Cytomegalovirus infection in pregnancy is a clinically manifest or latent infectious disease caused by cytomegalovirus that occurred before conception or during gestation. It is manifested by hyperthermia, catarrhal symptoms, cervical and submandibular lymphadenitis, sialoadenitis, general intoxication, whitish-blue whites, less often — hepatomegaly, splenomegaly, generalized lymphadenopathy. It is diagnosed using serological and molecular laboratory methods. Treatment is carried out with a specific human immunoglobulin, recombinant alpha-2-interferon, in severe cases — with synthetic analogues of nucleosides.
B25 Cytomegalovirus disease
Cytomegalovirus infection (cytomegaly, CMVI) is one of the most common infectious diseases that affect the fetus in utero and cause various congenital anomalies. Depending on the region, antibodies to cytomegalovirus are detected in 40-98% of patients of reproductive age. Cytomegaly is more common in population groups with a low level of social and economic development.
Cytomegalovirus infection in pregnancy is caused by a large DNA-containing cytomegalovirus (CMV) belonging to the herpes virus family. Experts identify three strains of the pathogen, each of which can independently infect the body of the same person. Infection occurs before conception or during pregnancy. Viruses persist for life in a woman’s body, affecting almost all types of tissues. Some infectious disease specialists consider CMV to be a conditionally pathogenic microorganism, clinically significant reactivation of which is observed only with significant suppression of immunity.
The increased pathogenicity of cytomegalovirus infection in pregnancy is associated with physiological immunosuppression, which protects a genetically alien fetus from rejection. Under the influence of estrogens, progesterone, cortisol in a pregnant woman, the absolute and relative number of T-lymphocytes directly involved in the elimination of viruses and damaged cells decreases, their cytotoxicity decreases. As a result, the replication of cytomegaloviruses accelerates, they spread faster through the body and, with insufficient protective antibodies, overcome the placental barrier.
A feature of cytomegalovirus infection in pregnancy is the multiplicity of ways of infection. The virus is spread by aerogenic, contact, fecal-oral, hemotransfusion, sexual, vertical methods, including transplacentally from the pregnant woman to the fetus. Due to the relatively low virulence, close contact with the infected person is important for infection. The causative agent of CMVI is determined in almost all biological media: saliva, blood, urine, lacrimal fluid, liquor, breast milk, cervical, vaginal, urethral secretions, semen, mucus from the rectum, amniotic fluid.
After entering the body, cytomegaloviruses are adsorbed on the surface of cells, penetrate into them, undergo a full cycle of DNA replication, after which the formed virions spread to neighboring cells, spread through the body with blood. The ductal epithelium of the salivary glands, primarily the parotid and other exocrine glands, is most sensitive to virions.
After lymphogenic and hematogenic generalization, a phase of unproductive infection (latent carrier) usually occurs with long-term preservation of the viral particle inside the infected cell and transmission during division to daughter cells. In women with normal immunity, clinical manifestation does not occur, the disease immediately acquires the character of a carrier. Cytomegalovirus can persist for a long time in an inactive form in sensitive cells. The penetration of CMV into lymphocytes and mononuclears provides its protection against antiviral antibodies.
With a drop in immunity in pregnant women, reactivation of cytomegalovirus infection with destruction of the nuclei of cells in which the virus persisted, hematogenic dissemination, damage to glandular organs, development of vasculitis, induction of specific cytomegalic metamorphosis of cells of different tissues is possible. During gestation, viruses from the interstitial space penetrate through the placenta and hematogenically infect the fetus. It has been established that CMV is capable of damaging the trophoblast membrane.
The systematization of the main forms of cytomegalovirus infection in pregnancy is carried out taking into account the severity of the clinical picture and the time of manifestation of the pathological process. This approach is most justified from the point of view of predicting possible complications of the disease and choosing the optimal tactics of pregnancy management. Specialists in the field of obstetrics and gynecology, infectious diseases distinguish the following infection variants:
- Primary manifest CMVI. The most unfavorable variant of the course of pathology. Occurs as a result of primary infection of a pregnant woman who lacks specific IgG. It is characterized by a high probability of transplacental virus transfer (up to 30-75%) and intrauterine fetal damage. During gestation, it is detected in no more than 4% of patients. In case of infection with acute symptoms in the first trimester, abortion is recommended.
