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Respiratory disease in pregnancy
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Respiratory disease in pregnancy
awareness of the physiological hyperventilation of pregnancy. Women most often present in the third trimester but may become symptomatic at any gestation. Classically, physiological breathlessness of pregnancy is present at rest or while talking and paradoxically improves with activity. Table 1 summarizes other causes. Other presenting symptoms of respiratory disease include chest pain, cough, sputum production, haemoptysis, fever or cyanosis. On examination, respiratory rate is unchanged by pregnancy. Presence of raised temperature should be noted. Expansion on inspiration reflects tidal volume and is reduced in many respiratory diseases. Percussion note may be dull in the presence of pleural effusion, consolidation, collapse or fibrosis. It is enhanced in the presence of a pneumothorax. Auscultation may reveal wheezes indicative of asthma; fine crepitations in the presence of pulmonary oedema; pleural rubs indicative of inflammatory conditions of the pleura in pneumonia or pulmonary infarction and bronchial breathing þ/ coarse crackles would suggest consolidation. Absent breath sounds occur with pneumothorax or extensive collapse. A simple non-invasive investigation is transcutaneous oxygen saturation. The normal oxygen saturation is greater than 95%. A fall in saturation on exercise e.g. climbing stairs indicates some form of cardiopulmonary disease and should be investigated further. Measurement of arterial blood gases should be reserved for those who are markedly breathless, those whose oxygen saturations are low at rest, or which drop on exercise and those women who appear unwell. When interpreting arterial blood gases in pregnancy it should be remembered that the progesterone-driven increase in minute ventilation may lead to relative hypocapnia and a respiratory alkalosis, and higher PaO2 but oxygen saturations are unaltered. Acidosis is poorly tolerated by the fetus. Reluctance to perform a chest X-ray in pregnancy may delay a diagnosis. Typical fetal dose range of ionizing radiation from a chest X-ray is 0.001e0.01 mGy and abdominal shielding will reduce fetal exposure further. This is unlikely to cause fetal death or malformation and the risk of childhood cancer is <1 in 10 000. Sputum should be sent for microbiological examination.
Sophia Stone Catherine Nelson-Piercy
Abstract Breathlessness in the absence of an underlying pathology is common in pregnancy. Asthma affects about 7% of women of child-bearing age. Treatment is the same as for the non-pregnant population and most drugs are safe in pregnancy. Educating women to continue preventer inhaled corticosteroid therapy will reduce the risk of attacks. Respiratory infections are associated with a higher morbidity in pregnancy and should be treated aggressively. Most chronic pulmonary diseases do not alter fertility. Large reserves in respiratory function allow the fetus and mother to survive without compromise in most cases. The use of chest X-rays should not be avoided in pregnancy. Women with a chronic respiratory disease should receive pre-pregnancy counselling and education. Women should be managed in a multidisciplinary setting with the respiratory team. The presence of pulmonary hypertension and cor pulmonale is associated with a high risk of death in pregnancy.
Keywords asthma; pneumonia; pregnancy; respiratory disease; tuberculosis
Introduction Severe lung disease leading to respiratory failure is uncommon in women of child-bearing age. However, respiratory symptoms are extremely common in pregnancy. This is because of the effect of physiological adaptation to pregnancy and because of reduced functional capacity and mobility from diaphragmatic elevation by the gravid uterus in late gestation. There is greater oxygen demand in normal pregnancy with a 20% increase in oxygen consumption, 40e50% increase in minute ventilation (secondary to tidal volume increase and not respiratory rate). The resultant maternal hyperventilation causes a mild fully compensated respiratory alkalosis (i.e. increased arterial pO2 and decreased arterial pCO2, compensatory fall in serum bicarbonate to 18e22 mmol/l; arterial pH 7.44).
Asthma Asthma is a common chronic inflammatory condition of the lung airways characterized by episodes of reversible bronchoconstriction as a result of various stimuli. It affects up to 7% of women of child-bearing age. The diagnosis of asthma is a clinical one based on the presence of symptoms (see Table 2) and evidence of variable airflow obstruction. There may be airway hyper-responsiveness and airway inflammation. There is often an associated personal or family history of atopy. Recognized triggers include pollen, dust, animals, infections etc. Confirmation hinges on demonstration of airflow obstruction varying over short periods of time. The British Thoracic Society guidelines for the management of asthma (2012) suggest that spirometry is preferable to measurement of peak expiratory flow (PEF) because it allows clearer identification of airflow obstruction, and the results are less dependent on effort. PEF rate and forced expiratory volume in 1 second (FEV1) are unaffected by pregnancy. Table 3
Respiratory symptoms, signs and investigations The commonest respiratory symptom in pregnancy is breathlessness. However this can often be attributed to an increased
Sophia Stone MD MRCOG is a Consultant in Obstetrics and Gynaecology at St Richard’s Hospital, Chichester, West Sussex, UK. Conflicts of interest: none declared. Catherine Nelson-Piercy MA FRCP FRCOG is a Consultant Obstetric Physician at Guy’s and St Thomas’ Hospitals Trust, London, UK. Conflicts of interest: none declared.
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Differential diagnoses of breathlessness in pregnancy Diagnosis
Investigations
Physiological
Diagnosis by exclusion and typical history Full blood count PEFR e response to bronchodilators Arterial blood gases (YPO2 and YPCO2)/VQ scan ECG, echocardiogram, chest X-ray
A summary of the BTS guidelines on drug use in pregnancy C
Anaemia Asthma Pulmonary embolus Mitral stenosis, cardiomyopathy Pneumonia Pneumothorax Hyperventilation/ anxiety
C
C C
C
Chest X-ray, sputum culture, serology Chest X-ray Arterial blood gases (YPCO2 but not YPO2)
C
C
Table 1
Effect of asthma on pregnancy A recent meta-analysis of adverse perinatal outcomes in women with asthma demonstrated that maternal asthma was associated with an increased risk of low birthweight (RR 1.46, 95% CI 1.22e1.75), small for gestational age (RR 1.22, 95% CI 1.14 e1.31), preterm delivery (RR 1.41, 95% CI 1.22e1.61) and preeclampsia (RR 1.54, 95% CI 1.32e1.81). The relative risk of preterm delivery and preterm labour were reduced to nonsignificant levels by active asthma management (RR 1.07, 95% CI 0.91e1.26 and RR 0.96, CI 0.73e1.26 respectively).
