The Value of Noninvasive Prenatal Screening (NIPS)
Unveiling Noninvasive Prenatal Screening (NIPS)
Prenatal screening tests can help identify pregnancies with a higher risk of certain birth defects. Noninvasive prenatal screening (NIPS) is one such screening test. Using a simple, single blood test, the risk of chromosome aneuploidies such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13) can be detected.
Screening tests like NIPS can give patients and providers the knowledge needed to make medical decisions regarding pregnancy, including the decision to pursue more invasive testing methods. Additionally, screening can help provide the best possible care to both mother and infant and allow adequate preparation for the baby’s birth.
Common Aneuploidy Conditions
Each cell in a person's body typically contains 23 pairs of chromosomes, which carry the genes inherited from our parents, for a total of 46 chromosomes. Chromosome aneuploidies are genetic conditions caused by an abnormal amount of chromosomes.
One of the most common types of chromosome aneuploidies is called trisomy, which occurs when three copies of a particular chromosome are present instead of the usual two. Trisomies of chromosomes 21, 18, and 13 are some of the most common chromosome aneuploidies in pregnancy, and can be detected with noninvasive prenatal screening. In addition to trisomies 21, 18, and 13, NIPS can screen for certain sex chromosome conditions (Monosomy X, XXX, XXY, and XYY) and determine the fetal sex (XX or XY).
Trisomy 21
Trisomy 21, also known as Down syndrome, occurs in about 1 in 700 newborns. This condition may cause mild to moderate intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy.
Affected individuals may have a variety of birth defects, and about half will have a heart defect. Trisomy 21 increases the risk of other severe medical problems, including celiac disease, gastroesophageal reflux, hypothyroidism, vision and hearing problems, Alzheimer’s disease, and leukemia. ¹
Trisomy 18
Trisomy 18, also known as Edwards syndrome, occurs in about 1 in 5,000 live-born infants. This condition may cause slow growth before birth (intrauterine growth retardation); a low birth weight; heart defects and abnormalities of other organs; a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers.
Only 5-10% of infants with trisomy 18 live past the first year. Surviving infants may have severe intellectual disabilities.
Trisomy 13
Trisomy 13, also known as Patau syndrome, occurs in about 1 in 16,000 newborns. Patau syndrome can cause heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia). Most infants with this condition live for only a short time after birth. ³
Traditional screening methods
Traditional aneuploidy screening consists of maternal serum screening which measures certain biochemical markers in the mother's blood that are secreted by the baby. Different patterns in these biochemical markers can indicate an increased risk for certain genetic conditions, including trisomies 21, 18, and 13.
Many screening methods also include an ultrasound which evaluates the thickness of the nuchal translucency, or fluid behind the baby's neck, which can be associated with certain genetic conditions.
At the earliest, this type of screening can be offered at 11-13 weeks of pregnancy 4,5. However, the most accurate traditional serum screens (integrated or sequential screening) require a blood draw in both the first and second trimester.
These screens are completed later in the pregnancy and the need for multiple appointments costs patients additional time and money. Traditional screening methods have an accuracy of 80-95%, depending on which method is used.
Additionally, these methods have an overall false positive rate of approximately 5% which may cause unnecessary worry and further procedures 6,7. Follow-up diagnostic testing for a positive screening result may include more invasive procedures such as chorionic villus sampling (CVS) or amniocentesis.
These follow-up tests, apart from being more invasive than the initial screens, have associated risks.
Noninvasive Prenatal Screening
Noninvasive prenatal screening is a single blood test that examines fetal DNA shed from the placenta. Fetal DNA from the placenta enters the mother's blood stream and analysis of this cell-free DNA (cfDNA) can be performed from a single maternal blood draw.
Noninvasive prenatal screening tests can be performed beginning at 10 weeks of gestation and require only one maternal blood draw. In fact, NIPS has the broadest screening window of any prenatal aneuploidy screening test, as testing can be performed at any point in the pregnancy at or after 10 weeks of gestation until just before birth 4,6.
With a detection rate of >99%, NIPS is the most accurate prenatal chromosomal aneuploidy screening option and is available for all pregnant women 4-8. Maternal serum alpha-fetoprotein (MSAFP) screening, which assesses the risk for neural tube defects such as spina bifida, should still be offered to all pregnant women, as NIPS cannot detect these conditions.
