A new genetic test has resulted in remarkably more applicable information than the current routine of prenatal testing, suggests a new study published in The New England Journal of Medicine.
The test uses microarray analysis to more effectively examine a fetus’s DNA than is currently possible with the karyotyping method, a visual examination of the fetus’s chromosomes.
The blinded trial, led by researchers from Columbia University Medical Center, consisted of 4,400 patients at 29 centers throughout the United States. It took them four years to collect all the data. The study included women of late maternal age and those whose fetuses were shown to be at an elevated risk for Down syndrome, to have structural abnormalities, or other problems according to an early screening.
This is the first and only study to compare karyotyping with microarray in a blinded head-to-head trial prospectively. The trial found that microarray analysis, which looks at the comparison between normal DNA and a fetus’s DNA, did as well as karyotyping in recognizing common aneuploidies.
Aneuploidies is the presence of an irregular number of chromosomes, either an extra or a missing chromosome, that can cause genetic abnormalities such as Edwards syndrome and Down syndrome. Microarray analysis was also able to reveal additional abnormalities that were not picked up by karyotyping.
Among fetuses in which a structural or growth abnormality had been discovered via ultrasound, microarray detected clinically important chromosomal deletions or duplications in one out of 17 cases (6 percent) that were not seen using karyotyping.
In the women with advanced maternal age or positive screening results, microarray analysis detected an abnormality in one out of every 60 pregnancies (1.7 percent) that when tested using karyotyping said it was normal.
Ronald J. Wapner, MD, professor and vice chairman for research at the Department of Obstetrics and Gynecology at CUMC and director of reproductive genetics at NewYork-Presbyterian/Columbia, and principal investigator said, “We hope that in the future, when microarray can be done non-invasively, every woman who wishes will be offered microarray, so that she can have as complete information as possible about her pregnancy.”
In a separate paper appearing in the same issue of NEJM the topic of microarray use in stillbirth is addressed. Results showed that microarray created a clinically important result in 87 percent of 532 cases, which were examined with microarray and karyotyping. In comparison, regular ways for analyzing a stillbirth, including karyotyping, have been shown in earlier studies to unsuccessfully return information in 25-60 percent of cases.
Study senior author, Brynn Levy, MSc(Med), PhD, associate professor of pathology and cell biology, and co-director of the Division of Personalized Genomic Medicine at CUMC, and director of the Clinical Cytogenetics Laboratory at NewYork-Presbyterian/Columbia, said:
“Microarray was significantly more successful at returning clinically relevant information because, unlike karyotyping, it does not require cultured cells. Viability does not come into play at all – DNA can be extracted from tissue that is no longer living. Not being able to explain why a stillbirth occurred can be very hard for families. These findings are important because they give us a significantly more reliable method to provide information to families and their physicians.”
The likelihood of obtaining more results is the most attractive benefit of using microarray analysis instead of karyotype analysis. It can be extremely helpful in stillbirth cases when karyotype has failed or when a birth defect is present. One potential hurdle could be the cost of microarray analysis which is considerably higher than karyotyping.
Both techniques, microarray and karyotyping pinpoint important information about conditions that can be life-threatening for a newborn or that can mean a potential health risk that could be treatable. All the current genetic testing like karyotyping, as well as microarray analysis could also have findings whose consequences are unknown.
Dr. Wapner explained:
“While the vast majority of abnormalities found with microarray are associated with known conditions, not all are. But with time, knowledge and understanding of what these abnormalities mean will continue to grow. When we started this study five years ago, the incidence of findings we did not understand was about 2.5% – now, with more information, that has fallen to 1.5%.”
Phase two of the microarray study is currently underway. Dr Wapner has begun a five-year study to look at children born to mothers who underwent microarray and learn the clinical meanings of micro-deletions or duplications that still remain a mystery.
Dr. Wapner concluded:
“Genetic medicine is about obtaining genomic information about an individual and predicting what affect it will have on that person. But we are all different, so genetic abnormality in one person may behave differently than in someone else. For example, an inherited disease could be mild in the mother but severe in her child. We are studying what these mean clinically, and science continues to catch up with our ability to obtain the information.”
In 2008, researchers from Baylor College of Medicine reported on an array (chip) that can rapidly detects disorders chromosomal abnormalities, including Down Syndrome. They described the array as an effective tool in prenatal diagnosis.
Written by Kelly Fitzgerald