The most recent widespread advance in the genetic evaluation of the fetus is the introduction of micro arrays for whole genome evaluation. Think of microarray analysis as a high definition image of the chromosome, compared to a traditional karyotype, which is more like a blurry web cam image.
Traditional prenatal diagnosis uses amniotic fluid or placental villi to grow fetal cells, then stain and count fetal chromosomes. This allows the diagnosis of numerical disparities or gross abnormalities of chromosomes, the most common of which is trisomy 21 (Down syndrome).
Microarray analysis starts the same way, with some form of fetal tissue, such as cells from an amniocentesis or CVS. Rather than just staining and counting, however, the microarray technique takes the fetal DNA and cuts it into small pieces, which are then matched to small standard sequences arranged on a microchip (the array). Pieces that don’t match are abnormal, and thus abnormal sequences or deletions and duplications of the DNA can be identified, in addition to confirming the correct number of chromosomes. These deletions and duplications would not be detected by traditional karyotyping and are not related to maternal age. In addition, because microarray analysis does not require growing and dividing cells it is more reliable than karyotype in cases of stillbirth.
Micro-deletions and duplications account for up to 15% of human genetic disease. Both the American College of Obstetricians and the Society for Maternal Fetal Medicine now recommend that microarray analysis replace traditional karyotyping for cases of fetal abnormality seen on ultrasound, and suggest that it has merit even in the normal appearing baby having an amniocentesis for other reasons. Studies have shown that babies with abnormalities on ultrasound with a normal karyotype have clinically significant microarray abnormalities in about 6% of cases. In addition, about 1-2% of babies with a normal ultrasound and normal karyotype can have an abnormal microarray analysis (“The use of chromosomal microarray analysis in prenatal diagnosis”. Committee Opinion No. 581. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:1374–7).
For this reason, Eastside Maternal Fetal Medicine has now transitioned to using FISH and microarray analysis in replacement of FISH and karyotype for all fetal chromosome analysis. In most cases the patient’s insurance will cover this in the same fashion as a traditional karyotype.
Like all new technology, there are occasions when information found can be confusing or of uncertain significance. We have dedicated genetic counselors that are happy to help providers and families navigate these issues.
For patients and their families who are interested in hearing more about prenatal screening and prenatal testing options, Eastside Maternal Fetal Medicine is planning to offer monthly free classes. Contact our genetic counselor Claire Clark at firstname.lastname@example.org for further details. Patients can call our front desk to register for these classes at 425 688 8111.
The ACOG committee opinion is available here: http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/The_Use_of_Chromosomal_Microarray_Analysis_in_Prenatal_Diagnosis