Prenatal tests are a fundamental tool for monitoring fetal health during pregnancy. Humans normally have 23 pairs of chromosomes; therefore, the most common chromosomal abnormalities are aneuploidies, particularly trisomies 21, 18, and 13. Throughout pregnancy, every woman should have access to appropriate prenatal examinations to assess these potential risks.
Today, we have several prenatal screening test options, each with specific characteristics. The Combined Test offers about 90% reliability in correctly identifying the risk group for the most common trisomies, while the fetal DNA test from maternal blood achieves an impressive 99% accuracy for trisomy 21. However, it is important to remember that these prenatal tests do not provide a certain and definitive diagnosis. To obtain diagnostic confirmation, it may be necessary to use invasive tests such as amniocentesis, which carries a miscarriage risk of about 1 in 500–1,000.
In this article, we will examine the different types of free and paid prenatal tests available in Italy, their advantages and limitations, and how to choose those best suited to your needs. We will explore when to opt for non-invasive screening exams and when more in-depth diagnostic tests may be necessary.
Criteria for choosing the most suitable prenatal test
Choosing the most appropriate prenatal test requires careful consideration of several personal factors. There is no universal approach: every expectant mother has specific characteristics and needs that significantly influence this decision. Let’s look at the main criteria you should consider together with your gynecologist.
Maternal age and risk of aneuploidies
Maternal age is one of the most relevant factors in evaluating the risk of fetal chromosomal abnormalities. This risk increases progressively with age and rises exponentially after 35. The main mechanism causing aneuploidies (changes in chromosome number) is non-disjunction during meiosis, a phenomenon that becomes more frequent as age increases.
For Down syndrome (trisomy 21), data show a significant increase in risk:
- At 35 years: 1 in 385
- At 37 years: 1 in 227
- At 40 years: 1 in 106
- At 43 years: 1 in 50
This has a considerable social impact, since in recent decades the average age at first childbirth has increased markedly, from 20–21 years to the current 29–30. As a result, advanced maternal age is now the most common indication for undergoing prenatal screening tests.
Family history and inherited genetic diseases
Beyond age, family history plays a key role. About 3–5% of pregnancies are complicated by congenital defects or genetic diseases. When there is a family history of genetic conditions, the risk that these conditions may be passed on to the unborn child increases significantly.
Many people are “healthy carriers” of genetic diseases: although they are in perfect health, they can pass these conditions to their children. In particular, when both parents are healthy carriers of the same genetic disease, the probability that the child will be born with that condition is 25% (1 in 4).
For this reason, even before conceiving a child, couples with a family history of genetic diseases should consider specific tests to identify possible carrier status. Genetic counseling is especially important in these cases and should be arranged in agreement with the gynecologist.
Type of pregnancy: single, twin, or assisted reproduction (ART)
The type of pregnancy also affects the choice of the most appropriate prenatal test. Non-invasive prenatal tests can be performed in both single and twin pregnancies; however, they have different features depending on the situation.
In twin pregnancies, traditional screening tests (such as the triple or quadruple test) show lower sensitivity and specificity compared with singleton pregnancies. In these cases, the fetal DNA test (NIPT) is often a more reliable choice, although it has some limitations. While in singleton pregnancies NIPT achieves sensitivity above 99%, in twin pregnancies it still remains more reliable than traditional tests.
One key aspect to consider carefully in twin pregnancies is that NIPT cannot indicate which of the two fetuses may be affected by a genetic abnormality, nor whether both are. To obtain this specific information, invasive tests such as chorionic villus sampling or amniocentesis would be necessary.
Non-invasive prenatal tests are also suitable for all pregnancies achieved through medically assisted reproduction (ART), both homologous (using the couple’s gametes) and heterologous (with donor eggs or sperm). This is a significant advantage for couples undergoing fertility treatment.
Comparison of non-invasive prenatal screening tests
In recent years, non-invasive prenatal exams have revolutionized pregnancy monitoring. These tests make it possible to assess the risk of fetal genetic abnormalities without the risks associated with invasive procedures. Let’s examine the main options available and their distinctive features.
Combined test: nuchal translucency and serum markers
The combined test is one of the most widely used prenatal screening exams. It is performed in the first trimester of pregnancy, specifically between the 11th and 14th week, and assesses the risk of chromosomal abnormalities—mainly Down syndrome (trisomy 21), but also Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13).
This test integrates two essential components:
- A maternal blood test to analyze two substances: free beta-hCG and pregnancy-associated plasma protein A (PAPP-A)
- An ultrasound measurement of nuchal translucency (NT), i.e., the space between the skin and the spine at the back of the fetal neck
The effectiveness of the combined test is notable: it correctly identifies about 85–90% of women carrying fetuses affected by Down syndrome. The false-positive rate is around 5%. Sensitivity can increase up to 93–95% when additional ultrasound parameters are assessed, such as the nasal bone, ductus venosus flow, and tricuspid valve regurgitation.
