Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Use of chromosomal microarray in obstetrics

David T Miller, MD, PhD
Section Editor
Louise Wilkins-Haug, MD, PhD
Deputy Editor
Vanessa A Barss, MD, FACOG


Prenatal diagnosis and postnatal evaluation of pregnancy loss often involves cytogenetic analysis of amniocytes, chorionic villi, or fetal cells. Although conventional Giemsa(G)-banding of metaphase chromosomes detects aneuploidies and large structural changes (eg, balanced or unbalanced translocations, inversions), this approach also has limitations: it does not consistently identify submicroscopic (ie, smaller than what is visible under a light microscope) genomic defects (<3 to 10 million base pairs [Mb]) and requires cell culture, which takes a minimum of seven days to obtain an adequate number of dividing cells. The use of fluorescence in situ hybridization (FISH) reduces the time to obtain a result and is less labor intensive, but can only detect a limited number of pre-specified targets.

Chromosomal microarray (CMA) is an array-based molecular cytogenic technique that can overcome some limitations of a karyotype, and is particularly useful for its ability to detect submicroscopic gains and losses on every chromosome (figure 1). This technique compares the genomic content (DNA) of a patient (target) with that of a normal control individual (or individuals) and detects gains and losses (duplications and deletions) ranging in size from very large, including aneuploidy of entire chromosomes, to very small (typically as small as about 200,000 base pairs or 0.2 Mb). Gains and losses may correspond to structural changes such as unbalanced translocations), but CMA cannot detect the physical location of the extra material (as in a translocation) nor can it detect structural chromosome changes that do not result in deletions or duplications (eg, balanced translocations or balanced inversions).

Different laboratories perform CMA using different technology platforms and with different array design and content [1-7].

This topic will discuss the use of CMA in obstetrics. Basic principles of genetics are reviewed separately, and include:

(See "Basic principles of genetic disease".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Oct 10, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Rauch A, Rüschendorf F, Huang J, et al. Molecular karyotyping using an SNP array for genomewide genotyping. J Med Genet 2004; 41:916.
  2. de Vries BB, Pfundt R, Leisink M, et al. Diagnostic genome profiling in mental retardation. Am J Hum Genet 2005; 77:606.
  3. Hochstenbach R, Ploos van Amstel HK, Poot M. Microarray-based genome investigation: molecular karyotyping or segmental aneuploidy profiling? Eur J Hum Genet 2006; 14:262.
  4. Vermeesch JR, Rauch A. Reply to Hochstenbach et al. 'Molecular karyotyping'. Eur J Hum Genet 2006; 14:1063.
  5. Vermeesch JR, Fiegler H, de Leeuw N, et al. Guidelines for molecular karyotyping in constitutional genetic diagnosis. Eur J Hum Genet 2007; 15:1105.
  6. Hoyer J, Dreweke A, Becker C, et al. Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays. J Med Genet 2007; 44:629.
  7. Wou K, Levy B, Wapner RJ. Chromosomal Microarrays for the Prenatal Detection of Microdeletions and Microduplications. Clin Lab Med 2016; 36:261.
  8. Brady PD, Vermeesch JR. Genomic microarrays: a technology overview. Prenat Diagn 2012; 32:336.
  9. Lo KK, Karampetsou E, Boustred C, et al. Limited Clinical Utility of Non-invasive Prenatal Testing for Subchromosomal Abnormalities. Am J Hum Genet 2016; 98:34.
  10. Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012; 367:2175.
  11. Reddy UM, Page GP, Saade GR, et al. Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med 2012; 367:2185.
  12. Shaffer LG, Dabell MP, Fisher AJ, et al. Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies. Prenat Diagn 2012; 32:976.
  13. Shaffer LG, Rosenfeld JA, Dabell MP, et al. Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 2012; 32:986.
  14. Scott F, Murphy K, Carey L, et al. Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic hybridization analysis as a first-line test: results from over 1000 consecutive cases. Ultrasound Obstet Gynecol 2013; 41:500.
  15. Callaway JL, Shaffer LG, Chitty LS, et al. The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenat Diagn 2013; 33:1119.
  16. de Wit MC, Srebniak MI, Govaerts LC, et al. Additional value of prenatal genomic array testing in fetuses with isolated structural ultrasound abnormalities and a normal karyotype: a systematic review of the literature. Ultrasound Obstet Gynecol 2014; 43:139.
  17. Giardino D, Corti C, Ballarati L, et al. De novo balanced chromosome rearrangements in prenatal diagnosis. Prenat Diagn 2009; 29:257.
  18. Warburton D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet 1991; 49:995.
  19. Baptista J, Prigmore E, Gribble SM, et al. Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals. Eur J Hum Genet 2005; 13:1205.
  20. Savage MS, Mourad MJ, Wapner RJ. Evolving applications of microarray analysis in prenatal diagnosis. Curr Opin Obstet Gynecol 2011; 23:103.
  21. Gribble SM, Prigmore E, Burford DC, et al. The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes. J Med Genet 2005; 42:8.
  22. De Gregori M, Ciccone R, Magini P, et al. Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: a study of 59 patients. J Med Genet 2007; 44:750.
  23. Feenstra I, Hanemaaijer N, Sikkema-Raddatz B, et al. Balanced into array: genome-wide array analysis in 54 patients with an apparently balanced de novo chromosome rearrangement and a meta-analysis. Eur J Hum Genet 2011; 19:1152.
  24. Hillman SC, Pretlove S, Coomarasamy A, et al. Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2011; 37:6.
  25. Breman A, Pursley AN, Hixson P, et al. Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature. Prenat Diagn 2012; 32:351.
  26. McGillivray G, Rosenfeld JA, McKinlay Gardner RJ, Gillam LH. Genetic counselling and ethical issues with chromosome microarray analysis in prenatal testing. Prenat Diagn 2012; 32:389.
  27. Lee CN, Lin SY, Lin CH, et al. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG 2012; 119:614.
  28. Duncan A, Langlois S, SOGC Genetics Committee, CCMG Prenatal Diagnosis Committee. Use of array genomic hybridization technology in prenatal diagnosis in Canada. J Obstet Gynaecol Can 2011; 33:1256.
  29. Novelli A, Grati FR, Ballarati L, et al. Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011. Ultrasound Obstet Gynecol 2012; 39:384.
  30. American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol 2013; 122:1374.
  31. Fiorentino F, Napoletano S, Caiazzo F, et al. Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities. Eur J Hum Genet 2013; 21:725.
  32. Manning M, Hudgins L, Professional Practice and Guidelines Committee. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010; 12:742.
  33. Nicolaides KH, Snijders RJ, Gosden CM, et al. Ultrasonographically detectable markers of fetal chromosomal abnormalities. Lancet 1992; 340:704.
  34. Hillman SC, McMullan DJ, Hall G, et al. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol 2013; 41:610.
  35. Sahoo T, Cheung SW, Ward P, et al. Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization. Genet Med 2006; 8:719.
  36. Shaffer LG, Coppinger J, Alliman S, et al. Comparison of microarray-based detection rates for cytogenetic abnormalities in prenatal and neonatal specimens. Prenat Diagn 2008; 28:789.
  37. Kleeman L, Bianchi DW, Shaffer LG, et al. Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype. Prenat Diagn 2009; 29:1213.
  38. Lu XY, Phung MT, Shaw CA, et al. Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics 2008; 122:1310.
  39. Goemaere N, Douben H, Van Opstal D, et al. The use of comparative genomic hybridization and fluorescent in situ hybridization in postmortem pathology investigation of congenital malformations. Pediatr Dev Pathol 2010; 13:85.
  40. Jansen FA, Blumenfeld YJ, Fisher A, et al. Array comparative genomic hybridization and fetal congenital heart defects: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015; 45:27.
  41. Warburton D, Susser M, Stein Z, Kline J. Genetic and epidemiologic investigation of spontaneous abortion: relevance to clinical practice. Birth Defects Orig Artic Ser 1979; 15:127.
  42. Reddy UM, Page GP, Saade GR. The role of DNA microarrays in the evaluation of fetal death. Prenat Diagn 2012; 32:371.
  43. Dhillon RK, Hillman SC, Morris RK, et al. Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG 2014; 121:11.
  44. Rajcan-Separovic E. Chromosome microarrays in human reproduction. Hum Reprod Update 2012; 18:555.
  45. Yatsenko SA, Peters DG, Saller DN, et al. Maternal cell-free DNA-based screening for fetal microdeletion and the importance of careful diagnostic follow-up. Genet Med 2015; 17:836.
  46. Wapner RJ, Driscoll DA, Simpson JL. Integration of microarray technology into prenatal diagnosis: counselling issues generated during the NICHD clinical trial. Prenat Diagn 2012; 32:396.