Copy number variants and placental abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study.
Copy number variants and placental abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study.
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DOI：
10.1111/1471-0528.17269
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发表时间：
2022-12
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探讨胎儿/胎盘DNA拷贝数变异（CNVs）与妊娠合并死产的病理性胎盘病变（PPL）之间的关系。死胎协作研究网络病例对照研究中死胎病例的二次分析。美国5个地理区域的59家多中心医院。387例死胎（2006-2008年）。使用标准定义，PPL按类型分类，包括母体血管、胎儿血管、炎症和免疫/特发性病变。单核苷酸多态性芯片检测到至少500 kb的CNVs。将CNVs分为两组：正常组，定义为无> 500 kb的CNVs或良性CNVs;异常组，定义为致病性或临床意义未知的变体。使用Wald卡方检验比较有和没有PPL的死胎病例中异常CNVs和正常CNVs的比例。在387例死胎中，327例（84.5%）有母体血管PPL，60例（15.6%）有异常CNV。母体血管PPL在CNV异常的死胎中比CNV正常的死胎更常见（81.7% vs. 64.2%; p=0.008）。与正常CNVs相比，CNVs异常的死胎中胎儿血管、母体/胎儿炎症和免疫/特发性PPL的比例相似。具有母体血管PPL的死产胎儿中的致病性CNV跨越几个已知基因。异常胎盘/胎儿CNV与死胎病例中母体血管PPL相关。研究结果可能提供与胎盘功能障碍和死产相关的特定遗传异常机制的见解。死胎胎盘和胎儿DNA拷贝数的异常变化与母体血管胎盘病变有关。
To examine the association of fetal/placental DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in pregnancies complicated by stillbirth. A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study. Multicenter, 59 hospitals in 5 geographic regions in the USA. 387 stillbirth cases (2006–2008). 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. The proportions of abnormal CNVs and normal CNVs compared between stillbirth cases with and without PPLs using the Wald Chi-squared test. 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. 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. Abnormal copy number changes in stillborn placental and fetal DNA are associated with maternal vascular placental lesions.