Thanks to the widespread use of non-invasive methods for the diagnosis of fetal genetic defects, it is many times possible to avoid invasive tests, which carry a certain risk of pregnancy complications. This article presents the available testing methods with which prenatal diagnosis should begin in every pregnant woman.
Table of contents:
- Early diagnosis of genetic defects
- Nuchal translucency
- Nasal bone
- The most common tests in prenatal diagnosis
Early diagnosis of genetic defects
In the ultrasound examination used for the early diagnosis of genetic defects in the fetus (in the 1st trimester of pregnancy), the most important markers are nuchal translucency and the presence of nasal bone.
Nuchal translucency
The nuchal translucency(HTN) is the width of the subcutaneous tissue on the posterior surface of the fetal neck. It is only measured between 11 and 14 weeks of pregnancy in order to obtain the most reliable result. Increased HTN (nuchal translucency) often coexists with aneuploidy (chromosomal abnormalities).
Widening of nuchal translucency can be associated with:
- the risk of Down's syndrome and other genetic defects,
- the occurrence of fetal heart defects,
- lung defects,
- bone dysplasia,
- delayed development of lymphatic vessels in the subcutaneous tissue,
- diaphragmatic or umbilical hernia
- other abnormalities.
It also represents an increased risk factor for having a baby with trisomy 21(Down syndrome), 18 (Edward syndrome) and 13 (Patau syndrome), triploidy, Turner syndrome. Accurate measurement of HTN and assessment of the risk of fetal abnormalities is made by taking into account the correlation of HTN width with the parietal-subparietal length dimension of the CRL and reliably determined gestational age and maternal age.
Nasal bone
The diagnosis of fetal aneuploidy up to the 12th week of gestation uses the visualisation of the nasal bone as a marker, while from the 13th week onwards it is already measured. The assessment of the regularity of the nasal bone sometimes poses many difficulties and therefore requires a great deal of experience on the part of the examiner. Delayed ossification of the nasal bone often coexists with Down's syndrome, as well as being characteristic of fragile X syndrome - one of the most common causes of mental retardation.
Prenatal diagnosis - information for patients, photo: panthermedia
The results of the ultrasound genetic test obtained are analysed by computer. A special computer programme calculates the risk of genetic defects based on the HTN, the age of the mother, certain dimensions of the embryo and other parameters. The Medical US result is a screening test and is only indicative in order to determine further management. Accurate assessment of both nuchal translucency and nasal bone has a significant impact on increasing the specificity of genetic testing.
The most common tests in prenatal diagnosis
PAPP-A test
Is a non-invasive test mainly for Down syndrome, Edwards syndrome and Patau syndrome in the fetus. It is performed between 10 and 14 weeks of pregnancy. Gestational age is determined from the date of the last menstrual period or determined by ultrasound after analysis of the basal dimensions. The first stage of the examination is a genetic ultrasound of the fetus with measurement of nuchal translucency and visualisation of the nasal bone. A venous blood sample is then taken from the pregnant woman and she is subjected to biochemical tests, consisting of the determination of pregnancy protein A (PAPP-A) and the free subunit of chorionic gonadotropin (free beta HCG).
In pregnancies complicated by Down syndrome, PAPP-A levels are reduced and free beta hCG and nuchal translucency are elevated. In pregnancies with Edwards syndrome and Patau syndrome, PAPP-A and beta-hCG levels are decreased and nuchal translucency is increased. The sensitivity of the test is approximately 90%.
Duplicate test
This test is an alternative for women who have missed the PAPP-A test by the specified date. It is mainly aimed at detecting Down's syndrome and open neural tube defects. The double test is performed between the 14th and 16th week of pregnancy. The gestational age is determined as for the PAPP-A test. An ultrasound examination is performed first, followed by analysis of AFP (alpha-fetoprotein) and free beta HCG concentrations.
Triple test
It is performed from the 17th to the end of the 20th week of pregnancy determined according to the date of the last menstrual period or the gestational age determined by Medical US examination. An ultrasound examination, usually supplemented by a UC examination of the fetal heart, is followed by an analysis of the concentrations of AFP (alpha-fetoprotein), free beta HCG and E3 (free oestradiol). The sensitivity of the test is, as with the duplicate test, approximately 60%.
Integrated test
This is a combination of the PAPP-A test, performed between 11 and 13 weeks of pregnancy, and the triple test at 15-20 weeks. The risk is calculated from the results of both tests together. The advantage of this test is the lower risk of false positives.
Based on the results obtained from the individual tests, only the risk of certain genetic defects can be determined and the need for invasive tests such as amniocentesis can be considered.
Despite their high sensitivity, they do not give 100% certainty that the baby has a defect, they only assess the risk of the defect. Only invasive tests are more precise. However, there are many chromosomal aberrations for which there are no ultrasound or biochemical markers used in non-invasive screening. Unfortunately, there are no diagnostic methods that can rule out or confirm 100% all the diseases that a foetus may be affected by, but with the capabilities of the methods currently available, it is possible to determine the risk of a defect with a high degree of accuracy.
In Poland, in comparison with other highly developed countries, prenatal tests are still carried out relatively little. This is probably due not only to the very high costs of such tests, but also to the low accessibility to them. There is still a small number of appropriately qualified specialists with the right authorisation to perform these tests, as well as a small number of centres with the right class of highly specialised equipment, which are two essential elements ensuring the highest reliability of the tests performed.
