Flashcards in Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants Deck (62):
What is kernicterus?
Pathological finding of deep yellow staining of neurons and neuronal necrosis of the basal ganglia and brainstem nuclei
What is acute bilirubin encephalopathy?
A clinical syndrome, in the presence of severe hyperbilirubinemia, of lethargy, hypotonia, and poor suck, which may progress to hypertonia (with opisthotonos and retrocollis) with a high-pitched cry and fever, and eventually to seizures and coma
What is chronic bilirubin encephalopathy?
The clinical sequelae of acute encephalopathy with athetoid cerebral palsy with or without seizures, developmental delay, hearing deficit, oculomotor disturbances, dental dysplasia, and mental deficiency
What is severe hyperbilirubinemia?
A total serum bilirubin concentration greater than 340umol/L at any time during the first 28 days of life
What is critical hyperbilirubinemia?
A TSB concentration greater than 425umol/L during the first 28 days of life
What percentage of term newborns develop jaundice?
What percentage of term newborns reach TSB concentration > 340umol/L?
What increases the risk of acute encephalopathy in the presence of severe hyperbilirubinemia?
3. Respiratory distress
What is the incidence of acute bilirubin encephalopathy?
1 in 10 000 live births
What is the incidence of chronic encephalopathy?
1 in 100 000 live births
What is the incidence of critical hyperbilirubinemia or requiring exchange transfusion?
4 in 10 000 live births
What are risk factors for the development of severe hyperbilirubinemia?
1. Visible jaundice at younger than 24h
2. Visible jaundice before discharge at any age
3. Shorter gestation (<38 weeks)
4. Previous sibling with severe hyperbilirubinemia (OR 4.8)
5. Visible bruising (OR 2.6)
6. Cephalhematoma (OR 3.6)
7. Male sex (OR 1.3 to 1.7)
8. Maternal age >25y of age (OR 2.6)
9. Asian or European background (OR 5.2 and 1.2, respectively)
11. Exclusive and partial breastfeeding
What is the best available method for predicting severe hyperbilirubinemia?
Timed TSB measurement (18h-72h) analyzed in the context of the infant's GA
For example to have a >10% risk of developing severe hyperbilirubinemia the infant <38wks GA must have a TSB >75th %ile and the infant 39-40wks GA must have a TSB >95th %ile
What is the predictive power of umbilical cord blood TSB?
TSB >30umol/L in cord blood correlated with peak TSB >300umol/L
PPV 4.8% term infant, 10.9% late preterm
Very poor specificity
What is the predictive power of universal hemoglobin assessment?
Routine umbilical cord blood hemoglobin or hematocrit does not aide in the prediction of severe hyperbilirubinemia
What is the OR for severe hyperbilirubinemia in babies whose mothers are blood group O?
When is it reasonable to perform a DAT?
In clinically jaundiced infants of mothers who are group O and in infants with an elevated risk of needing therapy
How is G6PD inherited?
Why should females be tested for G6PD deficiency?
Female heterozygotes can have >50% of RBC deficient in the enzyme due to random inactivation of the X chromosome
Who should be tested for G6PD deficiency?
1. Infants whose ethnic group (e.g. Mediterranean, Middle Easter, African, SE Asian) increases risk
2. Infants whose family history suggests increased risk
3. Consider in all infants with severe hyperbilirubinemia
What is the predictive value of end-tidal CO?
Exhaled CO increased during hemolysis
Prediction of severe hyperbilirubinemia is not improved by measurement of ETCO2
What are the recommendations re: prediction of severe hyperbilirubinemia?
1. All mothers should be tested for ABO and Rh (D) blood types and screened for red cell antibodies during pregnancy
2. If mother was not tested, cord blood from the infant should be sent for evaluation of the blood group and a DAT
3. Blood group evaluation and a DAT should be performed in infants with early jaundice of mothers of blood group O
4. Selected at-risk infants (Mediterranean, Middle Eastern, African, or SE Asian origin) should be screened for G6PD deficiency
5. A test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia
At what concentration is jaundice not evident on clinical examination?
When does the peak TSB concentration usually occur?
What are the 95% CI for TSB concentration based on the TcB measurement?
What is the difference between capillary or venous blood sample for bilirubin?
No systematic difference
What is free bilirubin?
Bilirubin not bound to albumin which is able to cross the blood-brain barrier and causes neuronal damage
What is the clinical value of measurement of free bilirubin?
Uncertain and not readily available
When should conjugated bilirubin fraction be estimated?
Persistent jaundice (longer than two weeks) and/or hepatosplenomegaly
What amount of conjugated bilirubin warrants further investigation?
1. Total conjugated bilirubin >18 umol/L
OR 2. >20% of the TSB concentration
What are the recommendations re: measurement of neonatal bilirubin?
1. TSB or TcB should be measured in all infants during the first 72h of life
2. TSB should be obtained at same time as metabolic screening test unless clinically required earlier
3. TcB should be obtained at discharge or at 72h of life
4. If TSB does not require immediate intervention plot on the predictive nomogram and follow-up should be arranged according to risk assessment
5. Provide parents with the TSB measurement, time it was obtained, and the risk zone
6. Any infant discharged before 24h of life should be reviewed within 24h by an individual with experience in the care of newborn who has access to testing and treatment facilities
7. There should be a systematic approach to the risk assessment of all infants before discharge and institution of follow-up care if the infant develops jaundice
8. All newborns who are visibly jaundiced in the first 24h of life should have their bilirubin level determined
9. TcB is acceptable as a routine procedure or in infants with visible jaundice
10. TcB results should be summed with the 95% CI of the device to estimate the max probable TSB
11. TSB maybe estimated on either a capillary or a venous blood sample
12. Infants with severe or prolonged hyperbilirubinemia should be further investigated, including measurement of the conjugated component of bilirubin
What interventions are ineffective in primary prevention of severe hyperbilirubinemia?
