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FATIMA C. DELA CRUZ
HYPERBILIRUBINEMIA
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
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)
Jaundice
Indirect Bilirubin (Unconjugated, B1)Non-polarReversibly, but tightly bound to albuminDoes not cross the BBBFree bilirubin: the form of indirect bilirubin
that crosses the BBB
Jaundice
Direct Bilirubin (Conjugated, B2)Always pathologicWater soluble, polarExcreted into the bile & into the small
intestine and filtered into the kidney
The serum bilirubin level required to cause jaundice
Face - 4 to 5 mg/dL (68 to 86 μmol/LUmbilicus - 15 mg/dL (258 μmol/L)Feet- 20 mg/dL (340 μmol/L)
Risk Factors for Hyperbilirubinemia in Newborns
Maternal factorsBlood type ABO or Rh incompatibilityBreastfeedingDrugs: diazepam (Valium), oxytocin (Pitocin)Ethnicity: Asian, Native AmericanMaternal illness: gestational diabetes
Risk Factors for Hyperbilirubinemia in Newborns
Neonatal factorsBirth trauma: cephalohematoma, cutaneous
bruising, instrumented deliveryDrugs: sulfisoxazole acetyl with erythromycin
ethylsuccinate (Pediazole), chloramphenicol (Chloromycetin)
Excessive weight loss after birthInfections: TORCInfrequent feedingsMale genderPolycythemiaPrematurityPrevious sibling with hyperbilirubinemia
Mechanisms of hyperbilirubinemia
Increased productionDecreased hepatic uptakeDecreased conjugationImpaired excretionImpaired bile flow (cholestasis)Increased enterohepatic circulation
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
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.
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.
Determine the cause of jaundice if:
Jaundice appears in the first 24-36 h of lifeTotal serum bilirubin (TSB) rises by > 5
mg/dL/daySerum bilirubin >12 mg/dL term and 10-14
mg/dL in preterm infantsJaundice persists after 10-14 days of lifeDirect-reacting bilirubin >2 mg/dL at any
time
Some of the most common pathologic causes
Immune and nonimmune hemolytic anemiaG6PD deficiencyHematoma resorptionSepsisHypothyroidism
Mechanism CausesIncreased enterohepatic circulation
Breast milk (breast milk jaundice)Breastfeeding failure (breastfeeding jaundice)Drug-induced paralytic ileus (Mg sulfate or morphine )Fasting or other cause for hypoperistalsisHirschsprung's diseaseIntestinal atresia or stenosis, including annular pancreasMeconium ileus or meconium plug syndromePyloric stenosis*Swallowed blood
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
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)SpherocytosisThalassemias (α, β–γ)
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 nutritionTumor or band* (extrinsic obstruction)
Neonatal Hyperbilirubinemia
mechanis causes
Undersecretion due to metabolic-endocrine conditions
Crigler-Najjar syndrome (familial nonhemolytic jaundice types 1 andDrugs and hormonesGilbert syndromeHypermethioninemiaHypopituitarism and anencephalyHypothyroidismLucey-Driscoll syndromeMaternal diabetesPrematurityTyrosinosis
Neonatal Hyperbilirubinemia
mechanis causes
Mixed overproduction and undersecretion
AsphyxiaIntrauterine infectionsMaternal diabetesRespiratory distress syndromeSepsisSevere erythroblastosis fetalisSyphilisTORCH infections
Evaluation
HistoryHistory of present illness should note age
of onset and duration of jaundiceImportant 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.
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).
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)
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
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)
Evaluation
Head and neck examinationany bruising and swelling of the scalp consistent
with a cephalohematoma are noted
Lungsare examined for rales, rhonchi, and decreased
breath sounds (pneumonia)
Abdomenis examined for distention, mass
(hepatosplenomegaly), or pain (intestinal obstruction)
Neurologic examination should focus on signs of hypotonia or weakness
(metabolic disorder, hypothyroidism, sepsis)
Treatment
Treatment is directed at the underlying disorder
Treatment
Breastfeeding jaundice increasing the frequency of feedingsIf 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
Treatment
Definitive treatment PhototherapyExchange transfusion
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
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.
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"
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