Fetal pathologies: at what stage are they detected, what tests to take, who is at risk. Intrauterine malformations of the fetus, definition (screening, analysis), prevention, causes

Who needs to see a geneticist when planning a pregnancy and definitely before it occurs?

There is such a thing as genetic risk groups. These groups include:

Married couples with hereditary family diseases;

Consanguineous marriages;

Women with an unfavorable history: having repeated miscarriages, stillbirth, infertility without an established medical cause;

Exposure of future parents to unfavorable factors: radiation, prolonged contact with harmful chemicals, use during the period of conception of drugs with teratogenic, i.e. causing deformities of the fetus, action;

Women under 18 and over 35 and men over 40 years old, because At this age, the risk of mutations in genes increases.

Thus, almost every second couple (more and more often women give birth after 35, doctors diagnose infertility, and first pregnancies end in miscarriages) should undergo a genetic consultation when planning a pregnancy.

When is genetic counseling necessary in early pregnancy?
Early pregnancy is the most important and vulnerable period of fetal formation. Various unfavorable situations can potentially disrupt the development of the organs of the unborn child. Patients are concerned about how it will affect the development of the child and whether they should have an abortion if they inadvertently in the early stages of pregnancy:

Got sick with influenza, ARVI, rubella, chicken pox, herpes, hepatitis, HIV-infected, etc.

Have taken medications whose labels indicate “contraindicated during pregnancy”;

Drank alcohol, drugs, smoked (“ drunken conception" - how dangerous is this?);

We treated the teeth with an X-ray examination and did fluorography;

They sunbathed, rode horses, went mountain climbing, diving, dyed their hair, got piercings, etc.

Laboratory diagnosis of malformations during pregnancy

And now the desired pregnancy has come. Is it possible to find out early on whether everything is okay? Modern medicine answers this question positively. Obstetricians-gynecologists and geneticists have at their disposal a variety of diagnostic methods that make it possible to judge with high probability the presence of developmental defects even when the child is in the womb. The chances of accuracy are increasing due to improvements in ultrasound technology and laboratory diagnostics. And in last years Screening research methods are being used more and more widely. Screening is a massive “sifting” study. It is carried out on all pregnant women to identify risk groups. Why is it carried out for everyone? Because statistics show that among mothers who gave birth to children with Down syndrome, only 46% were over 35 years old. And only 2.8% had a history of giving birth to children with chromosomal diseases or developmental defects. This once again proves that chromosomal pathology is the lot not so much of patients at risk, but of young unburdened families who do not have any diseases.

Screening methods include determination of biochemical markers (BM) in maternal blood serum and ultrasound of the fetus. Such BMs in the first trimester are pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG). In the second trimester, these BMs are alpha-fetoprotein (AFP), hCG and estriol. In the first trimester, BM examination is carried out from 8 to 12-13 weeks of pregnancy (early prenatal screening), in the second - from 16 to 20 weeks of pregnancy (late prenatal screening or triple test).

AFP is the main component of the blood of the developing fetus. This protein is produced by the fetal liver and is excreted into the fetal cavity in urine. ovum, is absorbed through the fruit membranes and enters the mother’s blood. By examining blood from the mother's vein, one can judge its quantity.

It must be said that an increase or decrease in the amount of AFP by 2.5 or more times compared to the norm is significant for diagnosis. For example, with anencephaly (absence of the brain), this figure increases 7 times!

It is very difficult for parents to hear that their child has been diagnosed with developmental disabilities. This information often becomes known during intrauterine diagnostics. As a rule, the family experiences severe psychological shock, but what’s even worse is that parents often begin to blame themselves for what happened, not hoping that they will ever be able to give birth healthy child. Why do they arise? birth defects, and what next for children with developmental disabilities?

