1. HYPERBILIRUBINEMIA
Fatima c. Dela cruz

2. Jaundice
Yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration)
1st week of life 60% term and 80% preterm infants
Jaundice is a yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration). The serum bilirubin level required to cause jaundice varies with skin tone and body region, but jaundice usually becomes visible on the sclera at a level of 2 to 3 mg/dL (34 to 51 μmol/L) and on the face at about 4 to 5 mg/dL (68 to 86 μmol/L). With increasing bilirubin levels, jaundice seems to advance in a head-to-foot direction, appearing at the umbilicus at about 15 mg/dL (258 μmol/L) and at the feet at about 20 mg/dL (340 μmol/L). Slightly more than half of all neonates become visibly jaundiced in the first week of life.

3. Jaundice
Accumulation in skin of unconjugated, non-polar, lipidsoluble bilirubin pigment formed from Hgb by the action of heme oxygenase, biliverdin reductase, & non-enzymatic reducing agents in the reticuloendothelial cells
May also be due in part to deposition of the pigment after it has been converted in the liver cell microsome by the enzyme uridine diphosphoglucuronic acid (UDP)-glucuronyl transferase to the polar, water-soluble ester glucuronide of bilirubin (direct reacting)

4. Jaundice Indirect Bilirubin (Unconjugated, B1) Non-polar
Reversibly, but tightly bound to albumin
Does not cross the BBB
Free bilirubin: the form of indirect bilirubin that crosses the BBB

5. Jaundice Direct Bilirubin (Conjugated, B2) Always pathologic
Water soluble, polar
Excreted into the bile & into the small intestine and filtered into the kidney

6. The serum bilirubin level required to cause jaundice
Face - 4 to 5 mg/dL (68 to 86 μmol/L
Umbilicus - 15 mg/dL (258 μmol/L)
Feet- 20 mg/dL (340 μmol/L)

7. Risk Factors for Hyperbilirubinemia in Newborns
Maternal factors
Blood type ABO or Rh incompatibility
Breastfeeding
Drugs: diazepam (Valium), oxytocin (Pitocin)
Ethnicity: Asian, Native American
Maternal illness: gestational diabetes

8. Risk Factors for Hyperbilirubinemia in Newborns
Neonatal factors
Birth trauma: cephalohematoma, cutaneous bruising, instrumented delivery
Drugs: sulfisoxazole acetyl with erythromycin ethylsuccinate (Pediazole), chloramphenicol (Chloromycetin)
Excessive weight loss after birthInfections: TORC
Infrequent feedings
Male gender
Polycythemia
Prematurity
Previous sibling with hyperbilirubinemia

9. Mechanisms of hyperbilirubinemia
Increased production
Decreased hepatic uptake
Decreased conjugation
Impaired excretion
Impaired bile flow (cholestasis)
Increased enterohepatic circulation

10. Physiologic hyperbilirubinemia
Shorter neonatal RBC life span increases bilirubin production
deficient conjugation due to the deficiency of UGT decreases clearance
low bacterial levels in the intestine combined with increased hydrolysis of conjugated bilirubin increase enterohepatic circulation.
Bilirubin levels can rise up to 18 mg/dL by 3 to 4 days of life (7 days in Asian infants) and fall thereafter
Physiologic hyperbilirubinemia occurs in almost all neonates. Shorter neonatal RBC life span increases bilirubin production; deficient conjugation due to the deficiency of UGT decreases clearance; and low bacterial levels in the intestine combined with increased hydrolysis of conjugated bilirubin increase enterohepatic circulation. Bilirubin levels can rise up to 18 mg/dL by 3 to 4 days of life (7 days in Asian infants) and fall thereafter.

11. Breastfeeding jaundice
 develops in one sixth of breastfed infants in the first week of life.
Breastfeeding increases enterohepatic circulation of bilirubin in some infants who have decreased milk intake and who also have dehydration or low caloric intake.
The increased enterohepatic circulation also may result from reduced intestinal bacteria that convert bilirubin to nonresorbed metabolites.

12. Breast milk jaundice develops after the first 5 to 7 days of life
peaks at about 2 weeks
thought to be caused by an increased concentration of β-glucuronidase in breast milk, causing an increase in the deconjugation and reabsorption of bilirubin.
Breastfeeding jaundice develops in one sixth of breastfed infants in the first week of life. Breastfeeding increases enterohepatic circulation of bilirubin in some infants who have decreased milk intake and who also have dehydration or low caloric intake. The increased enterohepatic circulation also may result from reduced intestinal bacteria that convert bilirubin to nonresorbed metabolites.