C
Table 3
a finding supported by the conclusions of a meta-analysis of 14 studies). Women, whose asthma worsened in pregnancy, were most symptomatic from 29 to 36 weeks’ gestation. Nonatopic patients with asthma tend to have more severe asthma in pregnancy and a higher incidence of pre-eclampsia. US studies suggest that 11e18% of pregnant women with asthma will have at least one emergency department visit for acute asthma and of these 62% will require hospitalization. Between 2006 and 2008 there were five indirect maternal deaths relating to asthma reported in the UK, one in a woman who was told to stop her course of steroids. The concern is that women stop their medication either of their own accord at the start of the pregnancy or on incorrect medical advice because of worries regarding the safety profile of the drugs for the fetus. There is some evidence that the course of asthma is similar in successive pregnancies. Asthma appears to be significantly less frequent and less severe during the last 4 weeks of pregnancy. Endogenous steroids in labour ensure that acute asthma attacks are very uncommon during labour and delivery. There may be a deterioration post-partum but in the majority, asthma reverts towards its pre-pregnancy course within 3 months of delivery.
Effect of pregnancy on asthma A systematic review has shown that baseline asthma severity does determine what happens to the course of asthma in pregnancy. An early study of 366 pregnancies complicated by asthma, reported worsening asthma in 35%, an improvement in 28%, and unchanged in 33% (approximate rule of thirds,
Features that increase the probability of asthma (from British Thoracic Society Scottish Intercollegiate Guidelines Network 2008; Revised May 2011) More than one of the following symptoms: wheeze, breathlessness, chest tightness and cough, particularly if: C symptoms worse at night and in the early morning C symptoms in response to exercise, allergen exposure and cold air C symptoms after taking aspirin or beta blockers
Management Pre-pregnancy and antenatal care: pregnancy is an ideal opportunity to optimize therapy although, ideally this should occur pre-pregnancy. Current emphasis in the management of asthma is on the prevention of rather than treatment of acute attacks. Women should be advised regarding the importance and safety of continuing inhalers to maintain good asthma control. Inhaler techniques should be checked; spacer devices should be introduced if necessary to improve drug delivery. Pregnant women must be monitored closely so that any change in course can be matched by an appropriate change in therapy. The aim of
History of atopic disorder Family history of asthma and/or atopic disorder Widespread wheeze heard on auscultation of the chest Otherwise unexplained low FEV1 or PEF (historical or serial readings) Otherwise unexplained peripheral blood eosinophilia Table 2
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Use short-acting b2 agonists as normal during pregnancy (B) Use long acting b2 agonists (LABA) as normal during pregnancy (C) Use inhaled steroids as normal during pregnancy (B) Use oral and intravenous theophyllines as normal during pregnancy (C) Check blood levels of theophylline in acute severe asthma and in those critically dependent on therapeutic theophylline levels (D) Use steroid tablets as normal when indicated during pregnancy for severe asthma. Steroid tablets should never be withheld because of pregnancy. Women should be advised that the benefits of treatment with oral steroids outweigh the risks (C) Leukotriene antagonists (LTRA) may be continued in women who have demonstrated significant improvement in asthma control with these agents prior to pregnancy not achievable with other medications. (D) Use chromones as normal during pregnancy (C)
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treatment is complete freedom from symptoms. Allergen and trigger avoidance should be discussed when atopy is also present. Antihistamines and therapy for allergic rhinitis may be safely prescribed. Those with the best safety profile are chlorpheniramine and intranasal beclomethasone, but cetirazine and loratidine may also be safely used. Women who smoke should be advised about the dangers for themselves and their babies and given appropriate support to stop smoking. Women with well controlled asthma may have midwifery-led care. Women with poorly controlled asthma require consultant led antenatal care with fetal surveillance and liaison with respiratory team and antenatal anaesthetic review.
Society guidelines on the management of asthma. The step-wise approach illustrated in Figure 1 is recommended. Mild intermittent asthma is managed with inhaled short-acting ‘reliever’ (b2-agonist) medication as required (Step 1). If usage of a ‘reliever’ (b2-agonist) inhaler exceeds >once/day, regular inhaled anti-inflammatory medication with a steroid ‘preventer’ (e.g. beclomethasone) inhaler [200e800 mg/day] should be commenced. (Step 2). The next step up in therapy is either the addition of a long acting reliever’ b2-agonist (LABA) e.g. Salmeterol, or an increase in the dose of inhaled steroid [800 mg/day].(Step 3). Further steps involve a trial of additional therapies e.g. leukotriene receptor antagonist (see below), slow release oral theophylline or oral b2-agonist. Alternatively the dose of inhaled steroid can be increased to 2000 mg/day. (Step 4). If these measures fail to achieve adequate control then
Drug therapy in pregnancy: is essentially the same as for the non-pregnant population and should follow the British Thoracic
Summary of step-wise management of asthma Step 5: Continuous/frequent use of oral steroids • daily steroid tablet – lowest dose for control • maintain high dose inhaled steroid • consider other drugs to minimise steroid use • refer for specialist care
Step 4: Persistent poor control • Increasing inhaled steroid up to 2000 μg/d • Addition of a 4th drug e.g. SR theophylline, β2 agonist tablet
Step 3: Initial add-on therapy 1. add inhaled long-acting β2agonist (LABA) 2. assess control: • good response – continue LABA •benefit but inadequate – LABA + inhaled steroid to 800 μg/d • no response – Stop LABA and increase inhaled steroid. If control still inadequate institute trial of leukotriene receptor antagonist or SR theophylline
Step 2: Regular preventer therapy • Add inhaled steroid 200–800 μg/d appropriate to disease severity • (400μg/d is appropriate starting dose)
Step 1: Mild intermittent asthma • Inhaled short-acting β2 agonist as required
Adapted from the British Thoracic Society Guidelines
Figure 1 Start treatment at the step most appropriate to initial severity. Regular review to maintain control by stepping up treatment as necessary; stepping down treatment when control is good.
