Chromosomal Microarray Analysis OK for Prenatal Diagnosis

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have issued guidelines on the use of chromosomal microarray analysis (CMA) in prenatal testing. The guidelines were published in the December issue of Obstetrics and Gynecology.

CMA detects copy number variations (deletions and duplications) that are beneath the radar of conventional cytogenetics while also confirming aneuploidy. The technology detects genomic imbalances in up to 15% of children who have unexplained congenital anomalies, intellectual disability, or autism spectrum disorders but have normal karyotypes.

A variation of CMA that detects single nucleotide polymorphisms (SNPs) can indicate homozygosity (including stretches that suggest consanguinity), heterozygosity, and uniparental disomy. CMA may include DNA sequences known to cause syndromes or cover entire genomes.

Because CMA has been so valuable in pediatrics, researchers tested its use in prenatal diagnosis. In December 2012, a team from the Eunice Shriver National Institute of Child Health and Human Development published findings of a large cohort study comparing CMA with conventional karyotyping in prenatal diagnosis.

The new recommendations cite several advantages of CMA over standard karyotyping of cells obtained from amniocytes and chorionic villi cells: resolution is higher; CMA does not require that cells be cultured, speeding the process and enabling analysis of DNA after fetal demise; and CMA analysis is entirely automated and therefore may be more reliable than other methods that require interpretation of chromosome banding patterns.

The 2012 report demonstrated the accuracy of CMA and its ability to distinguish anomalies too small to be visualized in karyotypes. CMA is particularly valuable in detecting copy number variations or altered SNP patterns in cases of normal karyotypes but abnormal ultrasound findings, and it even detected abnormalities in fetuses with both normal karyotypes and ultrasound scans.

The test is not perfect, however. For example, CMA cannot detect all cases of mosaicism, balanced translocations, or inversions. In addition, the technique identifies copy number variations that are of unknown or uncertain clinical significance, which patients find distressing.

The recommendations support:

Use of CMA for fetuses with abnormal ultrasound findings having invasive prenatal diagnosis.
Either CMA or standard karyotyping for fetuses with normal ultrasound findings having invasive prenatal diagnosis.
CMA for women of any age, because the anomalies detected do not correlate to maternal age.
CMA as the method of choice to analyze genetic material in cases of fetal demise or stillbirth.
Not using CMA to evaluate first- and second-trimester pregnancy loss.
Pretest and posttest genetic counseling, delivered by a geneticist or genetic counselor. Documented informed consent must include discussion of findings of uncertain significance, consanguinity, nonpaternity, and adult-onset disease.

Obstet Gynecol. 2013;122.

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