Genome-wide array-based copy number profiling in human placentas from unexplained stillbirths

R. Alan Harris, Francesca Ferrari, Shay Ben-Shachar, Xiaoling Wang, George Saade, Ignatia van den Veyver, Fabio Facchinetti, Kjersti Aagaard-Tillery

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Objective: Accumulating evidence suggests that genomic structural variations, particularly copy number variations (CNV), are a common occurrence in humans that may bear phenotypic consequences for living individuals possessing the variant. While precise estimates vary, large-scale karyotypic abnormalities are present in 6-12% of stillbirths (SB). However, due to inherent limitations of conventional cytogenetics, the contribution of genomic aberrations to stillbirth is likely underrepresented. High-resolution copy number variant analysis by genomic array-based profiling may overcome such limitations. Methods: Prospectively acquired SB cases > 22 weeks underwent classification of 'unexplained' stillbirth by Wigglesworth and Aberdeen criteria after extensive testing and rigorous multidisciplinary audit. Genome-wide analysis was conducted using high-resolution Illumina single nucleotide polymorphism (SNP) arrays (Human CNV370-Duo) on placental and fetal samples. Potential alternate detection methods were completed by one or more of three independent means (quantitative PCR, Illumina1M, or Agilent105K comparative genomic hybridization arrays). Results: In our cohort of 54 stillbirths, 29 met strict unexplained criteria. Among these, we identified 24 putative novel CNVs. Subsequent interrogation detected 18 of 24 CNVs (75%) in placental samples, 8 of which were also confirmed in available fetal samples; none were present in maternal blood. Conclusion: We describe the potential of whole-genome placental profiling to identify small genomic imbalances, which might contribute to a small proportion of well-characterized, unexplained stillbirths.

Original languageEnglish (US)
Pages (from-to)932-944
Number of pages13
JournalPrenatal Diagnosis
Issue number10
StatePublished - Oct 2011
Externally publishedYes


  • Copy number variants
  • Deletion syndromes
  • Duplication syndromes
  • Fetal death
  • Stillbirth

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Genetics(clinical)


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