Obstentrics_Williams

Obstentrics_Williams. V ricella LK, Louis )M, Mercer BM, et al: Epidural-associated hypotension is more common among severely preeclamptic patients in labor. Amt) Obstet GynecoIt207(4):335.e1,t2012 Ward K, Taylor RN: Genetic factors in the etiology of preeclampsia/eclampsia. In Taylor RN, Roberts )M, Cunningham FG, et al (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2015 Wasden SW, Ragsdale ES, Chasen ST, et al: Impact of non-steroidal antiinflammatory drugs on hypertensive disorders of pregnancy. Pregnancy Hypertens 4:259,t2014 Webster LM, Myers )E, Nelson-Piercy C, et al: Labetalol versus nifedipine as antihypertensive treatment for chronic hypertension in pregnancy: a randomized controlled trial. Hypertension 70:915, 2017 Weissman-Brenner A, Schoen R, Divon MY: Aortic dissection in pregnancy. Obstet Gynecol 103: 1110, 2004


Obstentrics_Williams

Obstentrics_Williams. Weissman-Brenner A, Schoen R, Divon MY: Aortic dissection in pregnancy. Obstet Gynecol 103: 1110, 2004 Working Group Report on High Blood Pressure in Pregnancy: Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am) Obstet Gynecol 183:S1, 2000 Yanit E, Snowden )M, Cheng W, et al: he impact of chronic hypertension and pregestational diabetes on pregnancy outcomes. Am ) Obstet Gynecol 207(4):333.e1,t2012 Zetterstrom K, Lindeberg SN, Haglund B, et al: Chronic hypertension as a risk factor for ofspring to be born small for gestational age. Acta Obstet Gynecol Scand 85(9):1046,t2006 ASTHMA................i.............i.....i.....988 ACUTE BRONCHITIS ...i.....i......i...............991 PNEUMONIA.i...............i.......i.......i..... 992 TUBERCULOSIS.. . .................i............ 995 SARCOIDOSIS.....................i............997 CYSTIC FIBROSIS.. . ................i............ 997


Obstentrics_Williams

Obstentrics_Williams. TUBERCULOSIS.. . .................i............ 995 SARCOIDOSIS.....................i............997 CYSTIC FIBROSIS.. . ................i............ 997 CARBON MONOXIDE POISONING.. . ..i............ 999 A lung which is partialy destroyed or thrown out of function may suice or the respiration of a normal individual, but be unable to respond to the added demands of pregnancy, particulary in the latter months, when the enlarged restricts the mobiliy of the diaphragm. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) As indicated by the above, it has long been appreciated that women in advanced pregnancy tolerate lung disease poorly. Nevertheless, pulmonary disorders are frequently encountered during pregnancy. Chronic asthma or an acute exacerbation is the most common and afects up to 8 percent of pregnant women. Moreover, asthma along with community-acquired pneumonia accounted for almost 10 percent of nonobstetrical antepartum hospitalizations in one managed care plan (Gazmararian, 2002). Pneumonia is also a frequent postpartum complication requiring readmission (Belfort, 2010). These and other pulmonary disorders are superimposed on several important pregnancy-induced changes of ventilatory physiology. For example, pregnant women, especially those in the last trimester, are susceptible to complications of severe acute pneumonitis as evidenced by the disparate number of maternal deaths during influenza pandemics.


Obstentrics_Williams

Obstentrics_Williams. The important and sometimes marked changes in the respira tory system induced by pregnancy are reviewed in Chapter 4 (p. 64), and values for associated tests can be found in the Appendix (p. 1260). Lung volumes and capacities that are measured directly to assess pulmonary pathophysiology may be signiicantly altered. In turn, these change gas concentrations and acid-base values in blood. Some of the physiological alterations induced by pregnancy were summarized by Wise and associates (2006): 1. ital capaciy and inspiratory capaciy increase by approximately 20 percent by late pregnancy. 2. Expiratory reserve volume decreases from 1300 mL to approximately 1100 mL. 3. idal volume increases approximately 40 percent as a result of respiratory stimulation by progesterone. 4. Minute ventilation increases 30 to 40 percent due to increased tidal volume. As a result, arterial P02 increases from 100 to 105 mm Hg. 5.


Obstentrics_Williams

Obstentrics_Williams. 4. Minute ventilation increases 30 to 40 percent due to increased tidal volume. As a result, arterial P02 increases from 100 to 105 mm Hg. 5. Increasing metabolic demands cause a 30-percent rise in carbon dioxide (C02) production. But, because of its concomitantly increased difusion capacity and hyperventilation, the arterial Peo2 decreases from 40 to 32 mm Hg. 6. Residual volume decreases approximately 20 percent from 1500 mL to approximately 1200 mL. 7. Chest wal compliance is reduced by a third by the expanding uterus and increased intraabdominal pressure. This causes a 10-to 25-percent decrease in functional residual capacithe sum of expiratory reserve and residual volumes.


Obstentrics_Williams

Obstentrics_Williams. In a longitudinal cohort study, Grindheim and colleagues (2012) also showed that forced vital capacity and peak expiratory flow rose progressively across pregnancy after 14 to 16 weeks' gestation. The end result of these pregnancy-induced changes is substantively increased ventilation due to deeper but not more frequent breathing. hese are thought to be stimulated by basal oxygen consumption as it rises incrementally from 20 to 40 mLimin in the second half of pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Reactive airway disease is seen frequently in young women and therefore oten complicates pregnancy. Asthma prevalence grew steadily in many countries beginning in the mid-1970s but may have plateaued in the United States with a prevalence in adults of approximately 10 percent (Barnes, 2015; Centers for Disease Control and Prevention, 201Oc, 2013). The estimated asthma prevalence during pregnancy ranges between 4 and 8 percent, and this appears to be rising (Kelly, 2015; Racusin, 2013). Finally, evidence is accruing that fetal and neonatal environmental exposures may contribute to the origins or mitigation of asthma (Grant, 2016; Litonjua, 2016; Spiegel, 2016).


Obstentrics_Williams

Obstentrics_Williams. Asthma is a chronic inlammatory airway syndrome with a major hereditary component. Increased airway responsiveness and persistent subacute inflammation are associated with polymorphism genes on chromosomes 5q that include cytokine gene clusters, 3-adrenergic and glucocorticoid receptor genes, and the T-cell antigen receptor gene (Barnes, 2015). Asthma is etiologically and clinically heterogeneous, and an environmental allergic stimulant such as influenza or cigarette smoke serves as a promoter for susceptible individuals (Bel, 2013).


Obstentrics_Williams

Obstentrics_Williams. he hallmarks of asthma are reversible airway obstruction from bronchial smooth muscle contraction, vascular congestion, tenacious mucus, and mucosal edema. Mucosal inlammation is characterized by infiltration with eosinophils, mast cells, and T lymphocytes. hese causes airway inflammation and increased responsiveness to numerous stimuli that include irritants, viral infections, aspirin, cold air, and exercise. Several inflammatory mediators produced by these and other cells include histamine, leukotrienes, prostaglandins, cytokines, IgE, and many others. Importantly, because F-series prostaglandins and ergonovine exacerbate asthma, these commonly used obstetrical drugs should be avoided if possible.


Obstentrics_Williams

Obstentrics_Williams. Pulmonary unction changes are more pronounced in asthmatics compared with healthy women (Zairina, 2015). Asthma manifestations range from mild wheezing to severe bronchoconstriction, which obstructs airways and decreases airflow. his lowers the forced expiratory volume in 1 second/forced vital capacity (FEVJFVC) ratio and the peak expiratory flow (PEF). The work ofbreathing progressively increases, and patients note chest tightness, wheezing, or breathlessness. Subsequent alterations in oxygenation primarily reflect ventilation-perfusion mismatching because the distribution of airway narrowing is uneven. Varied manifestations of asthma have led to a simple classiication that considers severity, onset, and duration of symptoms (Table 51-1). With persistent or worsening bronchial obstruction, clinical stages progress as shown in Figure


Obstentrics_Williams

Obstentrics_Williams. Hypoxia initially is mitigated by hyperventilation, which maintains arterial P02 within a normal range but lowers Peo2' creating respiratory alkalosis. As airway narrowing worsens, ventilation-perusion defects increase, and arterial hypoxemia ensues. With severe obstruction, ventilation becomes impaired as fatigue causes early CO2 retention. Because ofhyperventilation, this may only be seen initially as an arterial Peo2 returning to the normal range. With continuing obstruction, respiratory failure follows from fatigue. Although these changes are generally reversible and well tolerated by the healthy nonpregnant individual, even early asthma stages may be dangerous for the pregnant woman and her fetus. This is because smaller functional residual capacity and increased pulmonary shunting render the woman more susceptible to hypoxia and hypoxemia. Effects of Pregnancy on Asthma


Obstentrics_Williams

Obstentrics_Williams. Effects of Pregnancy on Asthma Pregnancy has an unpredictable efect on underlying asthma. In their review of six prospective studies of more than 2000 gravidas, Gluck and Gluck (2006) reported that approximatelyaa third each improved, remained unchanged, or clearly TABLE 51-1. Classification of Asthma Severity FIGURE 51-1 Clinical stages of asthma. FEV1 = forced expiratory volume in 1 second. worsened. Exacerbations are more common with severe disease (Ali, 2013). In a study by Schatz and associates (2003), baseline severity correlated with asthma morbidity during pregnancy. With mild disease, 13 percent of women had an exacerbation and 2.3 percent required admission; with moderate disease, these numbers were 26 and 7 percent; and for severe asthma, 52 and 27 percent. Others have reported similar observations (Charlton, 2013; Hendler, 2006). Finally, morbidity rates are disproportionately increased in black compared with white women.


Obstentrics_Williams

Obstentrics_Williams. Up to 20 percent of women with mild or moderate asthma have been reported to have an intrapartum exacerbation (Schatz, 2003). Conversely, Wendel and associates (1996) reported exacerbations at the time of delivery in only 1 percent of women. Mabie and coworkers (1992) reported an 18-fold increased exacerbation risk following cesarean versus vaginal delivery. Women with asthma have had improved pregnancy outcomes during the past 20 years. he incidence of spontaneous abortion in women with asthma may be slightly increased (Blais, 2013).


Obstentrics_Williams

Obstentrics_Williams. Women with asthma have had improved pregnancy outcomes during the past 20 years. he incidence of spontaneous abortion in women with asthma may be slightly increased (Blais, 2013). Maternal and perinatal outcomes for nearly 30,000 pregnan cies in asthmatic women are shown in Table 51-2. Findings are not consistent among these studies. For example, in some, but not all, the incidences of preeclampsia, preterm labor, growth restricted infants, and perinatal mortality are slightly increased (Murphy, 2011). Other reports cited a small rise in the incidence of placental abruption and previa, preterm rupture of mem branes, and gestational diabetes (Getahun, 2006; Wang, 2014). But, in a European report of 37,585 pregnancies of women with asthma, the risks for most obstetrical complications were not increased (Tata, 2007). Finally, Cossette and coworkers (2013) and increasing inhaled-corticosteroid dosage.


Obstentrics_Williams

Obstentrics_Williams. Increased morbidity appears to be signiicantly linked to severe disease, poor control, or both. In the study by the Maternal-Fetal Medicine Units (MFMU) Network, delivery before 37 weeks' gestation was not increased among the 1687 pregnancies of asthmatic women compared with those of 881 controls (Dombrowski, 2004a). But for women with severe asthma, the rate was increased approximately twofold. In a prospective evaluation of 656 asthmatic pregnant women and 1052 pregnant controls, Triche and coworkers (2004) found that women with moderate to severe asthma, regardless of treatment, are at increased risk of preeclampsia. Finally, the MFMU Network study suggests a direct relationship of baseline pregnancy FEV] with birthweight and an inverse relationship with rates of gestationl hypertension and preterm delivery (Schatz, 2006).


