Prof. dr. Burhanuddin Nasution, SpPK(K)

A. NEONATUS & IBU DIABETES Pengendalian DM dengan insulin → kenaikan wanita DM yang bertahan hidup & melahirkan anak Karakteristik bayi : - Besar - Makrosomia - Morbiditas tinggi - Mortalitas tinggi, lebih 5X ibu non DM

Patofisiologi Hiperglikemia Ibu Hiperinsulinemia janin Respon Pankreas janin Hiperglikemia janin

Hiperinsulinemia - Hiperglikemia Ambilan glukose hepatik meningkat, sintesis glikogen meningkat, lipogenesis dan sintesis protein diperbesar Hipertropi & hiperplasia P.P langerhans Penambahan berat plasenta & organ bayi kecuali otak Hipertropi miokardium Penambahan jumlah sitoplasma dalam sel hati

Hiperinsulinisme  Asidosis janin  angka lahir meninggal meningkat Pelepasan plasenta  pemasukan glukose ke neonatus berkurang  hipoglikemia 75% bayi dari ibu diabetes dan 25% bayi dari ibu menderita diabetes selama kehamilan Hipoglikemia

Kadar glukose neonatus 40 mg/dl dianggap batas minimal : Lebih rendah dari 40 mg/dl  gangguan fungsi otak Otak bayi dapat menggunakan glukose pada kecepatan 4-5 mg/100 gr berat otak/menit Otak neonatus cukup bulan beratnya 420 gr pada bayi 3½ kg, memerlukan glukose dgn kecepatan 20 mg/menit

B. HIPERBILIRUBINEMIA Ikterus diawali pada usia 2 minggu pertama pd 60% bayi cukup bulan & 80% bayi pre-term Ikterus terjadi karena akumulasi pigmen bilirubin yang larut lemak (indirek) Ikterus biasa mulai pada muka (5 mg/dl) Ikterus tengah abdomen (15 mg/dl) Ikterus telapak kaki (20 mg/dl)

Ikterus Fisiologis (Ikterus Neonatorum) Normal kadar bilirubin direk dalam serum tali pusat adalah 1-3 mg/dl. Kemudian naik dengan kecepatan kurang dari 5 mg/dl/24 jam Ikterus terlihat : - Pada hari ke 2 s/d 3 - Puncaknya pd hari ke 2 s/d 4 (kadar 5-6 mg/dl) - Pada hari ke 5 s/d 7, turun s/d kadar 2 mg/dl Hal ini terjadi diduga karena : - Pemecahan sel darah merah - Keterbatasan konjugasi oleh hati

Secara keseluruhan : 6-7% bayi cukup bulan kadar bilirubin indireknya > 12,9 mg/dl Kurang dari 3% mempunyai kadar > 15 mg/dl Kadar menurun s/d kadar normal ( 1 mg/dl sesudah hari)

Faktor resiko untuk mengalami hiperbilirubinemia indirek adalah : Diabetes pada ibu Prematuritas Obat-obatan (Vit. K, Novobiosin) Tempat yang tinggi Polisitemia Laki-laki Trisomi 21 Sefal hematom Induksi Oksitosin Pemberian ASI BB menurun (dehidrasi) Pembentukan tinja lambat

Hiperbilirubinemia indirek persisten sesudah 2 minggu, memberi kesan : Hemolisis Defisiensi glukuronil tranferase herediter Ikterus ASI Hipotiroid atau Obstruksi usus

Penyebab ikterus diduga patologis bila : Muncul pada usia 24 jam pertama Bilirubin serum naik > 5 mg/24 jam Bilirubin serum > 12 mg/dl pada bayi cukup bulan Atau mg/24 jam pada bayi pre-term Bilirubin bereaksi direk lebih besar 1 mg/dl pada setiap saat

Hemolisis diduga kuat Bila retikukosit > 15% Kern ikterus terjadi pada saudara kandungnya Bilirubin 5 mg/dl atau lebih

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Newborn screening tests look for: Serious developmental, Genetic, Metabolic disorders That important action can be taken during the critical time before symptoms develop. 15

How to Prepare for the Test Between 24 hours and 7 days old, Typically before the baby goes home from the hospital. 16

Screening tests are used to detect a number of disorders, including: Amino acid metabolism disorders: Arginosuccinic acidemia Citrullinemia Homocystinuria Maple syrup urine disease Phenylketonuria (PKU) Tyrosinemia type I Congenital adrenal hyperplasia 17

Cystic fibrosis Galactosemia Glucose-6-phosphate dehydrogenase deficiency (G6PD) Congenital hypothyroidism 18

The most common disorders tested for are: 1. Cystic fibrosis 2. Galactosaemia 3. Congenital hypothyroidism 4. Phenylketonuria 19

Cystic fibrosis Cystic fibrosis (CF) is a genetic disorder known to be an inherited disease of the secretory glands, including the glands that make mucus and sweat. Cystic fibrosis affects males and females equally. (1:2500) 20

Signs and symptoms Lung and sinus illness Gastrointestinal, liver and pancreatic disease Endocrine disease and growth Infertility 21

Cause CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR) The CFTR gene is found at the q31.2 locus of chromosome 7 The product of this gene is a chloride ion channel important in creating sweat, digestive juices and mucus. 22

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Diagnosis Newborn screening Sweat testing Genetic testing Trypsinogen levels can be increased People with CF have increased amounts of sodium and chloride in their sweat. > 60 mmol/L ( < 40 mmol/L ) Identification of mutations in the CFTR gene 24

Galactosaemia Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly 1 per 60,000 births 25

Cause Lactose in food (such as dairy products) is broken down by the enzyme lactase into glucose and galactose. In individuals with galactosemia, the enzymes needed for further metabolism of galactose are severely diminished or missing entirely, leading to toxic levels of galactose in the blood, resulting in hepatomegaly (an enlarged liver), cirrhosis, renal failure, cataracts, brain damage, and ovarian failure. Without treatment, mortality in infants with galactosemia is about 75%. 26

Diagnosis A galactosemia test is a blood test (from the heel of the infant) or urine test that checks for three enzymes that are needed to change galactose-a sugar that is found in milk and milk products-into glucose, a sugar that your body uses for energy UDP galactose epimerase Galactokinase galactose-1-phosphate uridyl transferase 27

Congenital hypothyroidism Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants severe congenital hypothyroidism can lead to growth failure and permanent mental retardation. 28

Etiology iodine deficiency Congenital hypothyroidism can also occur due to genetic defects of thyroxine or triiodothyronine synthesis within a structurally normal gland Among specific defects are thyrotropin (TSH) resistance, iodine trapping defect, organification defect, thyroglobulin, and iodotyrosine deiodinase deficiency. 29

Diagnostic Measurement of TSH or thyroxine (T 4 ) on the second or third day of life. The TSH is high, or the T 4 low, 30

Phenylketonuria Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by a deficiency in the hepatic enzyme phenylalanine hydroxylase(PAH) This enzyme is necessary to metabolize the amino acid phenylalanine ('Phe') to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine. 31

It can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures. Eliminating foods high in phenylalanine, such as meat, chicken, fish, nuts, cheese, legumes 32

PKU is normally detected using the HPLC test, but some clinics still use the Guthrie test, using samples drawn by Neonatal heel prick) musty odor" to the baby's sweat and urine (due to phenylacetate, one of the ketones produced) 33