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NEONATOLOGY IV NEONATAL JAUNDICE Dr Ugolee Jerry INTRODUCTION • Jaundice is the yellowish discolouration of sclera, skin and mucus membrane following increased serum bilirubin levels. • Up to 60% of term newborns and 80% of preterm develop jaundice in the 1st week of life. • From an evolutionary s...
NEONATOLOGY IV NEONATAL JAUNDICE Dr Ugolee Jerry INTRODUCTION • Jaundice is the yellowish discolouration of sclera, skin and mucus membrane following increased serum bilirubin levels. • Up to 60% of term newborns and 80% of preterm develop jaundice in the 1st week of life. • From an evolutionary standpoint, hyperbilirubinemia must confer some biologic advantage as bilirubin is a potent antioxidant and peroxly scavenger. • Normal serum bilirubin levels are 2-3mg/dL and clinical jaundice is evident at levels above 5mg/dL. • Hyperbilirubinemia can be toxic and may result in kernicterus. INTRODUCTION • The exact mechanism by which bilirubin is toxic to cells is unknown but is assumed that when the amount of lipid-soluble unconjugated bilirubin exceeds binding sites on albumin, free bilirubin enters and damages neurons. • The blood-brain barrier plays an important role in protecting the brain but its integrity is impossible to measure clinically and exact levels above which bilirubin would cause brain damage is not known. • Certain factors like hypoxia, acidosis, prematurity, infection, hypoalbuminemia and ICH reduce the integrity of the BBB. INTRODUCTION • In clinical practice an arbitrary bilirubin index of 20mg/dL below which bilirubin must be kept as above which has been associated with increased risk of kernicterus is commonly used. • It is believed that jaundice appearing on the face of a neonate is ≈ 5mg/dl, on the trunk ≈10mg/dl, on the abdomen and mid thigh ≈ 15mg/dl and up to the feet ≈ 20mg/dl. • One common approach is to use 1% of the BW in grams as the exchange level in mg/dl eg, 12mg/dl for a 1200g newborn. PATHOPHYSIOLOGY • Heme is broken down by heme oxygenase to iron, CO and biliverdin. Biliverdin is metabolized to bilirubin by reductase. Bilirubin is carried bound to albumin to the liver where it is conjugated with two glucuronide molecules by UDPGT. • Conjugated bilirubin is excreted through bile into the intestine where it is partly metabolized to stercobilin in stool by the normal gut flora, and partly deconjugated by ß-glucuronidase and reabsorbed(enterohepatic circulation). AETIOLOGY • The cause of jaundice may follow overproduction or a decreased rate of conjugation and clearance of bilirubin. • Neonatal jaundice maybe described as conjugated or unconjugated hyperbilirubinemia, as acute or chronic/prolonged(˃6weeks), or as pathologic or physiologic. • Conjugated hyperbilirubinemia may follow hepatic or non-hepatic(post hepatic) causes. It more often results in prolonged jaundice. • Unconjugated hyperbilirubinemia may be pathologic or physiologic. Pathologic unconjugated jaundice may follow haemolytic, nonhaemolytic or non-organic causes. AETIOLOGY • Hepatic causes of conjugated hyperbilirubinemia include: sepsis, TORCH infection, hepatitis A&B infections. • Non-hepatic / post-hepatic causes of conjugated hyperbilirubinemia include: galactosemia, α 1-antitrypsin deficiency, Dubin-Johnson syndrome, Rotor syndrome, Alagille syndrome, biliary atresia, choledochal cyst, TPN, cystic fibrosis, idiopathic. • Pathologic unconjugated jaundice is characterized by the clinical appearance of jaundice in the 1st 24hrs of life or greater than 14days, increases in total bilirubin by more than 0.5mg/dl/hr or 5mg/dl/day and rises to levels more than 20mg/dl. AETIOLOGY • Physiologic unconjugated hyperbilirubinemia is characterized by its onset at day 2-3, peaking at days 4-6 and declining by 10days in term newborns. And later onset on days 4-6 in preterms, peaking by days 7-10 and declining by day 14. • It rarely rises to 15mg/dl and the child is otherwise well. It occurs because the immature liver is unable to keep up with the conjugation of breaking down fetal haemoglobin, which has a shorter life span. • Pathologic unconjugated jaundice may follow haemolytic or nonhaemolytic causes. Haemolytic causes maybe intrinsic or extrinsic. AETIOLOGY • Haemolytic intrinsic causes include: membrane defects( spherocytosis, eiliptocytosis, pyknocytosis), membrane enzyme abnormalities (G6PD deficiency, pyruvate kinase deficiency, hexokinase deficiency), globin synthesis defects(SCA, α-thalassemia). • Haemolytic extrinsic causes include: Alloimmune causes (would give a +ve coombs test result) like ABO incompatibility- typically mother is group O and father & child are group A,B or AB. Rhesus