Obstentrics_Williams

Obstentrics_Williams. Maternal morbidity includes life-threatening complications from status asthmaticus. his causes muscle fatigue with respiratory arrest, pneumothorax, pneumomediastinum, acute cor pulmonale, and cardiac arrhythmias. Not surprisingly, maternal and perinatal mortality rates rise substantively when mechanical ventilation is required. TABLE 51-2. Maternal and Perinatal Outcomes in Pregnancies Complicated by Asthma blncidence not significantly diferent compared with control group or generan l obstetrical population. clncidence significantly greater than control group or general obstetrical population. NS = not stated.


Obstentrics_Williams

Obstentrics_Williams. clncidence significantly greater than control group or general obstetrical population. NS = not stated. As discussed, with reasonable asthma control, perinatal outcomes are generally good. In the Network study cited above, rates of adverse neonatal sequelae caused by asthma were not signiicantly increased (Dombrowski, 2004a). he caveat is that severe asthma was uncommon in this closely monitored group. When respiratory alkalosis develops, earlier animal and human studies suggest that fetal hypoxemia develops well before the alkalosis compromises maternal oxygenation (Rolston, 1974). It is hypothesized that the fetus is jeopardized by decreased uterine blood flow, decreased maternal venous return, and an alkaline-induced letward shit of the oxyhemoglobin dissociation curve (Chap. 47, p. 920).


Obstentrics_Williams

Obstentrics_Williams. The fetal response to maternal hypoxemia is decreased umbilical blood flow, increased systemic and pulmonary vascular resistance, and decreased cardiac output. Observations by Bracken and colleagues (2003) confirm that the incidence of fetal-growth restriction increases with asthma severity. Because the fetus may be seriously compromised as asthma severity increases, the need for aggressive management is underscored. Monitoring the fetal response is, in efect, an indicator of maternal status. Possible teratogenic or adverse fetal efects of drugs given to control asthma have been a concern. Several reports show a slightly greater risk for varied abnormalities such as cleft lip and palate and autism spectrum disorders. However, not all studies have veriied this (Eltonsy, 2016; Gidaya, 2016; Murphy, 2013b; Wang, 2014). It is worrisome that up to half of these women discontinue essential treatment between 5 and 13 weeks' gestation (Enriquez, 2006).


Obstentrics_Williams

Obstentrics_Williams. he subjective severity of asthma frequently does not correlate with objective measures of airway function or ventilation. Although clinical examination can also be an inaccurate predictor, useful signs include labored breathing, tachycardia, pulsus paradoxus, prolonged expiration, and use of accessory muscles. Signs of a potentially fatal attack include central cyanosis and altered consciousness.


Obstentrics_Williams

Obstentrics_Williams. Arterial blood gas analysis provides objective assessment of maternal oxygenation, ventilation, and acid-base status. With this information, the severity of an acute attack can be assessed (see Fig. 51-1). That said, in a prospective evaluation, Wendel and associates (1996) found that routine arterial blood gas analysis did not help to manage most pregnant women who required admission for asthma control. If used, the results must be interpreted in relation to normal values for pregnancy. For example, a Pco2>35 mm Hg with a pH <7.35 is consistent with hyperventilation and CO2 retention in a pregnant woman.


Obstentrics_Williams

Obstentrics_Williams. Pulmonary function testing should be routine in the management of chronic and acute asthma. Sequential measurement of the FEV1 or of the peak expiratoy low rate-PEFR-is the best measure of severity. n FEV1 less than 1 L, or less than 20 percent of predicted value, correlates with severe disease defined by hypoxia, poor response to therapy, and a high relapse rate. The PEFR correlates well with the FEVl, and it can be measured reliably with inexpensive portable meters. It is advantageous for each woman to determine her own baseline when asymptomatic to compare with values when symptomatic. • Management of Chronic Asthma Asthma management by an experienced team produces the most salutary outcomes (Bonham, 2017; Lim, 2014; Wendel, 1996). Management guidelines include: 1. Patient education-general asthma management and its efect on pregnancy. 2. Environmental precipitating factors-avoidance or control.


Obstentrics_Williams

Obstentrics_Williams. Patient education-general asthma management and its efect on pregnancy. 2. Environmental precipitating factors-avoidance or control. Viral infections that include the common cold are frequent triggering events (Ali, 2013; Murphy, 2013a). 3. Objective assessment of pulmonary function and fetal status-monitor with PEFR or FEVl. 4. Pharmacological therapy-in appropriate combinations and doses to provide baseline control and treat exacerbations. Compliance may be a problem, and periodic medication reviews are helpful (Sawicki, 2012). In general, women with moderate to severe asthma ideally measure and record either their FEV1 or PEFR twice daily. The FEVl ideally is >80 percent of predicted. For PEFR, predicted values range from 380 to 550 L/min. Each woman has her own baseline value, and therapeutic adjustments can be made using this (American College of Obstetricians and Gynecologists, 2016a; Rey, 2007).


Obstentrics_Williams

Obstentrics_Williams. Treatment depends on disease severity. No therapeutic regimen for management of pregnant asthmatics is universally accepted (Bain, 2014). 3-Agonists help abate bronchospasm, and corticosteroids treat inflammation. Regimens recommended for outpatient management are listed in Figure 51-2. For mild asthma, inhaled 3-agonists as needed are usually suicient. For persistent asthma, inhaled corticosteroids are administered every 3 to 4 hours. The goal is to reduce the use of 3-agonists for symptomatic relie. A case-control study from Canada with a cohort of more than 15,600 nonpregnant women with asthma showed that inhaled corticosteroids reduced hospitalizations by 80 percent (Blais, 1998). At Parkland Hospital, Wendel and


Obstentrics_Williams

Obstentrics_Williams. FIGURE 51-2 Stepwise approach to asthma treatment.oICS = inhaled corticosteroids; LABA = long-acting 3-agonists; OCS = oral coticosteroids. (Modified from Barnes PJ: Asthma. In Kasper D, Fauci A, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGraw-Hili Education, 2015, p 1669.) sions for severe exacerbations with inhaled steroids. corticosteroids became available. Minimal beneit is gained with use of these compounds and they have a high rate of side efects. However, some theophylline derivatives are considered useful for oral maintenance therapy if the initial response to inhaled corticosteroids and 3-agonists is not optimal (Dom browski, 2004b).


Obstentrics_Williams

Obstentrics_Williams. zileuto n, zairlukast, and montelukast. hese drugs are given orally or by inhalation for prevention, but they are not efec tive for acute disease (Barnes, 2015). For maintenance, they are used in conjunction with inhaled corticosteroids to allow minimal dosing. Approximately half of asthmatics will improve with these drugs. hese agents are not as efective as inhaled corticosteroids, and there is little experience with their use in pregnancy (Fanta, 2009). mast cell degranulation. They are inefective for acute asthma and are used primarily to treat childhood asthma. • Management of Acute Asthma


Obstentrics_Williams

Obstentrics_Williams. mast cell degranulation. They are inefective for acute asthma and are used primarily to treat childhood asthma. • Management of Acute Asthma Treatment of acute asthma during pregnancy is similar to that for the nonpregnant asthmatic. Importantly, the threshold for hospitalization is signiicantly lower. Intravenous (IV) hydration may help clear pulmonary secretions, and supplemental oxygen is given by mask. The therapeutic aim is to maintain the P02 >60 mm Hg, and preferably normal, along with 90to 95-percent oxygen saturation. Baseline pulmonary function testing includes FEV) or PEFR. Continuous pulse oximetry and electronic fetal monitoring, depending on gestational age, may provide useful information. Antibiotics are not given unless there is concomitant pneumonitis, which is caused by the same organisms discussed on page 992 (T erraneo, 2014).


Obstentrics_Williams

Obstentrics_Williams. First-line therapy for acute asthma includes a short-acting 3-adrenergic agonist, such as terbutaline, albuterol, isoetharine, epinephrine, isoproterenol, or metaproterenol, which is given subcutaneously, taken orally, or inhaled. In severely ill women, these drugs can be given IV (Barnes, 2015). They bind to speciic cell-surface receptors and activate adenylyl cyclase to increase intracellular cyclic AMP and modulate bronchial smooth muscle relaxation. Long-acting preparations are used for outpatient therapy.


Obstentrics_Williams

Obstentrics_Williams. If not previously given for maintenance, inhaled corticosteroids are commenced. A nebulized anticholinergic drug may be added if the response at this point is unsatisfactory (Barnes, 2015). Also, for severe exacerbations, IV magnesium sulfate or theophylline may prove eicacious. Corticosteroids are given early to all patients with severe acute asthma. Unless the response to bronchodilator and inhaled corticosteroid therapy is prompt, oral or parenteral corticosteroids are given (Lazarus, 2010). One regimen is oral prednisone or prednisolone or IV methylprednisolone in a dose of 30 to 45 mg daily for 5 to 10 days without tapering (Barnes, 2015). Because their onset of action is several hours, corticosteroids are given initially along with 3-agonists for severe acute asthma.


Obstentrics_Williams

Obstentrics_Williams. At this juncture, further management depends on the severity and response to therapy. If initial therapy with 3-agonists is associated with improvement of FEV, or PEFR to above 70 percent of baseline, then discharge can be considered. Some women may beneit from longer observation. Alternatively, for the woman with obvious respiratory distress, or if the FEV) or PEFR is <70 percent of predicted after three doses of 3-agonist, admission is usually advisable (Lazarus, 2010). Intensive therapy is continued with inhaled 3-agonists, IV corticosteroids, and close observation for worsening respiratory distress or fatigue in breathing (Racusin, 2013). The woman is cared for in the delivery unit or an intermediate or intensive care unit (ICU) (Dombrowski, 2006; Zeeman, 2003).


Obstentrics_Williams

Obstentrics_Williams. Severe asthma of any type not responding after 30 to 60 minutes of intensive therapy is termed status asthmaticus. This has been termed by some as critical asthma symptoms (Kenyon, 2015). Generally, management of nonpregnant patients with status asthmaticus in an intensive care setting results in a good outcome. Consideration should be given to early intubation when maternal respiratory status worsens despite aggressive treatment (see Fig. 51-1). Fatigue, CO2 retention, and hypoxemia are indications for mechanical ventilation (Chan, 2015). Although Lo and colleagues (2013) described a woman with status asthmaticus in whom cesarean delivery was necessary to efect ventilation, Andrews (2013) cautioned that such clinical situations are uncommon.


Obstentrics_Williams

Obstentrics_Williams. For the laboring asthmatic, maintenance medications are continued through delivery. Stress-dose corticosteroids are administered to any woman given systemic corticosteroid therapy within the preceding 4 weeks. The usual dose is 100 mg of hydrocortisone given IV every 8 hours during labor and for 24 hours ater delivery. The PEFR or FEV) is determined on admission, and serial measurements are taken if symptoms develop. Oxytocin or prostaglandins E) or E2 are used for cervical ripening and induction. A nonhistamine-releasing narcotic such as fentanyl may be preferable to meperidine for labor, and epidural analgesia is ideal. For surgical delivery, conduction analgesia is preferred because tracheal intubation can trigger severe bronchospasm. Postpartum hemorrhage is treated with oxytocin or prostaglandin E) or E2. Prostaglandin F2: or ergotamine derivatives are contraindicated because they may cause signiicant bronchospasm.


Obstentrics_Williams

Obstentrics_Williams. Infection of the large airways is manifest by cough without pneumonitis. It is common in adults, especially in winter months. Infections are usually caused by viruses, and of these, influenza A and B, parainluenza, respiratory syncytial, coronavirus, adenovirus, and rhinovirus are frequent isolates (Wenzel, 2006). Bacterial agents causing community-acquired pneumonia are rarely implicated. The cough of acute bronchitis persists for 10 to 20 days (mean 18 days) and occasionally lasts for a month or longer. According to the 2006 guidelines of the American College of Chest Physicians, routine antibiotic treatment is not indicated (Smith, 2014).