Fetal DNA test (cfDNA) in maternal blood
The fetal DNA test, also known as NIPT (Non-Invasive Prenatal Testing), is currently the most advanced technology available. It analyzes fragments of fetal cell-free DNA circulating in maternal blood, detecting potential chromosomal abnormalities with extraordinary precision.
Unlike the combined test, NIPT can be performed as early as the 10th week of pregnancy and provides impressive accuracy: sensitivity for trisomy 21 exceeds 99%, with a false-positive rate below 0.1%. Reliability also remains high for trisomies 18 and 13.
Different versions exist with increasing levels of detail:
- Basic test: analyzes trisomies 21, 18, 13, and sex chromosomes
- Advanced tests: evaluate additional chromosomal abnormalities, including microdeletions and structural alterations
Despite its high accuracy, it is essential to remember that NIPT is still a screening test. Positive results always require confirmation through invasive diagnostic procedures.
Morphology ultrasound and nuchal translucency
Ultrasound plays a central role in non-invasive prenatal testing. Nuchal translucency measurement is an essential component of the combined test and also serves as a preliminary assessment for NIPT.
During the ultrasound between the 11th and 13th week, the specialist evaluates not only nuchal translucency thickness but also:
- Presence of the nasal bone
- Cardiac flow assessment
- General fetal anatomy that can be evaluated at that stage
A nuchal translucency value above 3.5 mm is an indication for further diagnostic assessment, regardless of the combined test result. In fact, increased translucency can be associated not only with aneuploidy risks but also with potential congenital heart defects and other structural abnormalities.
It is important to underline that first-trimester ultrasound remains an irreplaceable moment in pregnancy care and complements other analyses by providing additional diagnostic information. Even when choosing NIPT, it is always recommended to perform an in-depth ultrasound to evaluate fetal anatomy and measure nuchal translucency.
Invasive prenatal tests: when they are necessary
Invasive prenatal diagnosis represents an advanced stage of investigations during pregnancy, when screening tests show an increased risk of genetic abnormalities. These procedures allow fetal cells to be collected and analyzed to confirm with certainty the presence of possible conditions, going beyond the simple risk estimate offered by non-invasive tests.
Amniocentesis: indications and timing
Amniocentesis involves the collection of amniotic fluid using a needle inserted through the abdominal wall under continuous ultrasound guidance. The fluid contains fetal cells that, when cultured, allow analysis of the fetus’s complete karyotype.
This exam should be performed only from the 15th week of gestation, because earlier procedures are associated with a higher risk of complications. Clinical studies have shown that early amniocentesis (11–13 weeks) involves a significantly higher rate of fetal loss (7.6% vs 5.9%), anomalies such as clubfoot (1.3% vs 0.1%), and post-procedure fluid leakage (3.5% vs 1.7%) compared with standard amniocentesis.
Main indications for amniocentesis include:
- Advanced maternal age (≥35 years)
- Abnormal results in prenatal screening tests
- Parents with a previous child affected by a chromosomal disorder
- A parent carrying a structural chromosomal rearrangement
- Fetal abnormalities detected on ultrasound
The procedure-related miscarriage risk is relatively low, ranging from 0.2% to 0.5%, i.e., about 1 in 500–1,000.
Chorionic villus sampling (CVS): advantages and limitations vs amniocentesis
Chorionic villus sampling (CVS) involves aspiration of trophoblastic cells from the placenta. It can be performed from the 10th week of gestation, generally up to the 13th week.
The main advantage of CVS compared with amniocentesis is the possibility of obtaining results earlier in pregnancy. In addition, it allows genetic analysis for some specific inherited diseases that might not be detectable with amniocentesis alone.
However, it has some important limitations. The miscarriage risk after CVS is slightly higher than after amniocentesis, ranging between 1% and 2%. Moreover, sampling can occasionally lead to false-positive results due to confined placental mosaicism, requiring confirmatory amniocentesis.
Both procedures require careful evaluation of the risk–benefit ratio and should only be performed by experienced operators, since complication rates decrease significantly with greater operator experience.
Limitations and false positives in prenatal tests
Understanding the limitations of prenatal tests is essential to interpret results correctly and make informed decisions. Every screening test, no matter how advanced, has inherent limitations that should be understood before undergoing the exam.
Sensitivity and specificity of screening tests
Sensitivity indicates a test’s ability to correctly identify affected cases, while specificity represents its ability to correctly identify unaffected cases. No screening test can guarantee 100% sensitivity and specificity.
The fetal DNA test (NIPT) has very high sensitivity for trisomy 21, above 99%, with a false-positive rate below 0.1%. For trisomies 18 and 13, sensitivity is slightly lower, at about 98% and 99% respectively.