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continuous or frequent use of oral steroids becomes necessary. The lowest dose providing adequate control should be used, if necessary with steroid sparing agents. (Step 5).
hydrocortisone 100 mg 6e8 hourly in labour. Women with asthma may safely use all forms of pain relief in labour. Ergometrine has been reported to cause bronchospasm particularly in association with general anaesthesia, but syntometrine routinely used for active management of the third stage has not been associated with any adverse incidents. In the absence of acute severe asthma, caesarean section is reserved for obstetric indications only. If a caesarean section is required, regional anaesthesia is preferable to general anaesthesia in women with asthma.
Low-dose aspirin: it is important to consider the possibility of ‘aspirin sensitivity’ and severe bronchospasm in a minority of women with asthma. Pregnant women with asthma should be asked about a history of aspirin sensitivity before being advised to take low-dose aspirin. Acute asthma attacks: should be managed as for the nonpregnant patient with a low threshold for admission. The features of acute severe asthma are PEFR 33e50% best/predicted, respiratory rate >25/minute, heart rate > 110/minute, inability to complete sentences in one breath. Multidisciplinary care should be sought with a respiratory physician and obstetrician and early referral to critical care team. Oxygen is given to maintain saturation 94e98%, and intravenous rehydration when drinking is impossible and drug therapy as for the non-pregnant (Table 4). Continuous fetal monitoring should be instigated. The woman should be managed in a left lateral position to avoid aorta-caval compression. A chest X-ray should be performed if there is any clinical suspicion of pneumonia or pneumothorax, or if the woman fails to improve. A PEF rate of 33e50 per cent best/predicted indicates acute severe asthma, <33 per cent is life threatening. Other concerning signs are SpO2<92 per cent, PaO2 <8 kPa with normal PaCO2, silent chest, cyanosis, feeble respiratory effort, hypotension, altered consciousness and exhaustion.
Post-natal care: none of the medications for asthma are contraindicated in breast feeding. Less than 1% of the maternal dose of theophylline is excreted into breast milk. Prednisolone is secreted in breast milk, but milk concentrations of prednisolone are only 5e25% of those in serum and therefore it considered safe to prescribe prednisolone.
Practice points (BTS recommendations): C
C
Acute asthma. C Acute severe asthma in pregnancy is an emergency and should be treated vigorously in hospital. C Give drug therapy including corticosteroids for acute asthma as for the non-pregnant patient C Deliver oxygen to maintain saturation 94e98%, re-hydrate and instigate continuous fetal monitoring
Delivery: acute attacks of asthma are very rare in labour due to endogenous steroid production. Prostaglandin E2 for induction of labour does not cause bronchoconstriction and may be used. Prostaglandin F2a should be used only in extreme circumstances and with caution since it may precipitate an acute asthma attack. Likewise aspirin and non-steroidal anti-inflammatory drugs should generally be avoided. Encourage women to continue their regular medication in labour. Women taking >7.5 mg prednisolone for >2 weeks prior to the onset of labour require parenteral
In labour C Advise women that acute asthma is rare in labour C Advise women to continue their usual asthma medications in labour C In the absence of acute severe asthma, reserve caesarean section for the usual obstetric indications C If anaesthesia is required, regional blockade is preferable C Women receiving steroid tablets at a dose exceeding prednisolone 7.5 mg per day for more than two weeks prior to delivery should receive parenteral hydrocortisone 100 mg 6-8 hourly during labour C Use prostaglandin F2a with extreme caution in women with asthma because of the risk of inducing bronchoconstriction
Treatment of acute asthma (British Thoracic Society Guidelines) Oxygen
Give high flow oxygen
b2 agonist bronchodilators Ipratropium bromide
High-dose inhaled b2 agonists by oxygendriven nebulizer Add nebulized ipratropium bromide (0.5 mg 4 e6 hourly) if poor response to bronchodilators or severe acute asthma Systemic corticosteroids (i.v. hydrocortisone 100 mg and/or oral prednisolone 40e50 mg daily) in all cases for at least 5 days or until recovery Consider single dose i.v. Magnesium sulphate (1.2e2 g infusion over 20 minutes) or i.v. b2 agonist, or i.v. aminophylline Routine antibiotics are not recommended
Steroid therapy
Other therapies
Puerperium C Encourage women with asthma to breast feed C Use asthma medications as normal during lactation
Respiratory tract infections Pneumonia occurs in the pregnant population with a frequency equal to that in the general population.
Table 4
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Counsel women with asthma to continue their medication in pregnancy For women with poorly controlled asthma during pregnancy there should be close liaison between the respiratory physician and obstetrician
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Effects of pregnancy on pneumonia Pneumonia in pregnancy is often more virulent and mortality is higher. There is an increased risk of serious maternal complications including respiratory failure. The spectrum of pathogens is similar to that in the non-pregnant population and the management does not differ. Co-existing maternal disease including asthma and anaemia and immunosuppressive therapy increase the risk of contracting pneumonia.
number of severe cases was significantly less, the earlier oseltamivir was started after onset of symptoms. Severe and moderate cases occurred in all trimesters but the highest numbers were seen in the third trimester. Neonatal outcome was poor if the women delivered during a severe illness. Six women died e all were women who developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. Hence recommendations are that pregnant women with confirmed, probable, or suspected H1N1 virus should receive a 5 day course of antiviral treatment ideally from within 48 hours of symptom onset. Oseltamivir should be considered the preferred treatment for pregnant women because its higher systemic absorption might suppress influenza viral loads more effectively in sites other than the respiratory system (e.g., placenta) and might provide better protection against mother-child transmission. Pregnant women in close contact with a confirmed, probable, or suspected case should receive a 10-day course of prophylaxis with zanamivir or oseltamivir.