Obstentrics_Williams

Obstentrics_Williams. his is a leading cause of death in the United States (Heron, 2016). Current classiication includes communiy-acquired pneumonia (CAP), which is typically encountered in otherwise healthy young women, including during pregnancy. Healthcare-associated pneumonia (HAP) develops in patients in outpatient care facilities and more closely resembles hospitalacquired pneumonia (HAP). In most cases of community-acquired pneumonia, the ofending pathogen is not identified. In a recent study from the Centers for Disease Control and Prevention (CDC), pathogens were identified in only 38 percent of nearly 2S00 adults with pneumonia Gain, 201S). hese included viruses in 23 percent, bacteria in 11 percent, both in 3 percent, and ungi or protozoa in 1 percent. Half of bacterial isolates were Sreptococcus pneumoniae.


Obstentrics_Williams

Obstentrics_Williams. Pneumonia in pregnant women is relatively common (Brito, 2011; Sheield, 2009). Gazmararian and coworkers (2002) reported that pneumonia accounts for 4.2 percent of antepartum admissions for nonobstetrical complications. Pneumonia is also a frequent indication for postpartum readmission (Belfort, 2010). During inluenza season, admission rates for respiratory illnesses double compared with rates in the remaining months (Cox, 2006). Regardless of etiology, mortality from pneumonia is infrequent in young women, but during pregnancy severe pneumonitis with appreciable loss of ventilatory capacity is not as well tolerated (Callaghan, 201S; Rogers, 2010). Hypoxemia and acidosis are also poorly accommodated by the fetus and frequently stimulate preterm labor after midpregnancy. Because many cases of pneumonia follow viral upper respiratory illnesses, worsening or persistence of symptoms may represent developing pneumonia. Any gravida suspected of having pneumonia should undergo chest


Obstentrics_Williams

Obstentrics_Williams. cases of pneumonia follow viral upper respiratory illnesses, worsening or persistence of symptoms may represent developing pneumonia. Any gravida suspected of having pneumonia should undergo chest radiography.


Obstentrics_Williams

Obstentrics_Williams. Many bacteria that cause community-acquired pneumonia, such as Streptococcus pneumoniae, are part of the normal resident lora. Some factors that perturb the symbiotic relationship between colonizing bacteria and mucosal phagocytic defenses include acquisition of a virulent strain or bacterial infections following a viral infection. Cigarette smoking and chronic bronchitis favor colonization with S pneumoniae, HaemophiIus inluenzae, and Legionella species. Other risk factors include asthma, binge drinking, and human immunodeficiency virus (HIV) infection (Sheield, 2009).


Obstentrics_Williams

Obstentrics_Williams. Pregnancy itself does not appear to predispose to pneumonia. Jin and colleagues (2003) reported the antepartum hospitalization rate for pneumonia in Alberta, Canada, to be 1.S per 1000 deliveries-almost identical to the rate of 1.47 per 1000 for nonpregnant women. Likewise, Yost and associates (2000) reported an incidence of 1.S per 1000 for pneumonia complicating 7S,000 pregnancies cared for at Parkland Hospital. s discussed, at least hlf are caused by viruses. A fourth are bacterial, and S pneumoniae causes half of the latter. Over the past few years community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a common pathogen that may cause necrotizing pneumonia (Mandell, 201S; Moran, 2013). Occasionally, Legionnaires disease is encountered (Close, 2016). FIGURE 51-3 Chest radiograph in a pregnant woman with right lower lobe and left upper lobe pneumonia. Rounded right basilar and let apical infiltrates are consistent with the diagnosis.


Obstentrics_Williams

Obstentrics_Williams. Typical symptoms of pneumonia include cough, dyspnea, sputum production, and pleuritic chest pain. Mild upper respiratory symptoms and malaise usually precede these symptoms, and mild leukocytosis is usually present. Chest radiography is essential for diagnosis (Fig. SI-3). Radiographical findings do not accurately predict the etiology, and as discussed, the responsible pathogen is identiied in fewer than half of cases. According to the Infectious Diseases Society of America (IDSA) and the American horacic Society (A TS), tests to identiy a specific agent are optional (Mandell, 2007). hus, sputum cultures, serological testing, cold agglutinin identiication, and tests for bacterial antigens are not routinely recommended. The one exception to this may be rapid serological testing for inluenza A and B (Sheield, 2009).


Obstentrics_Williams

Obstentrics_Williams. Although many otherwise healthy young adults can be safely treated as outpatients, at Parkland Hospital we hospitalize all pregnant women with radiographically proven pneumonia. Another option is outpatient therapy or 23-hour observation, which is reasonable with optimal follow-up. At least for nonpregnant patients, the pneumonia severity index (PSI) and the CURB-6S scoring system are used as a guide to admission (Mandell, 201S). Neither has been studied in pregnancy. Given that, risk factors shown in Table 5a1-3 should prompt consideration for hospitalization. With severe disease, admission to an intensive or intermediate care unit is advisable. Approximately 20 percent of pregnant women admitted to Parkland Hospital for pneumonia require this level of care (Zeeman, 2003). Severe pneumo TABLE 51-3. Criteria for Severe Community-Acquired Pneumoniaa Leukopenia: WBC <4000/-LL Thrombocytopenia-platelets < 1 OO,OOO/-LL aCriteria of the Infectious Diseases Society of America/


Obstentrics_Williams

Obstentrics_Williams. TABLE 51-3. Criteria for Severe Community-Acquired Pneumoniaa Leukopenia: WBC <4000/-LL Thrombocytopenia-platelets < 1 OO,OOO/-LL aCriteria of the Infectious Diseases Society of America/ American Thoracic Society. Pao/Fio2 = partial pressure oxygen in arterial blood/ fraction of inspired oxygen; WBC = white blood cell. Adapted from Mandell, 2007. nia is a relatively common cause of acute respiratory distress syndrome (ARDS) during pregnancy, and mechanical ventilation may become necessary (Chap. 47, p. 919). Indeed, of the 51 gravidas who required mechanical ventilation in the review by Jenkins and coworkers (2003), 12 percent had pneumonia.


Obstentrics_Williams

Obstentrics_Williams. Initial antimicrobial and antiviral treatment is empirical (Mandell, 2015). Because most adult bacterial pneumonias are caused by pneumococci, mycoplasma, or chlamydophila, monotherapy initially is with a macrolide-azithromycin, clarithromycin, or erythromycin (Table 51-4). Yost and colleagues (2000) reported that erythromycin mono therapy, given IV and then orally, was efective in all but one of 99 pregnant women with uncomplicated pneumonia. During inluenza season, we routinely administer oseltamivir treatment along with empirical therapy for bacterial pneumonia.


Obstentrics_Williams

Obstentrics_Williams. For women with severe disease according to criteria in Table 51-3, Mandell and associates (2007) summarized IDSAI ATS guidelines, which call for either: (1) a respiratory luoroquinolone-Ievofloxacin, moxifloxacin, or gemiloxacin; or (2) a macrolide plus a preferred �-lactam-either high-dose amoxicillin or amoxicillin-clavulanate. �-Lactam alternatives include ceftriaxone, cefpodoxime, or cefuroxime (see Table 51-4). In areas in which the resistance of pneumococcal isolates to macrolides is great, these latter regimens are preferred. he teratogenicity risk of luoroquinolones is low, and these should be given if indicated (Briggs, 2015). IfCA-MRSA is suspected, then vancomycin or linezolid is added (Mandell, 2015; Moran, 2013; Wunderink, 2013).


Obstentrics_Williams

Obstentrics_Williams. Clinical improvement is usually evident in 48 to 72 hours with resolution of fever in 2 to 4 days. Radiographic abnormalities may take up to 6 weeks to completely resolve (Torres, 2008). Worsening disease is a poor prognostic feature, and subsequent radiography is recommended if fever persists. Even with improvement, however, approximately 20 percent of women develop a pleural eusion. Treatment of uncomplicated pneumonia is recommended for 5 to 7 days (Musher, 2014). Treatment failure may occur in up to 15 percent of cases, and a wider antimicrobial regimen and more extensive diagnostic testing is warranted. During the preantimicrobial era, as many as a third of pregnant women with pneumonia died (Finland, 1939). Although much improved, maternl and perinatl morbidity and mortality remain formidable. In ive studies with a total of 632 women published ater 1990, almost 7 percent required intubation and mechanical ventilation, and the maternal mortality rate was 0.8 percent.


Obstentrics_Williams

Obstentrics_Williams. Prematurely ruptured membranes and preterm delivery are frequent complications and have been reported in up to a third of cases of acute lung infection (Getahun, 2007; Shariatzadeh, 2006). Likely related are older studies reporting a twofold increase in low-birthweight neonates (Sheield, 2009). In one populationbased study from Taiwan of nearly 219,000 births, incidences of preterm and growth-restricted newborns and of preeclampsia and cesarean delivery were significantly increased (Chen, 2012). Two pneumococcal vaccines, a 23-serotype older preparation and a newer 13-serotype vaccine, are used in children (Swamy, 2015). he 23-serotype vaccine is 60-to 70-percent protective, and its use lowers emergence of drug-resistant pneumococci (Kyaw, 2006). he 13-serotype vaccine is not recommended for TABLE 51-4. Empirical Antimicrobial Treatment for Community-Acquired Pneumonia Uncomplicated, otherwise health' Macrolidesb: clarithromycin or azithromycin


Obstentrics_Williams

Obstentrics_Williams. TABLE 51-4. Empirical Antimicrobial Treatment for Community-Acquired Pneumonia Uncomplicated, otherwise health' Macrolidesb: clarithromycin or azithromycin Respiratory fluoroquinolones: moxifloxacin, gemifloxacin, or levofloxacin 3-lactams: amoxicillin/clavulanate, ceftriaxone, cefotaxime, or cefuroxime plus a macrolide aUse as inpatient or outpatient regimen. bDoxycyciine may be given instead if postpartum. (See Table 51-3 for criteria. otherwise healthy pregnant women. It is, however, recommended for women who are immunocompromised, including those with HIV infection; significant smoking history; diabetes; cardiac, pulmonary, or renal disease; and asplenia, such as with sicklecell disease (Table 9-7, p. 173). Protection against pneumococcal infection in women with chronic diseases may be less eicacious than in healthy patients (Moberley, 2013).


Obstentrics_Williams

Obstentrics_Williams. Each year, 10 percent of pregnant women develop influenza (Cantu, 2013). Influenza A and B are RNA viruses that cause respiratory infection, including pneumonitis, that is epidemic in the winter months. The virus is spread by aerosolized droplets and quickly infects ciliated columnar epithelium, alveolar cells, mucus gland cells, and macrophages. Disease onset is 1 to 4 days following exposure. Common symptoms include fever, cough, myalgia, and chills (Sokolow, 2015). In most healthy adults, infection is self-limited. Pneumonia is the most frequent complication of inluenza and mimics bacterial pneumonia. According to the CDC (201 Oa), infected pregnant women are more likely to be hospitalized and admitted to an ICU. Others have corroborated these observations (Mertz, 2017). At Parkland Hospital during the 2003 to 2004 inluenza season, pneumonia developed in 12 percent of gravidas with influenza (Rogers, 2010).


Obstentrics_Williams

Obstentrics_Williams. he 2009 to 2010 pandemic with the influenza (NHINI) pdm09 strain was particularly severe (Rasmussen, 2014). In an MFMU Network study, 10 percent of pregnant or postpartum women admitted with HINI inluenza were cared for in an ICU, and 11 percent of these patients died (Varner, 201I). Risk factors included late pregnancy, smoking, and chronic hypertension. Overall, inluenza accounted for 12 percent of pregnancy-related deaths during the 2009 to 2010 pandemic (Callaghan, 2015). During the 2013 to 2014 inluenza season, a fourth of pregnant women admitted to California ICUs died (Louie, 2015). Of865 pregnant women with influenza, Oboho and coworkers (2016) noted that 7 percent of their cohort had severe disease, and four women died. If inluenza causes ARDS, extracorporeal membrane oxygenation (ECMO) may be lifesaving (Anselmi, 2015; Saad, 2016).


Obstentrics_Williams

Obstentrics_Williams. Primary influenza pneumonitis is characterized by sparse sputum production and radiographic interstitial infiltrates (Cohen, 2015). More commonly, either secondary or mixed pneumonia develop from bacterial superinfection by streptococci or staphylococci after 2 to 3 days of initial clinical improvement. he CDC (2007) reported several cases in which CA-MRSA caused influenza-associated pneumonitis with a case-fatality rate of 25 percent. Other possible adverse efects of inluenza A and B on pregnancy outcome are discussed in Chapter 64 (p. 1213).


