DALLAS – Chromosomal microarray, or CMA, is as effective as karyotyping for identifying common aneuploidies during routine and high-risk prenatal screening, and it also provides clinically significant and relevant information in patients with a normal karyotype, according to findings from a prospective study involving more than 4,400 women.
The findings support a transition from the use of karyotyping to the use of CMA as the first tier test for invasive cytogenetic testing, Dr. Ronald Wapner said at the annual meeting of the Society for Maternal-Fetal Medicine.
Reporting on behalf of the Prenatal Microarray Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Dr. Wapner noted that the analyses were performed on 4,391 samples, of which about half were obtained by chorionic villus sampling and about half by amniocentesis. DNA extraction or microarray failed in 51 samples, for a CMA success rate of nearly 99%.
He reported the findings from 4,282 samples with nonmosaic karyotype results.
Indications for enrollment among the 4,401 women who participated in the study included advanced maternal age in about half of the patients, a positive first or second trimester screen in about 20%, and an abnormal ultrasound in about 25%, with "other" indications accounting for the remaining participants.
Of all cases with common autosomal or sex chromosome aneuploidy identified by karyotyping, 100% were confirmed by microarray testing, said Dr. Wapner, chief of maternal fetal medicine at Columbia University Medical Center, New York.
Eight of the samples were identified as mosaic by microarray testing, but none of those led to an incorrect diagnosis; interestingly, all eight were from chorionic villus samples, Dr. Wapner noted. "Therefore, we can say very comfortably that CMA is a 100% comparison with karyotyping for common autosomal and sex chromosome aneuploidies."
Consistent with what is known about the technique of microarray testing; however, none of the triploidy pregnancies were identified, but 15 of 17 were correctly called using maternal cell contamination results, he noted.
Among participants with normal karyotypes, 35 (0.9%) had a CMA finding included on a predetermined pathogenic list. Of 94 (2.5%) with another finding not on the list, about two-thirds were determined by a clinical advisory committee to be clinically relevant. Thus, 96 samples (2.5%) were found to have clinically relevant material beyond what was seen on the karyotype, Dr. Wapner said.
A break-down based on participant’s indication for testing showed that of cases with an ultrasound abnormality, 6% had additional clinically significant results on CMA despite a normal karyotype, and of those with advanced maternal age or a positive screen, 1.6%-1.7% had additional clinically significant results on CMA despite a normal karyotype.
The findings indicate that a transition from karyotyping to CMA for prenatal cytogenetic diagnosis is warranted, Dr. Wapner said. "But if we are going to use CMA in prenatal care, particularly, we will have to have an additional approach that will allow the detection of triploidy pregnancy, and there are many that are available," he added.
Also, the transition will require a very methodical, well-thought-out approach including development of standardized pre- and post-test counseling, and discussion of how to manage some of the unusual findings identified using CMA, he noted.
Dr. Wapner said he had no relevant financial disclosures.