Prenatal Testing

Prenatal testing allows for the early detection of congenital anomalies and genetic disorders in the fetus and consists of predictive (screening) and diagnostic tests.

Major congenital anomalies (MCA) are detected by ultrasound in approximately 1–3% of pregnancies and account for a significant proportion of pre- and perinatal deaths, as well as neonatal morbidity. Although many heterogeneous causes have been identified—including intrauterine infections, genetic factors, and environmental influences—in most cases, no recognizable underlying risk factors are present.

Early detection in the fetus is essential for informed decision-making by the couple regarding pregnancy management, prenatal and postnatal medical care, and targeted therapy.

Providing genetic counseling by qualified health professionals to parents at increased risk for fetal anomalies is essential to:

Understand and recognize indications for prenatal diagnosis in the fetus.

Understand the medical aspects of diagnosing a genetic disease or congenital anomaly (classification of the disorder, inheritance pattern, recurrence risk in future pregnancies).

The two main categories of prenatal tests are:

Screening tests are generally used to estimate the likelihood of serious, primarily genetic, conditions or other developmental anomalies in the fetus. When screening tests indicate that a fetus is at increased risk, diagnostic tests—often invasive—can be performed to confirm the presence of a disorder.

The most common screening tests include routine ultrasounds, blood tests, blood pressure measurement, and Non-Invasive Prenatal Testing (NIPT), which uses cell-free fetal DNA circulating in the mother’s blood.

Specifically:

• First-trimester biochemical screening, PAPP-A test for Down, Edwards, and Patau syndromes
• Placental growth factor (PlGF) for preeclampsia screening in asymptomatic pregnant women
• sFlt-1/PlGF ratio for high-risk pregnancies regarding preeclampsia development
• Non-Invasive Prenatal Testing (PrenaTest, NIPT), a next-generation, fast, safe, cost-effective test with the highest positive predictive value among similar tests

When screening tests indicate that a fetus is at increased risk, diagnostic tests—often invasive—are performed to confirm the presence of a disorder.

Common diagnostic invasive tests include conventional and molecular karyotyping (Chromosomal Microarray Analysis, CMA) performed on fetal cells obtained via chorionic villus sampling or amniocentesis. The next step for monogenic disorder analysis at the nucleotide level is fetal DNA analysis using Next Generation Sequencing (NGS).

The molecular karyotype (CMA) is now a key high-sensitivity test for detecting deletions and duplications across the genome associated with clinically significant syndromes.

Next Generation Sequencing (NGS), particularly Whole Exome Sequencing (WES) of coding regions, is a vital tool for detecting genetic disorders caused by single-nucleotide or small insertion/deletion variants (small INDELs) within the coding regions of the genome. The potential additional diagnostic value of NGS in fetuses with abnormal ultrasound findings is estimated at 10–12% on average.