Medical Genetics - V. M. Zaporozhan 2005

Prevention of Hereditary Diseases
Prenatal Diagnosis of Hereditary Diseases and Congenital Malformations
Non-invasive methods - Comprehensive screening program for prenatal diagnosis of congenital malformations and chromosomal syndromes. Prenatal screening

Non-Invasive Methods are used for screening hereditary pathologies during Pregnancy. The most effective approach combines serum markers and ultrasound.

Today, mass prenatal screening includes:

— Down syndrome and other chromosomal abnormalities;

— neural tube defects;

— other Congenital Malformations.

The following examination scheme for pregnant women has been proposed for mass screening (S. B. Arbuzova, 2002).

1. A two-stage prenatal Diagnosis is performed for women who register During the first trimester of pregnancy.

The First stage (10-14 weeks) involves the analysis of PAPP-A and β-hCG markers, along with an ultrasound scan (measuring nuchal translucency and visualizing nasal bones). This is performed to screen for fetuses with Down syndrome and other chromosomal syndromes. At this gestational age, up to 87% of fetuses with chromosomal abnormalities can be detected.

Down syndrome and other chromosomal abnormalities are characterized by increased nuchal translucency, absence of the Nasal bone, decreased PAPP-A concentration, and elevated β-hCG. In Edwards' syndrome, a decrease in both PAPP-A and β-hCG is observed. Special computer programs calculate the individual genetic risk for each pregnant woman, taking into account gestational age, maternal age, body weight, etc. To ensure accurate calculation of individual genetic risk using computer software, the ultrasound and biochemical examination of the pregnant woman should be performed simultaneously. Positive results allow classifying the pregnant woman into a high-risk group for chromosomal abnormalities, which requires diagnostic confirmation (invasive methods followed by fetal Cell karyotyping).

The Second Stage (15-20 weeks) involves AFP analysis (preferably at week 16) and ultrasound. The primary goal is to diagnose neural tube defects and other malformations. Elevated AFP concentration is characteristic of neural tube defects, whereas decreased levels indicate chromosomal abnormalities. Ultrasound may reveal Congenital malformations and markers of chromosomal abnormalities. The diagnostic efficacy for chromosomal abnormalities is significantly lower than in the first trimester. The obtained results are also analyzed using specialized computer programs. To confirm a neural tube defect, a detailed Ultrasound examination is performed; if necessary, amniocentesis is carried out to determine AFP concentration in the Amniotic Fluid. To confirm a chromosomal abnormality, invasive Diagnostics followed by karyotyping is required. To clarify the diagnosis of a congenital malformation, a repeated detailed fetal ultrasound is performed.

2. For women who register during the second trimester, a single-stage diagnosis is performed—AFP and hCG analysis at 15-20 weeks of gestation. An ultrasound is also performed during this timeframe. The purpose of the study is to diagnose Down syndrome and other chromosomal abnormalities, neural tube defects, and other malformations. The diagnostic efficacy for chromosomal abnormalities In the second trimester is 60-70%.

In some countries, three serum markers are determined during this period—AFP, hCG, and uE3 (the so-called "triple test"). The results of the triple test for two chromosomal syndromes are presented in Table 11.6.

Recently, a new biochemical marker, inhibin A, has been discovered, the concentration of which in the maternal serum is elevated in Down syndrome. Combined with AFP, hCG, and uE3, it forms the most informative "quadruple test". It is performed at the same time as the triple test. The detection rate for Down syndrome increases up to 75%.

An elevated AFP level is specific to neural tube defects. During this period, neural tube defects can also be diagnosed via ultrasound.