Professor of Pediatrics Children's Hospital of Michigan Pittsford, New York, United States
Background: Human autopsy findings suggest that bilirubin-induced neurotoxicity may involve central neurocircuitry mediating thermoregulation. However, the association of unconjugated bilirubinemia with maturation of thermoregulation (MTR) has not been well studied in extremely low birth weight (ELBW) infants. Unconjugated hyperbilirubinemia, indexed by peak unbound bilirubin (UB), but not peak total serum bilirubin (TSB) has been shown to be associated with bilirubin-induced neurotoxicity in premature infants. Objective: To evaluate if unconjugated bilirubinemia, indexed by peak UB, is associated with delayed MTR in ELBW infants. Design/Methods: A prospective nested observational study was performed including in-born ELBW infants admitted to the NICU. Infants with antenatal exposure to illicit drugs, chromosomal disorders, craniofacial anomalies, TORCH infections, direct bilirubinemia or who were moribund were excluded. In addition, infants who expired or were transferred before transitioning to an open crib were excluded. TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week and then as clinically indicated. TSB was measured using the colorimetric method. UB was measured by the modified peroxidase method using the FDA approved UB analyzer. A uniform and standardized institutional incubator weaning protocol was used by bedside nurses for each ELBW infant. MTR was defined by the post-menstrual age (PMA) when infant was weaned to an open crib for > 24 hours. Results: 161 infants were studied. The mean (median) GA and BW of infants were 26.3 (1.5) and 792 (129) g, respectively. The median PMA for MTR was 35.4 weeks and was used to divide study population into 2 groups: 1) Early MTR group (≤ 35.4 weeks, n=81) and 2) Delayed MTR group (> 35.4 weeks, n=80). On univariate analysis, there was no significant difference between the two groups in the peak TSB, peak UB, and days on phototherapy (Table). Birth weight, maternal diabetes, chorioamnionitis, clinical sepsis, necrotizing enterocolitis, days on enteral feeding with human milk, days on parenteral nutrition, days on oxygen, and days on mechanical ventilation were identified as confounders (p ≤ 0.2, Table) and included in full regression model. On logistic regression analyses, using backward selection method to include significant confounders, peak UB was associated with delayed MTR (OR 1.1, 95% CI: 1.01-1.2, p=0.03). Peak TSB was not associated with delayed MTR (OR 1.05, 95% CI:0.7-1.4, p=0.79).
Conclusion(s): Our findings suggest that unconjugated bilirubinemia, indexed by peak UB, may be associated with delayed MTR in ELBW infants.
Clinical Factors as a Function of Maturation of Thermoregulation (MTR) in ELBW Infants UB AND THERMOREGULATION PAS 2025 TABLE 1.pdf*denotes mean ± standard deviation; NS denotes p > 0.2; IQR denotes Interquartile range
