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Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

ABSTRACT: Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

SUBMITTER: Zou L

PROVIDER: S-EPMC6549084 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

Zou Liangyan L Yuan Hao H Liu Qing Q Lu Chunmei C Wang Laishuan L

Bioscience reports 20190604 6

Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, ...[more]

PMID: 31101685

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Project description:BackgroundTherapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH.MethodsThis was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15).FindingsData quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (β (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes.InterpretationPoint of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE.FundingThis clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).

Dataset Information

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

Publications

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

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