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Hyperbilirubinemia Hyperbilirubinemia and the preterm and the preterm

infant infant

Dr. SadeghniaDr. Sadeghnia

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Pathways of Bilirubin SynthesisPathways of Bilirubin Synthesis

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Bilirubin Production and Bilirubin Production and EliminationElimination

J Perinatol. 2001;21J Perinatol. 2001;21

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Bilirubin Nomenclature and Chemical Behavior

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TermsTerms Description

Unconjugated Bilirubin or Indirect Bilirubin Produced by heme degradation by heme oxygenase; indirect bilirubin requires an “accelerator” to react with diazo reagents

Conjugated Bilirubin Bilirubin conjugated with one or two glucuronic acid molecules; direct bilirubin

Direct Bilirubin Forms diazo derivatives immediately after the addition of diazo reagents (includes conjugated bilirubun and delta bilirubin

Albumin-bound Bilirubin or Bound Bilirubin Usually refers to bilirubin bound to albumin (it binds reversible to albumin), but bilirubin monoglucuronide or bilirubin diglucuronides also bind to albumin

Unbound Bilirubin or Free Bilirubin or nonalbumin-bound Bilirubin(neurotoxicity and maturity of albumin)

Usually refers to bilirubin not bound to albumin but also includes bilirubin monoglucuronide or bilirubin diglucuronides not bound to albumin

Delta Bilirubin Bilirubin covalently bound to albumin (reacts with direct bilirubin fraction of the diazo test)

Configurational Bilirubin Photoisomers Photolabile isomers of bilirubin occurring on exposure to light of wavelength 400 to 525 nm

Lumirubin; Structural Bilirubin Photoisomer Photolabile isomers of bilirubin occurring on exposure to light of wavelength 400 to 525 nm

Hyperbilirubinemia and BIND in the preterm infant

Govaert P, Lequin M, Swarte R, Robben S, De Coo R, Weisglas-Govaert P, Lequin M, Swarte R, Robben S, De Coo R, Weisglas-Kuperus N et al. Changes in globus pallidus with (pre) term Kuperus N et al. Changes in globus pallidus with (pre) term kernicterus. Pediatrics 2003; 112: 1256–1263. kernicterus. Pediatrics 2003; 112: 1256–1263.

Moll M, Goelz R, Naegele T, Wilke M, Poets CF. Are recommended Moll M, Goelz R, Naegele T, Wilke M, Poets CF. Are recommended phototherapy thresholds safe enough for extremely low birth weight phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia. Neonatology 2011; 99: despite only moderate hyperbilirubinemia. Neonatology 2011; 99: 90–94.90–94.

Sugama S, Soeda A, Eto Y. Magnetic resonance imaging in three Sugama S, Soeda A, Eto Y. Magnetic resonance imaging in three children with kernicterus. Pediatr Neurol 2001; 25: 328–331. children with kernicterus. Pediatr Neurol 2001; 25: 328–331.

Mazeiras G, Roze J-C, Ancel P-Y, Caillaux G, Frondas-Chauty A, Mazeiras G, Roze J-C, Ancel P-Y, Caillaux G, Frondas-Chauty A, Denizot S et al. Hyperbilirubinemia and neurodevelopmental Denizot S et al. Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT outcome of very low birthweight infants: results from the LIFT cohort. PLoS ONE 2012; 7(1): 1–8. cohort. PLoS ONE 2012; 7(1): 1–8.

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Hyperbilirubinemia and BIND in the preterm infant

In past decades, autopsy proven kernicterus was reported in sick, In past decades, autopsy proven kernicterus was reported in sick, very low birth weight infants who were exposed to low TSB levels very low birth weight infants who were exposed to low TSB levels

(the so-called (the so-called ‘low bilirubin kernicterus’‘low bilirubin kernicterus’))

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Funded to produce guidelines for the NHS (National Health Service)

by NICE (National Institute for Health and Care Excellence)National Institute for Health and Care Excellence)

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National Institute of Child Health and Human Development (NICHD) is one of the National

Institutes of Health (NIH)

In an earlier NICHD study infants with birth weights In an earlier NICHD study infants with birth weights ≤1000g, who received ≤1000g, who received aggressiveaggressive phototherapy, phototherapy, had a 19% increase in mortality compared with had a 19% increase in mortality compared with

control infants (no phototherapy). The reasons for control infants (no phototherapy). The reasons for these findings are not clear, but these tiny, these findings are not clear, but these tiny, immature infants have gelatinous, thin skin, immature infants have gelatinous, thin skin,

through which light will penetrate readily reaching through which light will penetrate readily reaching more deeplymore deeply

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The AAP The AAP Committee on Fetus and NewbornCommittee on Fetus and Newborn in 2007 asked in 2007 asked a group of experts to develop a guideline for the a group of experts to develop a guideline for the

management of jaundiced infants <35 weeks of gestation management of jaundiced infants <35 weeks of gestation (neonatologists who were involved at 2004 AAP guideline (neonatologists who were involved at 2004 AAP guideline

for infants ≥ 35 weeks) for infants ≥ 35 weeks)

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An approach to the management of hyperbilirubinemia An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestationin the preterm infant less than 35 weeks of gestation

MJ Maisels, JF Watchko, VK Bhutani and DK StevensonMJ Maisels, JF Watchko, VK Bhutani and DK StevensonJournal of Perinatology (2012) Journal of Perinatology (2012)

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