Effect of pneumonia on pregnancy Severe pneumonia may precipitate preterm delivery and result in low birthweight infants. Bacterial pneumonia Community acquired pneumonia is most commonly caused by streptococcus pneumoniae, haemophilus influenzae and mycoplasma pneumoniae. Clinical features: women may present with cough, fever, rigours, breathlessness and pleuritic pain. Signs include fever, purulent sputum, coarse crackles on auscultation and signs of consolidation. Diagnosis may be confirmed with a chest X-ray but radiographic changes lag behind the clinical picture. Blood and sputum cultures should be taken. Bacterial pneumonia is associated with a raised white blood cell count although mycoplasma pneumonia is not. Knowledge of the increased mycoplasma activity in the community during an epidemic period may help guide the clinician to the increased likelihood of mycoplasma infection. Mycoplasma and chlamydial pneumonias are diagnosed on serological assays with complement fixation tests.
Maternal varicella pneumonia: pneumonia can occur in up to 10% of pregnant women with chickenpox and severity increases with gestation. Mortality rates of 20e45% in the pre-antiviral era have fallen to 3e14% with antiviral therapy and improved intensive care. However, between 1985 and 2005 there were nine indirect maternal deaths and one late maternal death reported in the UK as complications of maternal varicella pneumonia, suggesting a case fatality rate of less than 1% but a rate five times higher in pregnancy than in the non-pregnant adult. A live attenuated vaccine is available in the USA and should be offered to non-immune women pre-pregnancy. Women should be asked about previous chickenpox infection before they are prescribed steroids in pregnancy, and those found not to be immune should be given VZIG. Table 5 summarizes the RCOG management guidance. Those women who do develop clinical varicella should be treated with acyclovir and intravenous therapy may be necessary. Maternal and neonatal morbidity and mortality in cases of maternal varicella pneumonia justifies the use of i.v. acyclovir. A study has suggested that later gestational age (perhaps because of increased immunosuppression) at the onset of varicella pneumonia is a significant risk factor for maternal mortality. Anyone with varicella should be examined at a distance from the antenatal clinic and ward to minimize exposure to other pregnant women.
Management: supportive measures include oxygen administration and rehydration especially in the presence of fever. Chest physiotherapy will help clear secretions and aid oxygenation. Oral antibiotic therapy should be commenced for community acquired bacterial infections. Betalactam and macrolide antibiotics are safe in pregnancy. Oral amoxicillin (500 mg e 1 g t.d.s.) and clarithromycin (500 mg b d) are current recommended strategies. For severe community acquired or hospital acquired infections, intravenous cefuroxime and clarithromycin should be used. Tetracyclines cause discolouration of the teeth in the fetus and should be avoided after 20 weeks’ gestation. Viral pneumonia Seasonal influenza epidemics and previous influenza pandemics have shown that pregnant women generally are at higher risk for influenza-associated morbidity and mortality compared with women who are not pregnant. Influenza vaccination can reduce the prevalence of hospitalizations among pregnant women during influenza season and is not contraindicated in pregnancy. Influenza vaccination administered in pregnancy has also been shown to confer immunity to the neonate.
Pneumocystis pneumonia (PCP) e in association with HIV: is the most common opportunistic infection in patients progressing to acquired immunodeficiency syndrome (AIDS). It should be suspected in the presence of profound hypoxia out of proportion to the chest X-ray findings and bronchoscopy should be considered. Treatment is with high-dose cotrimoxazole (Septrin) (þ/ pentamidine), usually contraindicated in pregnancy because of theoretical risks of neonatal kernicterus or haemolysis except in the presence of PCP. Those women presenting with a PaO2<9.3 kPa or SpO2<92% should receive a course of prednisolone (40 mg twice daily for 5 days then once daily for 5 days, then 20 mg daily for 10 days). Women with HIV and a past history of PCP or CD4 þ cell count of <200 cells/ml considering pregnancy, should receive prophylactic cotrimoxazole.
Novel influenza A (H1N1) virus in pregnancy: the most frequently reported symptoms among non-pregnant patients with swine fever have been fever, cough, and sore throat. Review of the known cases in the USA during the 2009 pandemic demonstrated that compared with non-pregnant cases, pregnant women had a higher hospitalization rate, and mortality rate. The
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without delay. The usual drugs are rifampicin (no proven adverse fetal effects but risk of maternal hepatotoxicity), isoniazid (in combination with pyridoxine 50 mg/d to reduce the risk of peripheral neuritis), pyrazinamide and ethambutol for 2 months followed by 4 months of isniazid and rifampicin. Directly observed therapy is recommended. Liver function should be monitored monthly. In the event that the transaminases more than double, all antituberculous chemotherapy should be temporarily withdrawn and then individual agents introduced in a step-wise fashion while liver function tests are monitored closely. Since rifampicin induces the enzyme cytochrome P450, vitamin K should be given to the mother in the same way it is given to mothers receiving enzyme-inducing antiepileptic drugs. After delivery the neonate should be given prophylactic isoniazid treatment if the mother is sputum positive and vaccinated as soon as possible. Breastfeeding is not contraindicated since very little of the drugs are excreted in breast milk. However, if the mother has newly diagnosed, untreated, active TB she should be separated from her infant regardless of mode of infant feeding because of aerosol spread. In women co-infected with HIV, the timing of ART initiation and regimen needs to take into account potential maternal and fetal toxicities when concomitantly treating TB. Latent TB may be reactivated by HIV and although there is some debate whether latent TB should be treated in pregnancy or deferred until post-partum, in the presence of HIV, isoniazid preventative therapy is recommended in pregnancy despite the risk of hepatotoxicity. UKOSS (UK Obstetric Surveillance System) recently carried out a national descriptive study reporting a minimum incidence estimate of 4.2 per 100 000 maternities in the UK. The study confirmed that the disease appeared to be limited in the UK to ethnic minority women, most commonly recent immigrants. Extrapulmonary disease (at sites such as lymph nodes, bone, liver, spleen, bone marrow, caecum, nervous system and eye) was as common as pulmonary disease in pregnancy with a greater delay in diagnosis. There was one case fatality. Two additional deaths were identified in the most recent CEMACH report; of these, two were from tuberculous meningitis and one in a woman with HIV. Globally, TB incident cases have risen to 9.4 million in 2008. TB is one of the leading causes of non-obstetric maternal mortality with an estimated one-third of deaths occurring in women of child-bearing age.
