The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial

PLoS One. 2014 Jun 13;9(6):e99466. doi: 10.1371/journal.pone.0099466. eCollection 2014.


Background and objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.

Methods: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.

Results: Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.

Conclusions: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.

Trial registration: ISRCTN74465643.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bilirubin / analysis*
  • Birth Weight
  • Female
  • Humans
  • Hyperbilirubinemia, Neonatal / blood*
  • Hyperbilirubinemia, Neonatal / therapy*
  • Infant, Newborn
  • Infant, Premature
  • Kernicterus / prevention & control*
  • Male
  • Phototherapy
  • Prospective Studies
  • Serum Albumin / analysis*


  • Serum Albumin
  • Bilirubin

Associated data

  • ISRCTN/ISRCTN74465643

Grant support

This study had been funded by the Netherlands Organisation for Health Research and Development (ZonMw), program cost-effectiveness number: 94507407. website: The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.