- The carrier. The most common form of cytomegalovirus disease in pregnant women. Carriers are women who, before conception, had an active form of the disease or infection against the background of strong immunity immediately passed into an unproductive phase. Immunoglobulins G circulating in the patient’s blood protect the fetus from CMV infection. With the exclusion of immunosuppressive effects, the risk of a pathological course of gestation is minimal.
- Reactivation of latent infection. With a significant decrease in immunity, cytomegalovirus carriers develop a characteristic clinical picture. The disease is more or less aggravated in 40-50% of seropositive pregnant women. In 0.15-0.36% of cases, the virus is transmitted transplacentally to the child. The greatest risk of congenital anomalies is observed with exacerbation of cytomegalovirus disease at 7-12 weeks of gestational age.
Symptoms of cytomegalovirus infection in pregnancy
With latent carrier, there is no clinical symptomatology. 4-5% of pregnant women with CMVI have a typical primary acute or reactivated latent infection with complaints of mucous discharge from the nose, an increase in temperature to 38-40 ° C, an increase and soreness of the submandibular, cervical lymph nodes, parotid salivary glands. General intoxication is usually expressed — weakness, weakness, fatigue, drowsiness, headache, nausea.
Whitish-blue vaginal discharge is possible. With a significant decrease in immunity, an increase in the liver, spleen with the appearance of heaviness, discomfort, swelling in the right and left hypochondria, generalized enlargement of lymph nodes is determined. The duration of the acute phase, as a rule, is up to 2-3 weeks.
The complicated course of gestation is observed mainly in acute or reactivated infection. Such patients are more likely to have spontaneous miscarriages associated with severe embryo and fetopathy, premature birth caused by uterine hypertension, frozen pregnancies, stillbirth. Due to damage to the trophoblast membrane, CMVI can be complicated by placental increment, hypertrophy and early aging of placental tissue, fetoplacental insufficiency, intrauterine hypoxia and fetal development delay.
During childbirth, premature placental abruption, massive blood loss due to atonic bleeding is possible. In the postpartum period, latent endometritis is noted. Subsequently, the likelihood of developing dysmenorrhea increases.
In acute primary cytomegalovirus disease, the risk of transplacental infection of the fetus and the development of polyhydramnios significantly increases. Children are often born prematurely, with a low small body. CMV infection in the 1st trimester is especially dangerous, often causing microcephaly, chorioretinitis, sensorineural hearing loss, and other developmental abnormalities.
Congenital cytomegaly after intrauterine infection may be asymptomatic, manifest as severe manifest forms or as the consequences of damage to individual organs (hepatomegaly, prolonged jaundice, sucking and swallowing disorders, persistent decrease in muscle tone, tremor, anemia, thrombocytopenia, mental and motor development, pneumonia, myocarditis, pancreatitis, colitis, nephritis). The long-term consequences of CMVI in children are blindness, deafness, speech disorders that manifest themselves in the 2nd-5th year of life.
In pregnant women with significant immunosuppression, CMVI is more severe, extragenital complications are detected more often. Unfavorable forms of the disease are cytomegalovirus lesions of the lungs (interstitial pneumonia), brain (meningitis, encephalitis), peripheral nervous system (myelitis, polyradiculoneuritis), heart (myocarditis, pericarditis), hematopoiesis (thrombocytopenia, hemolytic anemia). A direct threat to the life of a pregnant woman occurs with the rapid generalization of infection with the development of sepsis, infectious-toxic shock, DIC syndrome.
The difficulty of timely detection of CMVI is associated with the absence of symptoms in most pregnant women and the polymorphism of the clinical picture during manifestation. Taking into account the increased risk of perinatal infection of a child with cytomegalovirus infection, an analysis for a TORCH complex is recommended as a screening. The leading diagnostic methods are laboratory tests that allow to verify the infectious agent, detect serological markers and determine the severity of the process. The examination plan for patients with suspected cytomegaly includes such studies as:
- Enzyme immunoassay. ELISA is considered the most reliable and informative method of diagnosing cytomegalovirus disease. The presence of an active infection confirms the detection of IgM and a more than 4-fold increase in the IgG titer. The prescription of infection is indicated by data on the avidity of immunoglobulins G (with the indicator
- PCR diagnostics. Cytomegalovirus nucleic acids are detected in biological secretions that may contain the pathogen. Usually, blood, urine, cervical secretions, buccal smears are taken for analysis. The detection of viral DNA confirms infection, and quantitative research methods allow monitoring the course of infection.
