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.