The application of non-invasive prenatal screening using cell-free DNA in general risk pregnancies

Newswise – BETHESDA, Md., May 24, 2022 /PRNewswire/ — The American College of Medical Genetics and Genomics (ACMG) has published its highly anticipated second evidence-based systematic review (SER): “The application of non-invasive prenatal screening using cell-free DNA in general risk pregnancies.”

Non-invasive prenatal screening with cell-free DNA (cfDNA), also known as NIPS, was developed more than a decade ago and has rapidly become part of routine prenatal care in many parts of the world. NIPS is a simple blood test that is very accurate in detecting Down syndrome and several other chromosomal disorders. It is performed any time after 10 weeks of pregnancy. It identifies the fragments of the placenta that circulate in the maternal blood. These fragments come from the new pregnancy and therefore identify the chromosomal composition of the fetus. This test is used worldwide, but in the United States insurance coverage limits who is eligible to receive this test as a covered benefit. Many insurers only cover those most at risk, such as patients of advanced maternal age.

“We are pleased to report this systematic review of the evidence on cell-free DNA screening in pregnancy in a primarily general at-risk population to consolidate recent data available on various types of aneuploidies, twin pregnancies, maternal conditions and cost considerations regarding this test,” said co-author Nancy C. Rose, MD, FACMG. “We hope this report will inform public health policy in this area of ​​care.”

To determine whether scientific evidence would support a recommendation to offer NIPS in general risk pregnancies, the ACMG performed a systematic review of the evidence. (A SER focuses on a specific scientific question and then identifies, analyzes, and summarizes the results of relevant studies.) Clinical and laboratory geneticists, a genetic counselor, and methodologists at ACMG developed research questions to guide the research. These questions included determining the performance of the NIPS test in screening for the most common chromosomal disorders (Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13)) in singleton pregnancies. and twins. Additionally, the researchers wanted to determine how well NIPS worked in screening for sex chromosome abnormalities, copy number variant disorders like DiGeorge syndrome, or other rare chromosomal trisomies. Additional questions focused on the impact of genetic counseling, the economic impacts associated with NIPS, and the ability of NIPS to detect maternal conditions, such as cancer.

Eighty-seven studies were included in this systematic review of the evidence. The NIPS was very accurate in identifying sex chromosome abnormalities (>99%) and the most common trisomies in single and twin pregnancies.

This systematic review of the evidence found that the accuracy, positive and negative predictive values ​​of the NIPS, and overall test performance are extremely high for trisomies 13, 18, and 21 – higher than the most commonly used prenatal screening options – and are not limited to specific time windows during pregnancy.

Although the performance of the NIPS test has varied for other conditions, its high accuracy for the most common disorders means that fewer pregnant women can be mislabeled as high risk and need confirmatory testing. Overall, the results of this evidence review demonstrate that the performance of the NIPS test is superior to that reported for traditionally used screening methods. This information can be used to establish new standards of clinical care in the United States.

Co-author Marco L. Leung, PhD, FACMG said, “This SER validates the high sensitivity and specificity of NIPS in detecting common trisomies, as well as the variable performance in rare autosomal trisomies and number-number variants. copies. This SER can serve as a valuable resource for laboratories optimizing their NIPS assays, and for clinicians evaluating the use of this technology in their medical practices.

The SER concludes that the use of cell-free DNA is the most effective screening test for autosomal trisomies 21, 18 and 13 in single and twin gestations, with both high detection and low false positive rates. Although less accurate for sex chromosome aneuploidies, rare autosomal trisomies, and copy number variants, it is the only prenatal laboratory test capable of identifying them at present. Despite its accuracy, NIPS by cfDNA is a screen for which confirmation of a positive screening test with a diagnostic procedure is still indicated.

“In addition to providing the evidence base for an upcoming ACMG guideline, this systematic review of the evidence is a remarkably comprehensive study that stands on its own merits,” said ACMG CEO Max Muenke, MD, MBA, FACMG.

About the American College of Medical Genetics and Genomics (ACMG) and ACMG Foundation

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical professional organization dedicated solely to improving health through the practice of medical genetics and genomics , and the only medical specialty society in the United States that represents the full spectrum of medical genetics disciplines in a single organization. ACMG is the largest membership organization specifically for medical geneticists, providing education, resources, and a voice for more than 2,500 clinical and laboratory geneticists, genetic counselors, and other healthcare professionals, including nearly 80 % are certified in medical genetics specialties. ACMG’s mission is to improve health through the clinical and laboratory practice of medical genetics as well as advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics across medicine and health care, which will result in improved personal and public health outcomes. Four overarching strategies guide the work of ACMG: 1) Strengthen and expand ACMG’s position as a leading and leading authority in the field of medical genetics and genomics, including clinical research , while educating the medical community about the important role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) securing and developing the professional workforce for medical genetics and genomics; 3) defend the specialty; and 4) provide top-notch education to members and non-members. Genetics in medicine, published monthly, is the official journal of the ACMG. the ACMG website, offers resources including policy statements, practice guidelines, educational programs and a “Find a Genetics Service” tool. ACMG’s educational and public health programs depend on charitable donations from corporations, foundations, and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

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