Introduction
Stillbirth, most commonly defined in the U.S. as fetal death at ≥20 weeks’ gestation, occurs at an estimated rate of 5.7 per 1000 births in the United States.1 The causes of stillbirth are multi-factorial, and histologic examination of the placenta, cord, or membranes can identify a cause of death in 11-65% stillbirths.2, 3 Maternal and fetal vascular lesions in the placenta are commonly associated with stillbirth.4-6 Proper function of the placenta requires uninterrupted flow of adequately oxygenated maternal and fetal blood, which is critical for fetal survival.7Macroscopic abnormalities of the placenta, such as aberrations in shape and size, and microscopic variation in villous morphology, often reflect placental function.8, 9 Determining factors influencing placental pathological lesions will help facilitate understanding the pathogenesis, diagnosis, and treatment of stillbirth with an underlying placental etiology.10
Chromosomal assessment of the placenta and fetus with the use of single-nucleotide polymorphism (SNP) oligonucleotide microarray analysis is useful in determining causes of death in stillbirth and structural malformations in live births.11-13 Some forms of chromosomal structural abnormalities such as trisomy and monosomy are known to be associated with stillbirth. However, the relevance of other types of genetic aberrations in stillbirth cases is not well characterized, and the mechanism by which they contribute to stillbirth is not understood. Therefore, our objective was to evaluate the associations of placental and fetal CNVs with placental pathological lesions in a well characterized study of stillbirth. In addition, we discuss and highlight specific CNV deletions and duplications in genes associated with placental pathological lesions.