Infants With Bilirubin Levels of 30 mg/dL or More in a Large Managed Care Organization

Newman, Thomas B.; Liljestrand, Petra; Escobar, Gabriel J.

doi:10.1542/peds.111.6.1303

Cited by 82 publications

(62 citation statements)

References 36 publications

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“…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. 2 In an analogy to aviation safety standards, acute kernicterus events are akin to airline crashes.…”

Section: Background Reviewmentioning

confidence: 99%

Universal bilirubin screening for severe neonatal hyperbilirubinemia

2010

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To reduce the incidence of severe neonatal hyperbilirubinemia affecting newborns with jaundice in the United States and to prevent kernicterus, there is a need to implement proven prevention strategies for severe neonatal hyperbilirubinemia as recommended in the 2004 American Academy of Pediatrics Guidelines for newborns >35 weeks gestational age. The purpose of universal predischarge bilirubin screening is to identify infants with bilirubin levels >75th percentile for age in hours and track those with rapid rates of bilirubin rise (>0.2 mg per 100 ml per h). Early identification has been reported to predict severe hyperbilirubinemia and allow for evidence-based targeted interventions. A systems approach is likely to reduce the preventable causes of acute bilirubin encephalopathy. To do so, highest priority should be given to (i) designating extreme hyperbilirubinemia (total serum bilirubin >427 mmol l À1 or >25 mg per 100 ml) as a reportable condition by laboratories and health-care providers through public health mandates; (ii) implementation of Joint Commission's Sentinel Report for kernicterus; (iii) nursing outreach to communities for education of prospective parents; (iv) development of clinical pathways to monitor, evaluate and track infants with extreme hyperbilirubinemia; and (v) societal awareness. These efforts should be monitored by a state and national surveillance system in order to critically improve the timeliness and completeness of notifications and to allow evaluation and interventions at the policy and individual family level.

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Section: Background Reviewmentioning

confidence: 99%

Universal bilirubin screening for severe neonatal hyperbilirubinemia

2010

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“…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. Furthermore, assuming that at a hazardous TSB level of 35 mg per 100 ml the calculated serum B F concentration is approximately equal to the CNS B F concentration (at this level there may be rapid equilibration of bilirubin between serum and brain 1,27-29 ), calculated CNS B F levels ( Table 2) would range from 375 to 2751 nM depending on the human bilirubin-albumin binding constant and the serum albumin concentrations assumed for the calculation.…”

mentioning

confidence: 99%

Calculated free bilirubin levels and neurotoxicity

2009

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Although most bilirubin in the circulation is bound to albumin, a relatively small fraction remains unbound. The concentration of this 'free' bilirubin (B F ) is believed to dictate the biologic effects of bilirubin in jaundiced newborns, including its neurotoxicity. The threshold at which B F produces changes in cellular function culminating in permanent cell injury and cell death has been the subject of considerable debate. The objective of this study was to compare calculated central nervous system (CNS) B F levels in Gunn rat pups during (i) peak postnatal hyperbilirubinemia and (ii) sulfadimethoxine-induced acute bilirubin encephalopathy (ABE) previously reported from our laboratory with those predicted in human neonates with peak total serum bilirubin (TSB) levels of 35 mg per 100 ml (599 mmol l À1 ), a clinical cohort that often evidence moderate-to-severe adverse post-icteric neurodevelopmental sequelae. Homozygous j/j Gunn rat pups with neonatal hyperbilirubinemia due to a deficiency of the bilirubin conjugating enzyme uridine-diphosphate-glucuronosyl transferase 1A1 were studied along with non-jaundiced littermate heterozygous J/j controls. Sulfadimethoxine was used to displace bilirubin from albumin in hyperbilirubinemic j/j Gunn rat pups to increase their brain bilirubin content and induce ABE. Calculated Gunn rat CNS B F levels were determined as a function of genotype, sulfadimethoxine exposure and albumin-bilirubin binding constant. These data were compared with the human CNS B F predicted from the calculated serum B F in human neonates with a TSB of 35 mg per 100 ml as a function of albumin-bilirubin binding constant, albumin concentration and the assumption that at this hazardous bilirubin level there may be rapid equilibration of B F between serum and brain. There was a large gap between the upper limit of the calculated CNS B F 95% confidence interval (CI) range in non-jaundiced J/j pups (for example, 112 nM at k ¼ 9.2 l mmol À1 ) and the lower limit seen in the saline-treated hyperbilirubinemic j/j pups (556 nM at k ¼ 9.2 l mmol À1 ) as well as between the upper limit in saline-treated hyperbilirubinemic j/j pups (1110 nM at k ¼ 9.2 l mmol À1 ) and the lower limit seen in sulfadimethoxine-treated jaundiced j/j littermates (3461 nM at k ¼ 9.2 l mmol À1 ). There was considerable overlap and remarkable similarity between the predicted human CNS B F values at a TSB of 35 mg per 100 ml for a range of reported human serum bilirubin-albumin binding constants and albumin concentrations, and those calculated for saline-treated hyperbilirubinemic j/j Gunn rat pups. This exercise yielded strikingly similar apparent calculated neurotoxic B F levels for Gunn rat pups and human neonates rather than orders of magnitude differences that might have been predicted at the outset and add to a growing literature aimed at defining clinically germane neurotoxic B F thresholds.

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“…[13][14][15][16] Indeed, kernicterus has been reported in neonates who had hyperbilirubinemia associated with PK deficiency. 17 When hemolytic jaundice is diagnosed, such patients can generally be managed successfully using phototherapy or sometimes exchange transfusion.…”

Section: Discussionmentioning

confidence: 99%

“…For neonates with early jaundice, in addition to making the underlying diagnosis, considerable effort should be placed on bilirubin management, so as to avoid bilirubin neurotoxicity. [14][15][16][17] We speculate that the American Academy of Pediatrics goal of preventing cases of kernicterus 7 can be furthered by improving awareness of PK deficiency and other causes of neonatal hemolytic jaundice. Diagnosing hemolytic diseases such as PK deficiency, hereditary spherocytosis and G6PD deficiency during the first days after birth can facilitate anticipatory, aggressive, bilirubin management.…”

Section: Discussionmentioning

confidence: 99%