otak Zinc: replikasi syaraf dan pembentukan sinapsis Iodine: pembentukkan hormon tiroid Besi : Pembentukan syaraf otak Besi : fungsi neurotransmitter Vitamin A: Perkembangan penglihatan Asam Folat : Choline: prekursor pembentukkan DNA acetylcholine & senyawa yang lain Lozoff B et al. Nutr Rev 2006;64:S34–S91 Beard JL. J Nutr 2008;138:2534–2536 Lapisan otak terluar memiliki fungsi : • Perhatian • Daya ingat • Persepsi • Pemikiran • Bahasa Hipothalamus merupakan pusat ingatan : • Mencatat ingatan • Mengolah ingatan • Mentransfer ingatan jangka pendek ke ingatan jangka panjang Lozoff B et al. Nutr Rev 2006;64:S34–S91 Perubahan metabolik dan struktural terlihat pada korteks serebri pada tahapan kekurangan besi pada hewan uji 1,2 Perkembangan hipothalamus sangat rentan terhadap defisiensi besi1: • Perubahan metabolik pada masa pubertas • Akibat “ Iron deficiency” adalah adanya formasi yang abnormal antara synapses dan syaraf Data from rat models of brain development 1. Lozoff B et al. Nutr Rev 2006;64:S34–S91 2. Ward KL et al. J Nutr 2007;37:1043–1049 Axon bagian dari syaraf diselubungi oleh myelin untuk menghantarkan impuls listrik dengan baik antar syaraf . (sangat penting sebagai penghantar dari neuron satu kelainnya ) Myelin dibentuk oleh oligodendrocyt Di SSP, dan sangat sensitif terhadap kekurangan besi1 SSP – susunan saraf pusat 1. Beard JL. J Nutr 2008;138:2534–2536 Besi sangat penting untuk berbagai enzim yang memiliki fungsi dalam mensintesis neurotransmitter seperti : serotonin, dopamine dan norepinephrine Wigglesworth JM et al. Iron dependent enzymes in the brain. In: Youdim MBH, ed. Brain Iron: Neurochemical and Behavioural Aspects. New York: Taylor and Francis;1988:25–66 Kepadatan transporter seperti dopamine, norepinephrine dan serotonin dipengaruhi oleh defisiensi besi1 Defisiensi besi memengaruhi metabolisme dopamine dan norepinephrine1 • Sintesis dan pemecahannya terganggu2 • Densitas reseptor dopamin berubah1 Data from rat models of brain development & in vitro studies 1. Lozoff B et al. Nutr Rev 2006;64:S34–S91 2. Beard JL. J Nutr 2008;138:2534–2536 Kekurangan zat besi dapat berakibat mengurangi kandungan lemak dan protein pada myelin Komponen lainnya pada proses pembentukan myelin sangat berpengaruh (kepadatan myelin) Pembentukan myelin selama perkembangan otak yang tidak sempurna akan berpengaruh hingga dewasa meskipun kebutuhan besi akan terpenuhi dikemudian hari . Data from rat models of brain development Lozoff B et al. Nutr Rev 2006;64:S34–S91 Iron deficiency is the leading micronutrient deficiency in the world, but is most detrimental to infants and children 14 Title of Presentation | DD.MM.YYYY 15 Title of Presentation | DD.MM.YYYY Central nervous system → irritability, fatigue, decreased attentiveness shorter attention span, reduced cognitive performance, behavioural disturbances (eg. ADHD) Bourre JM. J Nutr Health Aging 2006;10:377-85 Kane A. ADHD and iron deficiency. http://www.mental-health-matters.com/articles/article.php?artID=751 Lanzkowsky P. Iron-deficiency anemia. In: Lanzkowsky P. Manual of pediatric hematology and oncology, 2nd ed. p.35 Conrad ME. Iron deficiency anemia. http://www.emedicine.com 16 Title of Presentation | DD.MM.YYYY sensory (auditory, visual) temperamen, emotion, affect attention, − hiperactivity, inhibition Information processing, − learning − memory problem solving − inteligency → school performance → behavior problems − 2. Joyce C McCann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavio ral function1 Am J Clin Nutr 2007;85:931– 45 − 3. Iannotti LL, Tielsch JM, Black MM, Black RE. Iron supplementation in early childhood : health benefit and risks. Am J Clin Nutr 2006;84: 1261-76. − 5. Grein J. The Cognitive Effect of Iron Deficiency in Non-Anemic Children. Nutrition Noteworthy 2001; 4(1). − 6. Gordon N. Iron deficiency and the intelect. Brain & Development 2003 ; 25: 3 – 8. 17 − Title 7. Algarin C, Peirano| P, Garrido M, Pizzaro F, Lozoff. Iron Deficiency Anemia in Infancy : Long-Lasting Effects on Auditory and Visual System Functioniong. Pediatr Res 2003;53:217-223 of Presentation DD.MM.YYYY 18 Title of Presentation | DD.MM.YYYY Age (months) Prevalence (%) 0 – 5 mos 6 – 11 mos 12 – 23 mos 61,3 64,8 58,0 24 – 35 mos 54,4 36 – 47 mos 38,6 48 – 59 mos 32,1 47,0 Total Untoro R. Peningkatan Kualitas Hidup Anak Melalui Pencegahan Anemia Gizi Besi. Disajikan pada Kampanye Anti Anemia 20062008. Depkes, Jakarta, 1 Maret 2007. 