New ACOG Guidelines Recommend cfDNA-Based NIPT for All Pregnancies, Not Just Risky Ones

The American College of Obstetricians and Gynecologists (ACOG) has revised its position on noninvasive prenatal testing (NIPT) and is now recommending prenatal aneuploidy screening for all pregnant patients regardless of age or other risk factors. ACOG previously recommended use of screening only in individuals 35 and older or with other known risk factors.

The Diagnostic Challenge

NIPT analyzes the free-floating cell-free DNA (cfDNA) fragments from the blood of a pregnant woman to estimate the risk that the fetus will be born with certain genetic abnormalities, the most common target being chromosomal disorders like Down syndrome that are caused by the presence of an extra or missing copy (aneuploidy) of a chromosome. Because the only blood drawn comes from the pregnant woman, the test poses no risk to the fetus.

Concerns about its predictive value has chilled utilization of NIPT for average-risk pregnancies. NPIT is used as a screening test estimating whether risks of certain genetic conditions are increased or decreased and cannot provide a definitive answer about whether a fetus actually has the condition, creating the need for confirmatory follow-up tests like amniocentesis. And as with other screening tests, NIPT carries the potential for false positives and false negatives—although the false-positive rate of cfDNA NIPT is significantly lower than with traditional serum protein screening with or without nuchal translucency ultrasound.

The New ACOG Recommendations

The headline of the new ACOG recommendations, which came out on August 17, is endorsement of screening for all pregnancies and removal of the previous 35-and-older and other-known-risk factor limitations. More precisely, ACOG endorses both serum protein screening and cfDNA NIPT assays but specifies that the latter are “the most sensitive and specific screening test for the common fetal aneuploidies.” At the same time, the recommendations call on physicians to be aware of the potential for false-positives and false-negatives results and that NIPT is “not equivalent to diagnostic testing.” According to the document, patients should have only one test—either NIPT or serum screen—and not have multiple tests performed simultaneously

ACOG also recommends that patients who get a positive screening test result for fetal aneuploidy undergo genetic counseling and a comprehensive ultrasound evaluation to confirm results.” Patients who get a negative screening test result should also be made aware that the negative result “substantially decreases their risk of the targeted aneuploidy but does not ensure that the fetus is unaffected.” When test results are uninterpretable or cannot be reported due to a laboratory test failure, the patient should be made aware that such results may be associated with elevated risk of aneuploidy and be offered comprehensive follow-up and diagnostic testing.

Takeaway

The broader new ACOG recommendations are welcome news for laboratories that currently offer cfDNA-based NIPT tests, including Natera whose share price shot up 15 percent on news of the new guidelines which are expected to boost use of the firm’s Panorama test for average-risk pregnancies just the way it did after the announcement of the previous guidelines endorsing ctDNA NIPT for high-risk pregnancies. Other big players in the ctDNA NIPT market include Roche (Harmony assay), LabCorp (MaterniT21 Plus test), Progenity (Innatal test) and Myriad Genetics (Prequel test).

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This article originally appeared in G2 Intelligence, Diagnostic Testing & Emerging Technologies, September 2020