Obstentrics_Williams

Obstentrics_Williams. Supportive treatment is recommended for uncomplicated influenza, and early antiviral treatment is efective Gamieson, 2011; Oboho, 2016). Hospitalization is considered for severely ill women, and for those with pneumonia. As discussed, inluenza hospitalization rates for those with advanced pregnancy are increased compared with nonpregnant women (Dodds, 2007; Schanzer, 2007). he CDC (2016b) recommends neuraminidase inhibitors given within 2 days of symptom onset for chemoprophylaxis and treatment of influenza A and B (Chap. 64, p. 1214). he drugs interfere with release of progeny virus from infected host cells and thus prevent infection of new host cells (Cohen, 2015). Oseltamivir is given orally, 75 mg twice daily, or zanamivir is given by inhalation, 10 mg twice daily. Recommended treatment duration with either is 5 days. The drugs shorten the course of illness by 1 to 2 days, and they probably reduce the risk for pneumonitis (Belgi, 2014; Muthuri, 2014). Our practice is to treat all


Obstentrics_Williams

Obstentrics_Williams. duration with either is 5 days. The drugs shorten the course of illness by 1 to 2 days, and they probably reduce the risk for pneumonitis (Belgi, 2014; Muthuri, 2014). Our practice is to treat all pregnant women with influenza whether or not pneumonitis is identiied (Rasmussen, 2014). Few data guide use of these agents in pregnant women, but the drugs are not teratogenic in animal studies and are considered low risk (Briggs, 2015).


Obstentrics_Williams

Obstentrics_Williams. A major potential concern for viral resistance comes from avian inluenza isolates. "Bird lu" with HPAI, H5N8, H5N2, and H5Nl isolates has been reported in the United States by the CDC Ohung, 2015). In Asia, human infection has been documented with some of these, and mortality rates are high. Preventively, vaccination for inluenza A is recommended by the American College of Obstetricians and Gynecologists (2016b) and the CDC (2016b). Vaccination is discussed in detail in Chapter 64 (p. 1214). Prenatal vaccination also afords some temporary protection for infants (Madhi, 2014; Tita, 2016). During the 2014 to 2015 lu season, the CDC reported that only half of pregnant women received influenza vaccine (Ding,a2015). Infection with varicella-zoster virus, the same agent responsible for chicken pox, results in pneumonitis in 5 percent of gravidas (Harger, 2002). Diagnosis and management are considered in Chapter 64 (p. 1212).


Obstentrics_Williams

Obstentrics_Williams. Fungal and parasitic pulmonary infections are usually of greatest consequence in immunocompromised hosts, especially in women with acquired immunodeficiency syndrome (AIDS). Of these, lung infection with Pneumoystis jiroveci, formerly called Pneumoystis carinii, is a common complication. The opportunistic fungus causes interstitial pneumonia characterized by dry cough, tachypnea, dyspnea, and difuse radiographic infiltrates. Although this organism can be identiied by sputum culture, bronchoscopy with lavage or biopsy may be necessary.


Obstentrics_Williams

Obstentrics_Williams. In an earlier report from the AIDS Clinical Trials Centers, Stratton and colleagues (1992) described pneumocystis pneumonia as the most frequent HIV-related disorder in pregnant women. In some cases, tracheal intubation and mechanical ventilation may be required. Ahmad and coworkers (200 I) reviewed 22 cases during pregnancy and cited a 50-percent mortality rate. Treatment is with trimethoprim-sulfamethoxazole for 14 to 21 days (Masur, 2015). Alternative agents include the more toxic pentamidine (Walzer, 2005). For prophylaxis, several international health agencies recommend one double-strength trimethoprim-sulfamethoxazole tablet orally daily for certain groups of HIV-infected pregnant women. These include women with CD4+ T-lymphocyte counts <2001LL, those whose CD4+ T lymphocytes constitute < 14 percent, or if there is an AIDS-defining illness, particularly oropharyngeal candidiasis (Centers for Disease Control and Prevention, 2016a).


Obstentrics_Williams

Obstentrics_Williams. Any of several fungi can cause pneumonia. In pregnancy, this is usually seen in women with HIV infection or who are oth erwise immunocompromised. Infection is usually mild and self-limited. It is characterized initially by cough and fever, and dissemination is infrequent (Mansour, 2015).


Obstentrics_Williams

Obstentrics_Williams. Histoplasmosis and blastomycosis do not appear to be more frequent or more severe during pregnancy (Youssef, 2013). Data concerning coccidioidomycosis are conlicting (Bercovitch, 2011; Patel, 2013). In a case-control study from an endemic area, Rosenstein and associates (2001) reported that pregnancy was a signiicant risk factor for disseminated disease. In another study, however, Caldwell and coworkers (2000) identified 32 serologically confirmed cases during pregnancy and documented dissemination in only three cases. Women with associated erythema nodosum have a better prognosis, whereas mediastinal lymphadenopathy may more likely relect disseminated disease (Caldwell, 2000; Mayer, 2013). Finally, Crum and Ballon-Landa (2006) reviewed 80 cases of antepartum coccidioidomycosis and found that almost all women diagnosed in the third trimester had disseminated disease. Although the overall maternal mortality rate was 40 percent, it was only 20 percent for 29 cases reported since 1973.


Obstentrics_Williams

Obstentrics_Williams. that almost all women diagnosed in the third trimester had disseminated disease. Although the overall maternal mortality rate was 40 percent, it was only 20 percent for 29 cases reported since 1973. Spinello (2007) and Bercovitch (201a1) with their colleagues have provided reviews of coccidioidomycosis in pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Most cases of cryptococcosis reported during pregnancy manifest as meningitis. Otherwise healthy pregnant women occasionally have cryptococcal pneumonia (Asadi Gharabaghi, 2014; Ely, 1998). Diagnosis is diicult because clinical presentation is similar to that of other community-acquired pneumonias. Treatment. The 2007 IDSNATS guidelines recommend itraconazole as preferred therapy for disseminated fungal infections (Mandell, 2007). Pregnant women have also been given IV amphotericin B or ketoconazole (Paranyuk, 2006; Pilmis, 2015). Amphotericin B has been used extensively in pregnancy with no embryofetal efects. Because of evidence that fluconazole, itraconazole, and ketoconazole may be embryo toxic in large doses in early pregnancy, Briggs and coworkers (2015) recommend that irst-trimester use should be avoided if possible.


Obstentrics_Williams

Obstentrics_Williams. hree echinocandin derivatives-caspofongin, micaongin, and anidulafungin-are efective for invasive candidiasis (Pilmis, 2015; Reboli, 2007). They are embryotoxic and teratogenic in laboratory animals, and use in human pregnancies has not been reported (Briggs, 2015). his coronaviral respiratory infection was first identiied in China in 2002, but no new cases have been reported since 2005. It caused atypical pneumonitis with a case-fatality rate of approximately 10 percent (Dolin, 2012). SARS in pregnancy had a case-fatality rate of up to 25 percent (Lam, 2004; Wong, 2004). Ng and coworkers (2006) reported that the placentas from 7 of 19 cases showed abnormal intervillous or subchorionic ibrin deposition in three, and extensive fetal thrombotic vasculopathy in two. Tuberculosis is still a major worldwide concern. Indeed, it is estimated that a third of the world population is infected (Getahun, 2015). However, it is uncommon in the United


Obstentrics_Williams

Obstentrics_Williams. Tuberculosis is still a major worldwide concern. Indeed, it is estimated that a third of the world population is infected (Getahun, 2015). However, it is uncommon in the United States. The incidence of active tuberculosis in this country has plateaued since 2000 (Scott, 2015). More than half of active cases are in immigrants (Centers for Disease Control and Pre vention, 2009b). Persons born in the United States have newly acquired infection, whereas foreign-born persons usually have reactivation of latent infection. In this country, tuberculosis is a disease of the elderly, the urban poor, minority groups especially black Americans, and patients with HIV infection (Khan, 2013; Raviglione, 2015).


Obstentrics_Williams

Obstentrics_Williams. Infection is via inhalation of Mycobacterium tuberculosis, which incites a granulomatous pulmonary reaction. In more than 90 percent of patients, infection is contained and is dor mant for long periods (Getahun, 2015; Zumla, 2013). In some, especially those who are immunocompromised or who have other diseases, tuberculosis becomes reactivated to cause clini cal disease. Manifestations usually include cough with minimal sputum production, low-grade fever, hemoptysis, and weight loss. Various iniltrative patterns are seen on chest radiograph, ated. Acid-fast bacilli are seen on stained smears of sputum in approximately two thirds of culture-positive individuals. Forms of extrapulmonary tuberculosis include lymphadenitis, pleural, genitourinary, skeletal, meningeal, gastrointestinal, and miliary or disseminated (Raviglione, 2015).


Obstentrics_Williams

Obstentrics_Williams. Resistance to antituberculosis drugs in the United States in the early 1990s was associated with emergence of strains of multidrug-resistant tuberculosis (MDR-TB). Because of this, the CDC (2009a) now recommends a multidrug regimen for initial empirical treatment of patients with symptomatic tuberculosis. Isoniazid, rifampin, pyrazinamide, and ethambutol are given until susceptibility studies are performed (Horsburgh, 2015). Cure rates with 6-month short-course directy observed therapy-DOT -approach 90 percent for new infections (Raviglione, 2015). Other second-line drugs may need to be added. Drug susceptibility is performed on all irst isolates.


Obstentrics_Williams

Obstentrics_Williams. The considerable influx of women into the United States from Asia, Africa, Mexico, and Central America has been accompanied by an increased frequency of tuberculosis in pregnancy. Sackof and coworkers (2006) reported positive tuberculin test results in half of 678 foreign-born women attending prenatal clinics in New York City. Almost 60 percent were newly diagnosed. Pillay and colleagues (2004) stress the prevalence of tuberculosis in HIV-positive pregnant women. At Jackson Memorial Hospital in Miami, Schulte and associates (2002) reported that 21 percent of 207 HIV-infected pregnant women had a positive skin test result. Recall also that silent endometrial tuberculosis can cause tubal infertility (Levison, 2010; Raviglione, 2015).


Obstentrics_Williams

Obstentrics_Williams. Without therapy, active tuberculosis appears to have adverse efects on pregnancy (Mnyani, 2011). Several studies indicate that outcomes are dependent on the site of infection and gestational age at diagnosis. J ana and colleagues (1994) from India and Figueroa-Damian and Arrendondo-Garcia (1998) from Mexico City noted that active pulmonary tuberculosis was associated with increased incidences of preterm delivery, low-birthweight and growth-restricted newborns, and perinatal mortality. Others have found similar efects (EI-Messidi, 2016; Lin, 2010; Sobhy, 2017). From her review, Eferen (2007) cited twofold greater rates of low birthweight, preterm delivery, and preeclampsia. The perinatal mortality rate was increased almost tenfold. Adverse outcomes correlate with late diagnosis, incomplete or irregular treatment, and advanced pulmonary lesions. Conversely, treated tuberculosis is associated with good pregnancy outcomes (Nguyen, 2014; Taylor, 2013).


Obstentrics_Williams

Obstentrics_Williams. Extrapulmonary tuberculosis is less common. Jana and coworkers (1999) reported outcomes in 33 pregnant women with renal, intestinal, and skeletal tuberculosis, and a third had low-birthweight newborns. Llewelyn and associates (2000) reported that nine of 13 pregnant women with extrapulmonary disease had delayed diagnoses. Prevost and Fung Kee Fung (I999) reviewed 56 cases of tuberculous meningitis in which a third of mothers died. Spinal tuberculosis may cause paraplegia, but vertebral fusion may prevent it from becoming permanent (Badve, 2011; Nanda, 2002). Psoas abscess develops in 5 percent of those with spinal infections (Nigam, 2013). Other presentations include widespread intraperitoneal tuberculosis simulating ovarian carcinomatosis and degenerating leiomyoma, and hyperemesis gravidarum from tubercular meningitis (Kutiu, 2007; Moore, 2008; Sherer, 2005).


