Genetics Societies Issue Recommendations for Fetal DNA Tests

Ricki Lewis, PhD

March 27, 2015

The Social Issues Committee of the American Society of Human Genetics and the Public and Professional Policy Committee of the European Society of Human Genetics published a position document online March 18 in the European Journal of Human Genetics that includes recommendations for using noninvasive prenatal testing (NIPT) based on screening maternal blood for cell-free DNA (cfDNA) in a responsible manner that embraces future applications.

Wybo Dondorp, PhD, an assistant professor in the Department of Health, Ethics, and Society at Maastricht University in the Netherlands, and colleagues wrote the initial draft of the statement. It extends past recommendations concerning NIPT using cfDNA to include ethical considerations. (NIPT is used synonymously with cfDNA testing, but technically, also includes ultrasound scanning.)

NIPT has been available since 2011 in several countries, including the United States, for detection of the major autosomal aneuploids (trisomies 13, 18, and 21). NIPT tests are more accurate for this indication and safer than invasive prenatal diagnostic techniques (amniocentesis and chorionic villus sampling). Extra chromosomes are detected using massive parallel sequencing of the cfDNA fragments, rather than traditional karyotyping. NIPT can also be used to sequence entire fetal genomes.

Pregnant women are typically referred for invasive diagnostic tests on the basis of advanced maternal age or the results of maternal serum biomarker analysis and fetal nuchal translucency thickness on ultrasound scans. The immediate goal of NIPT is to spare women from the invasive procedures that in the past would have been done simply on the basis of age.

However, false-positive NIPT results can arise from contamination with placental or maternal DNA, from a maternal tumor, or from a vanishing twin. Invasive diagnostic testing can confirm a chromosome imbalance detected with NIPT. False-negatives with NIPT are much less likely than false-positives, but can occur for a triploid fetus.

The committees note that the scope of NIPT will widen with the falling cost and time to sequence DNA, and already some testing companies are including sex chromosome anomalies and microdeletions among the tests they offer. Committee members were concerned that great expansion of the number of tests for each patient could increase the false-positive rate, which would counter the goal of avoiding more invasive prenatal diagnostic procedures. They also note that direct-to-consumer NIPT tests for fetal sex determination are available and can lead to sex-based pregnancy termination.

The committee advised that public programs not pressure women to terminate pregnancies found to have trisomies, which would also disturb disability rights organizations. "In order to avoid these ethical pitfalls, relevant policy documents stress that prenatal screening for fetal abnormalities is aimed, not at preventing the birth of children with specific abnormalities, but at enabling autonomous reproductive choices by pregnant women and their partners," the authors write.

Recommendations include:

  • Follow-up of a positive NIPT result with a confirmatory diagnostic procedure, preferably amniocentesis, for a woman considering termination.

  • Pretest counseling should ask patients whether they wish to receive secondary findings (chromosomal anomalies other than trisomies 13, 18, and 21).

  • NIPT should not be used to detect sex chromosome anomalies and microdeletions.

  • Public health programs should ensure the quality of the overall screening protocol, educate professionals who counsel patients, develop better evaluation tools, consider all whom the screening affects (including children born from screened pregnancies and people who live with the conditions that NIPT detects), and provide equitable access to screening.

  • NIPT should be expanded only to comprehensively evaluated serious congenital and childhood disorders.

One coauthor is a member of the Reproductive and Genetic Health Advisory Board for Illumina. Another coauthor is an employee of Bioscientia/Sonic Healthcare. The other authors have disclosed no relevant financial relationships.

Eur J Hum Genet. Published online March 18, 2015. Full text


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