Down Syndrome - Prenatal Screening and Diagnosis (Part One)

Prenatal Diagnosis and Its Objectives

Prenatal diagnosis is an integral part of maternal-fetal medicine aimed at the prenatal identification of various fetal diseases.

Initially, its subjects were genetic diseases, chromosomal abnormalities, and fetal malformations. Later, its objectives expanded to include the detection of pre-eclampsia, fetal hypoxia, fetal anemia in cases of RH isoimmunization, etc.

Addressing all these objectives is impossible in a single article, hence the subject of this writing will be chromosomal defects alone.

Screening and Prenatal Diagnosis of Chromosomal Defects

Screening

To detect various pathologies while they are still subclinical, medicine has at its disposal screening tests, which are parameters, characteristics, or substances found abnormally (more often, less often, more, less compared to the norm) in an individual with a specific pathology.

The purpose of screening programs is to select those patients who will undergo invasive tests that will certify the disease in question at a subclinical stage, when alternatives are more numerous, less expensive, more effective, and with fewer complications.

For a screening test to be valid, it must be: aimed at a relatively common disease, cost-effective, compliant, have high screening capability, and minimal false-positive results.

Screening and prenatal diagnosis of fetal anomalies represent a significant problem for maternal-fetal medicine. The goal is the prevention of the birth of a fetus with reduced biological potential that would constitute a significant burden for the family and society.

Without delving into ethical issues, prenatal screening can be seen as an improvement of the natural selection process, to which abnormal conception products are subjected. Active intervention is especially necessary in cases with defects where natural selection in utero is less effective (e.g., Down syndrome).

Chromosomal Defects and Down Syndrome

Among them, the most well-known is Down syndrome (DS), which in 95% of cases is caused by trisomy 21 (the presence of an extra chromosome in the 21st chromosome pair). Other chromosomopathies are trisomy 13, 18, Turner syndrome, Klinefelter, etc.

DS, being one of the few chromosomopathies that can result in the birth of a living fetus, consequently has a greater family and social impact, as it is associated with mental retardation, cardiac and gastrointestinal defects, leukemia, Alzheimer's dementia, and low immunity. (fig.4) Its incidence is 1/600 live births; (the most common trisomy), hence the justification for national screening programs.

These programs are standards that indicate the level of maternal-fetal medicine and public health. Unfortunately, such standards are only met in developed countries.

Strategy in Screening for Down Syndrome

Every pregnant woman has a certain risk that her child will be Down. The risk of giving birth to a Down fetus in a 20-year-old pregnant woman is 1/1500, while at 40 years old, it is 1/100. This risk increases with maternal age (especially after the age of 35) and decreases with pregnancy progression (as some are spontaneously aborted).

However, the majority of Down fetuses are born to women younger than 35 years, who are more numerous. The product of the risk associated with maternal age and that associated with pregnancy age is called the baseline risk (background risk or a priori).

The diagnosis of DS is certified by chorionic villus sampling or amniocentesis, these invasive procedures are associated with a 1% risk of abortion. These procedures are reserved only for pregnant women > 35 years old or those who have tested positive from the screening strategy. Therefore, the object of screening is only women younger than 35 years.

The screening strategy consists of a combination of several screening tests, aimed at calculating the final risk. If this risk is increased or higher than the abortive risk of invasive diagnoses, then the patient is selected for invasive diagnosis). The screening strategy starts in two different phases.

The 1st phase is ultrascreening in the first trimester (from week 11 to 14). At this moment, fetal nuchal translucency (TN) is measured through ultrasound, and the bi-test is performed.

* Nuchal Translucency represents the physiological collection of fluid in the area of the fetus's nape in the time interval from week 11 to 14. (fig.1) It has been known for years now that TN greater than the norm is associated with an increased risk for DS. (fig.2. 3)