Obstentrics_Williams

Obstentrics_Williams. Two types of tests are used to detect latent or active tuberculosis. One is the time-honored tuberculin skin test (TSj) and the others are inteeron-gamma release assays IGRAs)} which are becoming preferred (Getahun, 2015; Horsburgh, 2011). IGRAs are blood tests that measure interferon-gamma release in response to antigens present in M tuberculosis, but not bacille Calmette-Guerin (BCG) vaccine (Levison, 2010). he CDC (2005b, 2010b) recommends either skin testing or IGRA testing of gravidas who are in any of the high-risk groups. For those who have received BCG vaccination, IGRA testing is used (Mazurek, 2010). For skin testing, the preferred antigen is purified protein derivative (PPD) of intermediate strength of 5 tuberculin units. If the intracutaneously applied test result is negative, no further evaluation is needed. A positive skin test result measures �5 mm in diameter and requires evaluation for active disease, including a chest radiograph.


Obstentrics_Williams

Obstentrics_Williams. Two IGRAs are available: QuantiFERON-TB Gold and T-SPOT TB tests are recommended by the CDC (2005a,b) for the same indications as skin testing. Although these tests have not been evaluated as extensively as tuberculin skin testing, Kowada (2014) concluded that the tests are cost efective. Other essential laboratory methods for detection or verification of infection-both active and latent-include microscopy, culture, nucleic acid amplification assay, and drug-susceptibility testing (Horsburgh, 2015; Raviglione, 2015).


Obstentrics_Williams

Obstentrics_Williams. Latent Infection. In nonpregnant tuberculin-positive patients with latent infection who are younger than 35 years and who have no evidence of active disease, isoniazid, 300 mg orally daily, is given for 9 months. Isoniazid has been used for decades, and it is considered safe in pregnancy (Briggs, 2015; Taylor, 2013). Compliance is a major problem, and Sackof (2006) and Cruz (2005) and their associates reported a disappointing 10-percent treatment completion. One obvious disconnect is that care for tuberculosis is given in diferent health systems than prenatal care (Zenner, 2012). hese observations are important because most recommend that isoniazid therapy be delayed until ater delivery. Because of possibly increased isoniazid-induced hepatitis risk in postpartum women, some even recommend withholding treatment until 3 to 6 months ater delivery. hat said, neither method is as efective as antepartum treatment to prevent active infection. Boggess and colleagues (2000) reported that only


Obstentrics_Williams

Obstentrics_Williams. withholding treatment until 3 to 6 months ater delivery. hat said, neither method is as efective as antepartum treatment to prevent active infection. Boggess and colleagues (2000) reported that only 42 percent of 167 tuberculin-positive asymptomatic women delivered at San Francisco General Hospital completed 6-month therapy that was not begun until the irst postpartum visit.


Obstentrics_Williams

Obstentrics_Williams. There are exceptions to delayed treatment for latent infection in pregnancy. Known recent skin-test convertors are treated antepartum because the incidence of active infection is 5 percent in the first year (Zumla, 2013). Skin-test-positive women exposed to active infection are also treated because the incidence of infection is 0.5 percent per year. Finally, HIVpositive women are treated because they have an approximate 10-percent annual risk of active disease.


Obstentrics_Williams

Obstentrics_Williams. Active Infection. Recommended initial treatment for active tuberculosis in pregnant women is a four-drug regimen with isoniazid, rifampin, ethambutol, and pyrazinamide, along with pyridoxine. For meningitis, levoBoxacin may be added (Kalita, 2014). In the irst 2-month phase, all four drugs are givenbactericidal phase. his is followed by a 4-month phase of isoniazid and rifampin-continuation phase (Raviglione, 2015; Zumla, 2013). A few reports describe MDR-TB during pregnancy, and treatment options have been reviewed (Horsburgh, 2015; Lessnau, 2003). Breastfeeding is not prohibited during antituberculous therapy.


Obstentrics_Williams

Obstentrics_Williams. Treatment of active disease is of special concern if there is antiretroviral naivete. In these circumstances, beginning concomitant therapy with antituberculosis and antiretroviral therapy can cause the immune reconstitution inlammatory syndrome IRIS) with toxic drug efects (Lai, 2016; Torok, 2011). hat said, recent studies support earlier administration of highly active antiretroviral therapy (HAART)-within 2 to 4 weeksafter beginning antituberculosis therapy (Blanc, 2011; Havlir, 2011; Karim, 2011). lso, for HIV-infected women, rifampin or rifabutin use may be contraindicated if certain protease inhibitors or nonnucleoside reverse transcriptase inhibitors are being administered. If there is resistance to rifabutin or rifampin, then pyrazinamide therapy is given. Of the secondline regimens, the aminoglycosides-streptomycin, kanamycin, amikacin, and capreomycin-are ototoxic to the fetus and are contraindicated (Briggs, 2015).


Obstentrics_Williams

Obstentrics_Williams. Neonatal Tuberculosis. Tubercular bacillemia can infect the placenta, but the fetus infrequently becomes infected-con genital tuberculosis. The term also applies to newborns who are infected by aspiration of infected secretions at delivery. Each route of infection constitutes approximately half of the cases. manifests with hepatosplenomegaly, respiratory distress, fever, and lymphadenopathy (Dewan, 2014; Osowicki, 2016). Cantwell and associates (1994) reviewed 29 cases of congenital tuberculosis reported since 1980. Only 12 of the mothers had active infection, and tuberculosis was frequently demonstrated by postpartum endometrial biopsy. Adhikari and colleagues (1997) described 11 South African postpartum women whose endometrial biopsy was culture-positive. Six of their neonates had congenital tuberculosis.


Obstentrics_Williams

Obstentrics_Williams. Neonatal infection is unlikely if the mother with active disease has been treated before delivery or if her sputum culture is negative. Because the newborn is susceptible to tuberculosis, most experts recommend isolation from the mother suspected of having active disease. If untreated, the risk of disease in the infant born to a woman with active infection is 50 percent in the irst year Qacobs, 1988).


Obstentrics_Williams

Obstentrics_Williams. his is a chronic, multisystem inflammatory disease of unknown etiology characterized by an accumulation of T-helper lymphocytes and phagocytes within noncaseating granulomas (Baughman, 2015; Celada, 2015). Predisposition to the disease is genetically determined and characterized by an exaggerated response of helper T lymphocytes to environmental triggers. Pulmonary involvement is most common, followed by skin, eyes, lymph nodes, and then all other organ systems. The prevalence of sarcoid in the United States is 20 to 60 per 100,000, with equal sex distribution. It is more than 10 times more common for blacks than for whites (Baughman, 2015). Most patients are between 20 and 40 years. Clinical presentation varies, but more than half of patients have dyspnea and a dry cough without constitutional symptoms that develop insidiously over months. Disease onset is abrupt in approximately 25 percent of patients, and 10 to 20 percent are asymptomatic at discovery.


Obstentrics_Williams

Obstentrics_Williams. Pulmonary symptoms are dominant, and more than 90 percent of patients have an abnormal chest radiograph at some point. Interstitial pneumonitis is the hallmark of pulmonary involvement, and half of afected patients develop permanent radiological changes. Lymphadenopathy, especially of the mediastinum, is present in 75 to 90 percent of cases. A fourth each have uveitis and skin involvement, the latter usually manifest as eythema nodosum. In women, sarcoid causes approximately 10 percent of cases of erythema nodosum (Mert, 2007). Impor tantly, any other organ system may be involved (Kandolin, 2015; Powe, 2015; Wallmiiller, 2012). Conirmation of the diagnosis is with biopsy-preferably a lymph node. However, because the lung may be the only obviously involved organ, tissue acquisition is often diicult.


Obstentrics_Williams

Obstentrics_Williams. The overall prognosis for sarcoidosis is good, and it resolves without treatment in 50 percent of patients. Still, quality of life is diminished (de Vries, 2007). In the other 50 percent, permanent organ dysfunction, albeit mild and nonprogressive, persists. Approximately 10 percent die because of their disease. Glucocorticoids are the most widely used treatment for symptomatic disease. Permanent organ derangement is seldom reversed by their use (Paramothayan, 2002). Thus, the deci sion to treat is based on symptoms, physical indings, chest radiograph, and pulmonary function tests. Unless respiratory symptoms are prominent, therapy is usually withheld for a several-month observation period. If inlammation does not subside, then prednisone, 1 mg/kg, is given daily and tapered to < 10 mg by 6 months (Baughman, 2015). For those with an inadequate response, immunosuppressive or cytotoxic agents and cytokine modulators can be used.


Obstentrics_Williams

Obstentrics_Williams. Because it is uncommon and frequently benign, sarcoidosis is not often seen in pregnancy. Although it seldom afects pregnancy adversely, meningitis, heart failure, and neurosarcoidosis have been described (Cardonick, 2000; Maisel, 1996; Wallmiiller, 2012). In a study of the Nationwide Inpatient Sample of 678 cases of sarcoidosis in pregnancy, incidences of preeclampsia, preterm delivery, and thromboembolism were increased (Hadid, 2015). Selroos (1990) studied 252 women with sarcoidosis in Finland, and 15 percent had sarcoidosis during pregnancy. Disease did not progress in the 26 pregnancies in women with active disease. Three aborted spontaneously, and the other 23 women were delivered at term. Agha and coworkers (1982) reported similar experiences with 35 pregnancies at the University of Michigan.


Obstentrics_Williams

Obstentrics_Williams. Active sarcoidosis is treated using the same guidelines as for the woman who is not pregnant. Severe disease warrants serial determination of pulmonary function. Symptomatic uveitis, constitutional symptoms, and pulmonary symptoms are treated with prednisone, 1 mg/kg orally per day.


Obstentrics_Williams

Obstentrics_Williams. This autosomal recessive exocrinopathy is one of the most common fatal genetic disorders in whites. Cystic ibrosis is caused by one of more than 2000 mutations in a 230-kb gene on the long arm of chromosome 7 that encodes an amino acid polypeptide (Patel, 2015; Sorscher, 2015). his peptide functions as a chloride channel and is termed the cystic ibrosis transmembrane conductance regulator (CFTR). As discussed in Chapter 14 (p. 289), phenotypes vary widely, even among homozygotes for the common 6F508 mutation (Rowntree, 2003). Approximately 10 to 20 percent of afected newborns are diagnosed shortly after birth because of meconium peritonitis (Boczar, 2015; Sorscher, 2015). Currently, the median predicted survival is 37 years, and nearly 80 percent of females with cystic ibrosis now survive to adulthood (Gillet, 2002; Patel, 2015).


Obstentrics_Williams

Obstentrics_Williams. Mutations in the chloride channel cause altered epithelial cell membrane transport of electrolytes. his afects all sites in which epithelium expresses CFTR-secretory cells. These include the sinuses, lung, pancreas, liver, and reproductive tract. Disease severity depends on which two alleles are inherited, and approximately 10 percent are disease-causing mutations (Sorscher, 2015). Homozygosity for Phe508del (�F508) is one of the most severe, and 90 percent of individuals with clinical disease carry at least one F508 allele. Exocrine gland ductal obstruction develops from thick, viscid secretions (Rowe, 2005). In the lung, submucosal glandular ducts are afected. Eccrine sweat gland abnormalities are the basis for the diagnostic sweat test, characterized by elevated sodium, potassium, and chloride levels in sweat.


Obstentrics_Williams

Obstentrics_Williams. Lung involvement is commonplace and is usually the cause of death. Bronchial gland hypertrophy with mucous plugging and small-airway obstruction leads to subsequent infection that ultimately causes chronic bronchitis and bronchiectasis. For complex and not completely explicable reasons, chronic inflammation from Pseudomonas aeruginosa occurs in more than 90 percent of patients. In a minority,aS aureus, H inluenzae, and Burkholderia cepacia are recovered (Rowe, 2005). Colonization with the last has been reported to signiy a worse prognosis, especially in pregnancy (Gillet, 2002). Acute and chronic parenchymal inlammation ultimately causes extensive fibrosis, and along with airway obstruction, ventilation-perfusion mismatch develops. Pulmonary insuiciency is the end result. Lung or heart-lung transplantation has a 5-year survival rate of only 50 to 60 percent (Sorscher, 2015). A few women have successfully undergone pregnancy following lung transplantation (Kruszka, 2002; Shaner, 2012).


