Tuberculosis in pregnancy is a specific infectious disease with predominant destruction of lung tissue caused by Mycobacterium tuberculosis complex that occurred before, during or immediately after gestation. It is manifested by weakness, sweating, decreased appetite, weight loss, subfebrility, cough, hemoptysis, shortness of breath, chest pain. It is diagnosed with the help of tuberculin samples, lung X-ray examination, microscopy and back-seeding of biological materials. Derivatives of ethylenamides, isonicotinic acid, and ansamycins are used for treatment. In case of complications, thoracic and collapse therapy interventions may be performed.
O98.0 Tuberculosis complicating pregnancy, childbirth or the postpartum period
Despite the introduction of modern methods of rapid diagnosis and the success of complex drug therapy, tuberculosis infection remains one of the most common in the world. The incidence of tuberculosis in Russia has stabilized and even started to decline, but the incidence of infection in pregnant women continues to be 1.5-2 times higher than the same indicator in the general female population. Up to 70% of patients become infected with mycobacteria at the age of 25-34 years.
The prevalence of the disease is 3-7 cases of tuberculosis per 10 thousand births. In 78% of pregnant women, the lesion is unilateral, in 58% of patients, infiltrative forms of the process are diagnosed, in 18% of cases tuberculosis is determined at the stage of decay. Up to 2/3 of women are bacterial isolators. Pathology is often combined with other specific processes: HIV infection is detected in 15% of patients, syphilis in 10%, viral hepatitis in 4%.
The causative agents of the infectious and inflammatory process are microorganisms from the family of mycobacteria. Mycobacterium tuberculosis (Koch’s bacillus) is seeded in most patients. Much less often, the disease is caused by other representatives of the mycobacterium tuberculosis complex — M. africanum, M. bovis, M. caprae, M. microti, M. pinnipedii, some of which affect some animals (large and small cattle, pinnipeds, birds, rodents). In most cases, tuberculosis is transmitted by airborne droplets, sometimes the infection is alimentary (when using unpasteurized milk from tuberculous cows).
According to the observations of most researchers in the field of phthisiology, gestation adversely affects the course of the infectious process, causing its development or exacerbation. In pregnant women, both the primary occurrence of the disease as a result of contacts with the mycobacterium excretor and activation of the existing tuberculosis focus is possible. The most common prerequisites for the beginning of the pathological process are the antisocial environment, low material level, insufficient nutrition, alcohol abuse, nonspecific respiratory diseases caused by smoking. However, a number of physiological changes occurring during pregnancy and after childbirth contribute to the development of tuberculosis in socially well-off women. The main provoking factors are:
- Changes in cellular immunity. Immune processes occurring in the body of a pregnant woman are aimed not only at protecting the child and the woman from possible infection, but also at preventing rejection of the fetus as a foreign body. During gestation, the functional activity of T-lymphocytes, which ensure the elimination of mycobacteria, significantly decreases.
- Active consumption of calcium. This trace element in large quantities is required to build the fetal bone system, which leads to its increased leaching from the patient’s tissues. As a result, old calcified tuberculosis foci soften, which potentiates reactivation or exacerbation of the pathological process in previously infected patients.
- Postpartum abdominal decompression. Temporary improvement of the condition in the 3rd trimester, caused by high standing of the diaphragm, after childbirth is replaced by rapid bronchogenic insemination of the lungs. This is facilitated by the destruction of tuberculosis foci with a sharp decrease in intra-abdominal pressure with aspiration of caseous masses into previously healthy parts of the lungs.
- Breastfeeding. Milk secretion is accompanied by a high consumption of protein, fats, vitamins. Nutritional deficiency reduces resistance to tuberculosis. At the same time, old foci can be activated due to calcium leaching. These factors become especially significant when the maternity hospital stays in a poor socio-epidemiological situation.
According to experts in the field of obstetrics, additional prerequisites for the development of the disease are the mobilization of all systems in pregnant women, hormonal restructuring due to the functioning of the placenta. The risk group consists of patients with a newly diagnosed tuberculin test curve, who have contact with a bacterial separator, and suffer from severe extragenital pathology (diabetes mellitus, COPD, nonspecific pyelonephritis, gastric or duodenal ulcer). The likelihood of tuberculosis increases with prolonged use of corticosteroids, cytostatics, immunosuppressants, the presence of secondary immunodeficiency conditions, including HIV infection.
The mechanism of tuberculosis development in a pregnant woman does not differ from pathophysiological changes in the tuberculosis process outside the gestation period. The primary penetration of mycobacteria is accompanied by the formation of a specific focus of inflammation. In response to the action of the microorganism and its toxins, alveolar macrophages secrete interleukins and tumor necrosis factor, which potentiate the proliferation of T-lymphocytes — immune cells that play a key role in protecting against the causative agent of tuberculosis.
