A number of factors in pregnancy contribute to an increased risk of aspiration and aspiration pneumonitis. The risk of aspiration of gastric contents is increased during pregnancy due to elevated intra-abdominal pressure, decreased gastroesophageal sphincter tone, delayed gastric emptying, and diminished laryngeal reflexes. Aspiration may be the result of passive regurgitation or active vomiting. Aspiration was reported to account for 30–50% of maternal deaths related to anesthetic complications, and if bacterial infection after aspiration occurred, usually after 24–72 hours, the mortality rate could be even higher. Due to advances in obstetric— and particularly anesthetic—management, the incidence of aspiration pneumonitis and its complications has been considerably reduced. Aspiration pneumonitis has also been called Mendelson's syndrome, named after the physician who described a large series of women with this complication in association with aspiration at time of operative intervention.
Given the high risk associated with aspiration pneumonitis, including the possibility of maternal death, every effort should be made to prevent this potentially catastrophic condition. General anesthesia is the main risk factor related to aspiration, and expert airway management during induction and intubation is extremely important.
Oral intake during labor is not generally recommended. Women undergoing elective caesarean delivery should not be given anything by mouth for at least 6–8 hours before the procedure. All anesthetized obstetric patients should be intubated. Laryngeal reflexes will generally prevent aspiration while patients are awake, but the reflexes will be altered in patients who are given excessive sedation, in patients who are under anesthesia, or in patients with seizures. Pain, anxiety, narcotics, and labor itself may cause delayed gastric emptying and increased intragastric pressure. Lowering the volume of gastric contents to <25 mL and raising the gastric pH to >2.5 will reduce the risk of pulmonary injury if aspiration occurs. Clear, nonparticulate systemic alkalizers (eg, sodium citrate-Bacitra, or Alka-Seltzer) must be used instead of particulate oral antacids (eg, magnesium trisilicate, Maalox, Riopan). Thirty milliliters of a clear antacid should be routinely given to all women 30 minutes before induction of anesthesia.
Gastric acidity may also be reduced by histamine-2 (H2) receptor blockers. Cimetidine and ranitidine have been reported to be safe for use during pregnancy. Metoclopramide may increase lower esophageal sphincter tone and enhance gastric emptying. However, antacids are preferred, particularly in emergency situations, because they are reliable and fast acting. H2 blockers and metoclopramide are not recommended for routine use.
The pathologic mechanism, clinical manifestations, and outcome depend on the volume (≥25 mL), acidity (pH ≤2.5), and composition (presence or absence of solid particles) of the aspirate. Small volumes of a very acidic aspirate will be highly toxic, whereas relatively large volumes of a buffered aspirate can be relatively well tolerated. Aspiration of large, solid particulate matter may occlude portions of the larger bronchi, resulting in hypoxia, pulmonary hypertension, and even death. With smaller particles, bronchial obstruction occurs more distally, resulting in atelectasis, hypoxia, and inflammation of the bronchial mucosal and respiratory distress. Symptoms immediately after aspiration include dyspnea, bronchospasm, cyanosis, tachycardia, and even respiratory arrest. The patient will be hypoxic, hypercapnic, and acidotic. If infection supervenes, fever and leukocytosis will occur 48–72 hours later. The localization of the chest X Ray abnormalities will depend on the patient's position when the aspiration occurred: a) at the lung bases if she was upright, b) in the upper lobes or in the superior segment of the lower lobes if she was supine. A picture of diffuse interstitial pulmonary edema (“white out”) may be seen after aspiration of large amounts of very acidic material.
If aspiration occurs during anesthesia, immediate intubation and suction should be performed, followed by ventilation and adequate oxygenation. Positive end-expiratory pressure may help to better expand areas of fluid-filled collapsed lung. Bronchoscopic suction should be performed as soon as possible if the aspirate contains solid particles. A chest x-ray film should be taken and serial blood gas determinations made. These patients should be managed in the intensive care unit.
If the gastric fluid pH is >3.0 and the patient appears to be well oxygenated, she can be followed closely with periodic chest x-ray films and blood gas determinations. The picture usually resolves without antibiotics in 48–72 hours, except when infection occurs. Therefore, antibiotics should not be given routinely or empirically; they should be administered when clinical evidence and cultures indicate the presence of a superimposed bacterial infection. The bacterial flora is often polymicrobial but anaerobes from the mouth usually predominate, and therefore penicillin or clindamycin are the antibiotics more often recommended. The use of corticosteroids is not universally agreed upon.