Obstentrics_Williams

Obstentrics_Williams. This CFTR2 resource delineates gene variants with a clear etiological role-http://ww.cftr2.org. Women with clinical cystic fibrosis are sub fertile because of tenacious cervical mucus. Males have oligospermia or aspermia from vas deferens obstruction, and 98 percent are infertile (hmad, 2013). Despite this, the North American Cystic Fibrosis Foundation estimated that 4 percent of afected women become pregnant every year (Edenborough, 1995). he endometrium and tubes express some CFTR but are functionally normal, and the ovaries do not express the CFTR gene (Eden borough, 2001). Both intrauterine insemination and in vitro fertilization can be successful for afected women (Rodgers, 2000). Several ethical considerations regarding plans for pregnancy by these women were reviewed by Wexler and colleagues (2007). One important factor is the long-term prognosis for the mother. For male infertility, Sobczynska-Tomaszewska and associates (2006) have emphasized the importance of molecular


Obstentrics_Williams

Obstentrics_Williams. and colleagues (2007). One important factor is the long-term prognosis for the mother. For male infertility, Sobczynska-Tomaszewska and associates (2006) have emphasized the importance of molecular diagnosis.


Obstentrics_Williams

Obstentrics_Williams. he American College of Obstetricians and Gynecologists (20a17) recommends that carrier screening be ofered to all women currently pregnant or considering conception (Chap. 14, p. 289). The CDC also added cystic ibrosis to newborn screening programs (Southern, 2009) (Chap. 32, p. 614).


Obstentrics_Williams

Obstentrics_Williams. Pregnancy outcome is inversely related to severity of lung dysfunction. Advanced chronic lung disease, hypoxia, and frequent infections may prove deleterious. At least in the past, cor pulmonale was common, but even that does not preclude successful pregnancy (Cameron, 2005). In some women, pancreatic dyunction may cause poor maternal nutrition. Otherwise normal pregnancy-induced insulin resistance frequently results in gestational diabetes after midpregnancy (Hardin, 2005). In one study of 48 pregnancies, half had pancreatic insuiciency and a third required insulin (horpe-Beeston, 2013). Up to 25 percent of patients develop diabetes by age 20, and diabetes is most frequent with the Phe508del homozygous mutation (Giacobbe, 2012; Patel, 2015).


Obstentrics_Williams

Obstentrics_Williams. Cystic fibrosis per se is not afected by pregnancy (Schechter, 2013). Early reports of a deleterious efect on the course of cystic fibrosis were related to severe disease (Olson, 1997). When matched with nonpregnant women by disease severity, recent reports indicate no deleterious efects on long-term survival (Schechter, 2013). Prep regnancy counseling is imperative. Women who choose to become pregnant require close surveillance for development of superimposed infection, diabetes, and heart failure. Serial pulmonary function testing assists management and estimating prognosis. When the FEV] is at least 70 percent, women usually tolerate pregnancy well. Emphasis is placed on postural drainage, bronchodilator therapy, and infection control.


Obstentrics_Williams

Obstentrics_Williams. �-Adrenergic bronchodilators help control airway constriction. Inhaled recombinant human deoxyribonuclease I improves lung function by reducing sputum viscosity (Sorscher, 2015). Inhaled 7 -percent saline produces short-and long-term benefits (Elkins, 2006). Nutritional status is assessed and appropriate dietary counseling given. Pancreatic insuiciency requires replacement of oral pancreatic enzymes. Promising new therapy to correct CFTR protein dysfunction was recently described by Wainwright and colleagues (2015). Using a combination of lumacaftor and ivacaftor, these investigators showed that patients homozygous for the Phe508del mutation were significantly benefitted. No reports of either drug are available regarding pregnant women.


Obstentrics_Williams

Obstentrics_Williams. Infection is heralded by increasing cough and mucus production. Oral semisynthetic penicillins or cephalosporins usually suice to treat staphylococcal infections. Pseudomonas infection is problematic, and inhaled tobramycin and colistin have been used successfully to control this organism. Immediate hospitalization and aggressive therapy are warranted for serious pulmonary infections. he threshold for hospitalization with other complications is low. For labor and delivery, epidural analgesia is recommended (Deighan, 2014).


Obstentrics_Williams

Obstentrics_Williams. Earlier reports chronicled the poor maternal and perinatal outcomes of women with cystic ibrosis (Cohen, 1980; Kent, 1993). vlore recent reports describe better outcomes, but there still are serious complications. Disease severity is now quantified by pulmonary function studies, which are the best predictor of pregnancy and long-term maternal outcome. Edenborough and colleagues (2000) reported 69 pregnancies and found that if prep regnancy FEV! was <60 percent of predicted, the risk for preterm delivery, respiratory complications, and death of the mother within a few years of childbirth was substantive. Thorpe-Beeston (2013) and Fitzsimmons (1996) and their associates reported similar indings. Gillet and colleagues (2002) reported 75 pregnancies from the French Cystic Fibrosis Registry. Almost 20 percent of newborns were delivered preterm, and 30 percent had growth restriction. he one maternal death was due to Pseudomonas sepsis in a woman whose prepregnancy FEV! was 60 percent.


Obstentrics_Williams

Obstentrics_Williams. Almost 20 percent of newborns were delivered preterm, and 30 percent had growth restriction. he one maternal death was due to Pseudomonas sepsis in a woman whose prepregnancy FEV! was 60 percent. Long-term, however, 17 percent of women died, and four infants had conirmed cystic fibrosis.


Obstentrics_Williams

Obstentrics_Williams. Maternal complications are daunting. Patel and coworkers (2015) recently queried the National Inpatient Sample database and reported that the prevalence of cystic ibrosis in pregnancy had a signiicant linear increase from 2000 to 2010. They analyzed 1119 afected women in more than 12 million births and reported a litany of risks (Table 51-5). In contrast, perinatal outcomes were surprisingly good. Cystic fibrosis is a common antecedent disease leading to lung transplantation. Gyi and coworkers (2006) reviewed 10 pregnancies in such women and reported nine liveborn neonates. Maternal outcomes were less favorable. Of the three gravidas who developed rejection during pregnancy, all had progressively declining pulmonary function and died of chronic rejection by 38 months after delivery. TABLE 51-5. Odds Ratios for Maternal Complications in 11e19 Pregnant Women with Cystic Fibrosis Compared with Controls


Obstentrics_Williams

Obstentrics_Williams. TABLE 51-5. Odds Ratios for Maternal Complications in 11e19 Pregnant Women with Cystic Fibrosis Compared with Controls Carbon monoxide is a ubiquitous gas, and most nonsmoking adults have a carbon monoxyhemoglobin saturation of 1 to 3 per cent. In cigarette smokers, levels may be as high as 5 to 10 per cent. Carbon monoxide is the most frequent cause of poisoning worldwide (Stoller, 2007). Toxic levels are oten encountered in inadequately ventilated areas warmed by space heaters.


Obstentrics_Williams

Obstentrics_Williams. Carbon monoxide is particularly toxic because it is odorless and tasteless and has a high ainity for hemoglobin binding. hus, it displaces oxygen and impedes its transfer with resultant hypoxia. Besides acute sequelae including death and anoxic encephalopathy, cognitive defects develop in as many as half of patients following loss of consciousness or in those with carbon monoxide levels >25 percent (Weaver, 2002). Hypoxic brain damage has a predilection for the cerebral cortex and white matter and for the basal ganglia (Lo, 2007; Prockop, 2007). A Parkinson syndrome sometimes follows after recovery (Hemphill,a2015).


Obstentrics_Williams

Obstentrics_Williams. Through several physiological alterations, the rate of endogenous carbon monoxide production almost doubles in normal pregnancy (Longo, 1977). Although the pregnant woman is not more susceptible to carbon monoxide poisoning, the fetus does not tolerate excessive exposure (Friedman, 2015). With chronic exposure, maternal symptoms usually appear when the carboxyhemoglobin concentration is 5 to 20 percent. Symptoms include headache, weakness, dizziness, physical and visual impairment, palpitations, and nausea and vomiting. With acute exposure, concentrations of 30 to 50 percent produce symptoms of impending cardiovascular collapse. Levels > 50 percent may be fatal for the mother.


Obstentrics_Williams

Obstentrics_Williams. Because hemoglobin F has an even higher ainity for carbon monoxide, fetal carboxyhemoglobin levels are 10 to 15 percent higher than those in the mother. This may be due to facilitated difusion (Longo, 1977). Importantly, the half-life of carboxyhemoglobin is 2 hours in the mother but 7 hours in the fetus. Because carbon monoxide is bound so tightly to hemoglobin F, the fetus may be hypoxic even before maternal carbon monoxide levels are appreciably elevated. Several anomalies are associated with embryonic exposure, and anoxic encephalopathy is the primary sequela of later fetal exposure (Alehan, 2007; Aubard,a2000).


Obstentrics_Williams

Obstentrics_Williams. For all victims, treatment of carbon monoxide poisoning is supportive along with immediate administration of 100-percent inspired oxygen. Indications for hyperbaric oxygen treatment in nonpregnant individuals are unclear (Kao, 2005). Weaver and associates (2002) reported that hyperbaric oxygen treatment minimized the incidence of cognitive defects in adults at both 6 weeks and 1 year compared with that with normobaric oxygen. Hyperbaric oxygen is generally recommended in pregnancy if carbon monoxide exposure has been "significant" (Aubard, 2000; Ernst, 1998). The problem is how to deine signiicant exposure (Friedman, 2015). Although maternal carbon monoxide levels are not accurately predictive of those in the fetus, some clinicians recommend hyperbaric therapy if maternal levels exceed 15 to 20 percent. With fetal heart rate pattern evaluation, Towers and Corcoran (2009) described afected fetuses to have an elevated baseline, diminished variability, and absent accelerations and


Obstentrics_Williams

Obstentrics_Williams. 15 to 20 percent. With fetal heart rate pattern evaluation, Towers and Corcoran (2009) described afected fetuses to have an elevated baseline, diminished variability, and absent accelerations and decelerations. Treatment of the afected newborn with hyperbaric oxygen is also controversial (Bar, 2007).


