JAUNDICE - INVESTIGATION OF PROLONGED NEONATAL JAUNDICE
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1 Definition Unconjugated hyperbilirubinaemia Conjugated Hyperbilirubinaemia Causes of Neonatal Cholestatsis Flow Chart for Investigation of Neonatal Cholestasis First Line Investigations Second Line Investigations Third Line Investigations Interventions Fat soluble vitamins supplementation References Definition Prolonged jaundice = Jaundice persisting for more than 14 days. Children with clinically apparent jaundice present after 14 days of life require: 1) Clinical review including examination of stool colour 2) Conjugated and total bilirubin measured Any delay in follow-up for children with neonatal jaundice can lead to poor long term outcomes. Primary investigation of prolonged jaundice will include: feeding history, examination of the baby, examination of stool colour (acholic stools are highly characteristic of cholestasis in infancy). Initial laboratory tests should include: Bilirubin (total & direct (conjugated)), Urine (for infection and reducing substances), FBC and possibly a G6PD screen. Bilirubin fractionation is the most important test in any infant who has more than two weeks of jaundice. Unconjugated Hyperbilirubinaemia Total conjugated bilirubin < 20 umol/l and Conjugated bilirubin <20% total bilirubin Children with unconjugated hyperbilirubinaemia require assessment for underlying diagnosis and therapy. Important issues 1) Clinical assessment sepsis 2) Does the child require phototherapy? 3) Urine for Dipstick +- culture? 4) Consider FBC and film/ G6PD/ Coombs for haemolysis 5) Review maternal blood group for ABO/ rhesus incompatibility Conjugated Hyperbilirubinaemia Total conjugated bilirubin > 20 umol/l or Conjugated bilirubin >20% total bilirubin Any patient with conjugated hyperbilirubinaemia will be urgently reviewed by the Paediatric Gastroenterology/Hepatology service. Jaundice Investigation Vad är of lämpligast prolonged neonatal att tilltala jaundice Gendered pronomen Page: när man skriver 1 of 7 på engelska?
2 Important clinic issues 1) Most children with conjugated hyperbilirubinaemia look well but may have important disease. 2) Stool colour pale stool and dark urine suggests Biliary Atresia 3) All children with conjugated hyperbilirubinamia require additional Vitamin A,D,E,K Causes of neonatal cholestasis Disorders in bold are more common or have specific therapy available Bile duct abnormalities Endocrine disorders Inherited and metabolic disorders Biliary atresia Choledochal cyst Inspissated bile Caroli disease Gall-stones Spontaneous perforation of bile ducts Neonatal sclerosing cholangitis Hypopituitarism Hypothyroidism Hypoadrenalism α1-antitrypsin deficiency Alagille s syndrome Galactosaemia Cystic fibrosis Neonatal haemochromatosis Bile acid synthesis disorders Tyrosinaemia Progressive familial intrahepatic cholestasis Gauchers disease Neimann Pick type C Wolmans disease Peroxisomal disorders Congenital disorders of glycosylation Infections Toxic Dubin Johnson syndrome Septicaemia Urinary tract infection TORCH infections (toxoplasmosis, rubella, CMV, herpes viruses) Human Herpes virus-6, Varicella-zoster HIV, Hepatitis B Echo, Adeno, Coxsackievirus Parvovirus, EBV Parenteral nutrition Chloral hydrate Foetal alcohol syndrome Rotor syndrome Aagenaes syndrome Citrin deficiency Fatty acid oxidation disorders Mitochondrial disorders Transaldolase GSD IV Mevalonic acidemia Hereditary Fructose Intolerance Vascular disorders Chromosomal disorders Miscellaneous Perinatal asphyxia Budd Chiari syndrome Multiple haemangiomata Congestive heart failure Adapted from McKiernan 2002 Trisomy 21, 13, 18 Turner syndrome Haemophagocytic lymphohisticytosis ARC syndrome (Arthrogryposis, renal tubular dysfunction and cholestasis) Jaundice Investigation of prolonged neonatal jaundice Page: 2 of 7
