NEONATAL JAUNDICE

Indirect Hyperbilirubinemia of the Newborn

Hyperbilirubinemia is a common and, in most cases, benign problem in neonates.  Jaundice is observed during the 1st wk of life in approximately 60% of term infants and 80% of preterm infants.

Jaundice usually becomes apparent in a cephalocaudal progression, starting on the face and progressing to the abdomen and then the feet, as serum levels increase

IB > 1.3-1.5 mg/dl (every age) DB>1.5 mg/dl or >10% of total serum bilirubine

Whereas jaundice from deposition of indirect bilirubin in the skin tends to appear bright yellow or orange, jaundice of the obstructive type (direct bilirubin) has a greenish or muddy yellow cast

Yellow color usually results from the accumulation of ; unconjugated, nonpolar, lipid-soluble bilirubin pigment in the skin. 

This unconjugated bilirubin is an end product of heme-protein catabolism from a series of enzymatic reactions by heme-oxygenase and biliverdin reductase and nonenzymatic reducing agents in the reticuloendothelial cells

MAJOR ELIMATION …………………………………..GAITA ENTEROHEPATIC CIRCULATION……...BETA GLUKORUNIDASE

Neonatal jaundice is common..Because; Shorter life span of fetal red blood cells (70-90 days) Relatively low activity of the enzyme glucuronosyl transeferade which normally converts unconjugated bilirubin  to conjugated bilirubin that can be excreted into the gastrointestinal tract Low ligandin level High enterohepatic circulation

Physiologic Jaundice (Icterus Neonatorum) Abnormal circumstances, the level of indirect bilirubin in umbilical cord serum is 1-3 mg/dL and rises at a rate of <5 mg/dL/24 hr; thus, jaundice becomes visible on the 2nd or 3rd day, usually peaking between the 2nd and 4th days at 5-6 mg/dL and decreasing to <2 mg/dL between the 5th and 7th days of life

Physiological Jaundice It appears after 24-36 hr of life Serum bilirubin is rising at a rate slower than 5 mg/dL/24 hr or 0.2ml/dl/hr Serum bilirubin is < 12 mg/dL in a full-term infant (especially in the absence of risk factors) or 10-14 mg/dL in a preterm infant Jaundice does not persists after 10-14 days of life Direct bilirubin fraction is < 2 mg/dL at any time 

And the main question is; What are the risk factors of jaundice of newborn?

Risk Factors for Elevated Indirect Bilirubin Include; Maternal age Race (Chinese, Japanese, Korean, and Native American) Maternal diabetes Prematurity Drugs (Vitamin K3, Novobiocin) Altitude Polycythemia Male sex Trisomy 21 Blood extravasation (cephalohematoma) Oxytocin induction, Breast-feeding Weight loss (dehydration or caloric deprivation), Delayed bowel movement Family history or a sibling who had physiologic jaundice

Jaundice that first appears on the 2nd or 3rd day is usually physiologic

Pathogical Jaundice It appears in the first 24-36 hr of life Serum bilirubin is rising at a rate faster than 5 mg/dL/24 hr Serum bilirubin is >12 mg/dL in a full-term infant (especially in the absence of risk factors) or 10-14 mg/dL in a preterm infant, Jaundice persists after 10-14 days of life Direct bilirubin fraction is >2 mg/dL at any time 

Which etiologies are behind of the jaundice in first 24 hours?

Jaundice, that is present at birth or appears within the 1st 24 hr of life requires immediate attention and may be due to; Erythroblastosis fetalis Concealed hemorrhage Sepsis Congenital infections ( including syphilis, cytomegalovirus, rubella, and toxoplasmosis)

Neonatal Jaundice ---Diagnosis Serum bilirubin Maternal and babies blood type, Rh, Coombs test CBC, peripheral blood smear

Rh disease (also known as Rhesus Isoimmunisation, Rhesus Incompatibility) The disease typically occurs only in some second or subsequent pregnancies of Rh negative women where the fetus's father is Rh positive, leading to a Rh+ pregnancy. During birth, the mother may be exposed to the infant's blood, and this causes the development of antibodies, which may affect the health of subsequent Rh+ pregnancies.

