Noninvasive prenatal testing brings new options, opportunities, questions


New evidence, however, suggests that NIPT also is feasible in low-risk pregnancies.

For example, two studies in the July issue of Ultrasound in Obstetrics and Gynecology indicate that both routine and contingent implementation of NIPT for first trimester trisomy screening are feasible.

In one of the studies, Dr. M.M. Gil of King’s College Hospital, London, and his colleagues demonstrated that in 1,005 singleton pregnancies, routine NIPT for trisomies 21, 18, and 13 at 10 weeks’ gestation had a lower false positive rate than did the combined test performed at 12 weeks (0.1% vs. 3.4%), although abnormal results required confirmation using invasive testing.

"This study has shown that routine screening for trisomies by cfDNA testing at 10 weeks is feasible, allowing diagnosis of aneuploidies and the option of pregnancy termination within the first trimester," the investigators concluded (Ultrasound Obstet. Gynecol. 2013;42:34-40).

In the second study, which involved women with singleton pregnancies who underwent screening between March 2006 and May 2012, Dr. K.H. Nicolaides, also of King’s College Hospital, London, and his colleagues demonstrated that effective first trimester screening for Down syndrome can be achieved – with a 98% detection rate and an invasive testing rate below 0.5% – using contingent screening (Ultrasound Obstet. Gynecol. 2013;42:41-50).

"The results demonstrate that in contingent screening, a detection rate of 98% in fetuses with trisomy 21, at an overall invasive testing rate less than 0.5%, could be achieved by offering the cfDNA test to about 36%, 21%, and 11% of cases identified by first-line screening using the combined test alone, using the combined test with the addition of serum placental growth factor and alpha-fetoprotein, and using the combined test with the addition of placental growth factor, alpha-fetoprotein, and ductus venosus pulsatility index for veins, respectively," they said. "Screening for trisomy 21 by cfDNA testing contingent on the results of an expanded combined test would retain the advantages of the current method of screening, but with a simultaneous major increase in detection rate and decrease in the rate of invasive testing," they concluded.

Data also suggest that NIPT can be used successfully in twin pregnancies, albeit with the caveat that deeper sequencing may be necessary in these pregnancies, Dr. Bianchi noted.

These findings suggest that even wider implementation of NIPT is likely, she said, adding that there are major concerns about such implementation – not the least of which is fitting adequate pre- and posttest counseling into busy practices.

"It is not straightforward – there are multiple issues that need to be discussed," she said.

Questions also remain about the performance of the tests in normal- vs. high-risk pregnancies, she said.

Recently, a Blue Cross Blue Shield Technology Evaluation Center report concluded that NIPT meets the company’s criteria for both normal- and high-risk pregnancies, Dr. Bianchi noted.

"We’ll be hearing more about this in the coming year. Everyone is looking for more data," she said.

The results thus far – with more than 100,000 tests performed – undoubtedly have been encouraging. Since the integration of these tests into clinical practice began, many medical centers already are witnessing significant declines in the number of invasive procedures being performed for aneuploidy, Dr. Bianchi said, noting that such procedures have decreased by 34% in the first year at Tufts Medical Center, where NIPT is routinely offered as an option to high-risk women, and as an alternative to invasive procedures in average-risk women who test positive on traditional screening. Invasive procedures are strongly encouraged in those with aneuploidy detected on NIPT.

As a result of these outcomes, every aspect of the current standard of care is being questioned, Dr. Chitty and Dr. Bianchi wrote in their editorial. "For example, do we still need to measure maternal serum biomarkers, and what is the place of nuchal translucency measurement?" they asked.

The use of NIPT and the rapid advances taking place in the field, also raise important ethical questions.

Even before Sequenom introduced the MaterniT21 test to the market, the ethical implications of NIPT were being weighed. In a 2009 paper, Dr. Antina de Jong of Maastricht (the Netherlands) University and colleagues noted that although the introduction of NIPT would have some "ethically favorable consequences," such as the absence of iatrogenic miscarriage resulting from a test, earlier reassurance of a healthy fetus, a longer period for decision-making and the possibility of an early abortion, "which may be physically and psychologically less burdening and ethically less problematic because of presumed lower mortal fetal status," the possibility that NIPT would eventually include testing for a broader scope of abnormalities complicates the ethical issues.

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