1. به نام خدا 1

2. Hyperbilirubinemia and the preterm infant Dr. Sadeghnia 2

3. Pathways of Bilirubin Synthesis 3

4. Bilirubin Production and Elimination J Perinatol. 2001;21 4

5. Bilirubin Nomenclature and Chemical Behavior 5 TermsDescription Unconjugated Bilirubin or Indirect BilirubinProduced by heme degradation by heme oxygenase; indirect bilirubin requires an “accelerator” to react with diazo reagents Conjugated BilirubinBilirubin conjugated with one or two glucuronic acid molecules; direct bilirubin Direct BilirubinForms diazo derivatives immediately after the addition of diazo reagents (includes conjugated bilirubun and delta bilirubin Albumin-bound Bilirubin or Bound BilirubinUsually 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 BilirubinBilirubin covalently bound to albumin (reacts with direct bilirubin fraction of the diazo test) Configurational Bilirubin PhotoisomersPhotolabile isomers of bilirubin occurring on exposure to light of wavelength 400 to 525 nm Lumirubin; Structural Bilirubin PhotoisomerPhotolabile isomers of bilirubin occurring on exposure to light of wavelength 400 to 525 nm

6. Hyperbilirubinemia and BIND in the preterm infant  Govaert P, Lequin M, Swarte R, Robben S, De Coo R, Weisglas- Kuperus N et al. Changes in globus pallidus with (pre) term kernicterus. Pediatrics 2003; 112: 1256–1263.  Moll M, Goelz R, Naegele T, Wilke M, Poets CF. Are recommended phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia. Neonatology 2011; 99: 90–94.  Sugama S, Soeda A, Eto Y. Magnetic resonance imaging in three children with kernicterus. Pediatr Neurol 2001; 25: 328–331.  Mazeiras G, Roze J-C, Ancel P-Y, Caillaux G, Frondas-Chauty A, Denizot S et al. Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT cohort. PLoS ONE 2012; 7(1): 1–8. 6

7. Hyperbilirubinemia and BIND in the preterm infant In past decades, autopsy proven kernicterus was reported in sick, very low birth weight infants who were exposed to low TSB levels (the so-called ‘low bilirubin kernicterus’) 7

8. National Institute for Health and Care Excellence) Funded to produce guidelines for the NHS (National Health Service) by NICE (National Institute for Health and Care Excellence) 8

9. 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 ≤1000g, who received aggressive phototherapy, had a 19% increase in mortality compared with control infants (no phototherapy). The reasons for these findings are not clear, but these tiny, immature infants have gelatinous, thin skin, through which light will penetrate readily reaching more deeply 9

10. The AAP Committee on Fetus and Newborn in 2007 asked a group of experts to develop a guideline for the management of jaundiced infants <35 weeks of gestation (neonatologists who were involved at 2004 AAP guideline for infants ≥ 35 weeks) 10

11. An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestation MJ Maisels, JF Watchko, VK Bhutani and DK Stevenson Journal of Perinatology (2012) 11