{
  "abstract": "Importance: Preterm survivors of necrotizing enterocolitis (NEC) face substantial neurodevelopmental impairment, but the regional biology and timing of associated brain abnormalities remain poorly defined. Objective: To define the regional, cellular, molecular, and temporal features of NEC-associated brain pathology. Design: Prospective multimodal clinical cohort study (2012-2024), complemented by postmortem tissue analyses. Setting: Level IV neonatal intensive care unit at Children's National Hospital, Washington, DC. Participants: Of 400 infants screened, 253 preterm infants born before 37 weeks' gestation (128 with NEC and 125 without NEC) were included across neuroimaging, plasma metabolomic, and postmortem cohorts. Exposures: Medical or surgical NEC (modified Bell stage [≥]II). Main Outcomes and Measures: Primary outcomes were term-equivalent magnetic resonance imaging (MRI) abnormalities and serial ultrasound hindbrain growth; secondary outcomes were postmortem histopathology, brain and intestinal transcriptomics, and plasma metabolomics. Results: Among 179 infants with term-equivalent MRI (89 NEC, 90 controls; 102 [57.0%] male; mean [SD] gestational age, 26.3 [2.2] weeks), NEC was associated with a higher prevalence of pontine abnormalities (12.4% vs 1.1%; adjusted prevalence ratio, 9.14; 95% CI, 1.16-71.92), alongside white matter, callosal, and cerebellar abnormalities. In postmortem tissue (n = 27), white matter pathology qualitatively resembled that of prematurity, whereas the hindbrain showed distinct regional phenotypes. The cerebellum exhibited external granular layer contraction (42% reduction; P = .04), while the pons showed neuronal injury with increased morphological apoptotic burden (P [≤] .05). Brain and intestinal transcriptomics (n = 14), complemented by plasma metabolomics (n = 29), revealed divergent inflammatory and metabolic signatures. The pons showed increased neuroinflammatory and reduced mitochondrial programs, whereas the cerebellum showed reduced metabolic and cell-cycle programs alongside circulating lysophospholipid depletion. Serial ultrasonography (n = 159), anchored to the cohort mean NEC onset age of 29 weeks' postmenstrual age, identified earlier cerebellar dimensional deficits (P = .015) and later pontine growth deceleration (P < .001). Conclusions and Relevance: In this cohort study, NEC-associated hindbrain pathology showed asynchronous growth patterns accompanied by distinct cellular and molecular phenotypes. These findings support investigation of regional vulnerability and stage-specific neuroprotection; individual injury timing and causal mechanisms remain unresolved.",
  "abstract_shown": true,
  "affiliations": [
    "Children's National Hospital; The George Washington University School of Medicine and Health Sciences"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "name": "G. Sanidas"
    },
    {
      "name": "H. Chen"
    },
    {
      "name": "G. Simonti"
    },
    {
      "name": "J. Ghaemmaghami"
    },
    {
      "name": "R. Cardenas"
    },
    {
      "name": "C. Byrd"
    },
    {
      "name": "C. Lowe"
    },
    {
      "name": "L. Kim"
    },
    {
      "name": "M. Triantafyllou"
    },
    {
      "name": "N. Wolff"
    },
    {
      "name": "R. Vidva"
    },
    {
      "name": "A. Sandler"
    },
    {
      "name": "B. L. Short"
    },
    {
      "name": "T. Siahanidou"
    },
    {
      "name": "C. Kanaka-Gantenbein"
    },
    {
      "name": "H. S. Pettersen"
    },
    {
      "name": "M. Said"
    },
    {
      "name": "K. Rais-Bahrami"
    },
    {
      "name": "V. Gallo"
    },
    {
      "name": "F. Northington"
    },
    {
      "name": "I. Koutroulis"
    },
    {
      "affs": [
        0
      ],
      "name": "P. Kratimenos"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3g2gqg0j9qd61.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.30.763262",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763262v1.full",
  "id": "3g2gqg0j9qd61",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763262v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763262v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3g2gqg0j9qd61.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:09Z",
      "native_id": "10.64898/2026.10.30.763262",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763262v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Divergent Pontine and Cerebellar Pathology in Preterm Infants With Necrotizing Enterocolitis",
  "title_text": "Divergent Pontine and Cerebellar Pathology in Preterm Infants With Necrotizing Enterocolitis",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:19Z",
  "url": "https://research.draconitic.com/paper/3g2gqg0j9qd61",
  "venue": "bioRxiv",
  "versions": []
}