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- Most patients are diagnosed with asthma before pregnancy and already are receiving treatment.
- Symptoms suggestive of asthma include cough, dyspnea, chest tightness, and wheezing, particularly when episodes occur episodically.
- Pulmonary function studies are useful to confirm the diagnosis and should be part of the initial investigations.
The general prevalence of asthma appears to be increasing. Recent studies report that asthma occurs in up to 9% of the general US population and in 3.7–8.4% of pregnant women. Therefore, asthma has become one of the most common medical illnesses complicating pregnancy. The increased prevalence is reported worldwide, particularly in urban areas, and is generally attributed to industrial pollution. However, marked geographic variations occur, and the extent to which genetic predisposition plays a role is still under active investigation.
Common triggers of asthma include upper respiratory infections (more commonly viral); administration of beta-blockers, aspirin, or nonsteroidal anti-inflammatory drugs; sulfites and other food preservatives; allergens such as pollen, animal dander, mites, or molds; smoking; gastric reflux; and exercise or other causes of hyperventilation. Both cigarette smoking and other major environmental pollutants are specifically associated with fetal damage.
Childhood-onset asthma affects males more often than females. In contrast, adult-onset asthma reportedly occurs more frequently in women. Overall, the prevalence and severity of asthma are consistently reported to be greater in women than in men. Women also are reported to require more frequent emergency room visits and more hospitalizations. Therefore, sex hormones are believed to play a role in the differences observed in the occurrence of asthma, although the exact mechanisms are not completely understood. Asthma shows variations during the menstrual cycle, with premenstrual exacerbation more often reported. Reports on asthma during the menopause are more conflicting, with some studies noting improvement but others reporting more episodes of bronchospasm after 6 months of hormone replacement therapy.
No consistent effect (either worsening or improvement) during pregnancy has been observed, although one-third of women with more severe disease reportedly became worse late in the second trimester or early in the third trimester. Possible factors contributing to improvement include the higher levels of cortisol (anti-inflammatory) and progesterone (smooth muscle relaxant) and for worsening the higher (5–6 times) rate of sinusitis and gastroesophageal reflux during pregnancy. Others speculate that pregnancy does not have an effect on asthma and that the variations observed are simply part of the natural history of the disease or due to variable medication compliance when women find out that they are pregnant. Some become more compliant and their asthma improves, and others stop their medication, fearing for the fetus, and their disease worsens. The responses in subsequent pregnancies are somewhat more consistent and in 60% of women tend to be similar to those that occurred during the first pregnancy.
A diagnosis of asthma is usually made on clinical grounds and without much difficulty if an adequate history and physical examination are obtained. Most patients are diagnosed with asthma before pregnancy and already are receiving treatment. Symptoms suggestive of asthma include cough, dyspnea, chest tightness, and wheezing, particularly when episodes occur episodically. Pulmonary function studies are useful to confirm the diagnosis and should be part of the initial investigation and surveillance of disease. The forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio will be <70%, and the airway obstruction can be reversed by administration of a short-acting beta2-agonist preparations.
Asthma currently is classified according to severity as (1) mild intermittent, (2) mild persistent, (3) moderate persistent, and (4) severe persistent. In mild intermittent asthma, symptoms do not occur more often than twice per week, and nocturnal symptoms do not occur more often than twice per month. The peak expiratory flow (PEF) or the FEV1 is >80% of normal, with <20% variability. In mild persistent asthma, symptoms occur more often than twice per week but not daily, and nocturnal symptoms occur more often than twice per month. The PEF or FEV1 still is at least 80% of normal, but with greater (20–30%) variability. In moderate persistent asthma, symptoms occur daily, and nocturnal symptoms occur more than once per week. The PEF or FEV1 is <80% but >60% of normal, with >30% variability. In severe persistent asthma, daytime symptoms occur continually, and nocturnal attacks occur frequently. The PEF or FEV1 is <60% of normal, with >30% variability.
Rarely, bronchospasm is caused by a condition other than asthma. These conditions include acute left ventricular heart failure (also called cardiac asthma), pulmonary embolism, exacerbation of chronic bronchitis, carcinoid tumors, upper airway obstruction (laryngeal edema, foreign body), gastroesophageal reflux, and cough caused by some medications.
