Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy

• DOI: 10.1001/jamanetworkopen.2024.9119
• Publication Date: 2024-05-06T15:01:34Z
• Authors: Paolo Montaldo; Mario Cirillo; Constance Burgod; Elisabetta Caredda; Serena Ascione; Mauro Carpentieri; Simona Puzone; Alessandra D’Amico; Reema Garegrat; Marianna Lanza; Maria Moreno Morales; Gaurav Atreja; Vijaykumar Shivam...; Ujwal Kariholu; Narendra Aladangady; Paul Fleming; Asha Mathews; Balamurugan Palan...; Joanne Windrow; Karen Harvey; Aung Soe; Santosh Pattnayak; Palaniappan Sashi...; Sundeep Harigopal; Ronit Pressler; Martin Wilson; Enrico De Vita; Seetha Shankaran; Sudhin Thayyil; ; Emanuele Miraglia...; Carlo Capristo; Margherita Intern...; Anna Maietta; Giuseppe Montefusco; Umberto Pugliese; Ferdinando Spagnuolo; Mario Diplomatico; Sabino Moschella
• Keywords: Neonatal Encephalopathy; Apgar score

Importance Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. Objective To examine the effect of 48 72 hours HIE on cerebral magnetic resonance (MR) biomarkers. Design, Setting, Participants This open-label, 3-arm RCT was conducted between October 31, 2019, April 28, 2023, with masked outcome analysis. were neonates at 6 tertiary intensive care units UK Italy born or 36 weeks’ gestation severe birth acidosis, requiring continued resuscitation, an Apgar score less than 10 minutes evidence modified Sarnat staging. Statistical analysis per intention treat. Interventions Random allocation 1 3 groups (1:1:1) based age: younger normothermia 72-hour (33.5 °C), those older already receiving rewarming hypothermia. Main Outcomes Measures Thalamic N -acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by MR imaging thalamic spectroscopy 4 7 days using harmonized sequences. Results Of 225 eligible neonates, 101 recruited (54 males [53.5%]); (47.5%) 53 (52.5%) randomization. Mean (SD) gestational age weight 39.5 (1.1) weeks 3378 (380) grams group (n = 34), 38.7 (0.5) 3017 (338) 48-hour 31), 39.0 3293 (252) 36). More (14 31 [45.2%]) (13 [36.1%]) required intubation normothermic (3 34 [8.8%]). Ninety-nine (98.0%) had data 87 (86.1%), NAA data. Injury scores conventional biomarkers similar across groups. The mean level 10.98 (0.92) mmol/kg vs 8.36 (1.23) (mean difference [MD], −2.62 [95% CI, −3.34 −1.89] weight) 9.02 (1.79) (MD, −1.96 −2.66 −1.26] group. Seizures occurred beyond neonates: (2.9%) group, (3.2%) 2 (5.6%) Conclusions Relevance In this pilot RCT, did improve HIE, although sicker baseline. Safety should be RCTs. Trial Registration ClinicalTrials.gov Identifier: NCT03409770