First of all, you need to know: a child with congenital defects can be born in any family, even young and healthy parents. The frequency of these cases reaches 5% according to statistics. Identification of the causes of congenital malformations of the fetus (CHD) is one of the the most important tasks medicine, but at the same time it must be said that so far not all of them have been studied and classified. Up to 50% of pathologies cannot be associated with any specific cause. However, much work has already been done in this regard.

Developmental defects (anomalies, defects) are considered to be functional and structural deviations from the norm. The most severe defects include:

• Congenital heart defects;
• Neural tube defects;
• Down syndrome.

Fetal malformations: causes

All VPRs can be divided into two large groups: hereditary (gene mutations) and acquired during intrauterine development. Often, both of these factors can affect the occurrence of congenital malformation, and such causes are called multifactorial.

According to the severity, fetal anomalies can be classified as moderately severe (those that require treatment, but do not threaten the life of the child), severe - requiring immediate treatment, and fatal, incompatible with life.

Most congenital malformations occur during the first trimester. Gametopathies are the result of mutations in germ cells or abnormalities of sperm and eggs. Blastopathy develops during the first two weeks after fertilization. Embryopathies are the most common pathologies and occur between 2 and 8 weeks of pregnancy. Finally, fetopathy can occur after 9 weeks - for example, cryptorchidism or organ hypoplasia.

Fetal malformations can affect one organ or several at the same time. Systemic disturbances include anomalies respiratory system, nervous, cardiovascular, musculoskeletal, reproductive, urinary and digestive systems. Defects such as defects of the face, eyes, ears, neck, palate and lips are divided into separate groups.

Is it possible to assume in advance that the child may have congenital malformation? There are risk groups that include the following categories of parents:

• Families in which children with congenital malformation have already been born;
• Families where parents have blood relatives with congenital malformation;
• Parents' age is over 35 years for women and 50 years for men;
• Consanguinity between parents;
• Exposure to teratogenic factors (living in an environmentally unfavorable place, radiation, working in hazardous industries).

Teratogenic causes of fetal malformations are extremely extensive - there are at least four hundred of them. All parents, without exception, know about the dangers of drug addiction, alcoholism and smoking during pregnancy, but the causes of congenital malformation are not limited to these points.

One of the very hazardous factors impacts are viral diseases, suffered by a woman in the first trimester of pregnancy. This is especially true for the rubella virus. Unfortunately, in some cases, the fetus may experience irreversible changes that are not life-threatening.

Reception medicines(especially hormonal) in the first trimester can also be extremely dangerous, so doctors never tire of warning that any treatment during this period should only be carried out under the supervision of a doctor.

Endocrine disorders in the mother, including diabetes, also belong to risk groups. Irradiation (radiation, x-rays) in some cases can cause fetal development abnormalities, and that is why such examinations in the first trimester are carried out only for health reasons and under reliable protection.

Living in an environmentally unfavorable area - near mines, metallurgical enterprises and similar places - poses a great danger to the development of a child. In addition, developmental abnormalities of cardio-vascular system fetuses are also found in women living in high mountains with thin air. Injuries and falls incorrect position fetus, the presence of tumors can affect the blood supply to the fetus and cause congenital birth defects.

Maternal nutrition can also have an impact on the occurrence of fetal malformations - for example, it has been proven that deficiency folic acid increases the risk of neural tube developmental abnormalities in a child. Finally, the child’s father’s work in hazardous work can lead to sperm abnormalities, which is also one of the causes of congenital malformation.

What to do if a child has a developmental defect

We have already spoken about the shock that invariably befalls parents at this news. But you need to try to deal with it quickly - perhaps with the help of specialists. If the pathologies are incompatible with life and the timing allows for termination of the pregnancy, doctors will immediately say so.

The life of children with fetal developmental defects largely depends on the timeliness of measures taken. Today, even the most complex defects are successfully operated on, and operations are often carried out in the first days of life. A number of defects make it possible to postpone surgery or even undergo conservative treatment. Parents should try to collect maximum amount information about this disease in order to know all its symptoms and treatment features. Of course, such babies will be under constant medical supervision and undergo regular examinations. There are a number of dietary restrictions and physical activity, which the pediatrician will tell you about.

