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Noninvasive Prenatal Screening Can Replace Current Trisomy Screening in All Age Groups, ACMG Says

NEW YORK (GenomeWeb) – Noninvasive prenatal screening from cell-free DNA is ready to replace conventional screening for trisomies 21, 18, and 13 in most women, and may have a role in screening for sex chromosome aneuploidy and selected copy number variants, according to a new position statement published today by the American College of Medical Genetics and Genomics.

The document, appearing in Genetics in Medicine, replaces ACMG's original 2013 policy statement on noninvasive prenatal screening (NIPS). In that publication, ACMG had stated that NIPS for fetal aneuploidy "has arrived" but that "there is room for refinement." The new statement, published by the ACMG Noninvasive Prenatal Screening Work Group, makes a number of key recommendations on the clinical use of NIPS, also known as NIPT, both for healthcare providers and testing laboratories. 

Specifically, the document discusses patient education on prenatal screening and diagnostic options; use of NIPS in different pregnancy risk groups and reporting by laboratories; use of NIPS for conditions other than the three most common aneuploidies, including sex chromosomal disorders and copy number variations; how to avoid and manage no-calls; and special conditions, such as twin pregnancies and incidental findings. In addition, it lists a number of third-party resources for patient and healthcare provider education on genetic conditions and related topics.

"Clinical validation strongly suggested that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes," wrote the authors, led by Anthony Gregg at the Department of Obstetrics and Gynecology at the University of Florida, adding that "objective measures of clinical utility support this." In particular, NIPS can be applied across the maternal age spectrum and throughout pregnancy, beginning at 9 to 10 weeks of gestation, as long as the patient is not significantly obese, they wrote.

However, healthcare providers need to have "a thorough understanding of patient preferences," and be able to educate patients about the limitations of available tests.

In addition, they noted that "although clinical utility studies are limited, they point to a role for NIPS in sex chromosome aneupoloidy screening and screening for selected CNVs," in particular when the live birth frequency of those conditions is equal to that of currently screened disorders, and when the test metrics reach those of well-established prenatal screening approaches.

Specifically, ACMG recommends that patients should be informed early in pregnancy about different testing options, including diagnostic and screening approaches.

Pregnant women need to know that NIPS is the most sensitive screening option for the three traditionally screened trisomies. If they obtain a positive NIPS result, they should be referred to a genetic professional and be offered diagnostic testing.

Testing laboratories should clearly state the detection rate, specificity, positive predictive value, and negative predictive value for all conditions screened, both in their marketing materials and on their report, and patients with positive results should obtain a patient-specific PPV. In addition, the report should contain the fetal DNA fraction, which determines whether the results are reliable.

In cases of a no-call due to low fetal fraction, where the test did not yield a result, ACMG recommends diagnostic testing rather than a second NIPS test. Significantly obese women, who often have a low fetal DNA fraction, should be offered non-NIPT aneuploidy screening right away.

ACMG further recommends that all pregnant women be informed about the availability of NIPS for sex chromosome aneuplodies and for clinically relevant CNVs, though providers should deter patients from selecting the former for the sole purpose of fetal sex determination.

The College does not recommend the use of NIPS for rare chromosomal aneuplodies and for genome-wide CNV screening – for the latter, it recommends diagnostic testing.

In twin or other multiple pregnancies, or when donor oocytes were used, ACMG recommends contacting the testing laboratory regarding the validity of their NIPS for those conditions.

Patients should also be informed about the possibility of incidental findings, such as maternal genomic imbalances.