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Multicenter Study
. 2022 Dec;129(13):2125-2131.
doi: 10.1111/1471-0528.17269. Epub 2022 Aug 3.

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

Tsegaselassie Workalemahu  1 , Susan Dalton  1 , Amanda Allshouse  1 , Andrew Z Carey  1 , Jessica M Page  1   2 , Nathan R Blue  1 , Vanessa Thorsten  3   4 , Robert L Goldenberg  5 , Halit Pinar  6 , Uma M Reddy  7 , Robert M Silver  1   2
Affiliations
Multicenter Study

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

Tsegaselassie Workalemahu et al. BJOG. 2022 Dec.

Abstract

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 five geographical regions in the USA.

Population: 387 stillbirth cases (2006-2008).

Methods: Using standard definitions, PPLs were categorised by type including maternal vascular, fetal vascular, inflammatory and immune/idiopathic lesions. Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNV >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 compared between stillbirth cases with and without PPLs using the Wald Chi-square 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 than in those with normal CNVs (81.7% versus 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 and 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. The findings may provide insight into the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.

Keywords: copy number variants; pathologic lesions; placenta; stillbirth.

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Figures

Figure 1.
Figure 1.
Associations of CNVs with placental pathological lesions in stillborn fetuses
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