Potential maternal complications include hyperemesis gravidarum, pneumonia (women with asthma account for >60% of pneumonia cases in pregnancy), preeclampsia, vaginal bleeding, more complicated labors, and more caesarean deliveries. Fetal complications can include intrauterine growth restriction, preterm birth, low birth weight, neonatal hypoxia, and increased overall perinatal mortality. Women with severe asthma are at the highest risk. However, patients are at little or no increased risk when the disease is effectively treated and controlled.
The main goal of therapy is to maintain normal or near normal maternal pulmonary function to allow adequate fetal oxygenation, prevent exacerbations, and allow the patient to maintain her usual activities. In general, pregnant women are receptive to educational interventions that will improve their asthma management, and the benefits are likely to continue after delivery. A good example is learning the proper use of portable peak flow meters to objectively evaluate asthma severity, because clinical symptoms and the patient's own perception of the severity of asthma often are inaccurate. The PEF rate correlates well with FEV1 and allows the detection of worsening at an early stage before serious symptoms appear as well as the evaluation of response to treatment while the patient is still at home. Avoidance of potential asthma triggers also is extremely important. The general principles of management for pregnant asthmatic women are similar to those for nonpregnant patients and include removing pets if necessary, encasing mattresses and pillows in airtight covers, carefully washing the bedding, keeping ambient humidity <50%, avoid vacuuming (or at least wear a mask), using air conditioning and air filters, avoiding outdoor activities when allergens and air pollution levels are high, and avoiding nonallergen irritants, such as strong odors, food additives, aspirin, beta-blockers, and particularly tobacco smoke. Several recent studies have shown that these measures not only are beneficial, but are cost-effective as well. Every effort should be made to achieve smoking cessation during pregnancy, which is a very serious but modifiable factor associated with adverse outcome.
Patients undergoing immunotherapy may continue doing so during pregnancy but without any further dose increase. Starting immunotherapy de novo during pregnancy is not recommended because uterine contractions are likely to develop if anaphylaxis occurs.
Influenza vaccination is currently recommended for all pregnant women during the flu season. This recommendation is of the utmost importance for pregnant women with asthma. Asthma sufferers also should receive the pneumococcal vaccine but preferably before pregnancy.
Treating rhinitis and sinusitis, which often are associated with asthma and may trigger exacerbations, is important. Treatment of rhinitis includes reducing exposure to antigens (environmental control); intranasal cromolyn sodium, antihistamines (tripelennamine or chlorpheniramine), and intranasal steroids are very beneficial. For treatment of sinusitis, amoxicillin (erythromycin if allergic to penicillin), oxymetazoline (nasal spray or drops), and pseudoephedrine are more often used.
Many women have the impression that most, if not all, medications might be harmful to the fetus. However, they should be informed that the risk of uncontrolled asthma is far worse than any of the potential side effects of the most common medications used to treat asthma. Most women with asthma can be managed effectively during pregnancy, and complications are generally confined to patients with uncontrolled asthma.
These patients do not need daily medications. When symptoms occur, 2 puffs of a short-acting beta2 agonist can be used as needed. More data are available for use of albuterol than for any other beta2 agonist during pregnancy, and no harm to the fetus has been observed to date. These women may still experience severe exacerbations, which may be separated by long asymptomatic periods, and a short course of systemic corticosteroids may be needed.
The preferred therapy for this group of patients is a low-dose inhaled corticosteroid. More experience is available for budesonide use in pregnancy, and the published data regarding its safety and lack of risk for congenital anomalies are reassuring. Less experience is reported with beclomethasone, but the published data also are reassuring. Inhaled corticosteroids suppress and may even prevent airway inflammation, which plays a critical role in the pathogenesis of asthma and may decrease airway responsiveness as well. Because they may decrease and sometimes even obviate the need for systemic steroids, their use is now recommended at earlier stages of asthma. However, the full benefits may not be seen for 2–4 weeks, so they are not recommended as part of the treatment of acute attacks. Use of a mouth spacer to minimize systemic absorption is strongly recommended. Inhaled corticosteroids are likewise beneficial for rhinitis (2 sprays in each nostril twice daily).