Taking into account the possibility of reactivation of the cytomegalovirus process at any stage of gestation, planned virological monitoring is recommended for carriers at 8-12, 23-25, 33-35 weeks of pregnancy. If intrauterine fetal lesion is suspected, cordocentesis is performed with the determination of IgM in umbilical cord blood, amniocentesis with PCR diagnosis of the pathogen in the amniotic fluid.
To assess the condition of the fetus, to identify fetoplacental insufficiency, possible anomalies according to the indications,
- ultrasound of the fetus and placenta are carried out;
- dopplerography of uteroplacental blood flow;
- fetal phonocardiography;
- chorion biopsy.
Cytomegaly is differentiated with HIV infection, infectious mononucleosis, toxoplasmosis, listeriosis, herpes, viral hepatitis, bacterial sepsis, lymphogranulomatosis, acute leukemia. If necessary, the patient is advised by an infectious disease specialist, virologist, immunologist, oncologist, oncohematologist.
Treatment of CMVI in pregnancy
Choosing the tactics of gestation management, take into account the clinical form of CMVI and the duration of infection. Women with cytomegaly, which initially manifested during the 1st trimester, are recommended to have an abortion. Termination of pregnancy for medical reasons is also indicated for patients with clinically and laboratory-confirmed primary infection when ultrasound signs of fetal malformations are detected before 22 weeks. In other cases, prolongation of gestation is possible.
Pregnant women with carrier medication is not prescribed. In the absence of clinical and laboratory signs of reactivation of cytomegalovirus disease, lifestyle correction is required to prevent significant immunosuppression. Patients need sufficient rest and sleep, the exclusion of excessive physical and psychological stress, proper nutrition, vitamin and mineral complexes, prevention of acute respiratory viral infections, caution when prescribing drugs that reduce immunity.
Pregnant women with an active form of infection are treated to stop the exacerbation and stop the excretion of cytomegalovirus. The difficulty of choosing an adequate drug therapy is associated with the fetotoxicity of most antiviral agents. Taking into account possible indications and contraindications for the treatment of CMVI during gestation:
- Anticytomegalovirus human immunoglobulin. Hyperimmune drugs can restore the titer of specific IgG, block the replication of the pathogen and limit its dissemination. The use of human immunoglobulin significantly reduces the risk of intrauterine infection with cytomegaly virus.
- Recombinant α-2-interferon. The drug stimulates T-helpers and T-killers, increasing the level of T-cell immunity. Increases the activity of phagocytes and the rate of differentiation of B-lymphocytes. Inhibits the replication of cytomegaloviruses and promotes their inactivation by various immune agents. It is recommended in the form of rectal candles.
- Synthetic analogues of nucleosides. They are prescribed only for severe generalized forms of cytomegalovirus infection, when the risk of toxic effects of drugs is justified by saving the life of a pregnant woman. Antiviral drugs inhibit the DNA polymerase of viral particles and thereby inhibit the synthesis of cytomegalovirus DNA.
Inducers of interferogenesis, immunomodulators are used extremely rarely due to the possible premature termination of gestation. Endovascular laser irradiation of blood and plasmapheresis are acceptable as non-drug methods.
Childbirth at CMVI
The preferred method of delivery is natural childbirth. Cesarean section is performed in the presence of absolute obstetric or extragenital indications or with a combination of relative ones (intrauterine infection with cytomegalovirus, chronic fetal hypoxia, II-III degrees of delayed development, primary and secondary infertility in the anamnesis).
Prognosis and prevention
Timely detection of latent cytomegalovirus infection in pregnancy and prevention of its activation significantly improve the outcome of pregnancy for both the woman and the fetus. The prognosis is unfavorable with the generalization of primary cytomegalovirus infection. With the established diagnosis of cytomegaly, conception planning is shown taking into account the recommendations of an obstetrician-gynecologist, relief of the active process, pre-gravidar immunocorrection using peptide immunostimulators and recombinant interferons.
Antiviral therapy of women with manifest CMVI reduces the risk of reactivation of infection by 75% in the most dangerous for complications of the 1st trimester. General prevention of infection involves compliance with the rules of personal hygiene with frequent hand washing, refusal of close direct contact with other people.