13. Determine the cause of jaundice if:
Jaundice appears in the first h of life
Total serum bilirubin (TSB) rises by > 5 mg/dL/day
Serum bilirubin >12 mg/dL term and mg/dL in preterm infants
Jaundice persists after days of life
Direct-reacting bilirubin >2 mg/dL at any time
Pathologic hyperbilirubinemia in term infants is diagnosed if
Jaundice appears in the first 24 h, after the first week of life, or lasts > 2 wk
Total serum bilirubin (TSB) rises by > 5 mg/dL/day
TSB is > 18 mg/dL
Infant shows symptoms or signs of a serious illness
Some of the most common pathologic causes are
Immune and nonimmune hemolytic anemia
G6PD deficiency
Hematoma resorption
Sepsis
Hypothyroidism

14. Some of the most common pathologic causes
Immune and nonimmune hemolytic anemia
G6PD deficiency
Hematoma resorption
Sepsis
Hypothyroidism

15. Mechanism
Causes
Increased enterohepatic circulation
Breast milk (breast milk jaundice)
Breastfeeding failure (breastfeeding jaundice)
Drug-induced paralytic ileus (Mg sulfate or morphine )
Fasting or other cause for hypoperistalsis
Hirschsprung's disease
Intestinal atresia or stenosis, including annular pancreas
Meconium ileus or meconium plug syndrome
Pyloric stenosis*
Swallowed blood

16. Neonatal Hyperbilirubinemia
Mechanism
causes
Overproduction
Breakdown of extravascular blood (eg, hematomas; petechiae; pulmonary, cerebral, or occult hemorrhage)
Polycythemia due to maternofetal or fetofetal transfusion or
delayed umbilical cord clamping

17. Neonatal Hyperbilirubinemia
mechanis
causes
Overproduction due to hemolytic anemia
Certain drugs and agents in neonates with G6PD deficiency (eg, acetaminophen ,alcohol,antimalarials, aspirin ,bupivacaine ,corticosteroids, diazepam,nitrofurantoin , oxytocin  penicillin, phenothiazine, sulfonamides)
Maternofetal blood group incompatibility (eg, Rh, ABO)
RBC enzyme deficiencies (eg, of G6PD or pyruvate kinase)
Spherocytosis
Thalassemias (α, β–γ)

18. Neonatal Hyperbilirubinemia
mechanis
causes
Undersecretion due to biliary obstructio
α1-Antitrypsin deficiency*
Biliary atresia*
Choledochal cyst*
Cystic fibrosis* (inspissated bile)
Dubin-Johnson syndrome and Rotor's syndrome*
Parenteral nutrition
Tumor or band* (extrinsic obstruction)

19. Neonatal Hyperbilirubinemia
mechanis
causes
Undersecretion due to metabolic-endocrine conditions
Crigler-Najjar syndrome (familial nonhemolytic jaundice types 1 and
Drugs and hormones
Gilbert syndrome
Hypermethioninemia
Hypopituitarism and anencephaly
Hypothyroidism
Lucey-Driscoll syndrome
Maternal diabetes
Prematurity
Tyrosinosis

20. Neonatal Hyperbilirubinemia
mechanis
causes
Mixed overproduction and undersecretion
Asphyxia
Intrauterine infections
Maternal diabetes
Respiratory distress syndrome
Sepsis
Severe erythroblastosis fetalis
Syphilis
TORCH infections

21. Evaluation
History
History of present illness should note age of onset and duration of jaundice
Important associated symptoms include lethargy and poor feeding (suggesting possible kernicterus), which may progress to stupor, hypotonia, or seizures and eventually to hypertonia
Patterns of feeding can be suggestive of possible breastfeeding failure or underfeeding. 

22. Evaluation Review of systems
symptoms of causes, including respiratory distress, fever, and irritability or lethargy (sepsis); hypotonia and poor feeding (hypothyroidism, metabolic disorder); and repeated episodes of vomiting (intestinal obstruction).

