Non-Invasive Prenatal Test (NIPT)

General Description

The non-invasive prenatal test (NIPT) is a genetic test performed during pregnancy to analyze fetal DNA characteristics. This test does not pose a risk to the development of the pregnancy, making it a safer alternative to amniocentesis whenever possible. For laboratory analysis, only a peripheral blood sample from the mother is required.

NIPT assesses the risks of numerical or structural chromosomal abnormalities in the fetus:

• Numerical abnormalities (aneuploidies): There are more or fewer than the normal 23 pairs of chromosomes. The most common aneuploidies include:
• Trisomies: The presence of 47 chromosomes. If the extra chromosome is a sex chromosome, it generally does not pose a major health risk or affect fetal survival, although it may lead to fertility issues. However, if it affects an autosome, it can result in miscarriage or death within the first months of life.
• Monosomies: The presence of only 45 chromosomes. This condition is generally incompatible with life, except in cases where females have a single copy of the X chromosome, leading to Turner syndrome (characterized by developmental issues, infertility, and cardiac abnormalities).
• Down syndrome (Trisomy 21): Causes congenital heart defects, physical malformations, and intellectual disabilities.
• Edwards syndrome (Trisomy 18): Leads to malformations in the head and fingers, as well as defects in the heart, lungs, kidneys, and gastrointestinal system. Most affected fetuses die before birth or within the first few days of life.
• Patau syndrome (Trisomy 13): Results in developmental delays, particularly in the cardiovascular and musculoskeletal systems. Only a small percentage of individuals with this condition survive beyond ten years of age.
• Structural abnormalities:
• Duplications: One or more copies of a DNA segment, usually a complete chromosome, are present. The most common diseases associated with this condition primarily affect the central nervous system, such as:
• Huntington's disease: Causes progressive deterioration of nerve cells in the brain, affecting balance and movement. Symptoms usually appear between the ages of 30 and 40.
• Friedreich’s ataxia: Leads to the degeneration of the spinal cord and nerves in the arms and legs, resulting in coordination difficulties. Symptoms typically begin around age 5.
• Deletions: The loss of one or more nucleotides from a DNA segment, including an entire chromosome. The severity of the disease depends on the amount of missing genetic material. This condition can result in miscarriage, premature death, or disorders such as:
• Prader-Willi syndrome: Characterized by low muscle tone (hypotonia), psychomotor delay, physical abnormalities, and hypoventilation, among other symptoms.
• Williams syndrome: Causes intellectual disability, short stature, facial anomalies, pectus excavatum, hypertension, and kidney abnormalities.

This fetal DNA test from maternal blood can also be used to determine fetal sex in early stages of single pregnancies, providing reliable detection in pregnancies beyond eight weeks.

When Is It Indicated?

Any pregnant woman can undergo non-invasive prenatal testing starting from the 10th week of pregnancy, provided there are no more than two fetuses, regardless of whether conception was natural, through in vitro fertilization (IVF), or via gamete donation.

NIPT is particularly recommended in the following cases:

• Women identified as having a high risk of chromosomal abnormalities in first-trimester screening.
• Women with previous pregnancies affected by genetic disorders.
• Couples with personal or family histories of congenital conditions.

How Is It Performed?

To perform this prenatal test, only a maternal blood sample is needed, following the same procedure as routine blood tests:

1. Disinfection of the area and placement of a tourniquet above the elbow.
2. Insertion of a needle into a vein, usually in the inner elbow, followed by removal of the tourniquet.
3. Blood extraction using a syringe.
4. Application of a sterile dressing over the puncture site.

The genetic test during pregnancy requires only a small amount of blood—about 7 cc. In this case, a lavender-top tube is used, which contains ethylenediaminetetraacetic acid (EDTA) to prevent clotting before processing.

In the laboratory, the blood sample is centrifuged to separate plasma from cells. Staining techniques are then used to clearly visualize the DNA chain in the plasma, distinguishing between maternal and fetal DNA. This step is more straightforward when the fetus is male since the Y chromosome can be detected. In the case of a female fetus, alternative methods include analyzing DNA fragment lengths—since fetal DNA fragments are shorter—or studying gene methylation patterns, as molecular changes differ between adults and fetuses. Another option is identifying genetic traits inherited from the father that are absent in the mother’s genome.

Once the fetal DNA is identified, it is analyzed through the following steps:

1. Fragmentation into multiple segments.
2. Labeling with a primer to establish the starting point for analysis.
3. Amplification of each fragment using polymerase chain reaction (PCR) methods.
4. Reconstruction of sequences.
5. Observation under a microscope or with specialized technology to detect genetic abnormalities.

Risks

The non-invasive prenatal test poses no risk to the health of either the mother or the fetus.

Potential side effects are generally related to blood sample collection and may include hematoma formation and dizziness.

What to Expect from a Non-Invasive Prenatal Test

On the day of the blood draw, it is advisable to wear clothing that allows easy access to the arm. During the procedure, a slight pain may be felt when the needle is inserted, but it typically subsides quickly. Some patients experience dizziness after blood collection and may need to lie down with their feet elevated. To prevent bruising, pressure should be applied to the puncture site for a few minutes. Drinking plenty of fluids is recommended to replenish the blood volume as soon as possible.

Results for fetal DNA testing from maternal blood are typically available within approximately 15 days. While NIPT is highly accurate, it is a neonatal screening test, meaning that abnormal results must be confirmed with a chorionic villus sampling (CVS), which involves collecting a sample from the placenta.

Medical Specialties That Request Non-Invasive Prenatal Testing

NIPT is commonly requested in the fields of gynecology, obstetrics, and genetics.