In China, women of childbearing age receive active attention as a population with a high incidence of TB. TB is also the leading cause of death among women worldwide. According to statistics, more than one million women die every year, among which active TB is the main cause of maternal mortality. Therefore, it is necessary to raise awareness of the risk of TB in pregnancy.
The causes of TB in pregnancy may be as follows. First, anti-TB drugs lead to a decrease in the efficacy of contraceptives. The conventional anti-TB drug rifampicin, when used in combination with contraceptives (levonorgestrel), can increase the metabolism of steroid contraceptives and increase the plasma clearance rates of ethinylestradiol and norethisterone, resulting in accidental pregnancy during anti-TB treatment and increasing the incidence of pregnancy with TB. Second, the cellular immune function of the body decreases. The high level of human chorionic gonadotropin in pregnancy can inhibit the immune function of lymphocytes, and the early pregnancy response affects the nutritional absorption of pregnant women, resulting in metabolic disorder and then leading to a decrease in cellular immune function, which is not conducive to the clearance of TB. Third, the change in endocrine hormone levels is affected by increased ovarian hormones during pregnancy, which leads to disorders of autonomic nervous regulation, endocrine and metabolic function, lung hyperaemia, and upper respiratory tract swelling, among others. Adrenocortical hormone secretion in pregnant women is high, and capillary permeability increases, resulting in susceptibility to infection by Mycobacterium tuberculosis or recurrence of the original TB focus. Fourth, in pregnant women, with the increase in circulating blood volume, microvascular permeability increases gradually, and the upper respiratory tract becomes congested and swollen, which is very beneficial for TB bacterial invasion into blood circulation. Pregnancy causes hypoxia in the lungs due to the rise of the diaphragm and decrease in lung dilatation, resulting in lung susceptibility to TB infection. Fifth, postpartum TB infection or recurrence may be caused by rapid changes in hormone levels, changes in cellular immunity, the lowering of the diaphragm, nutritional consumption and a lack of sleep.
TB is an independent risk factor during pregnancy. Delayed diagnosis remains associated with a substantially elevated risk for poor maternal and foetal outcomes, including a threefold increase in maternal morbidity, ninefold increase in miscarriage, twofold increase in preterm birth and low birthweight, and sixfold increase in perinatal death[6, 13]. Therefore, the key to pregnancy with pulmonary TB is early diagnosis. However, TB during pregnancy is not easily diagnosed because the general symptoms after TB infection are nonspecific and manifest mainly as respiratory symptoms and signs: cough, expectoration, haemoptysis, low fever, night sweats, chest pain, shortness of breath and emaciation[7, 14]. It should be mentioned that the symptoms of TB are easily confused with the early pregnancy response. In the second or third trimester of pregnancy, if patients have cough, chest tightness, chest pain and related signs, it is difficult to distinguish them from pregnancy with pneumonia, so the diagnosis of TB is easily delayed in the clinic. The clinical presentation of this patient was similar to that of patients with the common symptoms of novel coronavirus infection (fever, cough, and dyspnoea), and this case was extremely difficult to differentiate from a typical COVID-19 case on the basis of clinical presentation alone. Therefore, to ensure the health of pregnant women and new-borns, it is urgent to make accurate diagnoses as soon as possible for patients with suspected pregnancy with TB. Currently, the diagnosis of TB is based mainly on its epidemiology, clinical manifestations, imaging, bacterial pathology and immunology. ① Aetiological examination (sputum smear or culture, TB antigen, antibody detection, etc.) is non-invasive, easily accepted by the patient, and can be used as the first choice approach during pregnancy; however, the sensitivity of acid-fast bacilli staining is low, so more than three sputum examinations are recommended to avoid a missed diagnosis. The sensitivity and specificity of isolation and culture of TB bacteria are relatively high, so it is recommended that pregnant women undergo isolation and culture evaluations for TB bacteria, and sputum culture can be used as the gold standard for diagnosis. ② Blood biochemical and immunological tests (routine blood tests, the erythrocyte sedimentation rate, the cutaneous tuberculin test (TST), TB T cell dot test (T-SPOT.TB), etc.) and the TST have been proven to be safe and effective during pregnancy, and the experimental results are not affected by pregnancy. Chen et al. found that T-SPOT.TB is highly sensitive for detection of active TB during pregnancy. It is suggested that interferon gamma release assays (IGRAs) be used in clinical practice to screen for TB in pregnancy. IGRAs during pregnancy may be more specific and sensitive than the TST, and