19 Title of Presentation | DD.MM.YYYY Sekartini et al (2005) Utan Kayu, East Jakarta 55 fullterm infants aged 4 – 12 mos Exclusively breast feeding 94.5 % No chronic disease Low and midle social economic status 38 % anemia, 73,3 % at 8 -12 mo of age the youngest 4 mo of age Hb 8,9 g/dl, feritin serum 3,2 ug. Sekartini R, Soedjatmiko, Wawolumaya C, Yuniar I, Dewi R. Prevalensi Anemia Defisiensi Besi pada Bayi Usia 4-12 Bulan di Kecamatan Matraman dan Sekitarnya, Jakarta Timur. Sari Pediatri 2005 ; 7(1):2-8 20 Title of Presentation | DD.MM.YYYY PREVALENSI ANEMIA DI 17 SEKOLAH DASAR DKI JAKARTA TH 2007 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% UTKU KBBW PSBR PDKL UTKU PSBR UTKS UTKS KBMG KBMG CPBS PDKP PDBB PDKL PDKL PDKL 07 01 05 01 11 07 13 20 08 09 03 06 05 11 12 02 DRS RATA2 W 10 Series1 36.9% 31.3% 29.3% 16.9% 11.1% 20.6% 22.6% 31.3% 37.5% 50.9% 14.4% 16.4% 25.1% 14.3% 15.3% 18.7% 27.0% 23.2% Sasongko A. Prevalensi Anemia pada 17 Sekolah Dasar di Jakarta. Disajikan pada Kampanye Anti Anemia 2006-2008. Depkes, Jakarta, 1 Maret 2007 21 Title of Presentation | DD.MM.YYYY Review of 40 studies : Cognitive or behavioral performance of children with iron deficiency Joyce C McCann JC, Ames BN. Am J Clin Nutr 2007;85:931– 45 ➢ 40 studies of various experimental designs ➢ cognitive or behavioral ➢ ID + Anemia, ➢ 60% <2 y of age Consistent association between ID + Anemia and poor performance 22 Title of Presentation | DD.MM.YYYY Review of 40 studies : Cognitive or behavioral performance of children with iron deficiency Joyce C McCann JC, Ames BN. Am J Clin Nutr 2007;85:931– 45 ➢ 20 iron-treatment trials children with ID+A, ➢ mostly double blind randomized clinical trial ➢ poorer performance ✓ improve with iron treatment in children > 2 y of age ✓ more resistant to improvement in children <2 y of age 23 Title of Presentation | DD.MM.YYYY Review of 26 RCT Iron Supplementation in Early Childhood Lora L Iannotti, James M Tielsch, Maureen M Black, and Robert E Black Am J Clin Nutr 2006;84:1261–76 26 randomized controlled trials. 0–59 mo, developing countries. No effect on morbidity. in Nepal, no effects on mortality in young children Iron supplementation in preventive programs to be targeted of iron-deficient children. Improved in cognitive and motor development deficits ✓ iron-deficient or anemic children, ✓ longer-duration, lower-dose regimens. 24 Title of Presentation | DD.MM.YYYY Benefit of Iron Supplementation in Early Childhood Lannotti LL, Tielsch JM, Black MM, and Black RE .Am J Clin Nutr 2006;84:1261–76 ▪Iron supplementation have some positive effects on developmental among preschoolaged children who were iron deficient or anemic before supplementation ▪ reducing preexisting deficits ▪ preventing losses cognitive and motor skill development ▪Treatment at lower doses for 2–12 mo more beneficial than very short courses of supplementation Two studies found a positive effect on height increases in iron-deficient children, 2 found a negative effect and 2 found no effect on height or length in iron-replete children 25 Title of Presentation | DD.MM.YYYY 26 Title of Presentation | DD.MM.YYYY 27 Title of Presentation | DD.MM.YYYY 28 Title of Presentation | DD.MM.YYYY 29 30 Title of Presentation | DD.MM.YYYY Iron supplementation recommendation Source 31 Dosage Frequency WHO1 10 – 12.5 mg/day 6–23 months for 3 consecutive months/year In settings ≥40% anemia prevalence AAP2 1 mg/kg/day infants ≥4 months exclusively breast-fed or consuming >1/2 intake from breast milk until receiving appropriate ironcontaining complementary foods CDC3 1 mg/kg/day Suggest supplement breast-fed infants ≥6 months consuming insufficient iron from supplementary foods (<1 mg/kg/day) ESPGHN4 - No convincing evidence for iron supplements of exclusively breast-fed term infant <6 months. except on individual basis Canada5 - Recommend meat, meat-alternatives & iron-fortified cereals for firs complementary foods at 6 months. Title of Presentation | DD.MM.YYYY 32 Title of Presentation | DD.MM.YYYY 1. Dua tahun pertama kehidupan merupakan periode kritis untuk perkembangan otak . 2. Pada masa yang bersamaan kebutuhan besi juga meningkat1 3. Besi sangat penting pada perkembangan otak : 4. ➢ Perkembangan metabolik dan struktural2,3 ➢ Pembentukan myelin dan neuron2,3 ➢ Fungsi neurotransmitter2,3 Akibatnya : ❖ 5. 33 Pada anak yang kekurangan besi pada usia 6-18 bulan akan mengalami perubahan persisten dan berakibat gangguan fungsi otak pada masa dewasa2,3 Pemberian suplementasi zat besi pada anak-anak dapat meningkatkan cognitive dan pertumbuhan Title of Presentation | DD.MM.YYYY 1. Johnson MH. Nat Rev Neurosci 2001;2:475–483 2. Lozoff B et al. Nutr Rev 2006;64:S34–S91 3. Beard JL. J Nutr 2008;138:2534–2536
