Prof. dr. Burhanuddin Nasution, SpPK(K)

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Prof. dr. Burhanuddin Nasution, SpPK(K)

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A. NEONATUS & IBU DIABETES

y Pengendalian DM dengan insulin e ge da a de ga su

→ kenaikan wanita DM yang bertahan hidup &

melahirkan anak Karakteristik bayi :

‐ Besar

‐ Makrosomia

‐ Morbiditas tinggi

‐ Mortalitas tinggi, lebih 5X ibu non DM

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fi i l i Patofisiologi

Hi lik i Ib Hiperglikemia Ibu Hiperglikemia janin Respon Pankreas janin

Hiperinsulinemia janin

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Hiperinsulinemia - Hiperglikemia pe su e a pe g e a

y Ambilan glukose hepatik meningkat, sintesis glikogen meningkat, lipogenesis dan sintesis protein diperbesar y Hipertropi & hiperplasia P.P langerhans

y Penambahan berat plasenta & organ bayi kecuali otak y Hipertropi miokardium

y Penambahan jumlah sitoplasma dalam sel hati

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y Hiperinsulinisme ⇒ Asidosis janin ⇒ angka lahir meninggal meningkat

P l l k l k k

y Pelepasan plasenta ⇒ pemasukan glukose ke neonatus berkurang ⇒ hipoglikemia

y 75% bayi dari ibu diabetes dan y 25% bayi dari ibu menderita y 25% bayi dari ibu menderita

diabetes selama kehamilan

Hipoglikemia

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Kadar glukose neonatus 40 mg/dl dianggap batas Kadar glukose neonatus 40 mg/dl dianggap batas minimal :

y Lebih rendah dari 40 mg/dl ⇒ gangguan Lebih rendah dari 40 mg/dl ⇒ gangguan fungsi otak

y Otak bayi dapat menggunakan glukose padaOtak bayi dapat menggunakan glukose pada kecepatan 4‐5 mg/100 gr berat otak/menit y Otak neonatus cukup bulan beratnya 420 gr p y 4 g

pada bayi 3½ kg, memerlukan glukose dgn kecepatan 20 mg/menitp g

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B HIPERBILIRUBINEMIA B. HIPERBILIRUBINEMIA

y Ikterus diawali pada usia² minggu pertama pd 60%

bayi cukup bulan & 80% bayi pre‐term

y Ikterus terjadi karena akumulasi pigmen bilirubin yang larut lemak (indirek)

Ikt bi l i d k ( /dl) y Ikterus biasa mulai pada muka (5 mg/dl) y Ikterus tengah abdomen (15 mg/dl)

y Ikt t l k k ki ( /dl) y Ikterus telapak kaki (20 mg/dl)

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Ikterus Fisiologis (Ikterus

N t )

Neonatorum)

Normal kadar bilirubin direk dalam serum tali pusat adalah 1 3 mg/dl Kemudian naik dengan kecepatan kurang dari 5 1‐3 mg/dl. Kemudian naik dengan kecepatan kurang dari 5 mg/dl/24 jam

Ikterus terlihat : Ikterus terlihat :

‐ Pada hari ke 2 s/d 3

‐ Puncaknya pd hari ke 2 s/d 4 (kadar 5‐6 mg/dl)u ca ya pd a e s/d 4 ( ada 5 6 g/d )

‐ Pada hari ke 5 s/d 7, turun s/d kadar 2 mg/dl Hal ini terjadi diduga karena :j g

‐ Pemecahan sel darah merah

‐ Keterbatasan konjugasi oleh hatij g

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Secara keseluruhan :

y 6‐7% bayi cukup bulan kadar bilirubin indireknya >

12 9 mg/dl 12,9 mg/dl

y Kurang dari 3% mempunyai kadar > 15 mg/dl y Kadar menurun s/d kadar normal

y Kadar menurun s/d kadar normal ( 1 mg/dl sesudah 10‐14 hari)

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Faktor resiko untuk mengalami

hiperbilirubinemia indirek adalah hiperbilirubinemia indirek adalah :

y Diabetes pada ibu

P t it

y Trisomi 21 S f l h t y Prematuritas

y Obat‐obatan

(Vit. K, Novobiosin)

y Sefal hematom y Induksi Oksitosin y Pemberian ASI

( , )

y Tempat yang tinggi y Polisitemia

y BB menurun (dehidrasi) y Pembentukan tinja lambat y Laki‐laki

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Hiperbilirubinemia indirek persisten sesudah 2 minggu, memberi kesan :

y Hemolisis

y Defisiensi glukuronil tranferase herediter y Ikterus ASI

y Hipotiroid atau y Obstruksi usus

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Penyebab ikterus diduga patologis bila :

p g

y Muncul pada usia 24 jam pertama y Bilirubin serum naik > 5 mg/24 jam

y Bilirubin serum > 12 mg/dl pada bayi cukup bulan y Atau 10‐14 mg/24 jam pada bayi pre‐term

y Bilirubin bereaksi direk lebih besar 1 mg/dl pada setiap saat

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li i did k

Hemolisis diduga kuat

y Bila retikukosit > 15%

y Kern ikterus terjadi pada saudara kandungnyaKern ikterus terjadi pada saudara kandungnya y Bilirubin 5 mg/dl atau lebih

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Newborn screening tests look for:

y Serious developmental, y Genetic,

y Metabolic disorders

That important action can be taken during the critical time before symptoms develop.

