Clinical report from the pilot USA Kernicterus Registry (1992 to 2004)

Abstract

To identify antecedent clinical and health services events in infants (>/=35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants >/=35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 micromol l(-1); range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age </=1 week. Along with a rapid rise of TSB (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age </=5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were </=35 mg per 100 ml (598 micromol l(-1)) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by 'crash-cart' initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a 'crash-cart' approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35 mg per 100 ml had post-icteric sequela...

Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes

“…Indeed, this The theoretical arguments are chemically and physiologically coherent (10). Also, the reports of apparent reversibility of acute intermediate-to-advanced stage bilirubin encephalopathy with timely aggressive therapy (19)(20)(21), support the need to learn more about the rate of photoisomerization as a function of the emission spectrum, the irradiance of the lights, the surface area exposed, and possibly the initial serum bilirubin level (3). The percentage conversion of bilirubin to 4Z,15E bilirubin is expected to increase with time until an equilibrium between Z,Z-bilirubin and Z,E-bilirubin is obtained, that is dependent only on the emission spectrum of the light (7).…”

Universal bilirubin screening for severe neonatal hyperbilirubinemia

“…In one report, infants with ABE who presented with TSB levels >35 mg per 100 ml (598 mmol l À1 ) sustained some degree of posticteric sequelae regardless of treatment. 2 On the other hand, not all infants with TSB levels >30 mg per 100 ml (513 mmol l À1 ) manifest classic kernicterus. [18][19][20] Vulnerability to chronic sequelae, in infants with TSB levels between 20 and 35 mg per 100 ml, is influenced by postnatal age, rate of TSB rise, duration of extreme hyperbilirubinemia, late prematurity (<37 weeks), gender (male), being large for gestational age, dehydration (>15% weight loss over birth weight) and infection that is often associated with genetic abnormalities.…”

“…[18][19][20] Vulnerability to chronic sequelae, in infants with TSB levels between 20 and 35 mg per 100 ml, is influenced by postnatal age, rate of TSB rise, duration of extreme hyperbilirubinemia, late prematurity (<37 weeks), gender (male), being large for gestational age, dehydration (>15% weight loss over birth weight) and infection that is often associated with genetic abnormalities. 2 In an analogy to aviation safety standards, acute kernicterus events are akin to airline crashes.…”

Calculated free bilirubin levels and neurotoxicity

“…In this issue of the Journal of Perinatology, Johnson et al 24 report that every infant in the United States Pilot Kernicterus Registry with a peak total serum bilirubin (TSB) level of >35 mg per 100 ml (599 mmol l À1 ) evidenced moderate-to-severe post-icteric neurodevelopmental deficits consistent with permanent bilirubin-induced brain injury; that is, no infant with this level of hyperbilirubinemia escaped overt evidence of brain damage. While recognizing (i) that the Registry predominantly represents kernicterus cases, that is, numerators as opposed to denominators and (ii) a previous report that some infants with TSB levels >35 mg per 100 ml suffer no adverse neurological sequelae, 25 Johnson et al's 26 observation nevertheless suggests that the serum B F at peak TSB >35 mg per 100 ml at times meets or exceeds the neurotoxic threshold.…”