1. Routine glycerine suppositories
2. Routine glycerine enemas
3. L-aspartic acid
4. Enzymatically hydrolyzed casein, whey/casein and clofibrate
5. Routine supplementation of breastfed infants with water or dextrose water
When do exclusively breastfed experience maximum weight loss?
By day three
What is the average % weight loss from birth for exclusively breastfed infants?
6-8% of their birth weight
At what % weight loss from birth should infants be carefully evaluated?
Lose more than 10% of their birth weight
What is the primary prevention for severe hyperbilirubinemia?
Is phenobarbitone effective in preventing severe hyperbilirubinemia in infants with hemolysis?
Did not improve clinically important outcomes
Is Tin-mesoporphyrin (SnMP) effective in preventing severe hyperbilirubinemia in infants with hemolysis?
Synthetic analogue of heme oxygenase strongly inhibits its activity and suppresses the production of bilirubin. Historical control studies SnMP eliminated the need for phototherapy and prevented severe hyperbilirubinemia. No prospective RCT yet and not commercially available.
Is prophylactic phototherapy in ABO isoimmunization clinically beneficial?
How does phototherapy work?
Energy from blue light conformational change in the bilirubin making it water soluble
What are side effects of phototherapy?
1. Temperature instability
2. Intestinal hypermotility
4. Interference with maternal-infant interaction
5. Bronze discoloration of the skin
What is the importance of hydration and enteral feeding in hyperbilirubinemia?
1. Replace missing fluids
2. Supply energy
3. Reduce enterohepatic reuptake of bilirubin
4. Reduce bilirubin levels
What is high intensity phototherapy?
Usually two phototherapy units or special high-intensity fluorescent tubes placed approx. 10cm from infant who can be nursed in a bassinet
What is conventional phototherapy?
A single bank of fluorescent lights placed above the incubator of an infant nursed with a diaper in place
What are the recommendations regarding phototherapy?
1. Intensive phototherapy for infants with severe hyperbilirubinemia or those at greatly elevated risk of developing severe hyperbilirubinemia
2. Option for conventional phototherapy for infants with a moderately elevated risk and a TSB of 35-50umol/L below the phototherapy thresholds
Should breastfeeding be interrupted during phototherapy?
Breastfeeding should be continued during phototherapy
What is the effect of IVIG?
Reduces bilirubin in newborns with Rh hemolytic disease and other immune hemolytic jaundice as it acts as a competitive inhibitor for those antibodies that cause RBC destruction, release hemoglobin and cause jaundice
When is it reasonable to use IVIG?
Infants with predicted severe disease based on antenatal investigation and in those with an elevated risk of needing exchange transfusion based on postnatal progression of TSB concentration
What is the evidence for SnMP?
No evidence of reduction in clinically important outcomes
Which infants should receive extra fluids?
Breastfed infants with an elevated risk of requiring exchange transfusion
What is the evidence for oral agar?
Oral agar to prevent enterohepatic reuptake of bilirubin is not supported by the available evidence
What are the recommendations regarding prevention of severe hyperbilirubinemia in infants with mild or moderate hyperbilirubinemia?
1. Breastfeeding support programs should be instituted in every facility where babies are delivered
2. Routine supplementation of breastfed infants with water or dextrose water is not recommended
3. Infants with positive DAT who have predicted severe disease based on antenatal investigation or an elevated risk of progressing to exchange transfusion based on the postnatal progression of TSB concentration should receive IVIG at a dose of 1g/kg
4. A TSB consistent with increased risk should lead to enhanced surveillance for development of severe hyperbilirubinemia, with follow-up within 24-48h, either in hospital or in the community, and repeat estimation of TSB or TcB in most circumstances
5. Intensive phototherapy should be given according to the guidelines in the phototherapy nomogram
6. Conventional phototherapy is an option at TSB 35-50 umol/L lower than the guidelines in the phototherapy nomogram
7. Breastfeeding should be continued during phototherapy
8. Supplemental fluids should be administered, orally or by IV infusion, in infants receiving phototherapy who are at an elevated risk of progressing to exchange transfusion
When should patients with severe hyperbilirubinemia have their TSB rechecked?
Within 2-6h of initiation of treatment
What else should be given in patients with severe hyperbilirubinemia?
IVIG in infants with isoimmunization
When should exchange transfusion be considered?
TSB between 375-425 umol/L despite adequate intensive phototherapy
For what tests should blood be taken and stored pre-exchange transfusion?
1. Red cell fragility
2. Enzyme deficiency i.e. G6PD or pyruvate kinase deficiency
3. Metabolic disorders
4. Hemoglobin electrophoresis
5. Chromosome analysis
What are the recommendations regarding severe hyperbilirubinemia?
1. Infants with TSB above the thresholds shown on the exchange transfusion nomogram should have immediate intensive phototherapy, and should be referred for further investigation and preparation for exchange transfusion
2. An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion
When should infants with isoimmunizations have their hemoglobin rechecked?
At 2 weeks if low at discharge and at 4 weeks if normal at discharge
Which infants should be referred to regional multidisciplinary follow-up programs?
1. Infants requiring exchange transfusion
2. Infants who exhibit neurological abnormalities
How should children with severe hyperbilirubinemia be screened for neurosensory hearing loss?
Brainstem auditory evoked potentials
What further investigations should occur in severe hyperbilirubinemia?
1. Pertinent history of baby and mother
2. Family history
3. Description of labour and delivery
4. Infant's clinical course
5. Conjugated and unconjugated bilirubin levels
6. direct Coombs test
9. CBC incld. differential
10. Blood smear and red cell morphology
11. Investigations for sepsis if indicated