AFP is the main component of the liquid part of the blood (serum) of the developing fetus. This protein is produced yolk sac and the liver of the fetus, enters the amniotic fluid with its urine, enters the mother’s blood through the placenta and is absorbed by the fetal membranes. By examining blood from a mother's vein, we can judge the amount of alpha-fetoprotein produced and secreted by the fetus. AFP is detected in the mother's blood from the 5-6th week of pregnancy. The amount of AFP in the mother's blood changes with a more massive release of this component. So, if any parts of the neural tube are not fused large quantity The baby's serum spills into the amniotic cavity and enters the mother's blood.

Elevated levels of AFP are determined in maternal blood:

• with defects in the fusion of the neural tube - herniation of the spinal cord or brain;
• with defects in the fusion of the anterior abdominal wall, when its muscles and skin do not cover the internal organs, and the intestines and other organs are covered with a thin film of the stretched umbilical cord (gastroschisis);
• for kidney abnormalities;
• with inflammation of the duodenum.

It must be said that an increase in the number of AFP by 2.5 or more times compared to the average for given period pregnancy. For example, with anencephaly (absence of the brain), the level of AFP increases approximately 7 times.

But a change in AFP level does not necessarily indicate any pathology of the fetus. It can also be observed in such conditions as the threat of miscarriage due to fetoplacental insufficiency, when the blood flow between the placenta and the fetus is disrupted, as well as when multiple pregnancy, during which this protein is produced by several fruits.

In 30% of cases of chromosomal disorders, when the fetus has additional chromosomes in one pair or another, which leads to the formation multiple defects development (Down, Edwards, Shereshevsky-Turner syndromes), the AFP level is reduced.

HCG is a protein produced by chorion cells (the chorion is the part of the embryo from which the placenta is subsequently formed). This protein is detected in a woman’s body from the 10-12th day after fertilization. It is its presence that allows you to confirm pregnancy using a test at home. The reaction that occurs on the test strip is qualitative, that is, it indicates the presence or absence of hCG. quantitation HCG allows us to judge the course of pregnancy: for example, with an ectopic or non-developing pregnancy the rate of increase in hCG is not normal. At the beginning of the second trimester, the level of human chorionic gonadotropin is used as one of the diagnostic signs of malformations and chromosomal pathology of the fetus.
The level of hCG in the blood of a pregnant woman with Down syndrome usually increases, and with Edwards syndrome (a disease characterized by multiple malformations internal organs And mental retardation) – decreases.

E3. The production of estriol begins in the fetal liver and ends in the placenta. Thus, both the fetus and the placenta take part in the “production” of this substance. The concentration of E3 in the blood serum of a pregnant woman can be used to judge the condition of the fetus. Normally, estriol levels increase throughout pregnancy.

WHEN, TO WHOM AND HOW IS THE TRIPLE TEST CONDUCTED

The triple test is performed between 15 and 20 weeks of pregnancy. At this time, the indicators of markers of genetic pathology are most standardized, that is, they are the same for all women whose pregnancy proceeds normally. Many medical institutions test AFP and hCG (double test) or only AFP. I would like to emphasize that when studying any one component of the triple test, the diagnostic significance of the study is reduced, since a deviation from the norm of only one of the indicators cannot reliably indicate fetal pathology. Overall, the diagnostic value of the triple test is up to 90% for detecting malformations nervous system, 60-70% - for detection of chromosomal diseases.

Currently, examination for markers of genetic pathology is mandatory for all pregnant women, but, unfortunately, the equipment of ordinary government medical institutions (antenatal clinics) in most cases allows you to examine only one or two components of the triple test. If abnormalities are detected, the patient is referred to a geneticist for further examination.

