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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
Authors:W Oh  DK Stevenson  JE Tyson  BH Morris  CE Ahlfors  G Jesse Bender  RJ Wong  R Perritt  BR Vohr  KP Van Meurs  HJ Vreman  A Das  DL Phelps  T Michael O’Shea  RD Higgins
Affiliation:1. Warren Alpert Medical School of Brown University, RI, USA;2. Stanford University, Palo Alto, CA;3. University of Texas, Houston, TX, USA;4. ZF Diagnostics Vashon, WA, USA;5. Research Triangle International, RTI, NC, USA;6. University of Rochester, Rochester, NY, USA;7. Wake Forest University Winston‐Salem, NC, USA;8. NICHD, Bethesda, MD, USA
Abstract:Objectives: 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. Method: 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.
Keywords:Extremely low birth weight infants  Neurodevelopmental outcomes  Plasma bilirubin  unbound bilirubin
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