Medical expert of the article
New publications
Prenatal diagnosis of congenital diseases
Last reviewed: 05.07.2025
All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Prenatal diagnostics is the most effective method of preventing congenital diseases. In many cases, it allows us to clearly resolve the issue of possible damage to the fetus and subsequent termination of pregnancy.
Conducting prenatal diagnostics in the first trimester of pregnancy includes determining the following biochemical markers: PAPP-A and free β-subunit of hCG (β-hCG) - from the 8th to the 13th week of pregnancy, and then - ultrasound examination of the nuchal translucency of the fetus from the 11th to the 13th week. This algorithm is the most effective screening system primarily for Down syndrome, as well as other chromosomal abnormalities (Edwards, Klinefelter, Turner syndromes, etc.), allowing them to be detected in approximately 90% of cases with a false-positive rate of 5%.
In addition to identifying chromosomal abnormalities, the combined determination of these biochemical markers allows us to assess the risk of a number of morphological defects in the fetus and obstetric complications.
The risk limit is considered to be a probability of 1:540 (that is, no higher than the population average).
A study of biochemical markers during the second trimester of pregnancy (14-18 weeks) allows us to assess the risk of the following disorders:
- chromosomal abnormalities in the fetus (Down, Edwards syndromes, etc.);
- neural tube and abdominal wall defects in the fetus;
- obstetric complications in the third trimester of pregnancy.
The risk of having a child with Down syndrome depends on the age of the pregnant woman and is 1:380 for women over 35 and 1:100 for women over 40. Neural tube defects are the most common morphological abnormalities, found in 0.3-3 out of 1000 newborns.
The possibility of prenatal detection of Down syndrome and neural tube defects is based on the relationship between changes in the concentration of a number of biochemical markers present in the blood of pregnant women and the presence of congenital malformations.
Prenatal diagnostics in the second trimester of pregnancy is based on the use of a triple or quadruple test.
The triple test includes determination of the concentration of AFP, free β-subunit of human chorionic gonadotropin and free estriol in the pregnant woman's blood. The optimal time for screening is 16-18 weeks. The effectiveness of detecting Down syndrome using these markers is approximately 69% (the frequency of false positive results is 9.3%).
The quad test is the most common and generally accepted method of prenatal screening for Down syndrome and trisomy 18. It involves determining the concentration of AFP, free estriol, inhibin A and human chorionic gonadotropin in the pregnant woman's blood. The test is performed between 15 and 22 weeks of pregnancy. The effectiveness of the quad test for detecting Down syndrome is 76% (the frequency of false positive results is 6.2%).
To detect congenital malformations of the fetus in the first and second trimesters of pregnancy, an integrated test is used (two-stage prenatal screening for Down syndrome and other chromosomal abnormalities, as well as neural tube defects). The first stage is optimally performed at the 12th week of pregnancy (between the 10th and 13th weeks), it includes determining the concentration of PAPP-A, β-chorionic gonadotropin in the blood of the pregnant woman and an ultrasound examination of the fetus. The second stage is performed 3-4 weeks after the first, it includes a study of the concentration of AFP, free estriol and chorionic gonadotropin in the blood of the pregnant woman. If the screening results are positive, the pregnant woman is offered an additional ultrasound examination and, in some cases, amniocentesis.
The use of the integral test is based on the fact that the markers of the first trimester do not correlate with the markers of the second trimester, so it is possible to calculate the risk independently for the two trimesters. The sensitivity of the integral test reaches 85%.
The reference level of markers (PAPP-A, AFP, β-hCG, free estriol) may vary in different populations and ethnic groups and depends on the method of determination. In this regard, individual marker levels in pregnant women are usually assessed using the MoM (Multiple of Median) indicator. This indicator is the ratio of the individual marker value to the median of the corresponding reference series established for a certain population. The reference values of serum markers for any gestational age are MoM values from 0.5 to 2.
Based on large statistical data, it has been established that in Down syndrome, the average AFP level is 0.7 MoM, hCG - 2 MoM, estriol - 0.75 MoM. In Edwards syndrome, the level of AFP, human chorionic gonadotropin and estriol is 0.7 MoM. When examining the distribution curves of the values of the main markers, a large overlap zone of the norm and pathology is observed, which does not allow using only one indicator for screening, so a full range of markers is needed.
[