Author: Stephanie Anderson Edited by: Ruchi Maniar
As of 2016, the fertility rates in the U.S have dropped to the lowest it ever been according to the US Center for Disease Control and Prevention (CDC). For one particular group of women in the age range of 30s-40s however, the rate has steadily increased since the 1990s. Research suggests that maternal age may be considered a risk factor that contributes to chromosomal abnormalities in infants (1). Due to chromosomal abnormalities, congenital malformations, etc. the amount of research and technological advancements in genetics has been life-changing. There are techniques to detect such chromosomal abnormalities such as Down's Syndrome (trisomy 21) or Edward’s Syndrome (trisomy 18) but they come with a risk: spontaneous fetal death or miscarriage due to invasive diagnostic procedures by amniocentesis or chorionic villus sampling (2). Now the exciting news is that there is a new non-invasive screening called cell-free fetal DNA that can detect chromosomal abnormalities and much more.
Cell-free fetal DNA (cffDNA) circulating in maternal blood was discovered back in 1997 (3). This major discovery opened up doors to new research which included the ability to screen for chromosomal defects in fetus' without being invasive and we know that at times - less is more. This new approach allowed physicians to assess the actual risk for certain chromosomal defects of a developing baby before determining whether or not a more invasive procedure is needed to confirm a diagnosis. The procedure is simple and fast. Maternal blood sample is drawn and then the cffDNA is analyzed for certain genetic markers. There are a range of DNA markers that can be screened for that include trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, fetal rhesus, fetal sex and blood type (4).
To be given the option of non-invasive cffDNA screening, the patient must be at least 10 weeks gestation and must have undergone genetic counseling. It is important to understand that the test is just a screening and not a diagnosis. If the screen comes out high risk then an amniocentesis or chorionic villus sample may be requested to confirm diagnosis. Some patients may not be given the option due certain situations that the Mayo Clinic has listed on their website (5). The screening may be less effective for pregnant women who are obese, expecting multiples, pregnant via donor egg or are less than 10 weeks into gestation. The testing is recommended for women with risk factors of having a child with chromosomal conditions or if the mother has an Rh negative blood type.
Multiple studies have been done to test the accuracy of cffDNA. One such study that was published in the Iranian Journal of Reproductive Medicine took place in Bucharest at Medlife Maternal and Fetal Medicine Department in 2013. The study tested 201 patients with 116 of them at an advanced maternal age and 28 patients that have high risk factors for trisomy 21. The results showed that those who had positive results after the cffDNA screening for trisomy 21, were confirmed by amniocentesis. The study concluded that using cffDNA for prenatal testing would have an increasing role in medicine due to its high accuracy (6).
As with any other experiments, there is a risk for false positives and false negatives. According to the UK National Health Service, false positives occur in about 0.3% of cases. These may result from cffDNA coming from the placenta which reflects an abnormal cell line that is not from the baby, may detect an issue from the mother instead of the baby or cffDNA may come from a 'vanishing twin' after embryonic demise. Non-invasive cffDNA detects more than 98 out of a 100 of all babies with Downs, Edwards and Patau syndromes but even then some false negatives may occur. These false negative results may occur because there isn’t enough cffDNA in maternal blood or simply due to technical issues (7). Due to these possible errors, The Society for Maternal-Fetal Medicine in the US states that all positive cffDNA screens require confirmation before any irreversible action (termination) occurs (8).
Finding a non-invasive screening method for chromosomal abnormalities was a must. Thankfully, the discovery of cffDNA propelled such research and became a viable option in genetic counseling for patients with increased risk factors. Those that were at high risk for miscarriages or are at least at 10 weeks gestation now have a safer method to determine the likelihood of the infant having a certain chromosomal defect. Only after a positive result would a more invasive procedure be needed to confirm diagnosis and help the patient determine what further actions they will take. Non-invasive prenatal testing has a bright future that will continue to improve as more groundbreaking research is continued and clinical trial experiments are done. The ever-continuing advancements will only improve our ability to diagnose and one day prevent abnormal chromosomal conditions.
- Kim YJ, Lee JE, Kim SH, Shim SS, Cha DH., 2013. Maternal age-specific rates of fetal chromosomal abnormalities in Korean pregnant women of advanced maternal age. Obstetrics & Gynecology Science, 56(3), pp.160-166.
- Hook, E. B., 1983. Chromosome abnormalities and spontaneous fetal death following amniocentesis: Further data and associations with maternal age. American Journal of Human Genetics, 35(1), pp.110–116.
- 2. Lo YM, Corbetta N, Chamberlain PF, et al., 1997. Presence of fetal DNA in maternal plasma and serum. Lancet., 350(9560), pp.485–487.
- Rafi, I., & Chitty, L., 2009. Cell-free fetal DNA and non-invasive prenatal diagnosis. The British Journal of General Practice, 59(562), pp.e146–e148.
- Mayo Clinic. 2017. Prenatal Cell-Free DNA Screening. [ONLINE] Available at: https://www.mayoclinic.org/tests-procedures/noninvasive-prenatal-testing/home/ovc-20187358. [Accessed 7 November 2017].
- Radoi, V. E., Bohiltea, C. L., Bohiltea, R. E., & Albu, D. N., 2015. Cell free fetal DNA testing in maternal blood of Romanian pregnant women. Iranian Journal of Reproductive Medicine, 13(10), pp.623–626.
- The NHS RAPID Project. 2014. NIPT for Down Syndrome. [ONLINE] Available at: http://www.rapid.nhs.uk/guides-to-nipd-nipt/nipt-for-down-syndrome/. [Accessed 6 November 2017].
- The Society for Maternal-Fetal Medicine. 2017. Cell free DNA Screening is not a simple blood test. [ONLINE] Available at: https://www.smfm.org/publications/183-cell-free-dna-screening-is-not-a-simple-blood-test. [Accessed 6 November 2017].