I - Introduction

The term hyperbilirubinemia refers to an excessive level of accumulated bilirubin in the blood and is characterized by jaundice, or icterus, a yellowish discoloration of the skin and other organs. Hyperbilirubinemia is a common finding in the newborn and in most instances is relatively benign. However, in extreme cases, it can indicate a pathologic state. Hyperbilirubinemia may result from increased unconjugated or conjugated bilirubins. The unconjugated form is the type most commonly in newborns. Possible causes of hyperbilirubinemia in the newborn are: Physiologic (developmental) factors (prematurity) An association with breast-feeding or breast milk Excess production of bilirubin (e.g hemolytic disease, biochemical defects, bruises) Disturbed capacity of the liver to secrete conjugated bilirubin (e.g enzyme deficiency, bile duct obstruction) Combined overproduction and undersecretion (increased hemolytic process) Some disease states (e.g glucose-6-phosphate dehydrogenase [G6PD] deficiency, hypothyroidism, galactosemia, infant of a diabetic mother)

COMPLICATIONS
Unconjugated bilirubin is highly toxic to neurons; therefore an infant with severe jaundice is at risk of developing bilirubin encephalopathy, a term that describes varying degrees of CNS damage resulting from the deposition of unconjugated bilirubin in brain cells. Kernicterus describes the yellow staining of the brain cells that may result in bilirubin encephalopathy. The damage occurs when the serum concentration reaches toxic level, regardless of cause. There are evidence that a fraction of unconjugated bilirubin crosses the blood-brain barrier in neonates with physiologic hyperbilirubinemia. When certain pathologic conditions exist in addition to elevated bilirubin levels, the infant has an increased permeability of the blood-brain barrier to unconjugated bilirubin and, thus, potential irreversible damage. The exact level of serum bilirubin required to cause damage is not yet known. Factors that enhance the development of bilirubin encephalopathy include: Respiratory Acidosis Lowered serum albumin levels Intracranial infections e.g Meningitis Abrupt fluctuations in blood pressure

The signs of bilirubin encephalopathy are those of CNS depressions or excitation. Generally, the clinical symptoms appear after the peak plasma bilirubin level has been established for several hours. Prodromal syndrome consists of decreased activity, lethargy,

irritability, and a loss of interest in feeding. Within several days these subtle findings may are followed by rigid extension of all four extremities, opisthotonos, fever, irritable cry, and seizures. Those who survive eventually show evidence of neurologic damage such as mental retardation, attention deficit hyperactivity disorder, delayed or abnormal motor movement, behavior disorder, perceptual problems or sensorineural hearing loss.

Classifications
Physiologic Jaundice Most common cause of hyperbilirubinemia is the relatively mild and self-limited physiologic jaundice, or icterus neonatorum. Two phases of physiologic jaundice has been identified
Phase one 1. Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 umol/l (12 mg/dL). 2. Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to 255 umol/l (15 mg/dL).

Phase two - bilirubin levels decline to about 34 umol/l (2 mg/dL) for two weeks, eventually mimicking adult values.
1. Preterm infants - phase two can last more than one month. 2. Exclusively breastfed infants - phase two can last more than one month

Causes
Mechanism involved in physiological jaundice are mainly: Relatively low activity of the enzyme glucuronosyltransferase which normally converts unconjugated bilirubin to conjugated bilirubin that can be excreted into the [4] gastrointestinal tract. Before birth, this enzyme is actively down-regulated, since bilirubin needs to remain unconjugated in order to cross the placenta to avoid being accumulated in the [5] fetus. After birth, it takes some time for this enzyme to gain function. Shorter life span of fetal red blood cells, being approximately 80 to 90 days in a full term [6] infant, compared to 100 to 120 days in adults. Relatively low conversion of bilirubin to urobilinogen by the intestinal flora, resulting in relatively [4] high absorption of bilirubin back into the circulation.
[4]

Pathological Jaundice of Neonates (Unconjugated Pathological Hyperbilirubinemia)

Any of the following features characterizes pathological jaundice: 1. Clinical jaundice appearing in the first 24 hours or greater than 14 days of life. 2. Increases in the level of total bilirubin by more than 8.5 umol/l (0.5 mg/dL) per hour or (85 umol/l) 5 mg/dL per 24 hours. 3. Total bilirubin more than 331.5 umol/l (19.5 mg/dL) (hyperbilirubinemia). 4. Direct bilirubin more than 34 umol/l (2.0 mg/dL).

III Pathophysiology
Neonatal Jaundice

Unconjugated Bilirubin

Conjugated Bilirubin

Pathologic

Physiological Jaundice of Neonates

Hepatic

Post - Hepatic

Hemolytic

Non - Hemolytic

Intrinsic Cause

Extrinsic Cause

Non Conjugated
Hemolytic Intrinsic causes of hemolysis
Membrane conditions Spherocytosis Hereditary elliptocytosis

Systemic conditions Sepsis Arteriovenous malformation

Enzyme conditions Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency) Pyruvate kinase deficiency

Globin synthesis defect sickle cell disease Alpha-thalassemia, e.g. HbH disease

Extrinsic causes of hemolysis

Alloimmunity (The neonatal or cord blood gives a positive direct Coombs test and the maternal blood gives a positive indirect Coombs test) Hemolytic disease of the newborn (ABO) Rh disease
[1] [1]

Hemolytic disease of the newborn (anti-Kell) Hemolytic disease of the newborn (anti-Rhc) Other blood type mismatches causing hemolytic disease of the newborn Breast milk feeding

Non-hemolytic causes
Cephalohematoma Polycythemia Sepsis Hypothyroidism Gilbert's syndrome Crigler-Najjar syndrome

Conjugated
Hepatic causes
Infections Sepsis Hepatitis B TORCH infections

Metabolic Galactosemia Alpha-1-antitrypsin deficiency Cystic fibrosis Dubin-Johnson Syndrome Rotor syndrome

Drugs Total parenteral nutrition Idiopathic

Post-hepatic
Biliary atresia or bile duct obstruction Alagille syndrome

Submitted By; Gin Paulo Q. Rodriguez RN Heals Pedia Ward