Alternative, but not preferred, therapies for this group include inhaled cromolyn sodium, leukotriene receptor antagonists, or sustained-release theophylline. Cromolyn sodium is also anti-inflammatory drug, but its efficacy is less predictable than that of the inhaled corticosteroids, and the benefits may not be seen for 4–6 weeks. Nevertheless, cromolyn sodium seems to be free of side effects for mother or fetus. Few data on the use of leukotriene receptor modifiers during pregnancy are available; they are reported to be safe in animals, but human data are limited. The extensive experience with theophylline during pregnancy indicates that it is safe for the fetus except when maternal levels exceed 12 μg/mL. In these cases, the fetus or newborn may develop jitteriness, tachycardia, and vomiting.
Moderate Persistent Asthma
The preferred treatment is a combination of a low-dose or medium-dose inhaled corticosteroid and a long-acting beta2 agonist. Alternative therapies (but again not preferred) include a low-dose or medium-dose inhaled corticosteroid and either theophylline or a leukotriene receptor antagonist. However, given the limited data on human pregnancy, the use of leukotriene receptor modifiers is reserved for patients who showed a very good response before pregnancy but are not responding well to other medications while pregnant.
The preferred treatment is a high-dose inhaled corticosteroid and a long-acting inhaled beta2 agonist as well as (if needed) a systemic corticosteroid, such as 2 mg/kg/d of prednisone or equivalent steroid not to exceed 60 mg/d, with an attempt to taper to the minimal effective dose. An alternative, but not preferred, treatment includes a high-dose inhaled corticosteroid and sustained-release theophylline (keeping maternal systemic levels at 5–12 μg/mL for the reasons explained previously).
The US Food and Drug Administration has recently issued warnings about the use of long-acting beta-agonists (LABAs). A paradoxical increase in exacerbations in some patients, particularly in children, has been reported mainly with LABA monotherapy. The specific recommendations include (1) not to use LABAs without other asthma-controller medications, (2) stop LABA use once asthma control is achieved and maintain it with other medications, (3) do not use LABAs if the asthma is controlled with inhaled steroids, and (4) use fixed-dose combinations with an inhaled steroid to minimize the likelihood of LABA use alone.
Systemic corticosteroids are used when any of the other drug combinations cannot control the asthma. They usually are given first as a short, rapidly tapering course (eg, 40–60 mg/d of prednisone or equivalent steroid for 1 week, tapering off during the second week). If these courses fail to effectively control symptoms for <2–3 weeks, long-term systemic corticosteroid treatment may be needed. In these cases, the lowest effective dose or alternate-day therapy, if possible, should be used. Potential maternal side effects include impaired glucose tolerance or frank diabetes mellitus, preeclampsia, intrauterine growth restriction, and premature delivery. With prolonged use (>1–2 months) of pharmacologic doses, maternal adrenal insufficiency may occur, and adequate coverage during periods of stress (including labor and delivery) is mandatory. Use during the first trimester is associated with a higher risk for facial clefts (lip and palate). Pregnant women with asthma who are steroid dependent should be managed by an internist/pulmonologist who is experienced in the treatment of asthma during pregnancy.
Nonselective beta agonists such as epinephrine and isoproterenol are sometimes given subcutaneously during acute asthma attacks. Epinephrine use during pregnancy should be avoided because epinephrine causes vasoconstriction and reduces fetal oxygenation. It is teratogenic in animals as well as in humans. Isoproterenol also is teratogenic in animals. Because many other alternative therapies are available, isoproterenol use in humans is best avoided. Iodine-containing medications should be avoided during pregnancy because the fetus may be at risk for developing a goiter, which may become very large and cause airway obstruction and even asphyxia. Nedocromil sodium is similar to cromolyn sodium. No reports on humans are available, but nedocromil sodium has not been observed to be teratogenic in animal experiments. Anticholinergic medications such as atropine (which block bronchoconstriction by inhaled irritants) may accelerate the fetal heart rate and inhibit breathing. Ipratropium has not been reported to be teratogenic in animals, but data on humans are lacking. Glycopyrrolate has been used safely in humans near term, and no defects have been reported in animal experiments.
During acute exacerbations, dyspnea, cough, wheezing, and chest tightness increase and expiratory flow decreases. A few, well-educated patients with relatively mild attacks might be managed at home, taking advantage of the judicious use of peak flow measurements. However, any serious exacerbation most likely will require hospitalization. Great care should be exercised to maintain a maternal PO2 >70 mm Hg and O2 saturation >95%. A maternal PO2 <60 mm Hg will result in marked fetal hypoxia.
