Infectious causes of non-pregnancy

The question of the etiological role of infection is widely discussed in the literature. Some researchers believe that infection is one of the most significant causes of miscarriage, both sporadic and habitual, while others believe that infection may play a role in sporadic miscarriage, but not in habitual miscarriage.

There are a great many studies on the role of infection in premature birth, premature rupture of membranes, showing that infection is the main cause of premature birth.

Infection is one of the leading factors in miscarriage. Almost 42% of women with habitual miscarriage have isthmic-cervical insufficiency, even if the main cause of miscarriage is APS.

And even with APS, the development of autoimmune disorders is associated with persistent viral infection.

Viral diseases during pregnancy can lead to anembryony, non-developing pregnancy, spontaneous abortions, antenatal death of the fetus, fetal malformations (compatible and incompatible with life), intrauterine infection manifesting in the postnatal period. The gestational age at which intrauterine infection occurred is of great importance in the nature of disorders caused by viral infection. The shorter the gestational age, the higher the probability of developmental arrest and developmental malformations. Fetal infection at later stages of development does not usually lead to the formation of gross developmental defects, but can disrupt the functional mechanisms of cell and tissue differentiation.

It has now been established that viruses can be transmitted to the fetus in several ways, but the most important is the transplacental route of infection.

The placenta is a physiological barrier that prevents the virus from penetrating the fetus, but in the early stages of pregnancy, rapidly dividing cells of the developing trophoblast, which have a high level of metabolic processes, are an excellent environment for the replication of viral particles, which can have a direct damaging effect on the placenta.

During physiological pregnancy, cytotrophoblast cells do not express the antigen of the major histocompatibility complex and are immunoindifferent. If a virus is expressed on these cells, they become a trigger for the activation of immune cells and a target for immune aggression, which aggravates damage to the placenta and thereby disrupts the function of this organ.

The passage of viruses through the placenta is significantly facilitated by various types of damage, for example, by the threat of miscarriage, autoimmune disorders, and toxicosis.

The placenta is permeable to almost all viruses. Viruses can reach the fetal membranes with the blood flow, be absorbed on them and infect the amniotic fluid, and then the fetus. Infection of the membranes and waters can also occur with ascending infection.

Of the acute viral infections, the most common disease is influenza.

The risk of illness and mortality for a pregnant woman with influenza is higher than for non-pregnant women, and the risk of mortality during epidemics is also higher. The frequency of miscarriages in those infected, especially in the first trimester, is 25-50%. However, the frequency of fetal malformations is not increased compared to population data. It is noteworthy that among healthy primiparous women who gave birth prematurely, 30% had acute respiratory viral infections in the first trimester of pregnancy. 35% of them had placental development anomalies - barrel-shaped placenta, marginal attachment of the umbilical cord, lobular placenta, etc. Due to the fact that there is an inactivated vaccine against influenza of types A and B, there is no risk of vaccination for the fetus. During epidemics, vaccination of pregnant women is recommended, especially pregnant women with extragenital diseases.

Treatment of flu during pregnancy is allowed only with non-drug, home remedies, vitamins. The use of rimantadine, amantadine is contraindicated in the first trimester, since a teratogenic effect is possible. Viferon, Wobenzym, immunoglobulins can be used.

Rubella - during pregnancy, the risk of contracting rubella is not increased compared to non-pregnant women. If a woman becomes ill in the first trimester of pregnancy, there is a high risk of miscarriage and congenital anomalies, so the pregnancy should be terminated. Vaccination during pregnancy is contraindicated, since a live attenuated vaccine is used and a teratogenic effect is possible. According to WHO recommendations, women of childbearing age are tested for antibodies to rubella during pregnancy. If antibodies are absent, vaccination is performed.

Measles - during pregnancy, the risk of the disease is not increased compared to non-pregnant women. The risk of termination of pregnancy is increased if the mother is ill, as with influenza, but this infection does not cause fetal developmental abnormalities. Vaccination is not carried out, since a live attenuated vaccine is used. To prevent severe disease upon contact in the first 6 hours, immunoglobulin (0.25 mg/kg of weight) can be used.

Poliomyelitis - the risk of the disease and its severity are increased during pregnancy. Up to 25% of fetuses of sick mothers carry poliomyelitis in utero, including with the development of paralysis. But this virus does not cause fetal development abnormalities. There is a live and killed vaccine against poliomyelitis. Vaccination during pregnancy with a killed vaccine is possible during an epidemic.

Mumps - the risk of the disease is not higher than outside pregnancy. Low morbidity and mortality are characteristic. The risk of fetal developmental abnormalities has not been confirmed. Vaccination is not performed during pregnancy, since a live attenuated vaccine is used. Since the disease is not severe, passive immunization is not indicated.