Obstentrics_Williams

Obstentrics_Williams. Elkharrat and colleagues (1991) reported successful hyperbaric treatments in 44 pregnant women. Silverman and Montano (1997) reported successful management of a woman whose abnormal neurological and cardiopulmonary indings abated in a parallel fashion with resolution of associated variable decelerations in fetal heart rate. Greingor and coworkers (2001) used 2.5-atm hyperbaric 100-percent oxygen for 90 minutes in a 21-week pregnant woman who was delivered of a healthy infant at term. According to the Divers Alert Network-DAN (201a6)-at Duke University, 700 chambers are located in North and Central America. Emergency consultation from the Network is available at 91a9-684-91a11a. Adhikari M, Pillay T, Pillay DG: Tuberculosis in the newborn: an emerging disease. Pediatr Infect Dis J 16: 1108, 1997 Agha FP, Vade A, Amendola A, et al: Efects of pregnancy on sarcoidosis. Surg Gynecol Obstet 155:817,t1982


Obstentrics_Williams

Obstentrics_Williams. Agha FP, Vade A, Amendola A, et al: Efects of pregnancy on sarcoidosis. Surg Gynecol Obstet 155:817,t1982 Ahmad A, Ahmed A, Patrizio P: Cystic fibrosis and fertility. Curr Opin Obstet GynecoIt25(3):167,t2013 Ahmad H, Mehta NJ, Manikal VM, et al: Pneumoystis carinii pneumonia in pregnancy. Chest 120:666, 2001 Alehan F, Erol I, Onay OS: Cerebral palsy due to nonlethal maternal carbon monoxide intoxication. Birth Defects Res A Clin Mol Teratol 79(8):614, 2007 Ali Z, Ulrik CS: Incidence and risk factors for exacerbations of asthma during pregnancy. J Asthma Allergy 6:53, 2013 American College of Obstetricians and Gynecologists: Asthma in pregnancy. Practice Bulletin No. 90, February 2008, Reairmed 2016a American College of Obstetricians and Gynecologists: Inluenza vaccination during pregnancy. Committee Opinion No. 608, September 2014, Reaffirmed 2016b


Obstentrics_Williams

Obstentrics_Williams. American College of Obstetricians and Gynecologists: Inluenza vaccination during pregnancy. Committee Opinion No. 608, September 2014, Reaffirmed 2016b American College of Obstetricians and Gynecologists: Carrier screening for genetic conditions. Committee Opinion No. 691, March 2017 Andrews W: Cesarean delivety for refractory status asthmaticus. Obstet Gynecol 121:417,t2013 Anselmi A, Ruggieri VG, Letheulle J, et al: Extracorporeal membrane oxygenation in pregnancy. J Card Surg 30(10):781,t2015 Asadi Gharabaghi M, llameh SF: Primary pulmonary cryptococcosis. BMJ Case Rep 2014:pii: bcr2014203821, 2014 Aubard Y, Magne I: Carbon monoxide poisoning in pregnancy. BJOG 107:833, 2000 Badve SA, Ghate SO, Badve MS, et al: Tuberculosis of spine with neurological deicit in advanced pregnancy: a report of three cases. Spine J 11 (1):e9, 2011 Bain E, Pierides KL, Clifton VL, et al: Interventions for managing asthma in pregnancy. Cochrane Database Syst Rev 10:CD010660, 2014


Obstentrics_Williams

Obstentrics_Williams. Bain E, Pierides KL, Clifton VL, et al: Interventions for managing asthma in pregnancy. Cochrane Database Syst Rev 10:CD010660, 2014 Bar R, Cohen M, Bentur Y, et al: Pre-labor exposure to carbon monoxide: should the neonate be treated with hyperbaric oxygenation? Clin Toxicol 45(5): 579, 200 Barnes PJ: Asthma. In Kasper 0, Fauci A, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hili Education, 2015, p 1669 Baughman RP, Lower EE: Sarcoidosis. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, 1cGraw-Hill Education, 2015, p 2205 Bel EH: Mild asthma. N Engl J Med 369(6):549,t2013 Belfort A, Clark SL, Saade GR, et al: Hospital readmission after delivety: evidence for an increased incidence of non urogenital infection in the immediate postpartum period. Am J Obstet Gynecol 202:35.e1, 2010


Obstentrics_Williams

Obstentrics_Williams. Belgi RH, Venkataramanan R, Caritis SN, et al: Oseltamivir for inluenza in pregnancy. Semin PerinatoIt38(8):503, 2014 Bercovitch RS, Catanzaro A, Schwartz BS, et al: Coccidioidomycosis during pregnancy: a review and recommendations for management. Clin Infect Dis 53(4):363,t2011 Blais L, Kettani FZ, Forget A: Relationship between maternal asthma, its severity and control and abortion. Hum Reprod 28(4):908,t2013 Blais L, Suissa S, Boivin JF, et al: First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma. Thorax 53:1025,t1998 Blanc FX, Sok T, Laureillard 0, et al: Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 365(16):14 1,2011 Boczar M, Sawicka E, Zybert K: Meconium ileus in newborns with cystic fibrosis-results of treatment in the group of patients operated on in the years 2000-2014. Dev Period Med 19(1):32, 2015


Obstentrics_Williams

Obstentrics_Williams. Boczar M, Sawicka E, Zybert K: Meconium ileus in newborns with cystic fibrosis-results of treatment in the group of patients operated on in the years 2000-2014. Dev Period Med 19(1):32, 2015 Boggess A, Myers ER, Hamilton CD: Antepartum or postpartum isoniazid treatment of latent tuberculosis infection. Obstet Gynecol 96:747, 2000 Bonham CA, Patterson KC, Strek ME: Asthma outcomes and management during pregnancy. Chest September 1, 2017 [Epub ahead of print] Bracken MB, Triche EW, Belanger K, et al: Asthma symptoms, severity, and drug therapy: a prospective study of efects on 2205 pregnancies. Obstet Gynecol 102:739,t2003 Briggs GG, Freeman RK (eds): Drugs in Pregnancy and Lactation, 10th ed. Philadelphia, Wolters Kiuwer, 2015 Brito V, Niederman MS: Pneumonia complicating pregnancy. Clin Chest Med 32:121,t2011 Caldwell JW, Asura EL, Kilgore B, et al: Coccidioidomycosis in pregnancy during an epidemic in California. Obstet Gynecol 95:236, 2000


Obstentrics_Williams

Obstentrics_Williams. Caldwell JW, Asura EL, Kilgore B, et al: Coccidioidomycosis in pregnancy during an epidemic in California. Obstet Gynecol 95:236, 2000 Callaghan WM, Creanga A, Jamieson OJ: Pregnancy-related mortality resulting from inluenza in the United States during the 2009-2010 pandemic. Obstet Gynecol 126:486,t2015 Cameron AJ, Skinner T A: Management of a parturient with respiratory failure secondary to cystic fibrosis. Anaesthesia 60:77, 2005 Cantu J, Tita AT: vlanagement of influenza in pregnancy. Am J Perinatol 30:99,t2013 Cantwell MF, Shehab ZM, Costello M, et al: Congenital tuberculosis. N Engl J Med 330:1051,t1994 Cardonick EH, Naktin J, Berghella V: Neurosarcoidosis diagnosed during pregnancy by thoracoscopic lymph node biopsy. J Reprod Med 45:585, 2000 Celada LJ, Drake P: Targeting CD4( +) T cells for the treatment· of sarcoidosis: a promising strategy? Immunotherapy 7(1):57,t2015


Obstentrics_Williams

Obstentrics_Williams. Celada LJ, Drake P: Targeting CD4( +) T cells for the treatment· of sarcoidosis: a promising strategy? Immunotherapy 7(1):57,t2015 Centers for Disease Control and Prevention: Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Disease Society of America. MMWR 54(12):1, 2005a Centers for Disease Control and Prevention: Guidelines for using the QuantiFERON-TB gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR 54(15):29, 2005b Centers for Disease Control and Prevention: Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with inluenza-Louisiana and Georgia-December 2006-January 2007. MMWR 56(14):325,t2007 Centers for Disease Control and Prevention: Plan to combat extensively drugresistant tuberculosis. MMWR 58(3): 1, 2009a Centers for Disease Control and Prevention: Trends in tuberculosis-United States, 2008. MMWR 58(10):1, 2009b


Obstentrics_Williams

Obstentrics_Williams. Centers for Disease Control and Prevention: Trends in tuberculosis-United States, 2008. MMWR 58(10):1, 2009b Centers for Disease Control and Prevention: 2009 pandemic influenza A (H1N1) in pregnant women requiring intensive care-New York City, 2009. MMWR 59(11):321, 2010a Centers for Disease Control and Prevention: Decrease in reported tuberculosis cases-United States, 2009. MMWR 59(10):289, 2010b Centers for Disease Control and Prevention: National Center for Health E-Stat: asthma prevalence, health care use and morbidity: United States, 2003-05. 2010c. Available at: http://www.cdc.gov/nchs/data/hestat/asthma03-05/ asthma03-05.htm. Accessed May 5, 2016 Centers for Disease Control and Prevention: Asthma attacks among persons with current asthma-United States, 2001-2010. MvlWR 62:93,t2013


Obstentrics_Williams

Obstentrics_Williams. Centers for Disease Control and Prevention: Asthma attacks among persons with current asthma-United States, 2001-2010. MvlWR 62:93,t2013 Centers for Disease Control and Prevention: Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, May 3,t2016. Available at: http://aidsinfo.nih.gov/contentfiles/Adulc OI.pd. Accessed May 5, 2016a Centers for Disease Control and Prevention: Influenza (flu). 2016b. Available at: http://www.cdc.gov/flu.l Accessed May 5,t2016 Chan L, Juarez MM, Gidwani N, et al: Management of critical asthma syndrome during pregnancy. Clin Rev Allergy ImmunoI45(l)45, 2015 Charlton A, Hutchison A, Davis KJ, et al: Asthma management in pregnancy. PLoS One 8(4):e60247, 2013 Chen H, Keller J, Wang IT, et al: Pneumonia and pregnancy outcomes: a nationwide population-base study. Am J Obstet :288.e1,2012


Obstentrics_Williams

Obstentrics_Williams. Chen H, Keller J, Wang IT, et al: Pneumonia and pregnancy outcomes: a nationwide population-base study. Am J Obstet :288.e1,2012 Close A, Gimovsky A, Macri C: Adult respiratory distress due to Legionnaires disease in pregnancy: a case report.] Reprod Med 610-2):83,t2016 Cohen LF, di Sant Agnese PA, Friedlander ]: Cystic fibrosis and pregnancy: a national survey. Lancet 2:842, 1980 Cohen YZ, Dolin R: Inluenza. In Kasper DL, Fauci AS, Hauser DL, et al: (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGraw-Hill Education, 2015, p 1209 Cossette B, Forget A, Beauchesne MF: Impact of maternal use of asthma-controller therapy on perinatal outcomes. Thorax 68:724, 2013 Cox S, Posner SF, McPheeters M, et al: Hospitalizations with respiratory illness among pregnant women during inluenza season. Obstet Gynecol 107:1315,t2006 Crum NF, Bailon-Landa G: Coccidioidomycosis in pregnancy: case report and review of the literature. Am] Med 119:993, 2006


Obstentrics_Williams

Obstentrics_Williams. Crum NF, Bailon-Landa G: Coccidioidomycosis in pregnancy: case report and review of the literature. Am] Med 119:993, 2006 Cruz CA, Caughey AB, Jasmer R: Postpartum follow-up of a positive puriied protein derivative (PPD) among an indigent population. Am ] Obstet GynecoIt192:1455,t2005 Deighan M, Ash S, McMorrow R: Anaesthesia for parturients with severe cystic ibrosis: a case series. Intt] Obstet Anesth 23(1):75, 2014 de Vries], Drent M: Qualiry of life and health status in sarcoidosis: a review. Semin Respir Crit Care Med 28:121,t2007 Dewan P, Gomber S, Das S: Congenital tuberculosis: a rare manifestation of a common disease. Paediatr Int Child Health 34(1):60,t2014 Ding H, Black CL, Ball S, et al: Inluenza vaccination coverage among pregnant women-United States, 2014-15 inluenza season. MMWR 64(36):1000, 2015 Divers Alert Network: Chamber location and availabiliry. Available at: http:// ww.diversalertnetwork.org/medical. Accessed May 5,t2016


Obstentrics_Williams

Obstentrics_Williams. Divers Alert Network: Chamber location and availabiliry. Available at: http:// ww.diversalertnetwork.org/medical. Accessed May 5,t2016 Dodds L, McNeil SA, Fell DB, et al: Impact of inluenza exposure on rates of hospital admissions and physician visits because of respirarory illness among pregnant women. CMA] 17:463, 2007 Dolin R: Common viral respiratory infections. In Longo 0, Fauci A, Kasper 0, et al (eds): Harrison's Principles of Internal Medicine, 18th ed. New York, McGraw-Hill Education, 2012, p 1485 Dombrowski MP: Asthma and pregnancy. Obstet Gynecol 108:667, 2006 Dombrowski MP, Schatz M, Wise R, et al: Asthma during pregnancy. Obstet Gynecol 103:5, 2004a Dombrowski MP, Schatz M, Wise R, et al: Randomized trial of inhaled beclomethasone dipropionate versus theophylline for moderate asthma during pregnancy. Am] Obstet GynecoIt190:737, 2004b Edenborough FP: Women with cystic ibrosis and their potential for reproduction. Thorx 56:648, 2001