General measures include reassuring the patient and avoiding sedatives, which may depress respiration. Oxygen can be administered by mask or nasal catheter with the goal of maintaining PO2 >70 mm Hg and O2 saturation >90% to ensure adequate fetal oxygenation at all times. A few patients may require endotracheal intubation and mechanical ventilation to maintain an adequate oxygen supply. Blood gas determinations are necessary for this purpose. A chest x-ray film should be part of the initial evaluation. Antibiotics are given only if evidence of bacterial infection is present. Some pregnant women receiving large amounts of intravenous fluids, beta2 agonists, and corticosteroids reportedly develop pulmonary edema, so this risk should be considered under these circumstances.
Initial pharmacologic treatment includes an inhaled beta2 agonist administered by a metered-dose inhaler, 2–4 puffs every 20 minutes to a maximum of 3 doses or less if side effects appear. A subcutaneous beta2 agonist (eg, terbutaline 0.25 mg) is also given and can be repeated once 20 minutes later. Systemic corticosteroids are recommended early in the course of treatment of acute exacerbations. The most frequently used corticosteroid is methylprednisolone administered intravenously at an initial dose of 1–2 mg/kg/d. At present, intravenous theophylline is used much less frequently for acute exacerbations because of the early use of corticosteroids. When necessary, the recommended initial loading dose is 5–6 mg/kg given intravenously over 20–30 minutes. The loading dose is not given if the patient was receiving adequate oral doses before the acute attack, or only half the loading dose is given if the patient was receiving theophylline but only intermittently. Maintenance doses are 0.7 mg/kg/h. Serum levels should be monitored to avoid maternal levels in excess of 12 μg/mL.
After admission to the hospital, administration of beta2-agonists is continued by nebulized aerosol every 4–6 hours; administration of intravenous corticosteroids also is continued (eg, methylprednisolone 0.5–1 mg/kg twice daily). If theophylline was started, it is continued per the maintenance dose protocol, with careful monitoring of maternal serum levels to avoid fetal toxicity. As the patient improves, the beta2-agonist aerosols are continued (2 puffs every 4–6 hours), and at this point the inhaled steroids (high dose, per the protocol for the severe persistent asthma) are resumed or the therapy initiated if the patient was not receiving them before the acute attack. If the clinical improvement continues, the systemic steroids can be switched to the oral route (eg, prednisone 0.5 mg/kg/d, with gradual tapering attempted while maximizing inhaled steroid treatment). If theophylline was being given, it also should be changed to the oral route (6 mg/kg), with close monitoring of maternal serum levels.
Management during Labor and Delivery
The medications that were being administered before the onset of labor should be continued. Adequate control should be maintained, because labor has been reported to trigger an acute attack in approximately 10% of women with asthma. Peak expiratory flow measurements should be obtained at regular intervals to monitor pulmonary status closely. Adequate hydration should be maintained and pain relief provided as necessary. Fentanyl is considered a good analgesic choice for these patients. Analgesics and/or narcotics, which can cause histamine release, should be avoided because of the possibility of respiratory depression and bronchospasm. Continuous O2 monitoring is mandatory to ensure that O2 saturation is >95% at all times.
Medications to avoid include prostaglandin F2 because it may cause bronchospasm. Prostaglandin E2, either gel or suppository, is safe for women with asthma and can be used if necessary from the obstetric standpoint. Oxytocin is safe and considered the medication of choice for induction.
Epidural anesthesia is preferred because it reduces O2 consumption and minute ventilation. General anesthesia may trigger an attack, but the risk may be reduced by pretreatment with atropine (see earlier for potential fetal effects) and glycopyrrolate, which have a bronchodilatory effect. A low concentration of halogenated anesthetic may provide bronchodilation as well. For induction, ketamine is preferred. It is very important that an anesthesiologist experienced in the care of pregnant women be consulted ahead of time when anticipating anesthesia needs.
Ergot derivatives should be avoided because they may precipitate bronchospasm. If postpartum hemorrhage occurs, oxytocin is the best choice. If a prostaglandin is needed, then prostaglandin E2 is preferred. Aspirin and nonsteroidal anti-inflammatory drugs (eg, indomethacin) may trigger severe bronchospasm as well as ocular, nasal, dermal, and gastrointestinal inflammation in 3–8% of asthmatic patients and are best avoided. Magnesium is safe for asthma but with careful monitoring to avoid respiratory depression.