There is a group of pregnant women who are prescribed genetic counseling regardless of test results: this is the so-called risk group, in which the likelihood of having children with congenital malformations and chromosomal abnormalities is higher than in the population as a whole.
Risk factors include:

• woman's age over 35 years,
• cases of familial carriage of chromosomal diseases,
• birth of previous children with developmental defects,
• radiation exposure of one of the spouses,
• taking cytostatics or antiepileptic drugs,
• recurrent miscarriage,
• determination of signs of fetal pathology by ultrasound.

If deviations are detected, it is advisable to repeat the analysis; if at the same time the indicators maintain a tendency to decrease or increase, additional studies are carried out. It is better to take the test at the beginning of the specified period, i.e. at 15-16 weeks, in order to be able to repeat the examination if necessary and confirm or refute certain assumptions..

Particular concern is caused by a decrease in AFP in combination with a persistent increase in hCG levels. This combination allows one to suspect that the child has Down syndrome. But only in 60% of cases, women carrying a fetus with Down syndrome have abnormal triple test results; in 40% of cases there are no deviations in laboratory parameters.

It should be emphasized that the study of markers of genetic pathology is screening, that is, it is carried out on all pregnant women to identify a risk group (in other words, you may not even suspect that within general examination This test was taken from you during pregnancy).

Patients at risk undergo a more detailed diagnosis of fetal malformations and chromosomal pathologies: as part of medical genetic counseling, they are prescribed additional ultrasound examinations and are offered invasive diagnostic methods (with penetration into the amniotic cavity). The most reliable way to make a diagnosis is to study the chromosome set of fetal cells. To obtain fetal cells, the anterior abdominal wall is pierced with a thin needle, and amniotic fluid, which contains fetal cells (amniocentesis) or fetal cord blood (cordocentesis), is removed. When conducting invasive methods diagnosis significantly increases the risk of fetal loss; In addition, as with any surgical intervention, there is a risk of infection. Therefore, invasive techniques are contraindicated in cases of threatened miscarriage and acute infectious diseases.

Considering the time frame within which it is customary to carry out a triple test, sometimes the question arises about the advisability of this analysis, because the time frame medical abortion limited to the 12th week. In this regard, it should be remembered that every woman who carries a baby under her heart, at one stage or another of pregnancy, is visited by doubts about the usefulness of the unborn child. A triple test will help you dispel unpleasant thoughts, and if changes in markers of genetic pathology of the fetus are detected, you will undergo additional examinations in a timely manner. If unpleasant assumptions are confirmed, it will be possible to terminate the pregnancy or, at least, prepare for the fact that immediately after birth the child may need surgical intervention to correct the detected malformations. At the same time, remember that the doctor has the right to suggest one or another option for managing pregnancy, and the final decision in any case is made by the family.

The presence of ideal tests and the wonderful well-being of the pregnant woman, her young age and an impeccable medical history (information about previous diseases, living conditions, surgery, injuries, chronic pathology, heredity, etc.) are not yet a 100% guarantee that the child does not have chromosomal abnormalities.

Chromosomal abnormalities of the fetus. Signs

Signs of the presence of a chromosomal abnormality (CA) of the fetus during pregnancy:

• threat of miscarriage or at least nagging pain lower abdomen from early pregnancy and throughout pregnancy,
• low levels of AFP and PAPP-A and increase in hCG on time,
• fetal cervical fold more than 2 mm at term,
• low fetal activity (movements),
• enlargement of the renal pelvis according to ultrasound during pregnancy,
• stunting tubular bones, beginning with ,
• early aging of the placenta,
• hypoplasia of the placenta,
• fetal hypoxia,
• poor Doppler and CTG indicators,
• oligohydramnios/polyhydramnios.

Each of these signs individually and even all together can be variants of the norm.

Diagnostics of CA

Of the usual tests, the first screening or double test is the most informative. It must be done strictly on time. It consists of an ultrasound of the fetus (measurement of the neck crease is especially important) and a blood test for AFP, PAPP-A and hCG.

