{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:57:44Z","timestamp":1779893864510,"version":"3.53.1"},"reference-count":97,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K01 HG013114"],"award-info":[{"award-number":["K01 HG013114"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K23 HD102589"],"award-info":[{"award-number":["K23 HD102589"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21 HG012397"],"award-info":[{"award-number":["R21 HG012397"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Each year, many neonates are born with genetic diagnoses that carry a range of prognoses. As the types and availability of genetic testing have expanded, neonatal intensive care units (NICUs) have served as \u201claunching points\u201d for their clinical application. Broad genetic testing has both improved diagnostic precision and expanded uncertainty. Genetic information may be explicitly uncertain, as in the case of a variant of unknown significance (VUS). But it is also frequently uncertain whether\/how the information relates to a patient\u2019s phenotype or what it may mean for a child\u2019s future. Even without ambiguity in the diagnosis or prognosis, the significance within a clinical and familial context may be less certain. Applying the information to clinical care is complex and may engender confusion among clinicians and families as readily as it offers guidance. Since genetic testing results can impact management and, at times, end-of-life decisions, misunderstanding and misapplication of genetic results pose a significant risk. We describe a hypothetical case of an infant with congenital hypotonia and respiratory failure. The family, after discussions with the care team about medically appropriate care paths, is navigating goals of care and considering tracheostomy placement for chronic mechanical ventilation. They consent to rapid genome sequencing in hopes of better understanding the etiology and severity of the neuromuscular condition. We explore three possible scenarios following different genomic results. With each, we discuss how the results may impact decision-making about the best plan of care. We propose a framework for navigating discussions about genetic testing results with families of critically ill children. We illustrate the importance of a multidisciplinary approach with collaboration between neonatology, genetics, and palliative care. By employing the strengths of each subspecialty, providers can manage the inherent uncertainty in genetic testing results, help determine the meaning of the results to the family in the context of their child\u2019s medical care, and enhance the care and support of critically ill neonates and their families.<\/jats:p>","DOI":"10.3390\/children13010034","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:25:51Z","timestamp":1766989551000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Managing the Uncertainty of \u201cPrecision\u201d While Navigating Goals of Care: A Framework for Collaborative Interpretation of Complex Genomic Testing Results in Critically-Ill Neonates"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7555-7829","authenticated-orcid":false,"given":"DonnaMaria E.","family":"Cortezzo","sequence":"first","affiliation":[{"name":"Division of Neonatology, Connecticut Children\u2019s, Hartford, CT 06106, USA"},{"name":"Division of Pain and Palliative Care, Connecticut Children\u2019s, Hartford, CT 06106, USA"},{"name":"Fetal Care Center, Connecticut Children\u2019s, Hartford, CT 06106, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Connecticut, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2221-6254","authenticated-orcid":false,"given":"Katharine Press","family":"Callahan","sequence":"additional","affiliation":[{"name":"Division of Neonatology, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Medical Ethics and Health Policy, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0115-949X","authenticated-orcid":false,"given":"Bimal P.","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Division of Genetic and Genomic Medicine, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-9638","authenticated-orcid":false,"given":"Elliott M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Treuman Katz Center for Pediatric Bioethics & Palliative Care, Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA 98101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-5031","authenticated-orcid":false,"given":"Monica Hsiung","family":"Wojcik","sequence":"additional","affiliation":[{"name":"Divisions of Newborn Medicine & Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-4669","authenticated-orcid":false,"given":"Krishna","family":"Acharya","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Schlegel","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4801-137X","authenticated-orcid":false,"given":"Kevin M.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Department of Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica T.","family":"Fry","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"},{"name":"Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1542\/peds.2018-1099D","article-title":"Rapid challenges: Ethics and genomic neonatal intensive care","volume":"143","author":"Gyngell","year":"2019","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1542\/peds.2018-1099J","article-title":"Neonatologists\u2019 attitudes about diagnostic whole-genome sequencing in the NICU","volume":"143","author":"Knapp","year":"2019","journal-title":"Pediatrics"},{"key":"ref_3","first-page":"1","article-title":"Fetal and Perinatal Mortality: United States, 2013","volume":"64","author":"MacDorman","year":"2015","journal-title":"Natl. 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