2 JaundiceYellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration)1st week of life 60% term and 80% preterm infantsJaundice 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 JaundiceAccumulation 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 cellsMay 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 albuminDoes not cross the BBBFree bilirubin: the form of indirect bilirubin that crosses the BBB
5 Jaundice Direct Bilirubin (Conjugated, B2) Always pathologic Water soluble, polarExcreted 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/LUmbilicus - 15 mg/dL (258 μmol/L)Feet- 20 mg/dL (340 μmol/L)
7 Risk Factors for Hyperbilirubinemia in Newborns Maternal factorsBlood type ABO or Rh incompatibilityBreastfeedingDrugs: diazepam (Valium), oxytocin (Pitocin)Ethnicity: Asian, Native AmericanMaternal illness: gestational diabetes
8 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
9 Mechanisms of hyperbilirubinemia Increased productionDecreased hepatic uptakeDecreased conjugationImpaired excretionImpaired bile flow (cholestasis)Increased enterohepatic circulation
10 Physiologic hyperbilirubinemia Shorter neonatal RBC life span increases bilirubin productiondeficient conjugation due to the deficiency of UGT decreases clearancelow 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 thereafterPhysiologic 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 weeksthought 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 lifeTotal serum bilirubin (TSB) rises by > 5 mg/dL/daySerum bilirubin >12 mg/dL term and mg/dL in preterm infantsJaundice persists after days of lifeDirect-reacting bilirubin >2 mg/dL at any timePathologic hyperbilirubinemia in term infants is diagnosed ifJaundice appears in the first 24 h, after the first week of life, or lasts > 2 wkTotal serum bilirubin (TSB) rises by > 5 mg/dL/dayTSB is > 18 mg/dLInfant shows symptoms or signs of a serious illnessSome of the most common pathologic causes areImmune and nonimmune hemolytic anemiaG6PD deficiencyHematoma resorptionSepsisHypothyroidism
14 Some of the most common pathologic causes Immune and nonimmune hemolytic anemiaG6PD deficiencyHematoma resorptionSepsisHypothyroidism
15 MechanismCausesIncreased enterohepatic circulationBreast 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
16 Neonatal Hyperbilirubinemia MechanismcausesOverproductionBreakdown of extravascular blood (eg, hematomas; petechiae; pulmonary, cerebral, or occult hemorrhage)Polycythemia due to maternofetal or fetofetal transfusion ordelayed umbilical cord clamping
17 Neonatal Hyperbilirubinemia mechaniscausesOverproduction due to hemolytic anemiaCertain 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)
18 Neonatal Hyperbilirubinemia mechaniscausesUndersecretion due to biliary obstructioα1-Antitrypsin deficiency*Biliary atresia*Choledochal cyst*Cystic fibrosis* (inspissated bile)Dubin-Johnson syndrome and Rotor's syndrome*Parenteral nutritionTumor or band* (extrinsic obstruction)
19 Neonatal Hyperbilirubinemia mechaniscausesUndersecretion due to metabolic-endocrine conditionsCrigler-Najjar syndrome (familial nonhemolytic jaundice types 1 andDrugs and hormonesGilbert syndromeHypermethioninemiaHypopituitarism and anencephalyHypothyroidismLucey-Driscoll syndromeMaternal diabetesPrematurityTyrosinosis
21 EvaluationHistoryHistory 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 hypertoniaPatterns 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 notedLungsare examined for rales, rhonchi, and decreased breath sounds (pneumonia)Abdomenis examined for distention, mass (hepatosplenomegaly), or pain (intestinal obstruction)Neurologic examinationshould focus on signs of hypotonia or weakness (metabolic disorder, hypothyroidism, sepsis)
27 TreatmentTreatment 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 appropriatereastfeeding 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.
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 glucuronidationprovides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterusPhototherapy 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 hPhototherapy: 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 hemolysisSmall 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 immunoglobulincan be effective adjunct to phototherapy in immune hemolytic diseasePhenobarbital 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"