The analysis does not give an exact answer to the question of the presence or absence of CA. Its task is to calculate risks depending on the results, as well as the age and medical history of the pregnant woman. The second screening, the so-called “triple test”, is not informative for identifying CA. It is possible to find out for sure whether the unborn child has CA only with the help of invasive methods - chorionic villus biopsy, sampling cord blood, analysis amniotic fluid. The purpose of these tests is to determine the karyotype of the fetus. Accuracy - 98%. The risk of miscarriage is 1-2%. CA cannot be treated. After CA is identified, all that medicine can offer is termination of pregnancy.

Should I do this analysis or not?

When making a decision, you need to answer the following questions:

• Doesn't the risk of miscarriage exceed the risk of having CA in the fetus?
• will you terminate the pregnancy if CA is detected?
• What kind of CA do doctors suspect, what is the prognosis for the child’s health?
• Are you ready for the birth of a child with CA?

Causes of chromosomal abnormalities

There are no clear causes of CA. Increased risk exists if:

• the age of the mother and father exceeds 35 years,
• blood relatives have CA,
• there is a balanced translocation in blood relatives or parents,
• parents work for hazardous industries, the family lives in an environmentally unfavorable area.

Mechanism of occurrence of CA

CA occurs in the fetus at the moment of formation of the zygote, i.e. during the fusion of egg and sperm. The mother and father cells each carry 23 chromosomes (23 from mom and 23 from dad). Both cells may already carry “broken” chromosomes (even if mom and dad are absolutely healthy). A failure can also occur at the moment of fusion of two absolutely healthy parent cells. In this case, the chromosomes of the fetus “diverge” incorrectly. This process has not yet been studied and cannot be controlled.

CA - chromosomal syndromes

More than 300 chromosomal syndromes have been studied and described.

Considering that humans have 23 paired chromosomes and there are several types of aberrations, the number of chromosomal syndromes that are not described in the literature and that arise again is not limited.

Aberrations can be different: complete and partial trisomies, deletions, monosomies, translocation mosaicism, etc. The severity of symptoms in chromosomal syndrome depends on the type of aberration. The most favorable type is a balanced translocation. People with such changes are no different from ordinary people; their peculiarity can only be identified by karyotyping, but they have an increased risk of having children with chromosomal syndromes - from 10 to 50% (the average risk in the population is 5%).

The next least “traumatic” type of aberration is mosaicism, in which a chromosomal disorder does not manifest itself in all cells and/or organs. Partial trisomies and deletions already cause significant developmental defects, sometimes incompatible with life.

The most severe type is complete trisomy or chromosome monosomy.

Most pregnancies with chromosomal pathology of the fetus are rejected by the body itself at the earliest stages or at 20-23 weeks, since with chromosomal pathology of the fetus there is a high probability of various pregnancy pathologies (miscarriage, threat of miscarriage, uterine hypertonicity, premature aging placenta, toxicosis, gestosis, fetal hypoxia, etc.). Also, many babies do not live to see one year old due to multiple developmental defects. Average duration The lifespan of people with CA is 30 years, but there are described cases of patients with CA who have lived to 60 years or more.

Development of people with CA

People with chromosomal syndromes can be both severely disabled and absolutely full-fledged members of society, who have received a full education and have a regular job. It all depends on the type of aberration, general condition the body and work of relatives and friends. In most cases, people with chromosomal syndromes can take care of themselves, communicate, and do feasible work. Intelligence is reduced, there are chronic diseases of organs and body systems.

The trend of babies being born with developmental defects is increasing. Today, according to statistics, in European countries For every thousand births, approximately 3-4 children are born with a developmental anomaly. In Russia, fetal anomalies are more common - per thousand newborns there are 5-6 children with congenital defects. Almost half of the cases of pathological intrauterine development of the fetus still remain unknown, perhaps due to the influence of several factors affecting the embryo. Why are fetal developmental anomalies so common? How are intrauterine abnormalities diagnosed?

