Other Methods for Detecting Down Syndrome and Other Common Chromosomal Abnormalities

Даун синдром

Cell-free fetal DNA (cffDNA) or fetal DNA circulates freely in the mother’s blood. Through venipuncture, i.e. taking blood from the vein of the pregnant woman, a specimen can be taken for the study. Sample analysis is a non-invasive method for detecting the most common aneuploidy in the fetus, determining gender and detecting certain genetic mutations. That’s why this test is also called NIPT/NIPD (non-invasive prenatal test/non-invasive prenatal diagnosis). Unlike invasive procedures like chorionic villus sampling and amniocentesis, which have an abortion rate of 1 in 100 procedures, NIPT is a safe, non-invasive method that does not pose a risk for an abortion. Another advantage is the use of NIPT instead of an invasive procedure in women with a Rh negative blood group. In NIPT, there is no risk of sensitisation of women with this blood group and eliminating the risk of Rh isoimmunization as well as subsequent anemia and Rh positive fetus damage from this condition, while invasive procedures can lead to this complication in pregnancy.

CffDNA originates from the placental trophoblast. It is found that about 2-6% of the mother’s blood is of fetal origin. Test limits are related to the level of fetal DNA in the mother’s blood. The non-invasive prenatal test can be administered after the 10th week of pregnancy.

There are 46 chromosomes in the human cells, two of which are related to gender XX or XY respectively for female and male gender. All chromosomes are in pairs. If there is an additional chromosome or a missing chromosome in some of these pairs, we signify this condition as an aneuploid. It may occur for various reasons and is most often associated with improper separation of the chromosomes in the division of the sex cells (ovum and sperm). The most common aneuploidy are Down syndrome (trisomy 21), Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18), and Turner syndrome (45 X0).

This is a method that does not require special conditions or a narrow specialist to do it. The method may be performed in an outpatient environment by medical professionals (nurse or midwife), paramedics, physicians, or any specialist authorized to perform venous manipulations according to the legislation of the respective country. Of course, the reasons for doing the test should be for good reason, by the appropriate specialist in fetal medicine. For now, the protocol at King’s Collage Hospital in London to test the cffDNA is at a risk of aneuploidy higher than 1:500. There may be other indications of its application as presence of some suspected genital mutations. Genetic mutations associated with X-chromosome for Duchenne muscular dystrophy and haemophilia. Some of the inherited genetic abnormalities for NIPT can include cystic sclerosis, beta-thalassimia, sickle cell anemia, spinal muscular atrophy, fragile X syndrome, Duchenne muscular dystrophy and haemophilia. For the private patients, who want, I can do the test upon their request.

The main reason for using NIPT is to screen for the most common aneuploidy. Screening through NIPT is very accurate, for Down Syndrome accuracy is 99.2%.

The use of NIPT allows us to detect these syndromes with great accuracy. The question of which syndromes and genetic mutations are involved in the test is still debatable because the more anomalies we involve, the higher the frequency of false-positive tests. A false positive screening test for a given disease means that if an individual is unaffected by the disease or syndrome, it will be claimed to be affected. This, in turn, will require an invasive procedure to confirm or reject the diagnosis. I.e. we have to find the balance between how many conditions we are studying to get the highest possible results from this brilliant test. That is why the reason for doing, and also interpreting the test, should be done by a specialist in fetal medicine. Yes, of course it is very easy to read whether a low or high risk is written,but that is not the only important aspect. This information itself is best compared to the initial risk, as well as all factors in the test, because in some cases this test of screening (with 99.2% confidence) test can become diagnostic (with 100% credibility).

It is important to know that this test is screening and when receiving a positive result will require confirmation by an invasive procedure. However, its accuracy is so great that the frequency of invasive procedures would decrease significantly when using NIPT.

The most common invasive procedures are chorion biopsy – Chorionic villus sampling (CVS) and amniocentesis.

Chorionic villus sampling is a prenatal diagnostic test whereby part of the placental tissue is taken to test, under ultrasound control, for chromosomal and genetic anomalies of the fetus. The procedure is performed after 12 WOP through the abdomen or through the vagina.

Reasons for doing CVS are:

  • High risk of combined screening test
  • Anomalies detected during the first trimester screening
  • Family history of chromosomal or genetic diseases
  • Parents who are carriers of genetic mutations
  • The risk of abortion after Chorionic villus sampling is 0.1%, i. 1 per 1,000 manipulations.
  • Risk of infections 1 per 1,000 manipulations
  • Risk of unreliability of the sample and need to repeat it 1 in 200
  • Risk of bruising of the manipulation place

After manipulation, there may be some bleeding and leakage of amniotic fluid.

Amniocentesis is another prenatal invasive procedure to diagnose chromosomal abnormalities, genetic mutations and fetal infections. In this procedure, a small amount of amniotic fluid is taken after 16 WOP.

Amniocentesis indications are:

  • High risk of chromosomal abnormalities after combined screening test or late biochemical screening
  • Risk of genetic anomalies
  • Suspicion of fetal infection (toxoplasmosis, rubella, CMV, etc.)
  • Analysis of the level of bilirubin in Rh isoimmunization disease
  • In case of the inability to perform a chorionic villus sampling

The risks from this procedure depend on the duration of the manipulation. Amiocentesis also has the risk of abortion at 0.1% in the second trimester. Other risks include premature birth, leakage of the amniotic fluid, chorioamnionitis (infection from the procedure), fetal injury, etc.

Another method for detecting chromosomal abnormalities and genetic mutations used in in vitro fertilization is the Pre-implantation genetic diagnosis (PGD or PIGD). PGD can potentially be used in order to select embryos with no genetic disease ,to increase the chances of a successful pregnancy and to reduce the  predisposition to cancer decreases, as well as to select gender. PGD biopsy can be performed on cells in different stages of fetal development. PGD is an invasive procedure that requires serious attention. One of the risks of PGD involves embryo damage during the biopsy procedure (which in turn destroys the embryo in general).


Center for Fetal Medicine

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