Non-Invasive Prenatal Testing (NIPT) has exploded over the last 5-7 years, transforming an industry seemingly in the blink of an eye. But what exactly is it and how is reality different from the NIPT testing expectations? Have we improved patient safety with it?
Let us start with what NIPT testing is. As cells degrade to allow for new cells, the DNA from the degraded cells floats in the blood stream. This floating DNA is called cell-free DNA or cfDNA. When a mother is pregnant, the placental cells which are usually representative of the fetus being carried, also turnover during pregnancy and the cfDNA ends up in the mother’s blood stream to be filtered out by the kidneys1. We can test that placental cfDNA in the mother’s blood to screen for genetic abnormalities in the fetus.
After 10 weeks gestation, 10-15% of the cfDNA circulating in the mother’s blood is from the placenta2. Most NIPT companies ask to wait until 12 weeks to do the test incase gestational dates are incorrect to ensure there is sufficient placental cfDNA to give accurate results. Based on the percentage of placental cfDNA circulating being 10-15%, sequencing the cfDNA can then provide genetic information regarding the fetus including sex and most common genetic conditions.
For example, if Y chromosomes are found circulating in the mother’s blood stream, and the pregnancy is a single-fetus pregnancy, then the fetus is male. If the mother is a carrier of cystic fibrosis having mutations in the CFTR gene, her own cfDNA would have 50% genetic mutation. If her cfDNA has CFTR mutations in over 60% of the identified cfDNA, then the fetus is likely affected by cystic fibrosis. Since this is based on the assumption of 10-15% cfDNA being representative of the fetus, cfDNA diagnostics are considered screens for most genetic testing3. Additional testing, which may include an amniocentesis or waiting until birth for the confirmatory testing, would be needed for a definitive diagnosis. This confirmatory step is critical, especially is the mother is considering ending the pregnancy4.
Besides understanding that NIPT is a screening test, other factors must also be considered. Pregnant morbidly obese patients should wait until 12 weeks gestation for NIPT testing to ensure at least 10% circulating cfDNA is placental2. Test is most accurate for single-fetus pregnancies; the introduction of multiple fetuses reduces the overall sensitivity and specificity for the genetic disorders1. This can be issue with an abnormal vanishing twin where NIPT cannot distinguish between chromosomal triploidy and remnant cfDNA from a vanishing twin1. Finally, maternal or placental mosaicism can also cause false-positive NIPT results1.
Overall, like all other laboratory testing, NIPT must be interpreted within its limitations. The benefits of having the minimally invasive screening test include reduced patient anxiety and reduced procedure-related miscarriage as compared to amniocentesis procedures, reduced overall cost of care, and more patient screening compliance5. Being able to screen more pregnancies than ever before with minimal risk to patient safety has elevated this test to a clinical practice game changer. NIPT has largely replaced amniocentesis and the risky procedure is now only done when absolutely necessary. The positive benefits of implementing NIPT screening far exceed the testing limitations and testing limitations can be appropriately mitigated with clinician and patient education.
- Liehr T. Non-invasive Prenatal Testing, What Patients Do Not Learn, May Be Due to Lack of Specialist Genetic Training by Gynecologists and Obstetricians? Frontiers in Genetics, 17 June 2021. https://doi.org/10.3389/fgene.2021.682980
- Hui L, Bianchi DW. Fetal fraction and noninvasive prenatal testing: What clinicians need to know. Prenatal Diagnosis, 10 Dec 2019. https://doi.org/10.1002/pd.5620
- Hixson L et al. An Overview on Prenatal Screening for Chromosomal Aberrations. Journal of Laboratory Automation. 13 Jan 2015. https://doi.org/10.1177/2211068214564595
- Kater-Kuipers A et al. Rethinking counselling in prenatal screening: An ethical analysis of informed consent in the context of non-invasive prenatal testing (NIPT). Bioethics. Sept 2020; 34(7) 671-678. https://doi.org/10.1111/bioe.12760
- Beulen L et al. The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology. Nov 2014. 182:53-61. https://doi.org/10.1016/j.ejogrb.2014.08.028