By Russ Jelsema, M.D., Senior Medical Director, Women’s Health, Natera™
For every 150 babies born, one has a chromosomal abnormality.1 Until recently, we had no way to identify these abnormalities before birth. Innovations in obstetrics have enabled us to gather fetal genetic data, powerfully equipping pregnant women and their doctors to make more informed clinical decisions.
While the ability to detect genetically driven disorders before birth represents a major milestone in prenatal care, early techniques suffered limitations. Maternal serum screening tests were the best we had, but we all knew that they had many false positives, which resulted in unnecessary invasive procedures.
Therefore, the challenge has been to develop screening tests with fewer false positives, and thus the need for fewer invasive procedures. Improvements in technology through the use of cell free DNA, also known as non-invasive prenatal testing (NIPT), provide such a test. With NIPT, we now have a highly effective method for evaluating the risk for chromosomal abnormalities.
The ability to analyze fetal-placental DNA changes the landscape of prenatal genetic screening
NIPT evaluates fragments of placental DNA that are found in the maternal bloodstream.2 NIPT screening for chromosomal abnormalities is associated with a much lower false positive rate and much fewer invasive procedures than traditional serum screening. Furthermore, NIPT has false negative rates of less than 1% for common aneuploidies in both high-risk and average-risk pregnancies.3
Initially, NIPT was not offered to women of all ages because of perceptions that the positive predictive values (PPV) would be much lower for women under 35. However, evidence for the value of NIPTs for pregnant women of all risk levels has been demonstrated, with data showing that the PPV for NIPT for trisomy 21 is 80.9%, compared to 3.4% for maternal serum and NT methods.4
Based on this data, last year ACOG and SMFM changed their recommendations regarding prenatal screening guidelines to recommend that NIPT be offered to all women, regardless of age or baseline risk. Furthermore, ACOG and SMFM acknowledged that NIPT is the most accurate screening test for common fetal aneuploidies.5
The future of NIPT: SNP-based technologies offer unprecedented opportunities
The latest advance in NIPT technology has been the development of a single-nucleotide polymorphism (SNP)-based NIPT. This NIPT technology is able to distinguish the different sources (mother and baby) of DNA found in pregnancy and was recognized by ACOG Practice Bulletin 226 for its unique clinical capabilities.
SNP-based NIPT can detect triploidies, vanishing twins, maternal contribution, and molar pregnancies, making it a more accurate screening method than other NIPT methodologies.6 SNP-based NIPT also improves the accuracy of fetal sex predictions, which has clinical benefit in early identification of disorders of sexual development.7
ACOG bulletin, for the first time, also endorses NIPT for screening twin pregnancies, highlighting unique capabilities of SNP-based NIPT in twin pregnancies – detection of zygosity to help triage higher risk twin pregnancies and assessment of individual fetal fraction in dizygotic twin pregnancies.8
Given the support of our ACOG & SMFM colleagues to offer NIPT to all women, regardless of age or risk factors, now is the perfect time to make sure that you are offering NIPT to all of your patients.
For more information about SNP-based NIPT, please visit: www.natera.com/NIPTforall
- Practice Bulletin No. 163: Screening for fetal aneuploidy. Obstetrics and gynecology. 2016;127(5):e123-e137. doi:10.1097/AOG.0000000000001406
- Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound in Obstetrics and Gynecology. 2017;50(3):302-314. doi:10.1002/uog.17484
- Taylor-Phillips S, Freeman K, Geppert J, et al. Open accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: A systematic review and meta-analysis. BMJ Open. 2016;6(1):10002. doi:10.1136/bmjopen-2015-010002
- Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. New England Journal of Medicine. 2015;372(17):1589-1597. doi:10.1056/nejmoa1407349
- Screening for fetal chromosomal abnormalities. Obstetrics & Gynecology. 2020;136(4):859-867. doi:10.1097/AOG.0000000000004107
- Curnow KJ, Wilkins-Haug L, Ryan A, et al. Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test. American Journal of Obstetrics and Gynecology. 2015;212(1):79.e1-79.e9. doi:10.1016/j.ajog.2014.10.012
- Dhamankar R, DiNonno W, Martin KA, Demko ZP, Gomez-Lobo V. Fetal Sex Results of Noninvasive Prenatal Testing and Differences With Ultrasonography. Obstet Gynecol. 2020;135(5):1198-1206. doi:10.1097/AOG.0000000000003791
- Hedriana H, Martin K, Saltzman D, Billings P, Demko Z, Benn P. Cell-free DNA fetal fraction in twin gestations in single-nucleotide polymorphism-based noninvasive prenatal screening. Prenat Diagn. 2020 Jan;40(2):179-184.