TOP 72 - Therapeutic Hypothermia for 34-35.6 Weeks Gestation Age in a Regional Registry: A Stratification Analysis

Publication Number: 3804.TOP 72

Nabeel Hashmi, Tufts Medical Center, Boston, MA, United States; Hoda El-Shibiny, Brigham and Women's Hospital, Boston, MA, United States; Mohamed El-Dib, Brigham and Women's Hospital / Harvard Medical School, Boston, MA, United States; Brooke Krbec, Tufts Childrens Hospital, Boston, MA, United States

Background: Neonatal encephalopathy (NE) is a clinical syndrome that affects 2-5 per 1000 live births. Therapeutic hypothermia (TH) is the only evidence-based neuroprotective treatment for NE due to hypoxia-ischemia at ≥36 weeks gestation. Risks and benefits of TH in the late preterm population remains a focus of ongoing investigation. Recent publication of a randomized controlled trial (RCT) by Faix et al. (2025) raised concerns about potential harm and lack of benefit of TH in 168 neonates 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy (HIE). A major limitation of this study was a lack of stratified randomization to assess for treatment effect variation across gestational age (GA). In post-hoc subgroup analysis, the mortality rate was apparently highest at 34 weeks GA but not at 33 or 35 weeks, raising the question whether the reported relationship was a spurious finding. A recent multi-center retrospective analysis of 436 infants with moderate to severe HIE at 34 to 35 weeks GA treated with TH demonstrated lower aggregate mortality than in the Faix et al. trial, demonstrating a need for further analysis (El-Dib et al, 2025).

Objective: To assess short-term outcomes in late preterm infants who received TH for NE, stratified by GA. We hypothesize that earlier GA is associated with increased adverse outcomes.

Design/Methods: Retrospective study of 36 preterm neonates 34 to 35.6 weeks GA treated with TH between years 2018 to 2022 at 4 cooling centers. Inclusion criteria: infants born at ≥34 weeks GA. Exclusion criteria: BW < 1750g, severe congenital anomalies, intracranial hemorrhage, sepsis or coagulopathy. Neonates will be stratified by GA and matched to infants 36-42 weeks GA who received TH in a 1:2 ratio and matched by 5 minute Apgar score, base deficit and encephalopathy severity. Institutional review board approval has been obtained. The primary combined outcome is in-hospital mortality and severity of brain injury on magnetic resonance imaging (MRI), scored using innovative artificial intelligence-generated predictive modeling. Secondary outcomes include time to full oral feeds, thrombocytopenia and subcutaneous fat necrosis. Analysis of variance (ANOVA) will be used for continuous outcomes and chi-square test will be used for categorical data. To adjust for confounding, multivariable linear regression analysis will be used for continuous outcomes, logistic regression analysis will be used for binary outcomes and Cox proportional hazards models will be used for time-to-event data.