Compared to traditional screening methods for common chromosome aneuploidies, NIPS has consistently demonstrated low false positive rates (higher specificity) and higher detection rate (higher sensitivity) 8-10.
As a result, NIPS can lead to 89% fewer unnecessary invasive tests as compared to traditional serum screening 4.
Therefore, NIPS offers the following benefits to patients:
- Better at detecting chromosome aneuploidy when present in a fetus (highly sensitive)
- Better at detecting when chromosome aneuploidy is not present in a fetus (highly specific)
- Available earlier in pregnancy
With the increase in NIPS availability, all expecting parents should have the choice between traditional screening methods and NIPS. Discussing both options and their limitations will provide greater understanding for patients making this important medical decision.
Current American College of Obstetrics and Gynecology guidelines state that “cell-free DNA is the most sensitive and specific screening test for the common fetal aneuploidies,” making NIPS a convenient and viable option for many patients. HNL Lab Medicine now offers NIPS through its Genomics division, allowing all providers and patients access to this incredible technology.
REFERENCES
¹ National Library of Medicine. (2020, June 01). Down Syndrome. U.S. Department of Health and Human Services. https://medlineplus.gov/genetics/condition/down-syndrome/.
² National Library of Medicine. (2021, February 16). Trisomy 18. U.S. Department of Health and Human Services. https://medlineplus.gov/genetics/condition/trisomy-18/.
³ National Library of Medicine. (2021, September 09). Trisomy 13. U.S. Department of Health and Human Services. https://medlineplus.gov/genetics/condition/trisomy-13/.
⁴ Bianchi, D. W., Parker, R. L., Wentworth, J., Madankumar, R., Saffer, C., Das, A. F., Craig, J. A., Chudova, D. I., Devers, P. L., Jones, K. W., Oliver, K., Rava, R. P., Sehnert, A. J., & CARE Study Group. (2014). DNA sequencing versus standard prenatal aneuploidy screening. The New England Journal of Medicine, 370(9), 799–808. https://doi.org/10.1056/NEJMoa1311037.
⁵ Bianchi, D. W., Platt, L. D., Goldberg, J. D., Abuhamad, A. Z., Sehnert, A. J., Rava, R. P., & MELISSA Study Group. (2012). Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstetrics and Gynecology, 119(5), 890–901. https://doi.org/10.1097/AOG.0b013e31824fb482.
⁶ Committee on Genetics, & Society for Maternal-Fetal Medicine. Practice Bulletin No. 226: Screening for fetal chromosomal abnormalities. (2020). Obstetrics and Gynecology, 136(4), e48–e69. https://doi.org/10.1097/AOG.0000000000004084.
⁷ Benn, P., Borell, A., Chiu, R., Cuckle, H., Dugoff, L., Faas, B., Gross, S., Johnson, J., Maymon, R., Norton, M., Odibo, A., Schielen, P., Spencer, K., Huang, T., Wright, D., & Yaron, Y. (2013). Position statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenatal Diagnosis, 33(7), 622–629. https://doi.org/10.1002/pd.4139.
⁸ Gregg, A. R., Skotko, B. G., Benkendorf, J. L., Monaghan, K. G., Bajaj, K., Best, R. G., Klugman, S., & Watson, M. S. (2016). Noninvasive prenatal screening for fetal aneuploidy, 2016 update: A position statement of the American College of Medical Genetics and Genomics. Genetics in Medicine, 18(10), 1056–1065. https://doi.org/10.1038/gim.2016.97.
⁹ Gil, M. M., Accurti, V., Santacruz, B., Plana, M. N., & Nicolaides, K. H. (2017). Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound in Obstetrics and Gynecology, 50(3), 302–314. https://doi.org/10.1002/uog.17484
¹⁰ Chen, E. Z., Chiu, R. W., Sun, H., Akolekar, R., Chan, K. C., Leung, T. Y., Jiang, P., Zheng, Y. W., Lun, F. M., Chan, L. Y., Jin, Y., Go, A. T., Lau, E. T., To, W. W., Leung, W. C., Tang, R. Y., Au-Yeung, S. K., Lam, H., Kung, Y. Y., … Lo, Y. M. (2011). Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS ONE, 6(7). https://doi.org/10.1371/journal.pone.0021791.