the experimental results are not significantly related to pregnancy, thereby providing a more accurate method for the diagnosis of TB in pregnancy. ③ Chest imaging examination (chest X-ray examination, CT examination and magnetic resonance imaging (MRI) examination, etc.) is also an option, but imaging examinations of pregnant women are rarely performed clinically because of concerns about the effects of radiation on foetal growth and development. Therefore, imaging examination is used only when pulmonary TB is highly suspected and requires the informed consent of the patient. The diagnostic value of CT is better than that of chest X-ray, while MRI is better as an alternative examination method in the early stage of pregnancy. The 2004 guidelines for diagnostic imaging during pregnancy from the American College of Obstetricians and Gynecologists (ACOG) state that the dose of radiation in diagnostic tests is not sufficient to affect the developing embryo or foetus. If the dose of X-rays during pregnancy is less than 5 rad, there is no effect on foetal development. In fact, the exposure dose of diagnostic radioactivity without contrast agent is less than 5 rad. The 2016 ACOG guidelines also state that because the amount of radiation used in X-rays, CT scans and nuclear medicine imaging is far lower than the dose that would cause harm to the foetus, there is no need to withhold this option from pregnant patients if it is clinically necessary or if diagnostic problems can be more easily addressed. The latest guidelines for imaging tests during pregnancy and lactation indicate that imaging tests such as X-rays and CT are safe during pregnancy and lactation and that the radiation dose is far lower than the ionizing radiation dose that can cause damage to the foetus. However, embryos at 8 to 15 weeks of gestation are most sensitive to radiation, and the effect is non-dose-dependent. Therefore, it is necessary to comprehensively consider the pregnant woman's condition and gestational week and decide whether to carry out radiological examination after weighing the advantages and disadvantages. The laboratory examination of this patient showed that the infection index increased and the lymphocyte count decreased, which was consistent with the changes associated with SARS-CoV-2 infection in laboratory examinations. SARS-CoV-2 nucleic acid testing of pharyngeal swabs was performed in this patient, and the results were negative. Because the nucleic acid test had a certain false negative rate, serum SARS-CoV-2-specific IgM/IgG antibody was measured, and the result was negative; thus, SARS-CoV-2 infection was excluded. Although chest CT showed no COVID-19 multiple ground-glass opacity in either lung, viral pneumonia could not be ruled out. Although the patient had a history of TB exposure, the diagnostic basis of TB was insufficient combined with chest CT. Therefore, sputum samples of the patient were obtained to detect Mycobacterium tuberculosis, the test results were positive, and the results of the T-SPOT.TB test were positive, which confirmed TB infection.
For pregnancy with pulmonary TB, there is a need not only for early diagnosis but also to grasp the opportunity for treatment. It is generally believed that TB with standard treatment does not have adverse effects on the foetus. Delayed diagnosis or nonstandard treatment can lead to an increased risk of abortion, intrauterine infection, foetal death and intrauterine and neonatal mortality. Jana et al. reported that perinatal mortality increased by 5 fold among 79 cases of pregnancy with active TB in India. Figueroa et al. reported that TB infection during pregnancy increased the morbidity and mortality of new-borns, and that the later the start of anti-TB treatment was, the more obvious the results were. Given poor maternal and foetal outcomes with untreated active TB disease, the benefits of treatment outweigh the potential risks from medications. In terms of drugs, a growing number of reports have shown that first-line anti-TB drugs, including rifampicin, isoniazid, pyrazinamide and ethambutol, have no adverse effects on foetuses at conventional doses[22, 23]. All first-line drugs, except for streptomycin, which has toxic effects on the foetus, can be used during pregnancy. The patient was in the second or third trimester of pregnancy and showed no specific discomfort after anti-TB treatment with INH, RFP, EMB and PZA. There was no apparent foetal abnormality after re-examination, so labour induction was not performed. Lesion absorption improved, and the patient was discharged from the hospital. Most scholars believe that TB is not an indication for termination of pregnancy but that termination of pregnancy should be recommended under the following circumstances: (1) Active pulmonary TB in early pregnancy that needs timely anti-TB treatment, while considering the unavoidable adverse effects of drugs on the foetus; (2) Severe pulmonary TB with decreased lung function, where the patient is unable to tolerate continued pregnancy and delivery; (3) AIDS patients who develop TB during pregnancy; and (4) Pregnancy with other systemic diseases that cannot be continued.