25 - Late Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

Publication Number: 1022.25

Emily Lo, The Hospital for Sick Children, Toronto, ON, Canada; Prakesh S Shah, Mount Sinai Hospital, Toronto, ON, Canada; Eugene W. Yoon, Mount Sinai Hospital, Toronto, ON, Canada; Marc Beltempo, McGill University Faculty of Medicine and Health Sciences, Montreal, PQ, Canada; Jehier Afifi, Dalhousie University Faculty of Medicine, Halifax, NS, Canada; Khorshid Mohammad, Alberta Health Services, Calgary, AB, Canada; Ipsita Goswami, McMaster University, Hamilton, ON, Canada; Asaph Rolnitsky, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada

Background: The current standard of treatment for eligible neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE) is therapeutic hypothermia (TH) initiated within 6 hours after birth. There is evidence to suggest that when TH cannot be initiated within 6 hours after birth, late TH (≥ 6 hours after birth) may reduce morbidity and mortality dependent on the degree of brain injury. Thus, the effective window for TH initiation after brain injury may be longer than previously demonstrated.

Objective: To compare mortality prior to discharge and/or brain injury on post-TH brain magnetic resonance imaging (MRI) of infants who received TH within 6 hours after birth (standard TH) and > 6 hours after birth (late TH).

Design/Methods: We conducted a retrospective cohort study including infants with HIE admitted to participating tertiary NICUs within the Canadian Neonatal Network with HIE. Infants were excluded if they were born < 36 weeks, birth weight < 1800 grams, had major congenital anomaly, or not treated with TH. Exposures were TH initiated before 6 hours after birth (standard TH) and TH initiated at > 6 hours after birth (late TH). Primary outcomes were mortality, brain injury on MRI, and the composite outcome of death and/or brain injury on MRI. Outcomes were compared using logistic regression analysis adjusted for known confounders.

Results: We identified 4280 infants who were admitted with HIE and treated with TH during the study period, 3309 received TH within 6 hours and 971 received TH > 6 hours after birth. The demographic characteristics are shown in Table 1. Standard TH group had a higher incidence of renal failure (26% vs 21%, p=0.002), coagulopathy (31% vs 27%, p=0.02), persistent metabolic acidosis (17% vs 13%, p=0.003), and disseminated intravascular coagulation (DIC) (15% vs 11%, p=0.005) compared to late TH group (Table 2). There was no statistical difference in the adjusted odds (95% CI) of mortality prior to discharge [0.8 (0.56, 1.13)], brain injury on MRI [1.11 (0.93, 1.34)], and in mortality or brain injury [1.12 (0.94, 1.35)] between both groups (Table 3).

Conclusion(s): There was no difference in odds of mortality prior to discharge, brain injury and the composite outcome of mortality or brain injury on MRI between standard TH and late TH. Higher incidence of complications in infants cooled ≤ 6 hours of age likely reflects greater baseline severity of perinatal hypoxic injury rather than the effect of earlier intervention.

Table 1.
Baseline characteristics of study population.

Table 2.
Primary and secondary outcomes of standard TH and late TH groups.

Table 3.
Odds of mortality and brain injury between infants cooled ≤ 6 hours compared to > 6 hours.