Review summary excerpts from the American Academy of Pediatrics (AAP) Clinical Guidelines which support the adoption of ETCOc tests for the detection and treatment of newborn babies.
American Academy Of Pediatrics Clinical Guidelines 2004
The overall aim of this guideline is to promote an approach that will reduce the frequency of severe neonatal hyperbilirubinemia and bilirubin encephalopathy and minimize the risk of unintended harm such as increased anxiety, decreased breastfeeding, or unnecessary treatment for the general population and excessive cost and waste. Recent reports of kernicterus indicate that this condition, although rare, is still occurring.
Analysis of these reported cases of kernicterus suggests that if health care personnel follow the recommendations listed in this guideline, kernicterus would be largely preventable.
Because of their poor specificity and sensitivity, the standard laboratory tests for hemolysis are frequently unhelpful. However, end-tidal carbon monoxide, corrected for ambient carbon monoxide (ETCOc), levels can confirm the presence or absence of hemolysis, and measurement of ETCOc is the only clinical test that provides a direct measurement of the rate of heme catabolism and the rate of bilirubin production. Thus, ETCOc may be helpful in determining the degree of surveillance needed and the timing of intervention. It is not yet known, however, how ETCOc measurements will affect management.
American Academy Of Pediatrics Clinical Guidelines 2022
More than 80% of newborn infants will have some degree of jaundice. Careful monitoring of all newborn infants and the application of appropriate treatments are essential, because high bilirubin concentrations can cause acute bilirubin encephalopathy and kernicterus. (…) Central to this guideline is having systems in place including policies in hospitals and other types of birthing locations to provide the care necessary to minimize the risk of kernicterus.
Since the publication of the previous guideline, the evidence base regarding the monitoring and treatment of hyperbilirubinemia has expanded. Key new research findings appear in the evidence tables included in Appendix B and in the accompanying technical report. In addition, the committee reviewed guidelines from the Northern California Neonatal Consortium and the Academy of Breastfeeding Medicine. Because the new evidence is insufficient to derive specific treatment thresholds by quantitatively estimating the risks and benefits of different approaches to care, the committee began with the previous AAP guidelines. On the basis of an evaluation of evidence published since 2004, the committee raised the phototherapy thresholds by a narrow range that the committee considered to be safe. The committee also used new research assessment approach based on the hour-specific bilirubin concentration and the approach to rapidly address elevated bilirubin concentrations, defined as “escalation of care.”
Infants with risk factors for hyperbilirubinemia (Table 1) require closer monitoring than infants without risk factors. Determining the presence of these risk factors requires examining the infant, assessing laboratory data, and obtaining a family history of blood disorders or neonatal jaundice.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive enzymopathy that decreases protection against oxidative stress, is now recognized as one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and across the globe. Identifying neonates with G6PD deficiency is a challenge. Most affected infants will not have a positive family history. Genetic ancestry from a population in which this condition is prevalent (eg, Sub-Saharan Africa, Middle East, Mediterranean, Arabian Peninsula, and Southeast Asia) can be helpful in predicting risk. This is an example of how the delivery of race-conscious medicine can lead to improved health outcomes. Knowing information about genetic ancestry can help inform the assessment of G6PD risk. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.
There are clinical events that should raise suspicion about the presence of G6PD deficiency. Newborn infants with G6PD deficiency are more likely to receive phototherapy before hospital discharge, probably because of both increased bilirubin production and decreased conjugation, and have a greater risk of readmission and retreatment. Severe hyperbilirubinemia or atypical development of hyperbilirubinemia, such as elevated TSB in a formula-fed infant or late-onset jaundice, should raise the possibility of G6PD deficiency.
An infant with G6PD deficiency can develop a sudden and extreme increase in TSB that may be hard to anticipate or prevent. Even after what appears to be an acute hemolytic event, there may be little or no laboratory evidence of hemolysis. It is important for clinicians to recognize that measuring the G6PD activity during or soon after the hemolytic event or after an exchange transfusion can lead to a falsely normal result. If G6PD deficiency is strongly suspected but the measurement of G6PD activity is normal or close to normal, the G6PD activity should be measured at least 3 months later.
“Decisions to initiate phototherapy or escalate care are guided by the gestational age, the hour-specific TSB, and the presence of risk factors for bilirubin neurotoxicity (Table 2). The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated.”
Lower gestational age and isoimmune hemolytic disease are risk factors both for developing significant hyperbilirubinemia and for bilirubin neurotoxicity. Although it is not clear if hemolysis attributable to causes other than isoimmunization also increases the risk of bilirubin neurotoxicity, it is prudent to assume that it does. Other important neurotoxicity risk factors are related to serious illness in the newborn infant (eg, sepsis). Low serum albumin can increase the risk of neurotoxicity because of the greater availability of unbound bilirubin (ie, bilirubin not bound to albumin).
KAS 7: Ifmore than 1 TcB or TSB measure is available, the rate of increase may be used to identify infants at higher risk of subsequent hyperbilirubinemia. A rapid rate of increase (0.3 mg/dL per hour in the first 24 hours or 0.2 mg/dL per hour thereafter) is exceptional and suggests hemolysis. In this case, perform a DAT if not previously done. (Aggregate Evidence Quality Grade D, Option)
If available, measurement of end tidal carbon monoxide production, corrected for ambient carbon monoxide (ETCOc), is a potentially useful method for quantifying hemolysis. Carbon monoxide is produced in equimolar amounts with bilirubin when heme is catabolized to bilirubin.
KAS 10: Intensive phototherapy is recommended at the total serum bilirubin thresholds in Fig 2 or Fig 3 on the basis of gestational age, hyperbilirubinemia neurotoxicity risk factors, and age of the infant in hours. (Aggregate Evidence Quality Grade X, Recommendation)
[The phototherapy treatment] thresholds, like those in the 2004 guidelines, are based on expert opinion rather than strong evidence that they distinguish between infants in whom the benefits of phototherapy do or do not exceed its risks.
