Array Comparative Genomic Hybridization for Genetic Evaluation of Fetal Loss Between 10 and 20 Weeks of Gestation

Warren, Jennifer E.; Turok, David K.; Maxwell, Teresa; Brothman, Arthur R.; Silver, Robert M.

doi:10.1097/aog.0b013e3181bc6ab0

Cited by 46 publications

(48 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 Microarray analysis, as compared with conventional karyotype analysis, has also increased the detection of genetic abnormalities in pregnancy loss at a gestation of less than 20 weeks. 21–23 Two small studies have assessed the usefulness of microarray analysis for the evaluation of stillbirths. A study of 15 stillbirths with abnormalities in two organs and either normal results on karyotype analysis or failed karyotyping identified an instance of trisomy 21 and another instance of an unbalanced translocation.…”

Section: Discussionmentioning

confidence: 99%

Karyotype versus Microarray Testing for Genetic Abnormalities after Stillbirth

et al. 2012

Self Cite

View full text Add to dashboard Cite

Background Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants. Methods The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery. Results In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P = 0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P = 0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P = 0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies. Conclusions Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.)

show abstract

Section: Discussionmentioning

confidence: 99%

Karyotype versus Microarray Testing for Genetic Abnormalities after Stillbirth

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, in these papers, the genome-wide prevalence of CNVs was examined in truly unexplained stillbirth, resulting in an overall detection ranging from 8-13% [11,29]. Retrospective studies in fetuses with multiple malformations also obtained a detection rate of causative imbalances from 8 to 15%, including common aneuploidies, by using array [7,30-32]. Our cohort tested by array, however, consisted of a heterogeneous group of fetal deaths, excluding a common aneuploidy which could clarify our lower detection rate.…”

Section: Discussionmentioning

confidence: 99%

Best diagnostic approach for the genetic evaluation of fetuses after intrauterine death in first, second or third trimester: QF-PCR, karyotyping and/or genome wide SNP array analysis

et al. 2014

View full text Add to dashboard Cite

BackgroundThe aim of this study was to evaluate the best diagnostic approach for the genetic analysis of samples from first, second and third trimester intrauterine fetal deaths (IUFDs). We examined a total of 417 IUFD samples from fetuses with and without congenital anomalies. On 414 samples, karyotyping (N = 46) and/or rapid aneuploidy testing by QF-PCR (N = 371) was performed). One hundred sixty eight samples with a normal test result were subsequently tested by genome wide Single Nucleotide Polymorphism (SNP) array analysis. Three samples were only analyzed by array.ResultsIn 50 (12.0%) samples an aneuploidy was detected by QF-PCR and/or karyotyping, representing 47.1% of first, 13.2% of second and 3.4% of third trimester pregnancies. Karyotyping and QF-PCR failed in 4 (8.7%) and 7 (1.9%) samples, respectively, concerning mostly contaminated amniotic fluid samples from third trimester pregnancies.Clinically relevant aberrations were identified in 4.2% (all fetuses with malformations) of the 168 samples tested by SNP array. Inherited copy number variants (CNVs) were detected in 5.4% and 8.9% showed CNVs of unknown clinical relevance as parental inheritance could not be studied yet. In a sample from a fetus suspect for Meckel-Grüber syndrome, the genotype information from the SNP array revealed various stretches of homozygosity, including one stretch encompassing the CEP290 gene. Subsequent CEP290 mutation analysis revealed a homozygous, pathogenic mutation in this gene.ConclusionsBased on our experience we recommend QF-PCR as the first-line test in IUFD samples of first and second trimester pregnancies to exclude aneuploidy before performing array analysis. The chance to detect aneuploidy in third trimester pregnancies is relatively low and therefore array analysis can be performed as a first-tier test. A tissue sample, instead of amniotic fluid, is preferred because of a higher success rate in testing.We emphasize the need for analysis of parental samples whenever a rare, unique CNV is detected to allow for better interpretation of such findings and to improve future pregnancy management. Furthermore, we illustrate the strength of SNP arrays for genotype analysis, even though we realize it is crucial to have detailed phenotypic information to make optimal use of the genotype data in finding candidate recessive genes that may be related to the fetal phenotype.

show abstract

“…20 Microarray analysis, as compared with conventional karyotype analysis, has also increased the detection of genetic abnormalities in pregnancy loss at a gestation of less than 20 weeks. [21][22][23] Two small studies have assessed the usefulness of microarray analysis for the evaluation of stillbirths. A study of 15 stillbirths with abnormalities in two organs and either normal results on karyotype analysis or failed karyotyping identified an instance of trisomy 21 and another instance of an unbalanced translocation.…”

Section: Discussionmentioning

confidence: 99%