Hepatitis A is an RNA virus, transmitted via the oral-fecal route. There are practically no complications during pregnancy, unless the disease is severe. There are no specific treatment methods. To prevent severe cases, immunoglobulin can be used - 0.25 mg per kg of weight. Vaccination during pregnancy is possible for endemic areas.

Hepatitis B is a DNA virus, there are several varieties: HBAg, HBcAg, HBeAg. The routes of infection are parenteral, perinatal and sexual. Up to 10-15% of the population are chronic carriers of hepatitis B.

A pregnant woman infects the fetus during labor when blood gets on the child, so if a pregnant woman has the hepatitis B antigen, monitoring control during labor from the fetal head is not recommended. When a child is born to a mother who is a carrier of the virus, it is necessary to wash the child, removing all contamination, inject the child with immunoglobulin (0.5 ml intramuscularly) and vaccinate on the first day of life and a month later.

Parvavirus is a DNA virus that passes through the placenta during pregnancy, causing non-immune edema syndrome in the fetus. The clinical picture in the mother is a rash, arthralgia, arthrosis, and transient aplastic anemia. 50% of women have antibodies against parvavirus. If the pregnant woman does not have antibodies, the greatest risk of losing the pregnancy is observed with the disease before 20 weeks. There is no specific treatment. Edema syndrome developing in the fetus occurs due to heart failure caused by anemia. To prevent severe complications, it is recommended to use immunoglobulin, octagam is recommended at 5.0 g intravenously 2-3 times.

Acute viral infections contribute to sporadic miscarriage. If there is a risk of miscarriage with such an acute infection, then maintaining the pregnancy is not advisable.

Much more complex and debatable is the problem of persistent viral infection and habitual miscarriage. The probability that episodes of acute viral infection will occur with each subsequent pregnancy at the same time, leading to habitual miscarriage, is negligible. Theoretically, to be the cause of repeated pregnancy losses, the infectious agent must persist, constantly being in the woman's genital tract for a long time, and at the same time be asymptomatic to avoid detection.

Analysis of literature data and experience of the department of miscarriage allow us to conclude that persistent infection, viral and bacterial, is one of the main factors of habitual miscarriage. Even in the absence of direct specific impact of infectious agents on the fetus, reproductive system disorders caused by their persistence in the endometrium, with the development of chronic endometritis, as well as concomitant endocrinopathies and autoimmune disorders lead to disruption of embryo/fetus development and to termination of pregnancy.

The frequency of morphologically verified, asymptomatic inflammatory process in the endometrium in patients with habitual miscarriage is 64% regardless of the clinical picture of termination of pregnancy. The frequency of asymptomatic persistence of opportunistic microorganisms in the endometrium of women with inflammatory genesis of miscarriage in the anamnesis is 67.7%.

A characteristic feature of endometrial microcenoses is the presence of associations of obligate anaerobic microorganisms. In patients with interruption of the type of non-developing pregnancy, chronic endometritis is caused by the persistence of viruses (herpes simplex virus, cytomegalovirus, etc.).

What is the reason for such a high frequency of persistence of infectious agents? On the one hand, there is evidence that the immune response to infection is determined, on the other hand, many viruses have an immunosuppressive effect. Thus, a vicious circle is created - activation of infection causes an immunodeficiency state, and a decrease in immunity, in turn, contributes to the activation of infection. Among persistent viral infections, the most important are:

1. Herpes virus infections (cytomegalovirus, herpes simplex virus, herpes zoster).
2. Enterovirus infections (Coxsackie A, B).
3. Human immunodeficiency virus.
4. Hepatitis B, C.
5. Adenoviruses.

In habitual miscarriage, persistence of the following viruses was detected: Coxsackie A in 98% of patients (in the control 16.7%), Coxsackie B in 74.5% (in the control 8.3%), entero-68-71 in 47.1% (in the control 25%), cytomegalovirus in 60.8% (in the control 25%), herpes simplex virus in 56.9% (in the control 25%), rubella in 43.1% (in the control 12.5%), influenza C in 43.1% (in the control 16.7%), measles in 60.8% of patients (in the control 16.7%).

There are practically no patients with habitual miscarriage who do not have persistence of several viruses. In these conditions, the matter is not so much in persistent viruses, but in the peculiarities of the patient's immune system. It is possible in such cases that one of the persistent viruses prevails, as is observed with simple herpes, and then there may be a clinical picture of an exacerbation of this particular infection. But, as a rule, there are no clinical pictures with persistent viral infection. Changes in immune parameters due to persistence of viruses can lead secondarily to activation of bacterial flora, development of autoimmune disorders, etc., and when terminating pregnancy, these secondary factors are taken into account and assessed as the cause of termination.

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