A summary of RCOG Green top guideline 13 Chickenpox in pregnancy Significant exposure to a non-immune pregnant woman: VZIG as soon as possible, up to 10 days after contact. May require a second dose of VZIG after 3 weeks if further exposure. Clinical varicella after 20 weeks gestation: oral acyclovir (800 mg five times a day for 7 days) if within 24 hours of the onset of the rash. Refer immediately if: chest symptoms, neurological symptoms, haemorrhagic rash or bleeding, a dense rash þ/ mucosal lesions. Consider hospital (multidisciplinary) assessment if: significant immunosuppression, taking corticosteroids, smokers, chronic lung disease, or are in the latter half of pregnancy Delivery during a viraemic period: maternal risks of bleeding, thrombocytopenia, disseminated intravascular coagulation and hepatitis; fetal risk of varicella transmission with significant morbidity and mortality. Aim to avoid delivery and provide supportive treatment and intravenous acyclovir - however, delivery may be required in women to facilitate assisted ventilation in cases complicated by respiratory failure. Anaesthesia: general anaesthesia may exacerbate varicella pneumonia; spinal anaesthesia has a theoretical risk of transmitting the virus from skins lesions to CNS. Therefore epidural anaesthesia may be safer because dura is not penetrated. A site free of cutaneous lesions should be chosen for needle placement. Table 5
Tuberculosis (TB) Mycobacterium tuberculosis characteristically causes caseating granulomas with the lungs as the primary site. The patient is often asymptomatic but typically can present with a cough, haemoptysis, weight loss and night sweats. The diagnosis is confirmed with sputum examination for acid-fast bacilli (ZiehleNeelsen stain). Culture of the organism takes about 6 weeks. If there is no sputum, washings from bronchoscopy must be obtained. The Mantoux test (0.1 ml of 10 tuberculin units of purified protein derivative of MBTB) is not affected by pregnancy. Newer diagnostic blood tests include interferon gamma release assays such as the enzyme-linked immunospot assays (ELISPOT) and QuantiFERON e TB. These blood tests can distinguish latent TB from BCG. They have greater specificity for diagnosing latent rather than active TB. Although pregnancy and TB appear to have little effect on each other, treatment should not be delayed. Congenital TB with infection via the umbilical vein or amniotic fluid is rare. One prospective study found that there were no significant differences in pregnancy complications compared with matched healthy controls except if women started TB treatment late in pregnancy with associated higher neonatal mortality and extreme prematurity. The WHO recommends that the treatment of TB in pregnant women should be the same as that in nonpregnant women, except that streptomycin should be avoided because of fetal ototoxicity. The advice of a respiratory physician must be sought and pregnant mothers with TB should be treated
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Aspiration pneumonia This complication of gastric regurgitation most commonly occurs during induction for general anaesthesia in late pregnancy or in the event of an excessively high regional block. Increased intraabdominal pressure, delayed gastric emptying and reduced gastro-oesophageal sphincter tone contribute to the risk and in consequence feeding in labour was discouraged in the past. However, a recent trial (RCT) suggested that despite the rising incidence of obesity in the UK, a light diet in labour did not confer an increased risk of aspiration pneumonia. Ranitidine, an H2 antagonist, which reduces gastric acid secretion and an antacid to neutralize the gastric acid are routinely prescribed for women in labour with risk factors for caesarean section or before an elective procedure.
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The main maternal morbidity in CF pregnancies includes: poor maternal weight gain e even those without pancreatic insufficiency are often underweight at the onset of pregnancy and have difficulty gaining weight during pregnancy; deterioration in lung function with worsening dyspnoea, exercise tolerance and oxygen saturation e although there is usually loss of lung function during pregnancy, this is regained following delivery; pulmonary infective exacerbations; congestive cardiac failure.
Practice points C
C
C
C
C
Pneumonia in pregnancy is often more virulent therefore treat aggressively All non-immune pregnant women exposed to varicella should be given zoster immunoglobulin (ZIG) as soon as possible Clinical varicella should be treated with acyclovir if within 24 hours of the onset of the rash and after 20 weeks gestation H1 N1 influenza should be treated as in the non-pregnant with oseltamivir Risk of TB should be assessed at booking especially in immigrant women
Management Fetal: pre-pregnancy genetic counselling should include a risk estimate of a child born with CF of 2e2.5% if the carrier status of the father is unknown (based on UK carrier status of 1 in 25) and 50% if the father is heterozygous for the gene. During pregnancy, fetal surveillance to detect early signs of growth restriction is essential.
