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Value of Noninvasive Prenatal Testing in Pregnant Women
Orlando—Noninvasive prenatal testing (NIPT) for fetal aneuploidy is a significantly better approach to prenatal screening and is likely to become the first tier test for all women, regardless of their prior risk, according to Peter Benn, PhD, DSc, department of genetics and genome sciences, University of Connecticut Health Center, who spoke on the topic during a session at the NAMCP forum.
Approximately 70% of women receive conventional screening such a maternal serum biochemical tests and fetal ultrasound markers to detect possible genetic abnormalities. However, data showed that the majority of patients with a positive result are not affected (false-positive) and undergo unwanted tests with inherent risk for unnecessary miscarriage, said Dr. Benn.
Two methods of NIPT have been developed and commercialized. In the first approach, fetal chromosome copy number is determined by comparing the number of sequence reads from the chromosome(s) of interest to those from reference chromosomes. The second approach entails targeted amplification and sequencing of single-nucleotide polymorphisms (SNPs), according to a study by Dar and colleagues [Am J Gynecol. 2014;211(5):527. e1.e17]. The counting method identifies the relative excess DNA for the trisomic chromosome. However, Dr. Benn noted that trisomy in the mother versus the fetus cannot be distinguished. The SNP-based method identifies trisomy, the parental origin, and recombination. SNPs provide a unique characterization (color) for each chromosome. Fetal chromosomes are not identical to parent chromosomes due to the recombination, he explained.
Studies have shown the clinical value of SNP-based NIPT. Dr. Benn referred to the Dar and colleagues study that sought to report on laboratory and clinical experience following 6 months of clinical implementation of an SNP-based NIPT aneuploidy test in high-and low-risk women. Samples that passed quality control (n=28,739) were analyzed for trisomy 21, trisomy 18, trisomy 13, and Monosomy X (also known as Turner syndrome). Within 17,885 cases included in the follow-up analysis for any of the 4 tested conditions, outcome information revealed 184 true positives and 38 false positives. The findings yielded an 82.9% positive predictive value (PPV) and a 90.9% PPV for trisomy 21.
Opinion statements published by national and international professional societies provide guidance for offering NIPT in pregnant women, including the American College of Obstetricians and Gynecologists, International Society for Prenatal Diagnosis, American College of Medical Genetics, and European Society of Human Genetics (ESHG)/American Society of Human Genetics (ASHG). For example, the recently published joint ESHG/ASHG position statement stated: “With recent publications sug- gesting equally good test performance in lower-risk populations, and depending on the healthcare setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible, including NIPT as an alternative first-tier test” [Eur J Hum Genet. 2015; DOI: 10.1038/ejhg.2015.56.]
A barrier to greater utilization of NIPT is a perceived increase in overall costs. Dr. Benn concluded the forum with a discussion on the cost-effectiveness of NIPT. He cited a study he and colleagues conducted that is currently in submission. The primary goal of the study was to establish the per-case cost of NIPT that would be cost neutral to the US healthcare system. The researchers used a decision-tree model for conventional and NIPT testing for trisomy 21, trisomy 18, trisomy 13, and Monosomy
X. The study, based on the US pregnancy population for 2012, took into consid- eration maternal age, cost of screening, all-related follow-up testing, and care for an affected child. Dr. Benn said that the model predicts NIPT is associated with large reductions in affected births, invasive tests, and procedure-related losses. The findings showed that NIPT can be cost neutral if the cost is ≤$744 for the general population.
“The healthcare benefits of NIPT are not confined to high-risk women and many providers feel they are obligated to offer NIPT to all women,” he said. “If NIPT can be provided for <$744 for a total US pregnancy population, there is no net increase in healthcare costs.” He noted, “The analysis does not include the intangible value of early diagnosis and reassurance.”—Eileen Koutnik-Fotopoulos
