{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T08:11:38Z","timestamp":1778919098235,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To apply a network medicine\u2010based approach to analyze the phenome of the prenatal fetal MRI and biometric findings in the Chiari II malformation (CM II) to detect specific patterns and co\u2010occurrences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A single\u2010center retrospective review of fetal MRI scans obtained in fetuses with CM II was performed. Co\u2010occurrence analysis was utilized to generate a phenotypic comorbidity matrix and visualized by Gephi software. Traditional univariate regression and geometric thin\u2010plate spline methodology were used to elucidate the mechanisms underlying\u00a0the relationships between morphometric measurements and geometric landmarks of the spine, skull, and brain deformations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CM II phenome consists of 35 nodes interconnected by 979 edges with a density of 0.828. Key \u201chubs\u201d identified within this network include spinal bony defects, reduced posterior fossa dimensions, and vermis ectopia. The brain edema phenotype appearing only in the fetal stage but disappearing after postnatal surgery, links to increased postnatal morbidity and demonstrates distinct shape patterns by geometric analysis. Traditional univariate regression reveals correlations among spinal defects, posterior fossa dimensions, and caudal extent of vermis ectopia. The degree of brain rearrangement versus spinal bony rearrangement shows a correlation (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.721, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0023) by partial least\u2010squares analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The CM II prenatal phenome is a multifaceted network centered around three key elements\u2014spinal bony defects, small posterior fossa, and vermis ectopia\u2014with strong interconnections. Fetal brain edema emerged as an exclusively prenatally detectable and transient phenotype of prognostic relevance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6741","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T05:06:22Z","timestamp":1735967182000},"page":"362-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterizing the In Utero Phenome of the Chiari II Malformation\u2014A Network Medicine Approach, Using Fetal MRI"],"prefix":"10.1002","volume":"45","author":[{"given":"Hui","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Radiology Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Prayer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Leinkauf","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Tischer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Medical Physics and Biomedical Engineering Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patric","family":"Kienast","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-7770","authenticated-orcid":false,"given":"Farjad","family":"Khalaveh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Feto\u2010Maternal Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-3347","authenticated-orcid":false,"given":"Gregor","family":"Kasprian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31989"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010017\u20101860\u20101"},{"issue":"2","key":"e_1_2_11_4_1","first-page":"463","article-title":"Developmental Morphology of the Subarachnoid Space, Brain Vasculature, and Contiguous Structures, and the Cause of the Chiari II Malformation","volume":"13","author":"McLone D. 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