An ultrasound examination in early pregnancy is useful to confirm dating and to provide a baseline to evaluate future growth assessment. Serial ultrasounds are recommended for women with moderate and severe asthma because they are the most at risk for fetal growth restriction. No specific guidelines have been issued for antepartum fetal surveillance other than very general recommendations such as “when needed in the third trimester to assure fetal well being” and “daily recording of fetal movements is encouraged.” Many institutions offer fetal surveillance starting at 32–34 weeks to patients with moderate and severe asthma and at any time during the third trimester when an exacerbation occurs. There is unanimous agreement that all patients with asthma should undergo continuous fetal monitoring during labor and delivery.
Inhaled beta2 agonists, cromolyn sodium, steroids (inhaled), and ipratropium are safe while breastfeeding. Systemic (oral or parenterally administered) steroids may enter into breast milk but only in small amounts if the total daily dosage contains <40 mg of prednisone (or equivalent steroid).
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- Although the incidence of pneumonia in pregnancy is not increased over nonpregnant women, pneumonia is associated with an increased risk of maternal and fetal complications.
- Pneumonia typically presents with fever, chills, and productive cough.
Pneumonia is a rare complication of pregnancy, affecting fewer than 1% of all pregnancies. However, it is associated with significant fetal and maternal morbidity. In fact, before the advent of antibiotics, pneumonia in pregnancy was associated with maternal mortality rate of >20%.
A number of different organisms are implicated in causing pneumonia during pregnancy. The most common identifiable organisms are pneumococcus and Haemophilus influenza. Viral agents are also implicated in causing pneumonia, including influenza A, infectious mononucleosis, and, less frequently, varicella. Influenza A has been of particular concern in recent years due to well-publicized outbreaks with exceedingly virulent strains. Influenza A has a higher mortality rate in pregnancy than in nonpregnant patients. Pregnant women with viral pneumonia can develop superimposed bacterial infection.
One important preventative measure is the injectable influenza vaccine. The intramuscular influenza vaccine consists of inactivated virus. This vaccine is safe when administered during any trimester of pregnancy. It is recommended that pregnant women receive this vaccine during the flu season.
Pneumonia usually presents with fever, chills, and productive cough. Patients may also experience pleuritic chest pain and shortness of breath. On physical examination, most women are febrile. Many women will be tachycardic or tachypneic. Chest auscultation reveals rales or decreased breath sounds over the affected fields. With bacterial pneumonia, chest radiograph demonstrates lobar consolidation or infiltrate. With viral pneumonia, chest radiograph may appear normal. Complete blood count reveals leukocytosis with a left shift in most cases.
Depending on the patient's presenting signs and symptoms, the differential diagnosis includes pulmonary embolism, bronchitis, and uncomplicated influenza.
Pneumonia during pregnancy increases the risk of a number of fetal and maternal complications, including pulmonary edema and preterm labor.
In general, inpatient management is advised for pregnant women with pneumonia. Treatment with antibiotics is the cornerstone of therapy. Community-acquired pneumonia should be treated with azithromycin or azithromycin plus ceftriaxone in severe cases. For patients with varicella pneumonia, acyclovir is recommended. Treatment of influenza and influenza pneumonia during pregnancy is recommended with oseltamivir. For cases of oseltamivir-resistant strains of influenza, zanamivir is recommended. Maternal oxygen saturation should be maintained ≥96% with oxygen nasal canula or face mask if needed.
- Pregnancy is not associated with an increased risk of contracting tuberculosis or progression from latent tuberculosis to active tuberculosis.
- Pregnancy and prenatal care do provide a unique screening opportunity for women at risk of tuberculosis.
- Effective treatment of tuberculosis during pregnancy and/or in the postpartum period is important to prevent transmission to the neonate.
Tuberculosis (TB) was the leading causes of death in the United States for many years until the introduction of effective therapy in the early 1950s. Since then, the number of reported cases declined steadily, until recently, when higher numbers are being identified. This situation is attributed to increased immigration from countries with a high tuberculosis prevalence and particularly to the HIV/acquired immunodeficiency syndrome (AIDS) epidemic. Worldwide, TB is very prevalent, with 8 million new cases and 2 million deaths annually. Eighty percent of TB deaths in women occur during their childbearing years, and pregnant women are not spared from TB effects. Many of these at-risk women will seek health care only when pregnant, thus providing an opportunity for diagnosis and treatment.