23. Evaluation Past medical history
focus on maternal infections (toxoplasmosis, other pathogens, rubella, cytomegalovirus, and herpes simplex [TORCH] infections)
disorders that can cause early hyperbilirubinemia (maternal diabetes)
maternal Rh factor and blood group (maternofetal blood group incompatibility)
history of a prolonged or difficult birth (hematoma or forceps trauma)

24. Evaluation Physical examination
Overall clinical appearance and vital signs are reviewed.
The skin is inspected for extent of jaundice.
Gentle pressure on the skin can help reveal the presence of jaundice. Also, ecchymoses or petechiae (suggestive of hemolytic anemia) are noted.
The physical examination should focus on signs of causative disorders

25. Evaluation The general appearance is inspected for
plethora (maternofetal transfusion)
macrosomia (maternal diabetes)
lethargy or extreme irritability (sepsis or infection)
and any dysmorphic features such as macroglossia (hypothyroidism)
flat nasal bridge or bilateral epicanthal folds (Down syndrome)

26. Evaluation Head and neck examination Lungs Abdomen
any bruising and swelling of the scalp consistent with a cephalohematoma are noted
Lungs
are examined for rales, rhonchi, and decreased breath sounds (pneumonia)
Abdomen
is examined for distention, mass (hepatosplenomegaly), or pain (intestinal obstruction)
Neurologic examination
should focus on signs of hypotonia or weakness (metabolic disorder, hypothyroidism, sepsis)

27. Treatment
Treatment is directed at the underlying disorder

28. Treatment Breastfeeding jaundice increasing the frequency of feedings
If the bilirubin level continues to increase > 18 mg/dL in a term infant with early breastfeeding jaundice, a temporary change from breast milk to formula may be appropriate
reastfeeding jaundice may be prevented or reduced by increasing the frequency of feedings. If the bilirubin level continues to increase > 18 mg/dL in a term infant with early breastfeeding jaundice, a temporary change from breast milk to formula may be appropriate; phototherapy also may be indicated at higher levels. Stopping breastfeeding is necessary for only 1 or 2 days, and the mother should be encouraged to continue expressing breast milk regularly so she can resume nursing as soon as the infant's bilirubin level starts to decline. She also should be assured that the hyperbilirubinemia has not caused any harm and that she may safely resume breastfeeding. It is not advisable to supplement with water or dextrose because that may disrupt the mother's production of milk.

29. Treatment
Definitive treatment 
Phototherapy
Exchange transfusion

30. Treatment Phototherapy
standard of care, most commonly using fluorescent white light. (Blue light is most effective for intensive phototherapy.)
Photoisomerize unconjugated bilirubin into forms that are more water-soluble and can be excreted rapidly by the liver and kidney without glucuronidation
provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus
Phototherapy is an option when unconjugated bilirubin is > 12 mg/dL (> 205.2 μmol/L) and may be indicated when unconjugated bilirubin is > 15 mg/dL at 25 to 48 h, 18 mg/dL at 49 to 72 h, and 20 mg/dL at > 72 h
Phototherapy: This treatment remains the standard of care, most commonly using fluorescent white light. (Blue light is most effective for intensive phototherapy.) Phototherapy is the use of light to photoisomerize unconjugated bilirubin into forms that are more water-soluble and can be excreted rapidly by the liver and kidney without glucuronidation. It provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus. Phototherapy is an option when unconjugated bilirubin is > 12 mg/dL (> 205.2 μmol/L) and may be indicated when unconjugated bilirubin is > 15 mg/dL at 25 to 48 h, 18 mg/dL at 49 to 72 h, and 20 mg/dL at > 72 h (see Fig. 1: Metabolic, Electrolyte, and Toxic Disorders in Neonates: Risk of hyperbilirubinemia in neonates ≥ 35 wk gestation.). Phototherapy is not indicated for conjugated hyperbilirubinemia. Because visible jaundice may disappear during phototherapy, though serum bilirubin remains elevated, skin color cannot be used to evaluate jaundice severity. Blood taken for bilirubin determinations should be shielded from bright light, because bilirubin in the collection tubes may rapidly photo-oxidize

31. Treatment Exchange transfusion
 This treatment can rapidly remove bilirubin from circulation and is indicated for severe hyperbilirubinemia, which most often occurs with immune-mediated hemolysis
Small amounts of blood are withdrawn and replaced through an umbilical vein catheter to remove partially hemolyzed and antibody-coated RBCs as well as circulating Igs These then are replaced with uncoated donor RBCs.

32. Neonatal Hyperbilirubinemia
IV immunoglobulin
can be effective adjunct to phototherapy in immune hemolytic disease
Phenobarbital 5-8mg/kg/d (takes days to work)
Metalloporphyrins (experimental)
Sn-Mesoporphyrin (6umol/kg IM x 1),
an inhibitor of bilirubin production, was effective at reducing need for photo therapy, compared with "usual care"

33. THANK YOU