By John C. Hobbins, MD

Professor, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora

Dr. Hobbins reports no financial relationships relevant to this field of study.

Synopsis: A single prenatal testing center with a large volume of patients has experienced a dramatic drop in the rate of chorionic villus sampling and amniocentesis after the introduction of noninvasive prenatal testing.

Source: Larion S, et al. Uptake of noninvasive prenatal testing at a large academic referral center. Am J Obstet Gynecol 2014;211:651.

Noninvasive prenatal testing (NIPT) has affected the logistics of screening for various forms of fetal aneuploidy, as well as the economics surrounding the delivery of NIPT to a large segment of the public.

Larion et al assessed how NIPT has affected the downstream need for invasive testing.1 They analyzed data regarding invasive procedures before and after the advent of NIPT. The study covered two time periods: the first being the 35 months prior to February 2012, when NIPT was first introduced in Virginia, and the second representing the next 16 months (March 2012-June 2013). During the first 4-month block of the “after” study group, NIPT was only offered to high-risk patients, but following a shift in policy, it was offered to all pregnant patients. During the last 16 months of the study (the after group), first trimester nuchal translucency and biochemistry testing (the standard “combined screen”) decreased by 48%, while NIPT rose by 55%. Prior to March 2012, the average rate of chorionic villus sampling (CVS) was 5.7 per month. This dropped dramatically during the next 4-month intervals to 1.8 per month, representing a 72% decrease from baseline rates prior to NIPT. Similarly, the amniocentesis rates decreased from pre-NIPT rates of 26 per month to 12 per month, representing a 52.5% drop in these invasive procedures.

Commentary

There is no doubt that the introduction of NIPT has changed the way we and patients think about the screening for, and the ultimate diagnosis of, fetal aneuploidy. In fact, our own statistics show even a more dramatic plunge in the number of invasive procedures done at our centers. This represents a huge spinoff bonus in patient care because the amniocentesis and CVS procedures are now being done for better reasons (and with a higher yield per procedure).

Today, there is a buffet of options for screening/diagnostic approaches to fetal aneuploidy, which include nuchal translucency (NT) alone, combined screening (NT and first-trimester biochemistry), NIPT, or the approach of yesteryear (usually in patients of advanced maternal age) CVS or amniocentesis. From a fetal risk standpoint, the last approach now seems inadvisable for most patients.

Since cost is also of concern today, screening first with a standard combined screen makes sense in low-risk patients, with NIPT being used as a second “contingency” option if the results are not reassuring. High-risk patients, however, could benefit from NIPT as a first-line approach to aneuploidy testing, with invasive testing being used for confirmation. Sonek and Cuckle have shown these approaches to be more cost effective, while maintaining a high detection rate.2Nevertheless, it is very likely that companies offering NIPT will soon be charging less for their services in order to be competitive in a potential market of 4 million pregnancies per year. Then it may be economically feasible to offer NIPT to all patients, which will set off a new set of logistical, ethical, and educational factors to manage.

It has been recommended that all patients with a positive NIPT result (as of now for trisomy 21, 18, 13, or XO) have confirmation of aneuploidy through invasive testing. However, we have had a few patients who have had positive NIPTs, as well as strong ultrasound evidence of aneuploidy, who have balked at the need for either CVS or amniocentesis prior to termination of pregnancy. Since this does involve cost and some discomfort, it is difficult to muster a strong argument against this stance under these specific circumstances. Nevertheless, without other supporting evidence, the false-positive rates, especially for trisomy 18 and trisomy 13, are high enough to warrant confirmation in the vast majority of cases. Also, an emerging concern is that patients whose fetuses have these two conditions, in particular, tend to have lower levels of fetal DNA in their circulations, causing a higher rate of “indeterminate” results. Since patients in this category have a risk as high as 1 in 5 for fetal aneuploidy,2 they also can benefit from invasive testing.

As the need for amniocentesis and CVS decreases, there will be fewer procedures available with which to train our clinicians. This will have the greatest impact on CVS-related complications, since loss rates, complications, and need for repeat insertions can vary according to the adequacy of training and the number of cases done per year by the individuals performing the procedures. In my opinion, you cannot adequately train an individual to do these procedures on a simulator. I can just see the wheels turning toward credentialing for yet another clinical activity.

References

  1. Larion S, et al. Am J Obstet Gynecol 2014;211:651.e1-7.
  2. Sonek JD, Cuckle HS. Ultrasound Obstet Gynecol 2014;44:621-630.