The reaction of cellular immunity and the accumulation of activated macrophages in the lesion contributes to the formation of tuberculous granuloma. The intra-thoracic lymph nodes are involved in a specific process. At the same time, the penetration of mycobacteria stimulates the synthesis of plasma antibodies. With an adequate protective reaction, the focus of primary tuberculosis heals and calcifies. A decrease in immunity causes reactivation of the infection with the further spread of the process.
The exact definition of the disease variant allows you to develop an optimal strategy for pregnancy management. The main criteria that are taken into account when systematizing the disease are the time of occurrence (primary, secondary tuberculosis), the phase of development (infiltration, decay, seeding, scarring, etc.), localization of the process and its extent (pulmonary, extrapulmonary), the presence or absence of bacterial excretion, therapeutic resistance of the pathogen, complications and residual phenomena. To predict the outcome of pregnancy, it is especially important to take into account the clinical form of the disease. Pregnant women may develop:
- Pulmonary tuberculosis. The most common variant of the disease in the gestational period. Contraindications for prolongation of pregnancy are fibrous-cavernous and cavernous forms of infection, a chronic process with dissemination and cirrhotic tuberculosis, complicated by pulmonary heart failure. Gestation is also recommended to be interrupted when progressive infiltrative pulmonary tuberculosis with decay is diagnosed for the first time.
- Extrapulmonary tuberculosis. Specific inflammatory lesions of mycobacteria of other organs in pregnant women are extremely rare. In casual cases, the infectious process is localized in the intestine, mesenteric lymph nodes, peritoneum, bones, joints, central nervous system, urinary organs. The danger in terms of the development of gestosis and other obstetric complications is kidney tuberculosis, complicated by chronic renal insufficiency of the I-III degree.
Symptoms of tuberculosis in pregnancy
Clinical manifestations of the disease that occurred or recurred during pregnancy are nonspecific. Weakness, malaise, loss of appetite, weight loss, subfebrility, sweating and other characteristic signs of tuberculosis infection in the first trimester of pregnancy are often regarded as physiological changes or early toxicosis. The high standing of the diaphragm in the third trimester causes a therapeutic effect similar to that occurring with pneumoperitoneum. As a result, the typical symptoms of even common infiltrative and caseous-destructive forms of tuberculosis are practically not manifested. The presence of infection can be suspected on the basis of complaints of a prolonged (more than 3 weeks) cough with or without sputum, hemoptysis, shortness of breath, chest pain.
In 54% of pregnant women with tuberculosis, the course of pregnancy is complicated. Against the background of intoxication affecting the secretory function of the adrenal glands, the frequency of anemia, early toxicosis, late gestosis increases. Violation of pulmonary ventilation and blood oxygenation is accompanied by fetoplacental insufficiency with a possible delay in fetal development. A decrease in the strength of the fetal membranes associated with infectious exposure leads to premature outpouring of amniotic fluid. Mycobacteria can be transmitted to the fetus through the umbilical cord or amniotic fluid. In the first case, primary tuberculosis foci are formed in the liver, in the second — in various organs. In some patients, violent labor activity is noted due to an increase in the activity of the myometrium under the action of accumulated lactic acid. Straining and increased breathing during exile increase the risk of spontaneous pneumothorax and pulmonary hemorrhage.
Although in most women with tuberculosis infection, the postpartum period proceeds without complications, abdominal decompression, exhaustion and blood loss during childbirth can exacerbate the infectious process with the development of miliary tuberculosis, tuberculous meningitis. Untimely diagnosis and lack of adequate treatment increases mortality from the disease in the first year after childbirth to 15-18%. 12% of newborns from mothers with pulmonary tuberculosis have signs of hypotrophy and gain body weight worse after birth. As a result of hypoxic brain damage, they often experience respiratory disorders, changes in the central nervous system.
The difficulty of timely diagnosis of tuberculosis in pregnancy is due to the non-specificity of the clinical picture, the scarcity of physical examination data, and the limited use of traditional X-ray screening during gestation. Recommended research methods for suspected presence of tuberculosis infection in a patient are:
- Skin tuberculin test. The technique is considered safe and informative. It is indicated for all patients from the risk group in the absence of information about the recent study and its results. An induration of more than 10 mm at the site of intradermal administration of the drug or a turn of the sample confirms infection with tuberculosis.
- Microbiological examination. Microscopy and culture seeding are used to detect mycobacteria in sputum, bronchial washing waters. Sampling of the material followed by bacterioscopic and bacteriological analysis is carried out three days in a row. With possible tuberculosis of the kidneys, urine is studied.
- PCR-sputum examination. A highly sensitive and specific diagnostic method makes it possible to detect single cells and DNA fragments of the pathogen in the biological material. If necessary, bronchial flushing waters, biopsies, and other media that may contain mycobacteria are examined.
