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Sustained lower bilirubin-binding affinity of albumin in extremely preterm infants
Kentaro Hirayama1,2, Sota Iwatani3, Hajime Nakamura4
1Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital, 1-6-7 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Insights
Extremely preterm infants have lower albumin-binding affinity for bilirubin, increasing the risk of brain injury. This sustained lower binding capacity, not reflected by bilirubin-albumin molar ratio, is crucial for understanding prolonged unbound hyperbilirubinemia.
Area of Science:
- Neonatal Medicine
- Biochemistry
- Pediatric Neurology
Background:
- Prolonged unbound bilirubin (UB) in preterm infants is linked to bilirubin encephalopathy.
- The underlying mechanisms for sustained UB elevation in extremely preterm (EPT) infants remain unclear.
- A hypothesis suggests reduced albumin-binding affinity in EPT infants may cause prolonged unbound hyperbilirubinemia.
Purpose of the Study:
- To investigate the bilirubin-binding affinity of albumin in very preterm (VPT) and extremely preterm (EPT) infants.
- To determine if reduced albumin-binding affinity contributes to prolonged unbound hyperbilirubinemia in EPT infants.
Main Methods:
- Retrospective study of 22 VPT infants (28-31 weeks GA) and 21 EPT infants (22-27 weeks GA).
- Albumin-binding affinity was assessed on postnatal days 14, 21, and 28.
- Measurements included unbound bilirubin/total bilirubin ratio, bilirubin-albumin molar ratio (BAMR), and binding affinity (Ka).
Main Results:
- EPT infants exhibited significantly higher UB/total bilirubin ratios on days 14, 21, and 28 compared to VPT infants.
- While BAMRs were similar between groups, EPT infants showed significantly lower binding affinity (Ka) values on all assessed days.
- Specific Ka values for EPT vs. VPT were: Day 14 (56.1 vs. 70.9 L/μmol), Day 21 (55.2 vs. 74.7 L/μmol), and Day 28 (53.0 vs. 86.5 L/μmol), all with p < 0.001.
Conclusions:
- Extremely preterm infants demonstrate a sustained decrease in albumin's bilirubin-binding affinity beyond the first week of life.
- This reduced binding affinity, independent of BAMR, contributes to prolonged unbound hyperbilirubinemia in EPT infants.
- BAMR should not be used as a surrogate for unbound bilirubinemia, particularly in EPT infants during later postnatal periods.
Background:
Elevated albumin-free or unbound bilirubin (UB) levels beyond the first week of life have been associated with the development of bilirubin encephalopathy in preterm infants. However, the mechanism(s) that induces this prolonged unbound bilirubinemia has remained unknown. We hypothesized that it may due to a sustained lower bilirubin-binding affinity of albumin in extremely premature infants.
Methods:
Twenty-two very preterm infants born at 28-31 weeks' gestational age (GA) (VPT Group) and 21 extremely preterm infants born at 22-27 weeks' GA (EPT Group) were retrospectively studied. On days 14, 21, and 28, bilirubin-binding affinity of albumin was assessed by calculating of the UB/total bilirubin ratio, bilirubin-albumin molar ratio (BAMR), and binding affinity (Ka).
Results:
On days 14, 21, and 28, significantly higher UB/total bilirubin ratios were found in the EPT than in the VPT Group. Although BAMRs were comparable, significantly lower Ka values on days 14, 21, and 28 were observed in the EPT than those in the VPT Group (56.1 vs. 70.9 L/μmol, p < 0.001; 55.2 vs. 74.7 L/μmol, p < 0.001; 53.0 vs. 86.5 L/μmol, p < 0.001, respectively).
Conclusions:
EPT infants have a sustained lower bilirubin-binding affinity of albumin beyond the first week of life.
Impact:
Bilirubin encephalopathy is still reported in extremely preterm (EPT) infants. EPT infants often have prolonged unbound bilirubinemia beyond the first week of life. Sustained lower bilirubin-binding affinity of albumin, regardless of the bilirubin-albumin molar ratio (BAMR), is observed in EPT infants. BAMRs should not be used as a surrogate marker of unbound bilirubinemia, especially in EPT infants at a later postnatal period.
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