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Noninvasive prenatal screening or advanced diagnostic testing: caveat emptor

American Journal of Obstetrics and Gynecology, Volume 215, Issue 3, September 2016, Pages 298 - 305

The past few years have seen extraordinary advances in prenatal genetic practice led by 2 major technological advances; next-generation sequencing of cell-free DNA in the maternal plasma to noninvasively identify fetal chromosome abnormalities, and microarray analysis of chorionic villus sampling and amniotic fluid samples, resulting in increased cytogenetic resolution.

Noninvasive prenatal screening of cell-free DNA has demonstrated sensitivity and specificity for trisomy 21 superior to all previous screening approaches with slightly lower performance for other common aneuploidies. These tests have rapidly captured an increasing market share, with substantial reductions in the number of chorionic villus sampling and amniocentesis performed suggesting that physicians and patients regard such screening approaches as an equivalent replacement for diagnostic testing. Simultaneously, many clinical programs have noted significant decreases in patient counseling.

In 2012 the Eunice Kennedy Shriver National Institute of Child Health and Human Development funded a blinded comparison of karyotype with the emerging technology of array comparative genomic hybridization showing that in patients with a normal karyotype, 2.5% had a clinically relevant microdeletion or duplication identified. In pregnancies with an ultrasound-detected structural anomaly, 6% had an incremental finding, and of those with a normal scan, 1.6% had a copy number variant.

For patients of any age with a normal ultrasound and karyotype, the chance of a pathogenic copy number variant is greater than 1%, similar to the age-related risk of aneuploidy in the fetus of a 38 year old. This risk is 4-fold higher than the risk of trisomy 21 in a woman younger than 30 years and 5- to 10-fold higher than the present accepted risk of a diagnostic procedure. Based on this, we contend that every patient, regardless of her age, be educated about these risks and offered the opportunity to have a diagnostic procedure with array comparative genomic hybridization performed.

Key words: array comparative genomic hybridization, cell-free fetal DNA, chorionic villus sampling, fetal chromosome abnormalities, maternal serum combined screening, next-generation sequencing.

Footnotes

a Comprehensive Genetics PLLC and Department of Obstetrics and Gynecology, New York, NY

b Mt Sinai School of Medicine, New York, NY

c Columbia University College of Physicians and Surgeons, New York, NY

Corresponding author: Mark I. Evans, MD.

Dr Evans is a consultant for Perkin Elmer. Dr Wapner has received research monies from the National Institutes of Health, Sequenom, Natera, and Ariosa. Dr Berkowitz reports no conflict of interest.