3 Flow Chart for Investigation of Neonatal Cholestasis Clinical & stool colour review First line investigations Liver Biopsy 2 nd and 3 rd line investigations No Diagnosis? Yes Specific therapy? Yes Biliary Atresia Kasai Note: Acholic stools are highly characteristic of cholestasis in infancy. Bilirubin fractionation is the most important test in any infant who has more than two weeks of jaundice. Liver enzymes are of limited help to differentiate between hepatocellular and cholestatic liver injury. Synthetic liver function is best assessed by albumin level and clotting function. Untreated hypothrombinaemia may lead to spontaneous bleeding and intracranial haemorrhage. Jaundice Investigation of prolonged neonatal jaundice Page: 3 of 7
4 First line investigations conjugated Hyperbilirubinaemia FBC and blood film Total and conjugated bilirubin AST, ALT, GGT, ALP Blood group and coombs T4 and TSH α1 Antitrypsin phenotype (not level) Ferritin Cholesterol / triglycerides INR/ APTT/ Fibrinogen Blood sugar q4 hours first 24hours Cortisol Urine CMV Liver Ultrasound Guthrie card result review Maternal toxoplasma serology Maternal Syphilis status Maternal Rubella status Maternal Hepatitis B status Date Result Jaundice Investigation of prolonged neonatal jaundice Page: 4 of 7
5 Second line investigations conjugated Hyperbilirubinaemia Date Result Urine organic acids Urine amino acids Serum amino acids Plasma ammonia Plasma Lactate Herpes simplex PCR (if clinically suspected) Hepatitis A Virus IgM Adenovirus serology Epstein Barr Virus serology Stool Enterovirus Parvovirus PCR HHV6 PCR HIV Spine x-rays Ophthalmology review Urine calcium/phosphate creatinine ratio Sweat test Jaundice Investigation of prolonged neonatal jaundice Page: 5 of 7
6 Third line investigations conjugated Hyperbilirubinaemia Date Result Metabolic review- Acyl-Carnitine profile (repeat if normal & suspect diagnosis) Urine bile acids Very long chain fatty acids White Blood Cell enzymes if indicated Karyotype Muscle/ skin biopsy Short synacthen Transferrin Isoelectric Focusing CSF Lactate Bone Marrow aspirate Jaundice Investigation of prolonged neonatal jaundice Page: 6 of 7
7 Interventions All infants with conjugated hyperbilirubinaemia are started on Vit A, D, E, K Early consideration for starting MCT based formula (peptijunior) Fat Soluble Vitamin Supplementation All infants undergoing investigation of conjugated hyperbilirubinaemia should commence fat-soluble vitamin supplementation as soon as possible. Vitamin A Available preparation: Vitadol C = 2000 micrograms vitamin A per gram = 1 ml =7500 IU Starting dose is 1ml once daily NB: Vitadol C is only partially subsidised in the community; families should be informed they will be required to pay a part charge for this medicine. Vitamin D Starting dose = nanograms/kg once a day rounded to nearest 100 nanograms Available preparation = Alfacalcidol (One-Alpha drops ) = 100 nanograms of 1-alpha-OH vitamin D3 per drop. NB: This preparation should be prescribed in drops. Vitamin E Starting dose = 50 mg (68 IU) once a day. Available preparation = d-alpha-tocopheryl acetate (Micelle E ) = 156 IU/ml Suggested dose is therefore 0.5 ml once daily. NB: SPECIAL AUTHORITY is required for vitamin E administration and will be completed by the child s paediatrician prior to the child leaving hospital. Vitamin K Suggested dose = 2.5 mg once a day This is ¼ of an adult 10 mg Konakion tablet which can be crushed and mixed with water References Mckiernan P. Neonatal cholestasis. Seminars in Neonatology (2): Jaundice Investigation of prolonged neonatal jaundice Page: 7 of 7
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