Chapter 7 – Prenatal Diagnosis

When talking about check-ups and examinations during pregnancy, one cannot help but think of another important topic, which is usually close to the heart of would-be parents, namely prenatal diagnosis.

Once, the public health service offered chorionic villus sampling or amniocentesis to all pregnant women aged 35 or older – and to all those with recognized risk factors. Two invasive tests that consist of withdrawing, with a syringe through the abdominal wall, a sample of placental tissue or amniotic fluid in order to analyze the genetic makeup of the fetus and accurately diagnose possible chromosomal abnormalities, such as Down syndrome, or genetic diseases such as cystic fibrosis.

Chorionic villus sampling can be performed between the 10th and 14th week, while amniocentesis is preferably done between the 16th and 18th week. Since 2017, with the approval of the new LEA (Essential Levels of Care), the free offer of CVS or amniocentesis remains available to women with specific risk factors. For all others, regardless of age, between the 11th and 14th week a screening test is recommended that includes an ultrasound measurement of fetal nuchal translucency combined with the so-called “bitest”, a blood test measuring the concentration of two proteins. From the combined result of these two tests, an estimate is obtained of the risk that the fetus may be affected by trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), or trisomy 13 (Patau syndrome).

The bitest combined with the nuchal translucency measurement does not provide a certain diagnosis, but a risk percentage. If the risk appears high, the woman is offered a free amniocentesis to confirm or rule out the suspicion.

In recent years, the offer of screening and diagnostic tests has further expanded thanks to advancements in DNA sequencing, which now allow for a review of the entire fetal genome from a sample of amniotic fluid or placental tissue, scanning for the genetic mutations responsible for hundreds of diseases. Thus, the most advanced laboratories offer expecting mothers “super-amniocentesis” or “super-CVS”, promoting their ability to diagnose or rule out most genetic diseases that the fetus may carry.

Future parents can request testing for the most common genetic diseases, such as cystic fibrosis and congenital deafness, or request analysis of a greater number of genes. The cost of the test varies accordingly, from 600–700 euros to over 1,000, and is not reimbursed by the national health service.

These highly “comprehensive” tests are not offered by the SSN (National Health Service), nor are they recommended by the Italian Society of Human Genetics (SIGU) (22), because they are essentially of limited utility.

In the absence of family history or consanguinity between partners, the probability that a couple will have a child affected by a genetic disorder is extremely low, less than 1%. Excluding a few hundred diseases does not significantly lower the overall risk, especially because the number of conditions for which the responsible genes are unknown — and thus cannot be diagnosed by these tests — is far greater than the number of known diseases.
Finally, there are cases where the test result does not make it clear whether the fetus is a healthy carrier or affected by the disease, and even if it is affected, the severity of the clinical condition cannot be predicted, since the same genetic variant can be expressed differently from one individual to another, with symptoms that may be so mild that it’s difficult to speak of an actual illness.
Prospective parents therefore learn from the report that there is an anomaly — but they cannot know what it means: this is a situation that generates anxiety with no resolution.

Another recently developed tool is the NIPT (Non-Invasive Prenatal Test), which allows for the analysis of fetal DNA without needing to extract amniotic fluid or chorionic villi cells — and thus without invasive procedures. It is based on the fact that small amounts of fetal genetic material cross the placental barrier during pregnancy and circulate in the mother’s blood. With current techniques, it is possible to isolate this DNA from a blood sample taken from the woman and analyze it to detect any chromosomal abnormalities, such as Down syndrome, and to screen for some specific genetic diseases, such as cystic fibrosis.

Although it is extremely reliable, much more so than the combination of bitest and nuchal translucency measurement, the NIPT is not yet considered a diagnostic test capable of providing a definitive result, but only a risk estimate. If the result shows an anomaly, it is still necessary to undergo the traditional invasive test to confirm the diagnosis.It can be done starting from the 10th week of pregnancy and its cost ranges from 600 to over 1,000 euros, depending on the information being sought.
It is not reimbursed by the National Health Service because it is much more expensive than the bitest and nuchal translucency measurement.