Little known and less understood: the benefits of a lower hematocrit (~40%) in reconstituted blood for double volume exchange transfusion.

A double volume exchange transfusion (DVET) is an important, if infrequently performed, intervention to acutely lessen the total serum bilirubin (TSB) and reduce the extravascular CNS bilirubin exposure when neonatal hyperbilirubinemia poses a neurotoxicity risk. The current analysis based on the seminal works of Valaes, and Sproul and Smith, predicts that a DVET blood product of lower hematocrit (~40%) via its greater plasma volume and corresponding higher albumin content optimizes the benefits of an DVET in several ways. First, by augmenting bilirubin clearance from the extravascular space and thereby further reducing the CNS bilirubin exposure, second, by favorably positioning the intravascular albumin-bilirubin binding capacity at DVET completion to accommodate additional bilirubin equilibration and rebound hyperbilirubinemia post-exchange, and third by correcting anemia if present.

ABO hemolytic disease of the newborn: a need for clarity and consistency in diagnosis.

The diagnosis of ABO hemolytic disease of the newborn (ABO HDN) has been the subject of considerable debate and clinical confusion. Its use as an overarching default diagnosis for hyperbilirubinemia in all ABO incompatible neonates regardless of serological findings is problematic and lacks diagnostic precision. Data on hemolysis indexed by carbon monoxide (CO) levels in expired air (ETCOc) and blood (COHbc) support an essential role for a positive direct antiglobulin test (DAT) in making a more precise diagnosis of ABO HDN. A working definition that includes ABO incompatibility, significant neonatal hyperbilirubinemia, and a positive DAT is needed to gain clarity and consistency in the diagnosis of ABO HDN. Absent a positive DAT, the diagnosis of ABO HDN is suspect. Instead, a negative DAT in a severely hyperbilirubinemic ABO incompatible neonate should trigger an exhaustive search for an alternative cause, a search that may require the use of targeted gene panels.

Management of severe hyperbilirubinemia in the cholestatic neonate: a review and an approach.

A review of the literature demonstrates that severe total hyperbilirubinemia (total serum bilirubin ≥ 20 mg/dL [340 µmol/L]) in some cholestatic term (≥37 weeks) and late-preterm (≥340/7-366/7 weeks) gestation neonates poses a risk for bilirubin-induced brain damage. When the direct bilirubin fraction is <50% of the total serum bilirubin this risk is associated with the total serum bilirubin alone and treatment decisions should be based on the total serum bilirubin. On the other hand, there are limited data on the risk of bilirubin-induced brain damage in the neonate with severe total hyperbilirubinemia and a direct bilirubin fraction that is equal to or exceeds 50% of the total serum bilirubin. When this rare combination occurs, efforts to keep the indirect bilirubin fraction from reaching severe levels might, nevertheless, be prudent.

Combating the Hidden Health Disparity of Kernicterus in Black Infants: A Review.

Importance: Kernicterus is a devastating, permanently disabling neurologic condition resulting from bilirubin neurotoxicity. Black neonates account for more than 25% of kernicterus cases in the US, despite making up only approximately 14% of all births. This is a largely overlooked health disparity. Observations: The black kernicterus health disparity exists despite a lower overall incidence of clinically significant hyperbilirubinemia among black neonates, a paradox recently explained by a previously unrecognized risk for hazardous hyperbilirubinemia. Aligned with national and global health initiatives to reduce or eliminate health disparities, this review highlights the multiple biologic and nonbiologic factors contributing to kernicterus risk in black infants and approaches to reduce this health disparity. This includes both parent-level and clinician-level kernicterus prevention strategies, with an emphasis on improving parental health literacy on neonatal jaundice and acute bilirubin encephalopathy and clinician awareness of the key factors that contribute to hazardous hyperbilirubinemia risk in this vulnerable group. Parent-level prevention strategies include efforts to improve their health literacy on neonatal jaundice and acute bilirubin encephalopathy and empower care seeking for jaundice. Clinician-level prevention strategies include efforts to eliminate community and institutional barriers that impede access to care, heighten clinician awareness of the factors that contribute to kernicterus risk in this vulnerable patient group, and strengthen newborn hyperbilirubinemia management and bilirubin surveillance. Conclusions and Relevance: There are multiple opportunities for intervention to reduce black kernicterus risk. Although kernicterus is a rare disorder, the incidence among black infants is not a trivial matter nor are efforts to prevent kernicterus. While the multiple interacting biologic and nonbiologic contributors to increased kernicterus risk among black infants pose a considerable challenge to clinicians, there are opportunities for intervention to reduce this risk and health disparity. Continued study is imperative to understand the current scope of kernicterus and its occurrence in black neonates.

Emergency release uncross-matched packed red blood cells for immediate double volume exchange transfusion in neonates with intermediate to advanced acute bilirubin encephalopathy: timely but insufficient?

Given the urgency of double volume exchange transfusion (ExT) in an infant with intermediate to advanced stages of acute bilirubin encephalopathy (ABE), it has been suggested that emergency release uncross-matched packed red blood cells (ER-PRBC) be used. The efficacy of an ExT in removing bilirubin from the brain, however, is a direct function of the mass of albumin exchanged. The very low albumin content of ER-PRBC may fail to be neuroprotective. Predicted changes in total serum bilirubin (TSB), serum albumin, the bilirubin/albumin (B/A) ratio, plasma volume (PV), and bilirubin equilibration from the extravascular space during ER-PRBC ExT are described. ExT using ER-PRBC is efficacious in lowering the TSB. However, this result is falsely reassuring as significant concurrent serum albumin loss, resultant hypoalbuminemia, contraction of PV, limited bilirubin clearance from the extravascular space, and sustained B/A ratio elevations above recommended ExT treatment thresholds suggest that bilirubin neurotoxicity will continue.