NIPT: a new screening tool during pregnancy

NIPT stands for Non-Invasive Prenatal Test, which is a regular blood test for the mother, holding no risks on the mother and her baby. Although pregnancy is a happy time during which future parents prepare for their newborn’s birth, it remains crucial to run some screening tests to identify any genetic disorder requiring further investigations. The most common diagnostic tools are amniocentesis and CVS, which are invasive techniques. Yet, the advancements in the medical field and technology made it possible to reduce the risks by running a preliminary screening test, the NIPT.
Dr. Emma Abboud, head of the Medical Laboratory at Mount Lebanon Hospital, explains all the details about this novelty.

1-NIPT: a new face for genetic testing during pregnancy
NIPT consists of a genetic testing which checks for the fetal DNA inside the maternal DNA using the SNP (Single Nucleotide Polymorphism) technique, which can easily study the DNA polymorphisms between 2 samples, hence detecting any chromosomal anormalities in the fetus.
The main purpose of NIPT is to avoid the risks held by invasive procedures such as amniocentesis and CVS including miscarriage, infections, and complications during pregnancy.

2- NIPT is an effective screening tool
The NIPT can screen for several chromosomal-related anormalities in the fetus including:
o Trisomy 21 or Down syndrome, which is located on chromosome 21. This is the most commonly encountered abnormality, occurring in 1 of 800 deliveries per year in the USA,
o Patau syndrome or Trisomy 13 located on chromosome 13,
o Edward’s syndrome or Trisomy 18 located on chromosome 18,
o XY disorders including: Klinefelter disorder and Turner’s syndrome.
In addition, it can detect the gender of the baby at a very early stage during pregnancy.

3- What are the microdeletions detected by NIPT?
The ACOG (American College of Obstetrics and Gynecology) recommends testing for only 5 microdeletions:
o DiGeorge syndrome: a primary immunodeficiency, often characterized by cellular (T-cell) deficiency, leading to facial malformations, congenital heart diseases and hypocalcemia.
o Angelman syndrome: a genetic disorder mainly affecting the nervous system, which causes delayed development, intellectual disabilities, severe speech impairment, and ataxia (movement and balance problems).
o Cri du chat syndrome: also known as 5pminus syndrome, which is a genetic condition causing a deletion of some genetic material on chromosome 5. People affected by this disorder will have a high-pitched cry sounding like that of a cat.
o Prader-Willi syndrome: a genetic disorder caused by the loss of function of specific genes. In newborns, symptoms include weak muscles, poor feeding, and slow development. In early childhood, symptoms include constant hunger, hence the increased risk of obesity and type 2 diabetes.
o 1P36 deletion syndrome: also known as monosomy 1p36, it is a congenital disorder characterized by moderate to severe intellectual disabilities, delayed growth, hypotonia, seizures, limited speech ability, malformations, hearing and vision impairment, and distinct facial features.

4- How is NIPT done?
The process of the NIPT screening tool is very smooth. In fact, the withdrawn maternal blood sample is sent to the laboratory, where the investigation is done over 2 steps:
o The first step consists of separating the maternal from the fetal DNA using the SNP technology.
o The second step revolves around investigating for the microdeletions listed earlier.

5- At what time during pregnancy can NIPT be done?
Since NIPT consists of a blood withdrawal like any regular blood test, it can be done anytime during pregnancy. However, the need to have a minimal concentration of 2.9% of fetal cell-free DNA circulating in the mother’s blood, makes the 9th week of pregnancy a cut-point to undergo this test. Nevertheless, this concentration tends to increase throughout pregnancy, hence, waiting for the 12th week of pregnancy increases the accuracy of the results. Therefore, the best time to undergo the NIPT is between the 11th and 12th week, in order to avoid the risk of redraw.

6- Limits do exist:
Like any other test, some limits can reduce its precision or make it an inaccurate screening tool. These include:
– A low percentage of cell-free DNA due to a high mother’s weight
– No call results (1.4% of the cases) indicating the need for further testing for syndromes other than the 5 microdeletions.
– Inability to read the DNA using this technique, which can sometimes be the case.
Despite these limitations, it has a benefit for twin pregnancies due to its ability to determine the gender while specifying if it is a dichorionic or monochorionic pregnancy.

7- Do the results take time?
In fact, it is a very quick process since the results require only 10 days to come out.

8- A word about its accuracy…
The NIPT is validated in both high and low risk patients based on its sensitivity and specificity, which is over 99.9%, hence it is a very high accuracy. Furthermore, it has a very low chance of false negative (0.6%), and false positive (0.03%).

9- When is it preferred over amniocentesis or CVS?
The NIPT, a screening tool, is done before recurring to amniocentesis or CVS, which are invasive diagnostic procedures. Based on its results, the need for further investigation will be decided. NIPT is recommended in the following cases:
High risk pregnancy: age of the pregnant woman is over 35 years, family history of Down syndrome or any other syndrome screened for using NIPT
Ultrasound screening or triple test showing high results
The physician will decide on further steps based on the results obtained:
● Positive results at the level of any microdeletion requires further investigation
● Negative results will relief the pregnant woman from the burden of invasive procedures.
Furthermore, amniocentesis is conducted between the 16th and 18th week, hence after obtaining a positive result from the NIPT screening, except when the physician decides to skip the NIPT screening step.

Reducing the risks on both the mother and the fetus became a possibility with the rise of the NIPT screening test as a prior step to the invasive techniques. This test is recommended to all pregnant women between the 11th and 12th week of pregnancy, on which further needed investigations will be decided. Since Mount Lebanon Hospital cares about the health and well-being of both the mother and her baby, this test is now available upon the physician’s request.

Dr. Emma Abboud
Head of the Medical Laboratory

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