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How to Prepare for the Test How to Prepare for the Test

y Between 24 hours and 7 days old,

y Typically before the baby goes home from Typically before the baby goes home from the hospital.

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Screening tests are used to detect a Screening tests are used to detect a

number of disorders, including:

y Amino acid metabolism disorders:

y Arginosuccinic acidemia

y Citrullinemia

y Homocystinuria

y Maple syrup urine disease

y Phenylketonuria (PKU)

y Tyrosinemia type ITyrosinemia type I

y Congenital adrenal hyperplasia

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y Cystic fibrosis y Galactosemia

y Glucose‐6‐phosphate dehydrogenase deficiency (G6PD)

C i l h h idi

y Congenital hypothyroidism

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The most common disorders The most common disorders tested for are:

1. Cystic fibrosis 2 Galactosaemia 2. Galactosaemia

3. Congenital hypothyroidism 4 Phenylketonuria

4. Phenylketonuria

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Cystic fibrosis Cystic fibrosis

y 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

the glands that make mucus and sweat.

y Cystic fibrosis affects males and females equally.

(1:2500) (1:2500)

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Signs and symptoms Signs and symptoms

y Lung and sinus illness

y Gastrointestinal, liver and pancreatic disease y Endocrine disease and growth

y Infertility

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Cause Cause

y CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR)

Th CFTR i f d h l f y The CFTR gene is found at the q31.2 locus of

chromosome 7

y The product of this gene is a chloride ion channel y The product of this gene is a chloride ion channel

important in creating sweat, digestive juices and mucus.

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Diagnosis Diagnosis

y Newborn screening y Sweat testing

y Genetic testing

y Trypsinogen levels can be increased

P l i h C h i d f di d

y People with CF have increased amounts of sodium and chloride in their sweat. > 60 mmol/L ( < 40 mmol/L )

y Identification of mutations in the CFTR geneIdentification of mutations in the CFTR gene

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Galactosaemia

y Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly

galactose properly y 1 per 60,000 births

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Cause Cause

y Lactose in food (such as dairy products) is broken down by the enzyme lactase into glucose and

galactose In individuals with galactosemia the galactose. In individuals with galactosemia, the

enzymes needed for further metabolism of galactose are severely diminished or missing entirely, leading to y g y, g toxic levels of galactose in the blood, resulting in

hepatomegaly (an enlarged liver), cirrhosis, renal

f il t t b i d d i f il

failure, cataracts, brain damage, and ovarian failure.

Without treatment, mortality in infants with galactosemia is about 75%.

g 75

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Diagnosis

y 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 are needed to change galactose‐a sugar that is found in milk and milk products‐into glucose, a sugar that your body uses for energyy gy

y UDP galactose epimerase

y Galactokinase

y galactose‐1‐phosphate uridyl transferase

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Congenital hypothyroidism

y Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth.

A i l i b i f

y Approximately 1 in 4000 newborn infants

y severe congenital hypothyroidism can lead to growth failure and permanent mental retardation

failure and permanent mental retardation.

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Etiology

y iodine deficiency

y Congenital hypothyroidism can also occur due to i d f f h i ii d h i genetic defects of thyroxine or triiodothyronine synthesis within a structurally normal gland

y Among specific defects are thyrotropin (TSH) y Among specific defects are thyrotropin (TSH)

resistance, iodine trapping defect, organification defect, thyroglobulin, and iodotyrosine deiodinase y g y deficiency.

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Diagnostic

y Measurement of TSH or thyroxine (T₄) on the second or third day of life.

Th TSH i hi h h T l

y The TSH is high, or the T₄ low,

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Phenylketonuria Phenylketonuria

y Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by a deficiency in the hepatic enzyme phenylalanine hydroxylase(PAH)

hepatic enzyme phenylalanine hydroxylase(PAH)

y This enzyme is necessary to metabolize the amino acid phenylalanine ('Phe') to the amino acid tyrosine

phenylalanine ( Phe ) to the amino acid tyrosine.

y When PAH is deficient, phenylalanine accumulates and is converted into phenylpyruvate (also known as p y py phenylketone), which is detected in the urine.

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y It can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures

seizures.

y Eliminating foods high in phenylalanine, such as meat, chicken fish nuts cheese legumes

chicken, fish, nuts, cheese, legumes

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y PKU is normally detected using the HPLC test, but some clinics still use the Guthrie test,

i l d b N l h l i k)

y using samples drawn by Neonatal heel prick)

y musty odor" to the baby's sweat and urine (due to phenylacetate one of the ketones produced)

phenylacetate, one of the ketones produced)

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