Copy number variants and placental abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study

Autor: Tsegaselassie Workalemahu, Susan Dalton, Amanda Allshouse, Andrew Z. Carey, Jessica M. Page, Nathan R. Blue, Vanessa Thorsten, Robert L. Goldenberg, Halit Pinar, Uma M. Reddy, Robert M. Silver
Rok vydání: 2022
Předmět:
Zdroj: BJOG
ISSN: 1471-0528
1470-0328
DOI: 10.1111/1471-0528.17269
Popis: OBJECTIVE: To examine the association of fetal/placental DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in pregnancies complicated by stillbirth. 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 vascular, fetal vascular, inflammatory and immune/idiopathic lesions. Single-nucleotide polymorphism array detected CNVs of at least 500kb. CNVs were classified into two groups: normal, defined as no CNVs>500kb 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 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 known genes. CONCLUSIONS: Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillbirth cases. Findings may provide insight on the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.
Databáze: OpenAIRE
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