Tuberculosis in adults is mainly (>95%) a disease of the pulmonary parenchyma caused by Mycobacterium tuberculosis, a nonmotile, acid-fast aerobic rod. Transmission usually occurs by inhalation of droplets produced by infected individuals when coughing. The droplets can remain suspended in the air for prolonged periods (several hours). The persons most at risk for becoming infected are family members and other close contacts, such as coworkers and roommates (elderly residents and employees in long-term care facilities, correctional institutions), homeless individuals, and intravenous drug users. After the initial inhalation, the bacilli multiply in the alveoli and subsequently spread to the regional lymph nodes and to other organs such as the upper lung regions, kidneys, bones, central nervous system, and, rarely, during pregnancy, to the placenta. In most people, the infection is contained by cell-mediated immunity, which develops 2–10 weeks after exposure, when the infected sites are walled off by granulomatous inflammation and the tuberculin tests then becomes reactive. At this stage, these persons are not infectious and are asymptomatic except for the positive tuberculin skin test. After the initial exposure, the risk of developing active disease during the following 2–5 years is generally given as 5–15%, but the risk later falls to very low levels <1–2%. However, active disease may ensue if a person is unable to contain the infection when first exposed or if the person subsequently becomes immunocompromised and the infection is reactivated at a time remote from the initial exposure.
Most cases of tuberculosis can be diagnosed on the basis of a history of cough, weight loss, positive tuberculin skin test, and chest x-ray film.
Primary TB infection is usually asymptomatic, except in the rare instances when dissemination occurs. Typical symptoms include cough, sometimes with hemoptysis, low-grade fever, weight loss, fatigue, night sweats, and anorexia, although some patients may have few symptoms. In extrapulmonary TB, the symptoms are related to the organ system involved.
The definitive diagnosis is made after positive identification of the bacilli by Ziehl-Neelsen staining and a positive culture, usually from a sputum sample. At times, the sample for culture will be obtained from the urine, other body fluid, or a body tissue. Although acid-fast bacilli can be identified on stained slides, culture confirmation is required, which may take several weeks. Faster detection methods are currently under development.
The tuberculin skin test is the most important screening test for tuberculosis. It should be performed early in pregnancy, especially in high-risk populations. An induration of 5 mm or greater is considered positive in individuals with HIV infection; those in close contact of persons with active, infectious tuberculosis; in persons with typical x-ray findings who were never previously treated; and in intravenous drug users. An induration of 10 mm or more is considered positive in persons who have risk factors other than HIV, such as diabetes mellitus, silicosis, chronic use of corticosteroids or other immunosuppressive drugs, cancer (solid tumors as well as leukemias and lymphomas), chronic renal insufficiency, gastrectomy or intestinal bypass, or malabsorption and chronic malnutrition with body weight 10% or less below the ideal. Data are being accumulated on the effectiveness of other methods that could be used as an alternative to the skin test.
With the abdomen shielded and preferably after the first trimester, a chest x-ray film should be taken in patients in whom skin testing is positive after an earlier negative test and in patients with a suggestive history or physical examination even though skin testing is negative. Findings suggestive of TB include upper lobes or superior lower lobe segments' nodular infiltrates that at times may become cavitary. A calcified hilar node and an also calcified peripheral nodule (Ghon's complex) constitute a healed primary lesion. A small number of patients may initially have a normal x-ray.
Congenital tuberculosis is rare, although cases of fetal infection have been reported. The infection may occur when the fetus swallows infected amniotic fluid or be bloodborne through the umbilical circulation. The criteria for diagnosis include positive bacteriologic studies occurring within the first few days of life with an exclusion of an extrauterine infection source, as more commonly contamination occurs after birth from an infected mother or a close relative. The most common signs are nonspecific and include fever, failure to thrive, lymphadenopathy, hepatomegaly, and splenomegaly. The disease usually is miliary or disseminated. An early diagnosis is necessary for effective treatment.
