What The NYTimes Got Wrong On Prenatal Screening

On January 1, The New York Instances printed an article, “When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong”, adopted by a dialogue with the writer on their fashionable The Every day podcast entitled, “An Investigation Into Flawed Prenatal Tests.” As a genetic counselor who runs a digital well being firm, I’ve watched from afar the sphere of prenatal screening rework tremendously. As I listened to the podcast after which learn the article on this matter, I used to be shocked on the inaccuracies in each the podcast and the article on the NYTimes.  

First, some background. There are lots of assessments that expectant dad and mom and their clinicians can use throughout being pregnant to find out if the fetus could have a distinction in chromosome quantity (larger or fewer than the standard 46 chromosomes) or construction.  A few of these assessments are screening assessments, and a few are diagnostic assessments. The important thing phrase on this dialogue, which was primarily lacking from the NYTimes items, is ‘screening’. In an imperfect analogy, take into consideration the screening you expertise each time you board an airplane in the US. You stroll by way of a detector and your carry-on luggage are scanned to find out in case you are bringing something on board that isn’t allowed. That’s the screening. If the detector beeps, you progress to the subsequent part of detection during which you might be patted down, a wand is used, or your luggage are opened and searched. That’s akin to diagnostic testing. Usually the diagnostics exhibits that we forgot to take away our telephone or a belt buckle – that does not imply that the screening was improper. The screening did its job. It screened out an individual who required additional research. 

For a few years there have been solely diagnostic assessments accessible to detect chromosomal abnormalities- amniocentesis (“amnio”) and chorionic villus sampling (CVS). These assessments had been usually provided to pregnant individuals who could be 35 or older at supply as a result of they’re statistically at greater danger to have a fetus with Down syndrome and different chromosome problems.  Throughout an amnio, a needle is inserted by way of the belly wall into the uterus to extract a number of teaspoons of the amniotic fluid surrounding the fetus. From this fluid, cells that the fetus has sloughed off throughout growth are collected. Throughout a CVS, a pattern of the placenta is eliminated by way of the cervix or stomach. With each amnio and CVS, testing is completed to find out what number of chromosomes are current within the fetus. These assessments are extremely correct and diagnostic, however are additionally invasive and related to some dangers, together with a small (<1%) danger of miscarriage. 

Over time, non-invasive screening research had been developed that had been simpler and safer for pregnant sufferers. Early variations of those screens concerned taking a blood pattern from the pregnant individual’s arm and utilizing biochemical markers from the serum to estimate the probability that the fetus had a chromosome abnormality or particular start defects. If the display screen confirmed elevated danger, these pregnancies then certified for diagnostic testing, comparable to amnio or CVS. These screening research improved and ought to be provided to all pregnant individuals. Notably, extra correct expertise referred to as cell-free DNA screening, additionally known as non-invasive prenatal screening (NIPS), was developed that would detect items of placental/fetal DNA within the maternal serum from a easy blood draw.  NIPS remains to be a screening (not diagnostic) check, however as a result of it analyzes DNA from the being pregnant, it’s extra dependable for figuring out danger of a chromosome abnormality than the older serum testing that checked out biochemical markers alone. In truth, NIPS is extremely correct in screening for further chromosomes, as seen in circumstances comparable to Down syndrome.

As famous within the NYTimes article, NIPS is much less dependable at pinpointing different uncommon findings, comparable to microdeletions and microduplications (that means {that a} small piece of a chromosome is lacking or duplicated).  In truth, for microdeletions the expertise is non-specific sufficient that most individuals who come again with a high-risk display screen will in reality not have a fetus with that syndrome. Screening research, that are utilized throughout all areas of medication, are designed to display screen many sufferers as a way to discover a small variety of individuals at elevated danger. Screening is just not diagnostic testing.

Regardless that screening and testing will not be synonymous, the phrases had been conflated all through the NYTimes article and the podcast. The significance of this error can’t be overemphasized. Each repeatedly acknowledged that NIPS outcomes had been “improper” if the diagnostic check didn’t mirror the identical discovering because the screening device. This blunder was repeated all through the article, the podcast, and within the title of each. The authors claimed that genetic counselors say that “medical doctors could not perceive how poorly the assessments work.” These screening instruments don’t work poorly, nonetheless, if the clinician and affected person perceive how they’re for use and interpreted. Sufferers should obtain correct data earlier than they’ve NIPS. That counseling should embody the truth that NIPS is not supposed to detect fetal intercourse, which attracts many individuals to this expertise, however as a screening device to find out if that being pregnant could warrant extra diagnostic testing as a result of elevated danger of a genetic situation.

