The evolution of microarray technology has changed the way clinicians and patients are preparing for the future of the patient and possibly the birth and future of the patient's children. Studies evaluating fetal chromosomes at the genetic level are becoming more common as technology advances, and these studies may provide more accurate predictions of child health and potential chromosomal deformities. In an interview, Ronald Wapner, MD, professor of obstetrics and gynecology at Columbia University Medical Center in New York, discussed a recent study examining the advantages and limitations of prenatal microarray testing.
Despite the introduction of microarrays, the standard in prenatal testing remains grounded in karyotyping. As the healthcare industry lingers in a transitional period, prenatal researchers are starting to utilize both approaches to evaluate chromosomal abnormalities, examining at the genetic level as well as on a more visual scale through microscopic images of fetal tissue. While karyotyping can help identify deletions or duplications in up to 10 million based pairs, Wapner's recent study demonstrated that microarrays can identify those same irregularities at the kilobase level while maintaining clinical relevance.
"Microarray testing offers significant additional information," Wapner said. "But one should consider that it's just the stepping stone of what future abilities we will have to identify additional genetic disorders of the fetus through new techniques, such as genome sequencing."
Part of the study's good outcomes can be attributed not only to the quality of microarray testing, but also the sheer amount of information produced from an exam. According to Wapner, so much information is contained in the genes that "we are constantly deciphering and adding to what is known for certain." Microarrays can sometimes offer information that simply can't be known. In prenatal medicine, this isn't unheard of - even in karyotyping, in which structural arrangements can differ.
As researchers continue to collect data of "unknown significance," as Wapner put it, microarrays will continue to be viewed as experimental in prenatal testing. But techniques like sequencing help researchers identify more and more of these abnormalities.
"Sequencing in which you can actually look at the sequence or the base pairs of the entire genome is possible," Wapner said. "That is possible even in prenatal acquired DNA. Now, it still is not ready to be offered clinically, because there are many, many more findings of unknown significance and it also has the ability to identify, at even a higher resolution, abnormalities."
In the 5 years Wapner and his team spent studying microarrays, tests were administered via chorionic villus sampling (CVS) at 10 to 13 weeks' gestation or amniocentesis at 16 weeks. One benefit of the microarrays was simply the detail of the information provided. If a piece of the chromosome breaks off, karyotyping could show the break.
But microarrays allowed the researchers to know if any DNA information was lost as a result. In his interview, Wapner discussed how the additional detail could be helpful in the instance of a problem that could be treated in utero.
"It would improve our ability to counsel parents when an abnormality is found in utero," he explained. "If we find an abnormality by ultrasound - for instance, a heart defect - that can go anywhere from a heart defect that's simply a heart problem that can be fixed to one that's associated with other genetic problems that would have different implications."
In terms of application of microarrays in healthcare, time could be their biggest advantage. The faster results are returned and determined accurate, the more time providers and parents have to make decisions about in utero or postnatal treatment.
The study identified the benefits of array-based testing over karyotypes, and Wapner's research team recommended that microarrays become a primary method of testing in prenatal medicine.
"The bottom line, I think, is that when we're offering tests that can give us incremental information about the fetus, they're always preceded by very careful counseling of the parent to make sure that they want this information and they understand what the implications are," Wapner said.
Having already cited the technology as a "stepping stone," Wapner emphasized the importance of deliberation in understanding the clinical implications of techniques like microarrays: "All of us have a responsibility as these new laboratory capabilities develop to carefully consider how we use them; to carefully consider how the information will be used."
For Further Reading
Wapner has authored and co-authored several peer-reviewed articles on microarray testing:
Crolla JA, Wapner R, Van Lith JM. Controversies in prenatal diagnosis 3: should everyone undergoing invasive testing have a microarray? Prenat Diagn. 2014;34(1):18-22.
Hillman SC, McMullan DJ, Hall G, Togneri FS, James N, Maher EJ, Meller CH, Williams D, Wapner R, Maher ER, Kilby M. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2013;41(6):10-20.
Wapner R, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367(23):2175-2184.
Michael Jones is a staff writer. Contact: firstname.lastname@example.org