Untreated tuberculosis is far riskier to the mother and fetus than any of the potential medications necessary to treat active disease. Treated TB does not seem to lead to adverse maternal or fetal outcomes, whereas untreated cases are associated with intrauterine growth restriction, low birth weight, and lower Apgar scores. A preventive course of isoniazid (isonicotinic acid hydrazide [INH]) is generally recommended for those with a positive skin test and no evidence of active disease. Unless there is high risk of developing TB (eg, close contact with a person with active disease), such preventive therapy is withheld in those older than 35 years and during pregnancy and early postpartum because of an increased risk for INH-related hepatitis, particularly in Latina and African American women. Some authors recommended antepartum INH prophylaxis if there is well-documented evidence of recent (<2 years) TB skin conversion to positive even if there are no other risk factors. The argument is that waiting until after delivery might not be as effective in preventing recurrences, perhaps because the high frequency of noncompliance with medication taking postpartum. When the duration of PPD positivity is unknown, but greater than 2 years, and no active disease, INH prophylaxis is postponed until after delivery. In those at high risk (particularly in cases of HIV/AIDS or close contacts with a person with active TB), preventive INH treatment is initiated as soon as evidence of tuberculosis infection (but no active disease) is documented. The recommended dose of INH is 300 mg/d for 6–9 months as well as pyridoxine (vitamin B6) to prevent INH-related neuropathy. Periodic evaluation of liver function is recommended to detect hepatotoxicity early if it occurs. Most studies have shown no teratogenic effects of INH.
Active tuberculosis should be treated as soon as the diagnosis is made. Most treatment programs consist of a 3-drug regimen, usually INH 5 mg/kg/d (total 300 mg/d), ethambutol 15 mg/kg/d, and rifampin 10 mg/kg/d (maximum 600 mg/d) for 8 weeks, and the INH and rifampin to complete 9 months. Local public health departments should be consulted to obtain data about drug resistance. These 3 medications cross the placenta, but no adverse fetal side effects have been reported to date. Pyrazinamide has been used in addition to the 3 medications mentioned in areas of highly drug-resistant tuberculosis but is not routinely recommended during pregnancy because of limited safety data. Because of the risk for fetal (and maternal) ototoxicity, streptomycin, kanamycin, and capreomycin should not be used. Isoniazid has many therapeutic advantages (eg, high efficacy, patient acceptability, and low cost) and appears to be the safest drug for use during pregnancy. The major side effects of INH are hepatitis, hypersensitivity reactions, peripheral neuropathy, and gastrointestinal distress. A baseline liver function test should be obtained and then repeated periodically because of higher risk of hepatotoxicity during pregnancy and the first 6 months postpartum. Pyridoxine 50 mg/d should be administered to prevent INH-induced neuritis due to vitamin B6 deficiency. Optic neuritis is a rare complication reported with ethambutol use. Rifampin may cause hepatitis, hypersensitivity reactions, occasional hematologic toxicity, flulike syndrome, abdominal pain, acute renal failure, and thrombocytopenia. Rifampin may increase the metabolic rate of oral contraceptives through activation of the hepatic P450 enzyme system, so an alternative form of contraception may be necessary after delivery in these patients while they are taking rifampin.
Routine antepartum obstetric management includes adequate rest and nutrition, family support, correction of anemia if present, and regular follow-up visits. Immediate neonatal contact is allowed if the mother has received treatment for inactive disease and no evidence of reactivation is present. In patients with inactive disease in whom prophylactic INH was not given or those with active disease in whom adequate treatment was given, early neonatal contact may be allowed, provided the mother is reliable in continuing therapy. A mother with active disease should receive at least 3 weeks of treatment before coming into contact with her baby, and the baby must also receive prophylactic INH.
There are no absolute contraindications to breastfeeding once the mother is noninfectious. Although antituberculosis drugs are found in breast milk, the concentrations are low, and the risk of toxicity in the infant is considered to be minimal. However, each case should be judged individually. In general, breastfeeding is not contraindicated while the mother is taking antituberculosis medications.
Immunization of the newborn with bacille Calmette-Guérin (BCG) vaccine remains controversial. If prompt use of INH as prophylaxis is unlikely or if the mother has INH-resistant disease, BCG vaccination of the infant should be considered.
If the pregnant patient is adequately treated with antituberculosis chemotherapy for active disease, tuberculosis generally has no deleterious effect, either during the course of pregnancy or the puerperium or on the fetus. Pregnant women have the same prognosis as nonpregnant women. Tuberculosis is not a reason for recommending a therapeutic abortion, as it was sometimes the case before the advent of effective treatment.
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