Cystic fibrosis Maternal: women with CF benefit from a pre-pregnancy assessment. Women with mild disease may be reassured that pregnancy is safe. For more severe cases, liaisons between a CF centre and an obstetrician with a special interest in CF can be planned ahead of the pregnancy. The presence of pulmonary hypertension, cor pulmonale or FEV1 <30e40% are contraindications to pregnancy. Since Burkholderia cepacia may be associated with rapid deterioration in lung function, recent acquisition or declining lung function in the presence of this organism may also be a contraindication to pregnancy. Screening for diabetes and baseline lung function tests as well as dietary supplementation, enzyme supplements, chest physiotherapy are important. Infective chest exacerbations should be treated aggressively with antibiotic therapy. There is no contraindication to vaginal delivery but a prolonged second stage should be avoided because of the risk of pneumothoraces. General anaesthesia should be avoided. There is no contra-indication to breastfeeding but women may need to continue nutritional supplements post-natally.
Cystic fibrosis (CF) is an autosomal-recessive disorder affecting the body’s exocrine glands, including the pancreas, sweat glands, and lungs. It has a carrier frequency of 1 in 25 in Caucasians. A gene deletion in 70% causes a defect in the CF transmembrane conductance regulator protein resulting in impaired movement of water and electrolytes across epithelial surfaces. Improvements in treatment have allowed survival to adulthood and pregnancy. The clinical entity varies, depending on severity and presence of infections. Some milder cases are not diagnosed until adulthood. CF is characterized by the production of very thick and sticky mucus. About 90% of cases involve the lungs with recurrent or persistent infections, development of bronchiectasis and respiratory failure. The ducts leading from the pancreas become obstructed causing pancreatic insufficiency, diabetes and malnutrition. Almost always, a productive cough is present, and patients often appear barrel-chested. Recurrent respiratory, gastrointestinal, and nutritional problems result in frequent hospital admissions. Effect of CF on pregnancy Malnutrition þ/or thickened cervical mucus may impair female fertility. Men are usually sterile. Most series of pregnancies in women with CF have shown that with careful planning and monitoring by a dedicated team, pregnancy outcomes are favourable. Commonly reported adverse events are fetal growth restriction and prematurity which includes iatrogenic early delivery in the unwell. Women with CF are at an increased risk of developing gestational diabetes. In a recent series of 20 pregnancies in women with CF, adverse fetal outcomes were significantly higher in women with an FEV1 <60% and/or pre-pregnancy BMI <20. Gestational diabetes occurred in 43%.
Bronchiectasis Bronchiectasis is a sequelae of cystic fibrosis, pneumonias, and rarer causes such as Kartagener’s syndrome. It is characterized by irreversibly dilated damaged bronchi predisposing to persistently infected mucus and bacterial infections. A cough productive of large amounts of sputum is characteristic. The condition is uncommon in child-bearing years but is associated with fetal growth restriction in pregnancy. Women should be managed jointly with respiratory physicians. Their condition can deteriorate in pregnancy. Hence close attention to postural drainage and physiotherapy is important as is regular sputum culture and intermittent or continuous antibiotic therapy for chest infections þ/ bronchodilators. As in CF, the presence of pulmonary hypertension and/or hypoxaemia adversely affects prognosis.
Effect of pregnancy on CF Pregnancy does not appear to influence the long-term course of disease and is not associated with a shortened survival or more rapid decline in lung function. Maternal mortality is no greater than non-pregnant age-matched women with CF except in the presence of pulmonary hypertension, cyanosis, arterial hypoxaemia (oxygen saturation <90%), moderate/severe lung disease (FEV1 <60% predicted) and/or malnutrition when both maternal and fetal outcome are poor. The last CEMACH reported one death from CF in a woman with severe disease.
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Pulmonary arterial hypertension Although mortality rate remains high (>50%), advances in the management of this condition have meant that successful pregnancies are reported in those with well controlled PAH and in those long-term responders to calcium channel blockers.
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disease remains unknown. The disease most commonly involves granuloma formation in the lungs. Other commonly involved organ systems include the lymph nodes (especially the intrathoracic nodes); the skin; the eyes; the liver; the heart; and the nervous, musculoskeletal, renal, and endocrine systems. The course of sarcoidosis is variable, ranging from self-limited acute disease to a chronic debilitating disease that may result in death. Spontaneous remissions occur in nearly two thirds of patients, but 10e30% of patients have a more chronic or progressive course. Because sarcoidosis can involve any organ system, the clinical presentation is often variable. Many patients are asymptomatic but there may be chest symptoms. Other features include erythema nodosum, anterior uveitis, hypercalcaemia, arthropathy, fever or CNS symptoms.
However, case series are small and the general recommendation is to avoid pregnancy in the presence of PAH.
Cystic fibrosis lung transplant recipients Although the physiological changes of pregnancy are generally well tolerated by lung þ/ heart transplant(s) recipients, the risk of allograft rejection during and after pregnancy is significant. These patients must be counselled pre-pregnancy of the impact of pregnancy on survival, citing a 50% 5-year mortality rate. An adequate level of immunosuppression must be maintained in pregnancy. A multidisciplinary team, involving maternofetal medicine, respiratory and transplant medicine specialists, anaesthetists, neonatologists, geneticists, and social service, is crucial to the care of these patients. The management plan should be individualized according to the status of the mother, the fetus, and the allograft. Of a series of 10 pregnancies in 10 women with CF lung transplant recipients, five with a long stable interval of >3 years between transplant and the pregnancy had favourable outcomes; the remaining five had preterm deliveries. All 10 sadly showed progressive decline in lung function and all died of chronic rejection within 38 months of delivery.
Effect of pregnancy on sarcoidosis: sarcoidosis either improves or remains the same in pregnancy. There is a tendency to relapse in the puerperium. This is not a contraindication to pregnancy except in severely affected cases. Factors indicating a poor prognosis include parenchymal lesions on chest radiograph, advanced radiographic staging, advanced maternal age, low inflammatory activity, requirement for drugs other than steroids, and presence of extrapulmonary sarcoidosis.