The genetic counselors I interviewed for this text, who specialise in reproductive genetics and prenatal testing, had a distinct tackle this topic from those that had been cited on this article.  One counselor felt it unlucky that the NYTimes selected to focus on solely the experiences of sufferers with a “false constructive” display screen, with out analyzing the efficiency enchancment NIPS presents over earlier variations of prenatal screening.  One other medical prenatal genetic counselor, Carly Bennett, factors out that enhancements in NIPS have led to an general lower in invasive, diagnostic testing. 

One other genetic counselor highlighted the suggestions of the American College of Obstetricians and Gynecologists that pre- and post-test counseling is crucial for any type of prenatal genetic analysis, be it a screening or diagnostic process. The authors of the NYTimes article famous that there aren’t sufficient licensed genetic counselors to see each pregnant affected person each earlier than and after screening and testing. That is true. However we will encourage the usage of telehealth genetic counselors and digital instruments that multiply their attain, in order that correct details about what to anticipate from a screening device is on the market to each affected person and each clinician, and that sufferers with a constructive display screen or check have instant entry to correct genetic counseling data. And we should be certain that genetic counseling providers and digital instruments are coated by CMS and different payers in order that sufferers have entry to not solely screening and diagnostic assessments, however in order that they and their well being care suppliers can perceive these instruments and their outcomes.

Licensed genetic counselor Amanda Luedecke identified that accumulating correct consequence information on all sufferers who’ve an irregular display screen is difficult and laboratories typically can not acquire that data. For that purpose, the result information introduced could also be incomplete and inaccurate. Luedecke additionally highlighted that sufferers who do obtain an irregular display screen could then be candidates for insurance coverage protection of extra ultrasounds. For instance, such ultrasounds are extra probably establish to coronary heart defects, if current, permitting the affected person the chance to satisfy with a pediatric heart specialist and to ship in a middle with a pediatric surgeon, if obligatory. For sufferers who’re confirmed to have a fetus with an irregular discovering, they’ve the choice of termination, or persevering with the being pregnant understanding their future baby’s analysis and using early intervention providers instantly, maximizing their potential.  These households can be recommended whether or not the situation is, or is just not, hereditary —- permitting them to grasp their probability of getting one other baby with the identical situation.

The authors of this text did shine a lightweight on a number of subjects which are worthy of examination. Nevertheless, the repeated use of inflammatory language detracted from their goal. For instance, the comparability of this expertise in any method to that of Theranos was inappropriate given the lots of of peer-reviewed articles printed on this topic. The truth that the Theranos founder was simply discovered guilty on four counts of fraud makes this reference much more egregious.  However, we must always study the next necessary points with care: What’s the screening threshold that should be reached earlier than a screening device is marketed and launched for medical use? Given the constraints of NIPS in sure areas, like microdeletions, is it unfair to alarm many expectant dad and mom to search out a number of genetic diagnoses? Are firms being incentivized to roll out screening instruments earlier than they’re prepared as a result of they’re accumulating some huge cash from insurance coverage firms to take action?  Is the advertising being utilized by these firms correct or misleading? Ought to these areas be extra tightly regulated? These are all questions very a lot price asking. As one other genetic counselor identified, we must also be analyzing well being fairness entry in reproductive genetics. Are these screening instruments, and the follow-up diagnostic testing which may be wanted, being provided to all teams of pregnant sufferers, or primarily the white and the rich?  Are sufferers ending up with massive payments they didn’t comply with after NIPS and follow-up diagnostics?

In closing, when sufferers and their clinicians perceive NIPS and it’s used and interpreted precisely, this expertise could be extremely useful to the households who need details about whether or not their fetus could have a chromosome abnormality. Licensed genetic counselors can and ought to be used to assist sufferers and their clinicians perceive NIPS, and can be found in individual, by way of telehealth, and thru digital instruments which are scalable and inexpensive.