Kernicterus: Epidemiological Strategies for Its Prevention through Systems-Based Approaches

Abstract

Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

Glucose-6-phosphate-dehydrogenase deficiency and its correlation with other risk factors in jaundiced newborns in Southern Brazil

“…Twenty-two patients had G6PD deficiency (4.6%), including 13 jaundiced patients (5.5%) and 9 in control group (3.7%), with the odds ratio as 1.5 (P=0.35 and CI=0.63-3.6). The mean activity of G6PD was 5.81 U/gHb in jaundice group and 5.54 U/gHb in control group.…”

“…G6PD deficiency has been considered as one of 10 most important etiologies of non-hemolytic neonatal jaundice [12] , accounting for 22% cases in the US Pilot Kernicterus Registry [13] .…”

Calculated free bilirubin levels and neurotoxicity

“…Even in Crigler-Najjar patients with very high bilirubin levels or homozygous Gunn rats there is no evidence of precipitation or aggregation of bilirubin in the circulation, observations that are consistent with circular dichroism studies on serum albumin-bilirubin binding by Lehner and colleagues 46 and their conclusion that 'even at pathophysiological total concentrations of bilirubin, the unbound portion does not exceed the solubility limit'. Case series that include several neonates with peak TSB levels of greater than 40 mg per 100 ml and as high as 59.9 mg per 100 ml, 26,47 as well as peroxidase measurements of serum B F in human newborns lend credence to this speculation. Apparent serum B F levels in human newborns often greatly exceed 70 nM, 31,48 and a recent report notes an infant with kernicterus whose B F was found to be 130 nM 3 using a modified technique 48,49 that appreciably reduces but does not eliminate sample dilution effects (sample dilution may lead to an underestimation of B F 31, [48][49][50] ).…”

Hyperbilirubinemia and Bilirubin Toxicity in the Late Preterm Infant

“…Hyperbilirubinemia is the most common clinical condition requiring evaluation and treatment in the newborn [1] and the most common cause for hospital readmission during the first week of postnatal life [2][3][4][5]. Although generally a benign transitional phenomenon of no overt clinical significance, in a select few, the total serum bilirubin (TSB) may rise to hazardous levels that pose a direct threat of brain damage.…”

“…Although generally a benign transitional phenomenon of no overt clinical significance, in a select few, the total serum bilirubin (TSB) may rise to hazardous levels that pose a direct threat of brain damage. Acute bilirubin encephalopathy, an uncommon disorder [4], may ensue, frequently evolving into kernicterus, a devastating, chronic and disabling condition characterized by the clinical tetrad of:…”