In contrast, traditional screening tests such as the combined test identify about 85–90% of fetuses with Down syndrome, with a false-positive rate around 4–5%.
False positives and false negatives: what they mean
A false-positive result occurs when the test indicates increased risk but the fetus is healthy. This happens in about 5% of combined tests, while with NIPT the percentage drops below 0.1%.
A false-negative result indicates low risk when the fetus actually has an abnormality. Even the most accurate tests cannot completely eliminate this risk.
It is important to remember that all screening tests provide a probability, not a diagnosis. A “positive” result simply means the risk exceeds a preset threshold (usually 1:250), not that the fetus is certainly affected.
Several factors can influence test accuracy:
- Chromosomal mosaicism (two cell lines with different chromosomal makeup)
- Twin pregnancies with a “vanishing twin”
- Maternal conditions such as cancer or chromosomal abnormalities
- Low fetal DNA fraction in the sample
Diagnostic confirmation with invasive tests
In the case of a positive screening result, diagnostic confirmation with an invasive test is always necessary. Amniocentesis and CVS are the only exams that can provide a definitive diagnosis through direct analysis of fetal cells.
CVS, performed between the 11th and 13th week, provides results sooner than amniocentesis, which is performed between the 15th and 18th week. Both carry a miscarriage risk estimated between 0.5% and 1%.
Despite these risks, invasive tests are the only way to obtain a certain diagnosis, turning a statistical probability into definitive confirmation or exclusion of the suspected condition.
Free and paid prenatal tests: what to know
Economic accessibility is a key factor in choosing prenatal tests. In Italy, free availability of these exams varies considerably depending on the region of residence, making it important to know the options available.
Which tests are offered by the National Health Service (SSN)
The Italian National Health Service provides some essential services free of charge during pregnancy. These include the first gynecological visit, rubella and syphilis screening, tests to evaluate hemoglobin levels, and the second-trimester ultrasound. The SSN also covers hepatitis B antigen testing and cardiotocography.
However, more specific exams such as the fetal DNA test (NIPT) are not yet included in the Essential Levels of Care (LEA) at the national level. Nevertheless, some regions have independently decided to offer it free of charge as an extra-LEA service.
Private tests: costs and insurance coverage
In the private sector, NIPT represents a significant expense. The average cost ranges between €500 and €700, making affordability a limiting factor for many families.
Fortunately, several insurance companies have started to recognize the value of these exams. Among those offering full or partial coverage for the fetal DNA test are Allianz, Generali, Poste, Fasdac, Fasi/Assidai, and Caspie. For reimbursement, a medical prescription must be attached to the request.
How to access free tests depending on the region
Currently, the availability of free prenatal tests varies widely between Italian regions. Emilia-Romagna stands out as a pioneer, offering NIPT free of charge from July 1, 2024 to all pregnant women residing in the region, regardless of age or risk factors. The test is offered between the 10th and 13th week of gestation.
Valle d’Aosta also guarantees this service to all resident pregnant women. Sardinia has recently introduced free NIPT as primary screening, while Lombardy offers it free only to women with an intermediate-risk result after the combined test. In Tuscany, a €200 co-payment is предусмотр for women with a risk between 1/301 and 1/1000.
Other regions such as Basilicata and Piedmont offer the test free only in cases of intermediate risk, while in areas such as Lazio, Liguria, and Friuli Venezia Giulia NIPT is still entirely paid by the patient.
Conclusion
Choosing prenatal tests is a personal decision that requires careful consideration. In this article, we explored the available options, highlighting how maternal age, family history, and pregnancy type significantly influence this decision.
Non-invasive tests such as NIPT offer high accuracy without risks to the fetus, while invasive procedures such as amniocentesis and CVS provide definitive diagnoses but carry a small risk of complications. Therefore, medical counseling is essential to evaluate the most appropriate risk–benefit balance for each individual situation.
We also remind you that no test offers absolute certainty. False positives and false negatives, although rare, can occur even with the most advanced technologies. Specifically, a positive screening result always requires confirmation through diagnostic procedures.
Economic accessibility varies considerably across Italian regions. Some offer NIPT free of charge to all pregnant women, while others limit it to specific cases or exclude it entirely from covered services. To explore this topic further, we encourage you to read our specific articles on NIPT tests available today.
Finally, the diagnostic pathway should always be chosen after an in-depth discussion with your gynecologist, who can recommend the most appropriate exams based on personal circumstances, preferences, and specific risk factors. Similarly, psychological support may be valuable during this process, especially when facing complex decisions based on test results.
Awareness of available options, combined with a realistic understanding of each test’s limitations, is the best ally for experiencing pregnancy with greater peace of mind.
