Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants.
OBJECTIVE
To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18-22 months corrected age in extremely low birth weight infants.


METHODS
Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 +/- 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18-22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors.


RESULTS
Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants.


CONCLUSIONS
In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18-22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Stevenson
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DK
Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Tyson
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Morris
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Ahlfors
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CE
Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Bender
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Wong
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Perritt
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Van Meurs
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Vreman
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Das
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Phelps
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
O'Shea
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Higgins
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Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
Warren Alpert Medical School of Brown University, RI, USAStanford University, Palo Alto, CAUniversity of Texas, Houston, TX, USAZF Diagnostics Vashon, WA, USAResearch Triangle International, RTI, NC, USAUniversity of Rochester, Rochester, NY, USAWake Forest University Winston-Salem, NC, USANICHD, Bethesda, MD, USA.
D001663:Bilirubin / Q000097:blood*; D002547:Cerebral Palsy / Q000209:etiology; D002658:Developmental Disabilities / Q000453:epidemiology* / Q000209:etiology; D005500:Follow-Up Studies; D006304:Health Status; D034381:Hearing Loss / Q000209:etiology; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000150:complications* / Q000401:mortality; D007226:Infant Mortality; D052577:Infant, Extremely Low Birth Weight / Q000097:blood / Q000254:growth & development*; D007231:Infant, Newborn; D016015:Logistic Models; D012307:Risk Factors
D001663:Bilirubin