Practice points on cystic fibrosis C C
C C C
Effect of sarcoidosis on pregnancy: sarcoidosis does not adversely affect pregnancy and is not transmitted to the fetus. There is one report of sarcoid granulomata found in the placenta of one patient.
Joint care with a CF centre Specialist dietary advice and nutritional supplements should be sought ideally pre-pregnancy, fat soluble vitamins should be continued in pregnancy Screen for gestational diabetes Infective exacerbations should be treated aggressively Avoid prolonged pushing in second stage of labour
Management: ideally, patients require evaluation before pregnancy to establish chronicity, baseline pulmonary function, inflammatory activity, staging, and response to treatment. Systemic steroids should be continued in pregnancy. Angiotensin converting enzyme levels, used as a marker of disease activity, are unreliable in pregnancy. Women should be advised to avoid vitamin D because of the risk of hypercalcaemia. Intravenous hydrocortisone should be administered in labour in women taking >7.5 mg daily of prednisolone.
Restrictive & fibrotic lung diseases Restrictive ventilatory defects are characterized by a reduction in lung volumes and an increase in the ratio of FEV1 to forced vital capacity (FVC) which occur when lung expansion is limited. This may be because of alterations in the lung parenchyma or abnormalities in the pleura, chest wall, or neuromuscular apparatus. The majority of pulmonary diseases do not alter fertility. A large reserve in respiratory function allows both fetus and mother to survive without compromise in most cases. FVC of >1 l or 50% of predicted FVC has been suggested as a cut off for successful pregnancies and although more severe cases can negotiate pregnancy, patients with severe restrictive lung disease should be advised against it and to consider a therapeutic termination. In addition, the associated polycythaemia confers an added thrombotic risk. Women with an associated kyphoscoliosis are often delivered preterm because of deterioration in lung function. Mode of delivery tends to be caesarean section because of abnormal fetal presentation due to associated bony pelvic abnormalities. Each case should be assessed individually.
Wegener’s granulomatosis This is a rare form of systemic vasculitis in which necrotizing granulomatous lesions affect the upper respiratory tract, lungs and kidneys. Without treatment the condition has a poor prognosis. Remission may be achieved with prednisolone and cyclophosphamide. Conclusions from 43 published cases suggest 65% of Wegener’s will flare during pregnancy and post-partum but this risk is halved when the disease is in remission at conception. It is impossible to predict flares in pregnancy. Antineutrophil cytoplasmic antibody (ANCA) titres are markers of disease activity. Despite the teratogenic risk, the pregnancies in which flares were treated with cyclophosphamide had better outcomes and there are good data to support the safe use of cyclophosphamide beyond the first trimester of pregnancy. It is associated with a 7% rate of fetal growth restriction and transient cytopenias after birth.
Conclusion
Sarcoidosis Sarcoidosis is characterized by non-caseating epithelioid granulomas that may affect any organ system. The aetiology of the
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Byrne BMP, Crowley PA, Carrington D. Chicken pox in pregnancy. Green top guideline No 13. RCOG, 2007. Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009; 374: 451e8. Knight M, Kurinczuk JJ, Nelson-Piercy C, Spark P, Brocklehurst P on behalf of UKOSS. Tuberculosis in pregnancy in the UK. BJOG 2009; 116: 584e8. Mnyani CN, McIntyre JA. Tuberculosis in pregnancy. BJOG 2011; 118: 226e31. Murphy VE, Namazy JA, Powell H, et al. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG 2011; 118: 1314e23. Nelson-Piercy C. Respiratory disease. In: Nelson-Piercy C, ed. Handbook of obstetric medicine. 4th edn. London: Informa Healthcare, 2010. Schatz M, Dombrowski MP. Clinical practice. Asthma in pregnancy. N Engl J Med 2009; 360: 1862e9. Soh MH, Hart HH, Bass E, Wilkinson L. Pregnancy complicating Wegener’s granulomatosis. Obstet Med 2009; 2: 77e80. Wu DW, Wilt J, Restaino S. Pregnancy after thoracic organ transplantation. Semin Perinatol 2007; 31: 354e62.
should not be avoided in pregnancy and most drugs can be used safely in pregnancy. It is important that women with a chronic respiratory disease should receive pre-pregnancy counselling and education regarding the risks of pregnancy and the importance of continuing medications. It also provides an opportunity to optimize their condition and so reduce adverse pregnancy outcomes. Women should be managed in a multidisciplinary setting with regular review by chest physicians and access to chest physiotherapy if necessary. Liaison with obstetric anaesthetists in the antenatal period will optimize care at delivery with regard to pain relief and reduce anaesthetic risks. Respiratory diseases complicated by pulmonary hypertension and cor pulmonale have a poor prognosis in pregnancy. A
FURTHER READING British Thoracic Society: guidelines for the management of community acquired pneumonia. Thorax 2009; 64(suppl. III). British Thoracic Society: Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma 2008, revised Jan 2012.
