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Copy number variants and placental abnormalities in stillborn fetuses: a secondary analysis of the Stillbirth Collaborative Research Network study
  • +8
  • Tsegaselassie Workalemahu,
  • Susan Dalton,
  • Amanda Allshouse,
  • Andrew Carey,
  • Jessica Page,
  • Nathan Blue,
  • Vanessa Thorsten,
  • Robert Goldenberg,
  • Halit Pinar,
  • Uma Reddy,
  • Robert Silver (USA)
Tsegaselassie Workalemahu
University of Utah Health

Corresponding Author:[email protected]

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Susan Dalton
University of Utah Health
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Amanda Allshouse
University of Utah Health
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Andrew Carey
University of Utah Health
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Jessica Page
Intermountain Medical Center
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Nathan Blue
University of Utah Health
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Vanessa Thorsten
RTI International
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Robert Goldenberg
Columbia University
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Halit Pinar
Brown University Warren Alpert Medical School
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Uma Reddy
Yale University School of Medicine
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Robert Silver (USA)
University of Utah Health
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Abstract

Objective To examine the association of DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in stillborn fetuses. Design A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study. Setting Multicenter, 59 hospitals in 5 geographic regions in the USA. Population 387 stillbirth cases (2006-2008). Methods Using standard definitions, PPLs were categorized by type including maternal and fetal vascular, inflammatory and immune/idiopathic lesions. Using single-nucleotide polymorphism array, CNVs of at least 500 kb were detected. CNVs were classified into two groups: normal, defined as no CNVs>500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. Main outcome measures The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without PPLs using the Wald Chi-squared test. Results Of 387 stillborn fetuses, 327 (84.5%) had maternal vascular PPLs and 60 (15.6%) had abnormal CNVs. Maternal vascular PPLs were more common in stillborn fetuses with abnormal CNVs compared with those with normal CNVs (81.7% vs. 64.2%; p=0.008). The proportions of fetal vascular, maternal/fetal inflammatory, and immune/idiopathic PPLs were similar among stillborn fetuses with abnormal CNVs compared to those with normal CNVs. Pathogenic CNVs in stillborn fetuses with maternal vascular PPLs spanned several genes with known relevant mechanisms. Conclusions Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillborn fetuses. Findings may provide insight on the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.
02 Feb 2022Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
07 Feb 2022Submission Checks Completed
07 Feb 2022Assigned to Editor
12 Feb 2022Reviewer(s) Assigned
15 Mar 2022Review(s) Completed, Editorial Evaluation Pending
28 Mar 2022Editorial Decision: Revise Major
01 May 20221st Revision Received
02 May 2022Submission Checks Completed
02 May 2022Assigned to Editor
02 May 2022Review(s) Completed, Editorial Evaluation Pending
16 May 2022Editorial Decision: Revise Minor
19 May 20222nd Revision Received
20 May 2022Assigned to Editor
20 May 2022Submission Checks Completed
20 May 2022Review(s) Completed, Editorial Evaluation Pending
28 May 2022Editorial Decision: Accept
03 Aug 2022Published in BJOG: An International Journal of Obstetrics & Gynaecology. 10.1111/1471-0528.17269