Prenatal diagnosis

Genetic disorders are difficult to treat.  It is very important to diagnose a genetic disorder. The prenatal diagnosis helps to detect genetic abnormalities before birth. Prenatal diagnosis involves various techniques such as ultrasonography, fetal blood sampling, fetoscopy, maternal serum screening, testing cell-free DNA, amniocentesis, and chorionic villus sampling.

What is the prenatal diagnosis?

The prenatal diagnosis serves in detecting the genetic abnormalities in a child before birth. Thus, it helps the parents in decision making.

The high-risk couples get a chance to decide.  Following couples get the benefit of prenatal diagnosis:

1.     The family history of genetic disorders

2.     Women above 35 years expecting a baby

3.     The family history of neural tube defects

4.     The first child has chromosomal abnormalities or any genetic condition

5.     Couples having a first child with Down's syndrome

6.     Diabetics

7.     Carrier mothers

Period of screening	Prenatal screening tests	Estimation of risk
First trimester	Blood tests	·        Estimate the level of pregnancy-associated placental protein A ·        Beta-human chorionic gonadotropin ·        Help in estimating the risk of Down’s syndrome
	Ultrasonography	·        Detection of the abnormalities associated with the neck and back of the fetus.
	Cell-free fetal DNA (cfDNA testing)	·        Determine chromosomal abnormalities.
	Chorionic villus sampling, amniocentesis	·        Amniocentesis helps in estimating the alpha-fetoprotein. ·        Help in the detection of chromosomal abnormalities.
Second trimester	Blood tests	·        Alpha-fetoprotein ·        Estriol ·        HCG ·        Inhibin A ·        Detection of neural tube defects ·     Complications associated with miscarriages
	Ultrasonography Amniocentesis Triple screening	·        Determine the presence of more than one fetus ·        Determine  defects

Table: Estimation of risk using prenatal diagnosis

Amniocentesis:

Amniocentesis involves chromosomal abnormalities to get detected by a collection of the amniotic fluid. It involves obtaining the cells of the developing fetus for analysis. The procedure gets performed between 14-16 weeks of pregnancy.

The amniotic fluid analysis helps in detecting neural tube defects by estimating alpha-fetoprotein with a raised level in the amniotic fluid. The amniotic fluid is a protective fluid that surrounds the developing fetus. It serves as a cushion against shock. The amniotic sac provides a favorable environment for fetal development. Amniocentesis is a very specialized procedure that requires an expert. The procedure is extremely risky and needs proper concentration and careful examination. The amniotic fluid is collected using a syringe needle injection through the uterine wall and amniotic sac. This fluid consists of fetal cells. These cells are analyzed further for the chromosome studies. The fetal cells are cultured in the laboratory. Various tests such as DNA tests and biochemical tests for enzyme deficiencies are carried out.

Image: Amniocentesis

Chorionic villus sampling:

Chorionic villus sampling is a form of biopsy. It involves sampling of the fetal tissue which contains a large number of fetal cells. It detects chromosomal disorders as well as single gene disorders. The procedure is carried out during 10 to 11 weeks of the gestation period. The risk of abortions reduces with this type of detection. This procedure is carried out at early stages of pregnancy. Chorionic villus sampling between the 8^th and 12^th weeks of pregnancy is ideal. The amniocentesis is ideal after the 12^th week of gestation. A membrane layer surrounding the fetus is known as a chorion.

Non-Invasive Prenatal Testing:

The reason for conducting a genetic test involves the detection of any mutations occurring in the fetus before birth. Prenatal diagnosis is an important application of genetic testing. Hence, we check whether the fetus is at risk. Two main procedures such as prenatal diagnosis and chorionic villus sampling involve a lot of risk for the mother and the baby. They are very painful too. Hence, it led to the development of non-invasive prenatal testing (NIPT). The maternal plasma shows the presence of fetal DNA. It is a cell-free DNA floating in the plasma of the expected mother. The abbreviation of cell-free DNA is known as cfDNA. Hence, it is possible to collect plasma samples of the expected mothers for analyzing cfDNA. NIPT is a simple, harmless, and painless procedure. It detects gene mutations and chromosomal abnormalities. The embryos with chances of serious genetic disorders get removed before the implantation stage.

Fetoscopy:

It is a kind of endoscopy that enables to visualize the fetus.  A fetoscope is a fibro-optic self-illuminated instrument that gets inserted in the amniotic cavity under local anesthesia. Cleft lip, cleft palate, facial malformations, limb defects, and skin disorders get detected with the help of fetoscopy.

Ultrasonography:

The 12^th week of pregnancy is an ideal period for performing ultrasonography test. However, the first and the second trimesters may involve the test. It is an ultrasound-based imaging technique involved in the purpose of diagnosis.  The high-frequency sound waves help in generating images. Ultrasounds help in confirming the pregnancy. It helps in checking the fetal heartbeat and help in detecting any abnormality in the fetus. It detects an ectopic pregnancy. It is a condition in which the fetus does not attach to the uterus. It is possible to determine the sex of the baby using ultrasonography. During the second trimester, it helps to determine the possible characteristics of the Down’s syndrome or any other physical abnormalities in the baby.

Maternal serum screening:

The indication of the level of alpha-fetoprotein uses maternal serum screening. The raised level of alpha-fetoprotein indicates neural tube defects, including spina bifida and anencephaly.

Fetal blood sampling:

It involves a prenatal diagnosis of hemophilia, thalassemia, sickle cell disease, immune deficiency disorders, and chromosomal analysis. It requires a small amount of blood from the fetus or the unborn baby.

Conclusion:

Although prenatal testing serves for the detection of many genetic conditions, still many babies are born with the genetic conditions every year. The reason involves the lack of proper knowledge regarding familial disorders, pregnancy risks, and many other environmental conditions. It is important for the physicians to be familiar with the risks associated with the genetic disorders and the genetic tests available for the same. The knowledge of prenatal testing and genetic counseling helps to prevent the birth of the babies with the defects and help in decision making.

References:
[1] Human Genetics, 3/e, Gangane
[2] Chromosome Abnormalities and Genetic Counseling, R.J. McKinlay Gardner, Grant R Sutherland, Lisa G. Shaffer
[3] Essential Medical Genetics, Edward S. Tobias, Michael Connor, Malcolm Ferguson-Smith
[4] Thompson & Thompson Genetics in Medicine, Robert L. Nussbaum, Roderick R. McInnes, Huntington F. Willard

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