Obstentrics_Williams

Obstentrics_Williams. Edenborough FP: Women with cystic ibrosis and their potential for reproduction. Thorx 56:648, 2001 Edenborough FP, Mackenzie WE, Stableforth DE: The outcome of 72 pregnancies in 55 women with cystic ibrosis in the United Kingdom 19771996. B]OG 107:254,t2000 Edenborough FP, Stableforth DE, Webb AK, et al: The outcome of pregnancy in cystic ibrosis. Thorax 50: 170, 1995 Eferen LS: Tuberculosis and pregnancy. Curr Opin Pulm Med 13:205,t2007 Elkharrat 0, Raphael ]c, Korach ]M, et al: Acute carbon monoxide intoxication and hyperbaric oxygen in pregnancy. Intensive Care Med 17:289, 1991 Elkins MR, Robinson M, Rose BR, et al: A controlled trial of long-term inhaled hypertonic saline in patients with cystic ibrosis. N Engl ] Med 354:229, 2006 El-Messidi A, Czuzoj-Shulman N, Spence AR, et al: Medical and obstetric outcomes among pregnant women with tuberculosis: a population-based study of .8 million births. Am] Obstet GynecoI215:797.e6, 2016


Obstentrics_Williams

Obstentrics_Williams. Eltonsy S, Blais L: Asthma during pregnancy and congenital malformations: the challenging task of separating the medication efect from asthma itself. ] Allergy Clin ImmunoIt137(5):1623, 2016 Ely EW, Peacock ]E, Haponik EF, et al: Cryptococcal pneumonia complicating pregnancy. Medicine : 153, 1998 Enriquez R, Pingsheng W, Griin MR, et al: Cessation of asthma medication in early pregnancy. Am] Obstet Gynecol 195: 149, 2006 Ernst A, Zibrak ]0: Carbon monoxide poisoning. N Engl ] Med 339: 1603, 1998 Fanta CH: Asthma. N Engl ] Med 360: 1002, 2009 Figueroa-Damian R, Arrendondo-Garcia ]L: Pregnancy and tuberculosis: inluence of treatment on perinatal outcome. Am] Perinatol 15:303, 1998 Finland M, Dublin TO: Pneumococcic pneumonias complicating pregnancy and the puerperium.]AMA 112:1027,t1939 Fitzsimmons Sc, Fitzpatrick S, hompson 0, et al: A longitudinal study of the efects of pregnancy on 325 women with cystic ibrosis. Pediatr Pulmonol 113:99, 1996


Obstentrics_Williams

Obstentrics_Williams. Fitzsimmons Sc, Fitzpatrick S, hompson 0, et al: A longitudinal study of the efects of pregnancy on 325 women with cystic ibrosis. Pediatr Pulmonol 113:99, 1996 Friedman P, Guo M, Stiller R], et al: Carbon monoxide exposure during pregnancy. Obstet Gynecol Surv 70(11):705, 2015 Gazmararian ]A, Petersen R, Jamieson OJ, et al: Hospitalizations during pregnancy among managed care enrollees. Obstet Gynecol 100:94, 2002 Getahun 0, Ananth CV, Oyelese Y, et al: Acute and chronic respiratory diseases in pregnancy: associations with spontaneous premature rupture of membranes.t] Matern Fetal Neonatal Med 20:669, 2007 Getahun 0, Ananth CV, Peltier MR: Acute and chronic respiratory disease in pregnancy: association with placental abruption. Am ] Obstet Gynecol 195:1180,t2006 Getahun H, Matteelli A, Chaisson R. et al: Latent Mycobacterium tuberculosis infection. N Engl] Med 3 2:2127,t2015


Obstentrics_Williams

Obstentrics_Williams. Getahun H, Matteelli A, Chaisson R. et al: Latent Mycobacterium tuberculosis infection. N Engl] Med 3 2:2127,t2015 Giacobbe LE, Nguyen RH, Aguilera MN, et al: Efect of maternal cystic ibrosis genotype on diabetes in pregnancy. Obstet Gynecol 120(6): 1394, 2012 Gidaya NB, Lee BK, Burstyn 1, et al: In utero exposure to 3-2-adrenergic receptor agonist drugs and risk for autism spectrum disorders. Pediatrics 137 (2): 1, 2016 Gillet 0,de Brackeleer M, Bellis G, et al: Cystic ibrosis and pregnancy. Report from French data 0980-1999). B]OG 109:912,t2002 Gluck Jc, Gluck PA: he efect of pregnancy on the course of asthma. Immunol Allergy Clin North Am 26:63, 2006 Grant CC, Crane ], Mitchell EA, et al: Vitamin 0 supplementation during pregnancy and infancy reduces aero allergen sensitisation: a randomised controlled trial. Allergy 71(9):1325,t2016


Obstentrics_Williams

Obstentrics_Williams. Grant CC, Crane ], Mitchell EA, et al: Vitamin 0 supplementation during pregnancy and infancy reduces aero allergen sensitisation: a randomised controlled trial. Allergy 71(9):1325,t2016 Greingor ]L, Tosi JM, Ruhlmann S, et al: Acute carbon monoxide intoxication during pregnancy. One case report and review of the literature. Emerg Med J 18:399,t2001 Grindheim G, T oska K, Estensen ME, et al: Changes in pulmonary function during pregnancy: a longitudinal cohort study. B]OG 119:94,t2012 Gyi KM, Hodson ME, Yacoub MY: Pregnancy in cystic ibrosis lung transplant recipients: case series and review. J Cyst Fibros 5(3):171, 2006 Hadid V, Patenaude V, Oddy L, et al: Sarcoidosis and pregnancy: obstetrical and neonatal outcomes in a population-based cohort of 7 million births. J Perinat Med 43(2):201, 2015 Hardin OS, Rice ], Cohen RC, et al: he metabolic efects of pregnancy in cystic ibrosis. Obstet Gynecol 106(2):367, 2005


Obstentrics_Williams

Obstentrics_Williams. Hardin OS, Rice ], Cohen RC, et al: he metabolic efects of pregnancy in cystic ibrosis. Obstet Gynecol 106(2):367, 2005 Harger ]H, Ernest ]M, hurnau GR, et al: Risk factors and outcome of varicella-zoster virus pneumonia in pregnant women. ] Infect Dis 185:422, 2002 Havlir DV, Kendall MA, Ive P, et al: Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl] Med 365(16):1482, 2011 Hemphill JC, Smith WS, Gress DR: Neurologic critical care, including hypoxic-ischemic encephalopathy and subarachnoid hemorrhage. In Kasper DL, Fauci AS, Hauser DL, et al: Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hill Education, 2015, p 1782 Hendler I, Schatz M, Momirova V, et al: Association of obesity with pulmonaty and nonpulmonary complications of pregnancy in asthmatic women. Obstet Gynecolt108(1):77, 2006


Obstentrics_Williams

Obstentrics_Williams. Hendler I, Schatz M, Momirova V, et al: Association of obesity with pulmonaty and nonpulmonary complications of pregnancy in asthmatic women. Obstet Gynecolt108(1):77, 2006 Heron M: Deaths: leading causes for 2013. Nat! Vital Stat Rep 65(2):1,t2016 Horsburgh CR ]r, Barry CE, Lange C: Treatment of tuberculosis. N Englt] Med 373:2149,t2015 Horsburgh CR]r, Rubin E]: Latent tuberculosis infection in the United States. N Engl] Med 364:15:1441,t2011 Jacobs RF, Abernathy RS: Management of tuberculosis in pregnancy and the newborn. Clin Perinatol 15:305, 1988 Jain S, Self H, Wunderink RG, et al: Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl] Med 373:415,t2015


Obstentrics_Williams

Obstentrics_Williams. Jain S, Self H, Wunderink RG, et al: Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl] Med 373:415,t2015 Jamieson 0], Rasmussen SA, Uyeki TM, et al: Pandemic inluenza and pregnancy revisited: lessons learned from 2009 pandemic inluenza A (H 1 N 1). Am] Obstet Gynecol204(6 Suppl 1):Sl, 2011 lana N, Vasishta K, Jindal SK, et al: Perinatal outcome in pregnancies complicated by pulmonary tuberculosis. Int J Gynecol Obstet 44: 119, 1994 lana N, Vasishta K, Saha SC, et al: Obstetrical outcomes among women with extrapulmonary tuberculosis. N Engl] Med 341 :645, 1999


Obstentrics_Williams

Obstentrics_Williams. Jenkins TM, Troiano NH, Grave CR, et al: Mechanical ventilation in an obstetric population: characteristics and delivery rates. Am ] Obstet Gynecol 188:549,t2003 ]hung A, Nelson 01, Centers for Disease Control and Prevention (CDC): Outbreaks of avian inluenza A (H5N2), and (H5N8), and (H5N1) among birdsUnited States, December 20 14-]anuary 2015. MMWR 64(4):111,t2015 lin Y, Carriere KC, Marrie T], et al: he efects of community-acquired pneumonia during pregnancy ending with a live birth. Am] Obstet Gynecol 188: 800,t2003 Kalita ], Misra UK, Prasad S, et al: Safety and eicacy of levoloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial. J Antimicrob Chemother 69(8):2246,t2014 Kandolin R, Lehtonen J, Airaksinen], et al: Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study. Circulation 131(7):624,t2015 Kao L W, Naiagas A: Carbon monoxide poisoning. Med Clin North Am 89(6):1161,t2005


Obstentrics_Williams

Obstentrics_Williams. Kao L W, Naiagas A: Carbon monoxide poisoning. Med Clin North Am 89(6):1161,t2005 Karim SSA, Naidoo K, Grobler A, et al: Integration of antiretroviral therapy with tuberculosis treatment. N Engl] Med 365(16):1492, 2011 Kelly W, Massoumi A, Lazarus A: Asthma in pregnancy: physiology, diagnosis, and management. Postgrad Med 127(4):349, 2015 Kent NE, Farquharson DF: Cystic fibrosis in pregnancy. Can Med Assoc ] 149:809, 1993 Kenyon N, Zeki AA, lbertSon TE, et al: Definition of critical asthma syndromes. Clin Rev Allergy ImmunoI48(1):1, 2015 Khan AD, Magee E, Grant G, et al: Tuberculosis-United States, 1993-2010. MMWR 3:149,t2013 Kowada A: Cost efectiveness of interferon-gamma release assay for TB screening of HI V positive pregnant women in low TB incidence countries.] Infect 688:32,t2014 Kruszka S], Gherman RB: Successful pregnancy outcome in a lung transplant recipient with tacrolimus immunosuppression. A case report. ] Reprod Med 47:60,t2002


Obstentrics_Williams

Obstentrics_Williams. Kruszka S], Gherman RB: Successful pregnancy outcome in a lung transplant recipient with tacrolimus immunosuppression. A case report. ] Reprod Med 47:60,t2002 Kutlu T, Tugrul S, Aydin A, et al: Tuberculosis meningitis in pregnancy presenting as hyperemesis gravidarum. ] Matern Fetal Neonatal vIed 20:357, 2007 Kyaw MH, Lynield R, Schafner W, et al: Efect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl] Med 354:1455, 2006 Lai RP, Meintjes G, Wilkinson R]: HIV-1 tuberculosis-associated immune reconstitution inflammatory syndrome. Semin Immunopathol 38(2):185, 2016 Lam CM, Wong SF, Leung TN, et al: A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. B]OG 1,t2004


Obstentrics_Williams

Obstentrics_Williams. Lam CM, Wong SF, Leung TN, et al: A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. B]OG 1,t2004 Lazarus SC: Emergency treatment of asthma. N Engl] Med 363(8):755, 2010 Lessnau KD, Qarah S: Multidrug-resistant tuberculosis in pregnancy: case report and review of the literature. Chest 123:953, 2003 Levison ]H, Barbieri RL, Katx ]T, et al: Hard to conceive. N Engl ] Med 363(10):965,t2010 Lim AS, Stewart K, Abramson M], et al: Multidisciplinary approach to management of maternal asthma (MAMMA): a randomized controlled trial. Chest 145(5):1046, 2014 Lin HC, Lin HC, Chen SF: Increased risk of low birthweight and small for gestational age infants among women with tuberculosis. B]OG 117(5):585, 2010