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Randomized Controlled Trial
. 2014 Jun 13;9(6):e99466.
doi: 10.1371/journal.pone.0099466. eCollection 2014.

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

Christian V Hulzebos  1 , Peter H Dijk  1 , Deirdre E van Imhoff  1 , Arend F Bos  1 , Enrico Lopriore  2 , Martin Offringa  3 , Selma A J Ruiter  4 , Koen N J A van Braeckel  1 , Paul F M Krabbe  5 , Elise H Quik  5 , Letty van Toledo-Eppinga  6 , Debbie H G M Nuytemans  6 , Aleid G van Wassenaer-Leemhuis  6 , Manon J N Benders  7 , Karen K M Korbeeck-van Hof  7 , Richard A van Lingen  8 , Liesbeth J M Groot Jebbink  8 , Djien Liem  9 , Petri Mansvelt  9 , Jan Buijs  10 , Paul Govaert  11 , Ineke van Vliet  11 , Twan L M Mulder  12 , Cecile Wolfs  12 , Willem P F Fetter  13 , Celeste Laarman  13 ; BARTrial Study Group
Collaborators, Affiliations
Randomized Controlled Trial

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

Christian V Hulzebos et al. PLoS One. .

Abstract

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: Controlled-Trials.com ISRCTN74465643.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exist.

Figures

Figure 1
Figure 1. Enrollment, randomization, and follow-up.
At follow up there were no significant baseline differences between infants with known and those with unknown neurodevelopmental status.
See this image and copyright information in PMC

References

    1. Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM (2006) Toward understanding kernicterus: A challenge to improve the management of jaundiced newborns. Pediatrics 117: 474–485. - PubMed
    1. McDonagh A, Maisels MJ (2006) Bilirubin unbound: Deja vu all over again? Pediatrics 117: 523–525. - PubMed
    1. Ahlfors CE (2010) Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr 22: 129–133. - PubMed
    1. Watchko JF, Tiribelli C (2013) Bilirubin-induced neurologic damage–mechanisms and management approaches. N Engl J Med 369: 2021–2030. - PubMed
    1. Hulzebos CV, van Imhoff DE, Bos AF, Ahlfors CE, Verkade HJ, et al. (2008) Usefulness of the bilirubin/albumin ratio for predicting bilirubin-induced neurotoxicity in premature infants. Arch Dis Child Fetal Neonatal Ed 93: F384–8. - PubMed

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