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For decades, karyotyping has represented the gold standard for assessing fetal chromosomal status and investigating causes of stillbirth. Now, two multi-institutional teams have compared microarray technology with conventional karyotyping.
In the prenatal diagnosis study, >4000 women with indications including advanced maternal age (47%), abnormal ultrasound findings (25%), and abnormal aneuploidy screening results (19%) were assessed. Microarray resulted in successful analysis of fetal chromosomal status in 99% of attempts. Following a normal karyotype, microarray revealed clinically significant abnormalities in 6% of cases tested because of abnormal ultrasound findings and in 2% of cases referred for either abnormal Down syndrome screening results or maternal age. Although microarray assessment identified every instance of aneuploidy or unbalanced translocation detected with karyotyping, the newer technology did not identify balanced translocations or triploidy.
In the stillbirth study, microarray analysis was more likely than karyotyping to yield results (87% vs. 70%, P<0.001) and was more likely to detect genetic abnormalities (8% vs. 6%) in a sample of >500 stillbirths. In both settings, microarray testing yielded some findings of “uncertain clinical significance.”
Wapner RJ et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012 Dec 6; 367:2175. (http://dx.doi.org/10.1056/NEJMoa1203382)
Reddy UM et al. Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med 2012 Dec 6; 367:2185. (http://dx.doi.org/10.1056/NEJMoa1201569)
Comment
In recent years, microarray analysis has become the technology of choice to assess children with developmental disabilities or congenital anomalies. Although microarray analysis does not detect balanced chromosomal translocations, these events are rare and less likely to cause disease. The authors also point out that after 12 weeks' gestation, ultrasound reveals abnormalities in most triploid pregnancies. The primary advantage of microarray in assessing stillbirths is that nonviable tissue can be used. In both settings, interpreting genetic abnormalities of uncertain clinical significance can be vexing and will require close coordination between geneticists, counselors, practitioners, and laboratory directors. Taken together, these reports indicate that — despite its higher cost — microarray analysis will play an important role in chromosomal testing both for prenatal diagnosis and for stillbirth assessment.