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Objective: The aim of this study was to evaluate pre-resection risk factors for neurodevelopmental impairment (NDI) in infants with necrotizing enterocolitis (NEC) that might better inform the timing of intestinal resection., Summary Background Data: Surgical NEC is associated with a 57% risk for NDI., Methods: A retrospective study of patients with NEC who underwent intestinal resection within 10 days of diagnosis between 2010 and 2019 was conducted in 11 US children's hospitals. The primary outcome was NDI at 16-26 months. Demographics, findings at NEC diagnosis, and the presence and trajectory of appearance of five established indicators of metabolic derangement were assessed as risk factors for NDI., Results: Of 365 total patients, 297 underwent resection for NEC within 10 days and 77 (26%) died. NDI was identified in 112 (55%) of patients who were assessed and was more likely in males; infants with lower birth weight, gestational age, or Apgar scores; or older age at diagnosis. Risk for NDI was associated with more indicators of metabolic derangement prior to resection (1.78 vs 1.15, P=0.002) and was progressively greater when more indicators were detected (44%-83% with 0-5 indicators, P=0.04). The median times to identification of one (15 min) to five (48 h) indicators increased progressively., Conclusions: Risk for NDI in surgical NEC was associated with the number and trajectory of identification of indicators of metabolic derangement prior to resection. As these indicators progressively appear over hours to days, their assessment might offer an objective means of defining failure of medical management and lead to improvement in neurodevelopmental outcomes in NEC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)