Causes of fetal development abnormalities

On intrauterine development many factors influence - they can be external, for example, ecology, or internal - the embryo is influenced by the state of health of the mother. Heredity plays key role in question proper development fetus Let's look in as much detail as possible at each reason why a child may be born with some kind of anomaly.

1. Heredity. Very often, the cause of improper formation of organs and systems in the fetus is a hereditary factor. If the parents have a history of developmental defects, then the chances of giving birth to an unhealthy child increase.

2. Infections, suffered by the mother, especially in the early stages, are dangerous for the embryo. These include viral diseases such as cytomegalovirus, measles, rubella, mumps and others. Even the flu virus is dangerous. Infections suffered by a pregnant woman lead to heart defects, underdevelopment of the brain, deafness, eye abnormalities and other problems.

3. Bad habits mothers– if a pregnant woman takes drugs, alcohol, or smokes, then toxic substances reaching the fetus through the mother’s bloodstream can cause significant abnormalities in its development.

4. Medications. Taking various medications in the early stages of pregnancy has a detrimental effect on the embryo. If the need for treatment arises, pregnant women should not take pills and mixtures at their own discretion, only under the supervision of a doctor.

5. Exposure to chemicals. During pregnancy (especially in the 1st trimester), strong toxic chemicals - mercury vapor, lead, benzene - pose a particular danger to the embryo. If a woman’s work is somehow connected with contact with these substances, it is necessary to leave her place of work even when planning pregnancy.

6. Irradiation. The embryo is many times more susceptible to x-ray radiation. It has a particularly strong effect on the central nervous system and in some cases leads to underdevelopment of the brain, hydrocephalus, and mutations of the limbs and genitals.

7. Mechanical factors. Injuries during pregnancy, tumors in the uterus, and abnormal position of the fetus can also cause the development of intrauterine anomalies. Fortunately, modern medicine allows you to find out in advance whether the baby is developing correctly. Let's consider methods for diagnosing fetal abnormalities during pregnancy.

Diagnosis of intrauterine anomalies

On initial stage At pregnancy, the woman undergoes an ultrasound to confirm that she is pregnant. This method allows you to confirm the introduction of the egg into the mother’s endometrium and exclude.

1st trimester

At the next stage, starting from 9 to 13 weeks of pregnancy, expectant mothers undergo the first screening test. To do this, the woman’s venous blood is taken and tested for biochemical markers:

1. Human chorionic gonadotropin person ( hCG hormone), which in the first trimester constantly increases in a certain progression. If the hCG level is reduced, this will help determine any abnormalities during pregnancy.

2. Plasma protein - with increasing gestation period, this indicator is constantly growing. Its decrease may indicate the presence of gene abnormalities in the fetus - trisomy 21 () and trisomy 18 (the so-called Edwards syndrome).

Ultrasound examination in the 1st trimester allows you to identify chromosomal abnormalities by measuring the thickness of the collar zone of the embryo. If it exceeds 3 mm, the likelihood of pathology is high.

2nd trimester

Second trimester screening is performed from 16 to 20 weeks of gestation. At this stage, other biochemical markers are examined:

1. Alpha fetoprotein - produced by the fetal liver. This protein enters the mother’s blood and its content is very informative in terms of identifying intrauterine anomalies. A multiple increase in this hormone can signal a pathology such as the absence of a brain in the fetus.

2. HCG - the second screening also includes the determination hCG level in a woman.

3. Estriol - its production increases during pregnancy by the placenta, and this hormone is also produced by the liver of the embryo. Deviations from the norm of estriol in the mother's blood serum allows us to judge intrauterine anomalies.

If there is a suspicion of abnormal development of the baby in the womb, women are recommended additional methods for diagnosing anomalies. Among them, such studies are chorionic villus biopsy, amniocentesis, as well as placentocentesis and cordocentesis. Each of these studies is conducted and is informative on at a certain stage gestation. All of the above procedures are performed under anesthesia and are prescribed only if there are strict indications.