The recent New England Journal of Medicine study has been reported by the media as meaning non-invasive prenatal screening is ready for the general population. The Society for Maternal-Fetal Medicine disagrees.
As covered in this post, the New England Journal of Medicine published a study by researchers affiliated with the NIPS lab Illumina (nee Verinata). The study was of a general population of patients. It found that NIPS had a positive predictive value of 45.5%, which is more predictive than traditional screening tests. The authors concluded that their results suggest that NIPS may be ready for the general population. The Society for Maternal-Fetal Medicine (SMFM), however, has issued a statement saying, in effect, “not so fast my friend:”
While this measured conclusion appears reasonable, the serious consideration that the authors propose requires further data, and the study by Bianchi et al has to be viewed in the context of its many limitations.
Those many limitations are identified by the SMFM as:
- The study only tested the positive predictive value for Trisomy 21 and 18, but all NIPS tests now also return results for Trisomy 13 and sex aneuploidies, whose positive predictive values remain unreported/unknown.
- The study compared NIPS with a variety of traditional screening methods, but only 3% had integrated screening, the screening with the highest accuracy of the traditional methods. Therefore, NIPS may not be more accurate than the most accurate traditional screening test.
- Traditional screening results also can suggest other health concerns beyond chromosomal, including concerns for the mother’s health. Those health issues may have a higher incidence among low risk moms than Down syndrome and other aneuploidies, making traditional screening more clinically useful in low risk populations (as was reported at the annual SMFM clinical meeting–more at this post).
- The study had a higher incidence rate for Down syndrome–almost double–than what is found in the natural general population. An article in the New England Journal of Medicine (yes, the same Journal as the Illumina study) just seven months ago raised concerns about NIPS labs reporting results from populations with unnaturally high incidence rates. Here again, is another study with an unnaturally high incidence rate used to justify wider implementation of NIPS.
- Associated with the concern of high incidence rates, the study had a rate of tests that returned no results that was far lower than what has been experienced in actual clinical practice.
The SMFM statement concludes:
this new report is not enough to change current ACOG and SMFM recommendations [of reserving NIPS for high risk pregnancies]. Given that just 8 aneuploidies were present in the entire cohort of patients, the true test performance is difficult to determine.
For all the excited reporting about the New England Journal of Medicine report, the SMFM statement demonstrates why skepticism and more research is still needed before NIPS is offered to all expectant mothers.