isoimmunization-typically mother is Rh –ve and father & child is Rh +ve. Mother is usually sensitized following a previous preg, abortion or procedure. AETIOLOGY • Non-haemolytic causes include: Breastfeeding jaundice( caused by insufficient breastmilk intake with resultant reduced bowel movts & increased enterohepatic circulation), Breast milk jaundice (breast milk contains glucoronidase which increases gut de-conjugation of bilirubin and lipoprotein lipase which inhibits hepatic glucuronyl transferase), polycythaemia, cephalhematoma, sepsis, hypothyroidism, Gilbert’s syndrome, Crigler-Najjar &pyloric stenosis. CLINICAL MANIFESTATION • Kernicterus named after the yellow staining of the subthalamic nuclei(kerns) seen at autopsy. • Early symptoms consists of lethargy, hypotonia and poor suck, progressing to hypertonia, opisthotonos, wind-milling rolling hand movt’s and a high-pitched cry. • Long-term sequelae include chorio-athetoid cerebral palsy, sensorineural deafness, impaired upward qaze and dental dysplasia. DIAGNOSIS • Diagnosis is often clinical and by measuring serum bilirubin level in blood. Usually total and conjugated values are given. When conjugated fraction is more than 20% of the total bilirubin it is considered largely conjugated. • Transcutaneous bilirubinometer – hand held, expensive, portable and rechargeable device with a photo probe pressed against the subcutaneous tissue. • Icterometer, piece of transparent plastic painted in 5 transverse strips of graded yellow, it is obsolete. • Do other relevant investigation to determine cause eg, blood group, G6PD assay, blood culture, FBC, direct Coombs test. TREATMENT • Phototherapy is used most commonly as it is safe and noninvasive. • Light at a specific wave length(470ɲm) and spectrum (blue or white light)is used to convert unconjugated trans-bilirubin into a water-soluble stereoisomer (cis-bilirubin) which is easily excreted. • Effectivity is improved by increasing exposed surface area of child, by lying child on a reflective biliblanket and by placing light close to child(≤ 45cm) with eyes and groin covered. TREATMENT • Indication for phototherapy include: for prophylaxis for at risk newborns like preterms, IDM’s and infants of Rh –ve mothers, for mild to moderate unconjugated hyperbilirubinemia, postEBT to prevent rebound hyperbilirubinemia. • Complications following phototherapy may include : dehydration, retinal damage, infertility ( from gonadal damage), photo dermatitis, diarrhoea, bronze baby syndrome. • Contraindications to phototherapy include porphyria and conjugated hyperbilirubinemia. TREATMENT • Exchange blood transfusion(EBT)-Aseptic transfusion procedure during which the total blood volume (or twice the volume) is removed and exchanged with freshly donated whole blood that is grouped and crossed matched and compatible with child & mothers blood. • The umbilical vein is catheterized and blood in aliquots of 25mls with withdrawn, discarded and an equal amount exchanged back into the newborn after a dwell time of 23minutes. Requires and assistant with good record keeping. TREATMENT • EBT done under ideal circumstances would employ a proper EBT set with a 3-way tap system and a manometer for measuring central venous pressure. • EBT may be single volume ( 80ml x body wt) or double volume ( 80mls x body wt x 2). • Pre and post EBT samples for serum bilirubin are withdrawn, 1ml of Calcium gluconate is given after every 100mls of blood exchanged and 10% dextrose and a top –up blood volume is commonly given at the end of the exchange. TREATMENT • Indications for single volume EBT include severe anaemia and severe sepsis. Indication for double volume EBT is severe hyperbilirubinemia (˃250μmol/l for preterms and ˃340μmol/l for term babies). • Complications of EBT include complications of blood transfusion( acute febrile reaction, acute blood transfusion reactions, transmission of blood borne diseases and malaria) and complications of the procedure ( gut perforation, circulatory overload, anaemia, embolization, omphalitis, bleeding, thrombocytopenia, hypocalcaemia, hypoglycaemia, arrthymias from cardiac catheterization e.t.c). TREATMENT • Contraindication for EBT is cardiopulmonary instability. • Other treatment modalities include Pharmacotherapy ( used of phenobarbitone to stimulate cytochrome p450 enzymes stimulation in the liver to increase hepatic uptake but no longer practised due to side effect on respiration). • Also the use of protoporphyins as inhibitors of heme oxygenase. Still experimental. • Sunlight exposure is NOT treatment for any form of NNJ. • Further readings- Read biliary atresia and other causes of prolonged conjugated hyperbilirubinemia.