- Immunological blood tests. The fact of the presence of latent or active tubinfection in the body can be confirmed with the help of modern enzyme immunoassays: interferon test and T-spot test. However, it is impossible to carry out topical diagnostics of the infectious process using these methods.
- Lung X-ray. X-ray examination of a pregnant woman is performed in a direct projection, which reduces the possible radiation load on the fetus by 10 times. An examination using a rubberized protective apron or performed on digital low-dose installations is considered even safer.
Indirect confirmation of the diagnosis is changes in the general blood test (acceleration of ESR, an increase in the level of leukocytes with an increase in the number of neutrophils, a shift of the leukocyte formula to the left and a decrease in the content of lymphocytes mainly due to T-helpers), increased protein concentration and hyperglobulinemia in blood plasma, a decrease in the activity of immunoglobulins (IgA, IgM). To exclude extrapulmonary tuberculosis, it is possible to conduct MRI, ultrasound, invasive endoscopic examinations with a biopsy. Differential diagnosis is carried out with focal pneumonia, neoplasms of the bronchi and lungs.
Treatment of tuberculosis in pregnancy
Prenatal support of the patient is provided by an obstetrician-gynecologist and a phthisiologist. The first task after the diagnosis of tuberculosis infection is to resolve the issue of the possibility of prolongation of pregnancy. Currently, the list of indications for artificial termination of gestation is limited to progressive destructive forms of the disease, active osteoarticular tuberculosis and bilateral kidney damage with signs of their functional insufficiency. Medical abortion is usually performed before the 12-week gestational age. Later termination of pregnancy is fraught with exacerbation and rapid progression of tuberculosis.
Pregnant women who decide to bear a child are hospitalized three times in a planned hospital (up to 12 weeks, 30-36 weeks and 1-4 weeks before delivery), and the rest of the time are observed and treated in a tuberculosis dispensary. The main objectives of therapy are to stop the active infectious process, stop bacterial excretion, prevent pulmonary bleeding, respiratory failure, obstetric complications. Patients are shown rehabilitation in specialized sanatoriums, phytotherapy, protein-rich food. Drug treatment is carried out in 2 stages — bactericidal, lasting 2 months, and 4-month sterilizing. The choice of drugs for tuberculosis chemotherapy is limited to drugs that have minimal effect on the fetus. Most often, pregnant women are prescribed so-called medicines of the 1st row:
- Derivatives of isonicotinic acid. Due to the inhibition of DNA-dependent RNA polymerase and inhibition of the synthesis of mycolic acids of the cell membrane, they have a pronounced bacteriostatic effect on Mycobacterium tuberculosis. Due to penetration through the placenta, they are usually used in combination with vitamin B6 or in the form of a dosage form containing iron.
- Synthetic derivatives of ethylenediamines. The drugs have extremely low toxicity. No evidence of their teratogenic effects has been found. They act bacteriostatically on intensively multiplying microorganisms. They disrupt the lipid metabolism of mycobacteria, the structure of their ribosomes and protein synthesis. They are used in combined treatment regimens.
- Ansamycins. Semi-synthetic antibiotics of this group inhibit the synthesis of RNA by mycobacteria, due to which they have a pronounced bactericidal effect. They affect resistant forms of microorganisms. Spiropiperidyl derivatives of ansamycins are even more effective. Since the funds are able to increase the tone of the myometrium, they are practically not prescribed in the 1st trimester.
Thoracoplasty, thoracostomy, pleurectomy, surgical collapse therapy and other surgical interventions are carried out only for vital indications with a complicated course of tuberculosis, detection of progressive tuberculosis, destructive variants of the disease with bacterial excretion. At the stage of preoperative preparation, the clinical expert commission often has to decide on the termination of pregnancy. With effective conservative therapy, gestation is recommended to be completed by natural childbirth with the use of anesthesia and antispasmodics. Delivery operations (application of a vacuum extractor, obstetric forceps) and cesarean section are performed only in the presence of appropriate obstetric indications (premature detachment of a normally located placenta, hypoxia of the child, clinically narrow pelvis, placenta previa, transverse fetal position).
Prognosis and prevention
Until recently, tuberculosis was one of the most frequent medical indications for termination of gestation. Nowadays, timely detection, systematic observation, and comprehensive treatment allow most women with diagnosed small-focal, limited fibrotic-focal, hematogenically disseminated pulmonary tuberculosis to carry a healthy child without risk. Prevention involves planning gestation by patients who have previously had a tuberculosis infection, mandatory screening of the disease in relatives of pregnant women. Rational nutrition with a sufficient amount of protein products, quitting smoking and alcohol abuse, limiting heavy physical exertion and stress are recommended. BCG vaccination is indicated for newborns for preventive purposes. Breastfeeding is allowed only with inactive tuberculosis.