ABO hemolytic disease of the newborn Maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells  which can lead to fetal anemia and HDN In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

Breast feeding jaundice «Early onset type Breastfeeding jaundice» or «Lack of breastmilk jaundice» 2. «Late onset type Breastmilk jaundice»

1. Early Type Breastfeeding jaundice or "lack of breastfeeding jaundice" Early Type Breastfeeding jaundice or "lack of breastfeeding jaundice," is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. Hyperbilirubinemia (>12 mg/dL) develops in 13% of breast-fed infants in the 1st wk of life and may be due to decreased milk intake with dehydration and/or reduced caloric intake. This can usually be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.

2.Jaundice Associated with Breastmilk Significant elevation in unconjugated bilirubin (breast milk jaundice) develops in an estimated 2% of breast-fed term infants after the 7th day of life, with maximal concentrations as high as 10-30 mg/dL reached during the 2nd-3rd week. If breast-feeding is continued, the bilirubin gradually decreases but may persist for 3-10 wk at lower levels. The etiology of breast milk jaundice is not entirely clear but may be attributed to the presence of glucuronidase in some breast milk.

Late type Breastmilk jaundice : First, at birth, the gut is sterile, and normal gut flora takes time to establish. The bacteria in the adult gut convert conjugated bilirubin  to stercobilinogen which is then oxidized to stercobilin and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border β-glucuronidase and reabsorbed. This process of re-absorption is called enterohepatic circulation. It has been suggested that bilirubin uptake in the gut (enterohepatic circulation) is increased in breast fed babies Second, the breast-milk of some women contains a metabolite of progesterone called 3-alpha 20 beta pregnanediol . This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid glucronyl transferase (UDPGT) responsible for conjugation and subsequent excretion of bilirubin. Third, an enzyme in breast milk called lipoprotein lipase produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase, which again leads to decreased conjugation and subsequent excretion of bilirubin.

Jaundice Associated with Breast-Feeding Even when breast-feeding jaundice develops, breast-feeding should be continued if possible!!!

Gilbert's syndrome  It is the most common hereditary  cause of increased bilirubin and is found in up to 5% of the population

Gilbert's syndrome A major characteristic is;  Jaundice, supposedly caused by elevated levels of unconjugated bilirubin in the bloodstream The cause of this hyperbilirubinemia is the reduced activity of the enzyme glucuronyltransferase  

Crigler–Najjar syndrome The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants

  Risk designation of term and near-term well newborns based on their hour-specific serum bilirubin values.

TREATMENT

Phototherapy Further investigation lead to the determination that blue light, wavelength of 420-480 nm, oxidized the bilirubin to biliverdin, a soluble product that does not contribute to kernicterus Phototherapy works through a process of isomerization that changes trans-bilirubin into the water-soluble cis-bilirubin isomer

Exchange transfusions Much like with phototherapy the level at which exchange transfusions should occur depends on the health status and age of the newborn It should however be used for any newborn with a total serum bilirubin of greater than 428 umol/l ( 25 mg/dL )

An exchange transfusion requires that the patient's blood can be removed and replaced. In most cases, this involves placing one or more thin tubes, called catheters, into a blood vessel. The exchange transfusion is done in cycles: each one usually lasts a few minutes The patient’s blood is slowly withdrawn (usually about 5 to 20 mL at a time, depending on the patient’s size and the severity of illness). An equal amount of fresh, prewarmed blood or plasma flows into the patient's body. This cycle is repeated until the correct volume of blood has been replaced.

Prognosis - Complications

Kernicterus Infants with severe hyperbilirubinemia may present with lethargy and poor feeding and, without treatment, can progress to acute bilirubin encephalopathy

Kernicterus Localisation Basal ganglions Cranial nerves Hipocampus Neuronal injury + Bilirubin accumulate in the gray matter of the central nervous system Localisation Basal ganglions Cranial nerves Hipocampus Spinal cord’s anterior horn

CLINICAL FEATURES OF KERNICTERUS ACUTE FORM Phase 1 (1st 1-2 days): poor suck, stupor, hypotonia, seizures Phase 2 (middle of 1st wk): hypertonia of extensor muscles, opisthotonos, retrocollis, fever Phase 3 (after the 1st wk): hypertonia CHRONIC FORM 1st year: hypotonia, active deep tendon reflexes, obligatory tonic neck reflexes, delayed motor skills After 1st yr: movement disorders (choreoathetosis, ballismus, tremor), upward gaze, sensorineural hearing loss