Advancing precision care in pregnancy through a treatable fetal findings list

Jennifer L Cohen¹, Michael Duyzend², Sophia M Adelson³, Julie Yeo⁴, Mark Fleming⁵, Rebecca Ganetzky⁶, Rebecca Hale⁷, Deborah M Mitchell⁸, Sarah U Morton⁹, Rebecca Reimers¹⁰, Amy Roberts¹¹, Alanna Strong¹², Weizhen Tan¹³, Jay R Thiagarajah¹⁴, Melissa A Walker¹⁵, Robert C Green¹⁶, Nina B Gold¹⁷

Affiliations

¹ Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA.
² Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Brigham and Women's Hospital, Boston, MA, USA; Stanford School of Medicine, Stanford, CA, USA.
⁴ Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA.
⁵ Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Center for Computational Genomic Medicine and Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA.
⁷ Department of Pediatrics, Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Division of Pediatric Endocrinology, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Pediatrics, Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁰ Rady Children's Institute for Genomic Medicine, Rady Children's Hospital Division of Perinatology, Scripps Research Translational Institute, University of California, San Diego, San Diego, CA, USA.
¹¹ Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Cardiology, Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
¹² Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹³ Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Pediatric Nephrology, Massachusetts General Hospital for Children, Boston, MA, USA.
¹⁴ Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
¹⁵ Department of Neurology, Division of Pediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ Mass General Brigham, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Ariadne Labs, Boston, MA, USA.
¹⁷ Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: ngold@mgh.harvard.edu.

PMID: 40209713
PMCID: PMC12256799 (available on 2025-12-05)
DOI: 10.1016/j.ajhg.2025.03.011

Review

Advancing precision care in pregnancy through a treatable fetal findings list

Jennifer L Cohen et al. Am J Hum Genet. 2025.

. 2025 Jun 5;112(6):1251-1269.

doi: 10.1016/j.ajhg.2025.03.011. Epub 2025 Apr 9.

Authors

Affiliations

¹ Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA.
² Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Brigham and Women's Hospital, Boston, MA, USA; Stanford School of Medicine, Stanford, CA, USA.
⁴ Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA.
⁵ Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Center for Computational Genomic Medicine and Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA.
⁷ Department of Pediatrics, Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Division of Pediatric Endocrinology, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Pediatrics, Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁰ Rady Children's Institute for Genomic Medicine, Rady Children's Hospital Division of Perinatology, Scripps Research Translational Institute, University of California, San Diego, San Diego, CA, USA.
¹¹ Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Cardiology, Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
¹² Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹³ Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Pediatric Nephrology, Massachusetts General Hospital for Children, Boston, MA, USA.
¹⁴ Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
¹⁵ Department of Neurology, Division of Pediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ Mass General Brigham, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Ariadne Labs, Boston, MA, USA.
¹⁷ Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: ngold@mgh.harvard.edu.

PMID: 40209713
PMCID: PMC12256799 (available on 2025-12-05)
DOI: 10.1016/j.ajhg.2025.03.011

Abstract

The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade. Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS. In the United States, GS for adults and children is recommended to include a list of "secondary findings" genes (ACMG SF v.3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v.3.2 predominantly cause adult-onset disorders. Importantly, many genetic disorders with fetal and infantile onset are treatable as well. A proposed solution is to create a "treatable fetal findings list," which can be offered to pregnant individuals undergoing fetal GS or, eventually, as a standalone cell-free fetal DNA screening test. In this integrative review, we propose criteria for a treatable fetal findings list, then identify genetic disorders with clinically available or emerging fetal interventions and those for which clinical detection and intervention in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of a treatable fetal findings list.

Keywords: actionable findings; genomic sequencing; prenatal diagnosis; prenatal therapies.

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Conflict of interest statement

Declaration of interests J.L.C. has received compensation for advising at Bayer HealthCare Pharmaceuticals and served as an advisor on a Sanofi Advisory Board. M.D. has received a speaking honorarium from Illumina, Inc. M.F. has received compensation for advising the following companies: Vertex Pharmaceuticals, Affyimmune Pharmaceuticals, and Evolve Immune Pharmaceuticals. He also serves on scientific advisory boards for Disc Medicine and Minerva Biotechnologies. R.G. is a paid consultant for Nurture Genomics & Minovia Therapeutics. D.M.M. receives compensation for advising the following companies: Amolyt and Ascendis. W.T. serves as a paid consultant for Amgen Pharmaceuticals and participates on an Advisory Board for cystinosis. M.A.W. is an author on a pending patent application, US Provisional Patent Application 63/034,740 “Methods of Detecting Mitochondrial Diseases.” R.C.G. has received compensation for advising the following companies: Allelica, Atria, Fabric, and Juniper Genomics; and is a co-founder of Genome Medical and Nurture Genomics. N.B.G. has received an honorarium from Ambry Genetics.

References

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Advancing precision care in pregnancy through a treatable fetal findings list

Affiliations

Advancing precision care in pregnancy through a treatable fetal findings list

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Grants and funding

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Medical

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