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awareness of the physiological hyperventilation of pregnancy. Women most often present in the third trimester but may become symptomatic at any gestation. Classically, physiological breathlessness of pregnancy is present at rest or while talking and paradoxically improves with activity. Table 1 summarizes other causes. Other presenting symptoms of respiratory disease include chest pain, cough, sputum production, haemoptysis, fever or cyanosis. On examination, respiratory rate is unchanged by pregnancy. Presence of raised temperature should be noted. Expansion on inspiration reflects tidal volume and is reduced in many respiratory diseases. Percussion note may be dull in the presence of pleural effusion, consolidation, collapse or fibrosis. It is enhanced in the presence of a pneumothorax. Auscultation may reveal wheezes indicative of asthma; fine crepitations in the presence of pulmonary oedema; pleural rubs indicative of inflammatory conditions of the pleura in pneumonia or pulmonary infarction and bronchial breathing þ/ coarse crackles would suggest consolidation. Absent breath sounds occur with pneumothorax or extensive collapse. A simple non-invasive investigation is transcutaneous oxygen saturation. The normal oxygen saturation is greater than 95%. A fall in saturation on exercise e.g. climbing stairs indicates some form of cardiopulmonary disease and should be investigated further. Measurement of arterial blood gases should be reserved for those who are markedly breathless, those whose oxygen saturations are low at rest, or which drop on exercise and those women who appear unwell. When interpreting arterial blood gases in pregnancy it should be remembered that the progesterone-driven increase in minute ventilation may lead to relative hypocapnia and a respiratory alkalosis, and higher PaO2 but oxygen saturations are unaltered. Acidosis is poorly tolerated by the fetus. Reluctance to perform a chest X-ray in pregnancy may delay a diagnosis. Typical fetal dose range of ionizing radiation from a chest X-ray is 0.001e0.01 mGy and abdominal shielding will reduce fetal exposure further. This is unlikely to cause fetal death or malformation and the risk of childhood cancer is <1 in 10 000. Sputum should be sent for microbiological examination.
Sophia Stone Catherine Nelson-Piercy
Abstract Breathlessness in the absence of an underlying pathology is common in pregnancy. Asthma affects about 7% of women of child-bearing age. Treatment is the same as for the non-pregnant population and most drugs are safe in pregnancy. Educating women to continue preventer inhaled corticosteroid therapy will reduce the risk of attacks. Respiratory infections are associated with a higher morbidity in pregnancy and should be treated aggressively. Most chronic pulmonary diseases do not alter fertility. Large reserves in respiratory function allow the fetus and mother to survive without compromise in most cases. The use of chest X-rays should not be avoided in pregnancy. Women with a chronic respiratory disease should receive pre-pregnancy counselling and education. Women should be managed in a multidisciplinary setting with the respiratory team. The presence of pulmonary hypertension and cor pulmonale is associated with a high risk of death in pregnancy.
Keywords asthma; pneumonia; pregnancy; respiratory disease; tuberculosis
Introduction Severe lung disease leading to respiratory failure is uncommon in women of child-bearing age. However, respiratory symptoms are extremely common in pregnancy. This is because of the effect of physiological adaptation to pregnancy and because of reduced functional capacity and mobility from diaphragmatic elevation by the gravid uterus in late gestation. There is greater oxygen demand in normal pregnancy with a 20% increase in oxygen consumption, 40e50% increase in minute ventilation (secondary to tidal volume increase and not respiratory rate). The resultant maternal hyperventilation causes a mild fully compensated respiratory alkalosis (i.e. increased arterial pO2 and decreased arterial pCO2, compensatory fall in serum bicarbonate to 18e22 mmol/l; arterial pH 7.44).
Asthma Asthma is a common chronic inflammatory condition of the lung airways characterized by episodes of reversible bronchoconstriction as a result of various stimuli. It affects up to 7% of women of child-bearing age. The diagnosis of asthma is a clinical one based on the presence of symptoms (see Table 2) and evidence of variable airflow obstruction. There may be airway hyper-responsiveness and airway inflammation. There is often an associated personal or family history of atopy. Recognized triggers include pollen, dust, animals, infections etc. Confirmation hinges on demonstration of airflow obstruction varying over short periods of time. The British Thoracic Society guidelines for the management of asthma (2012) suggest that spirometry is preferable to measurement of peak expiratory flow (PEF) because it allows clearer identification of airflow obstruction, and the results are less dependent on effort. PEF rate and forced expiratory volume in 1 second (FEV1) are unaffected by pregnancy. Table 3
Respiratory symptoms, signs and investigations The commonest respiratory symptom in pregnancy is breathlessness. However this can often be attributed to an increased
Sophia Stone MD MRCOG is a Consultant in Obstetrics and Gynaecology at St Richard’s Hospital, Chichester, West Sussex, UK. Conflicts of interest: none declared. Catherine Nelson-Piercy MA FRCP FRCOG is a Consultant Obstetric Physician at Guy’s and St Thomas’ Hospitals Trust, London, UK. Conflicts of interest: none declared.
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Differential diagnoses of breathlessness in pregnancy Diagnosis
Investigations
Physiological
Diagnosis by exclusion and typical history Full blood count PEFR e response to bronchodilators Arterial blood gases (YPO2 and YPCO2)/VQ scan ECG, echocardiogram, chest X-ray
A summary of the BTS guidelines on drug use in pregnancy C
Anaemia Asthma Pulmonary embolus Mitral stenosis, cardiomyopathy Pneumonia Pneumothorax Hyperventilation/ anxiety
C
C C
C
Chest X-ray, sputum culture, serology Chest X-ray Arterial blood gases (YPCO2 but not YPO2)
C
C
Table 1
Effect of asthma on pregnancy A recent meta-analysis of adverse perinatal outcomes in women with asthma demonstrated that maternal asthma was associated with an increased risk of low birthweight (RR 1.46, 95% CI 1.22e1.75), small for gestational age (RR 1.22, 95% CI 1.14 e1.31), preterm delivery (RR 1.41, 95% CI 1.22e1.61) and preeclampsia (RR 1.54, 95% CI 1.32e1.81). The relative risk of preterm delivery and preterm labour were reduced to nonsignificant levels by active asthma management (RR 1.07, 95% CI 0.91e1.26 and RR 0.96, CI 0.73e1.26 respectively).
C
Table 3
a finding supported by the conclusions of a meta-analysis of 14 studies). Women, whose asthma worsened in pregnancy, were most symptomatic from 29 to 36 weeks’ gestation. Nonatopic patients with asthma tend to have more severe asthma in pregnancy and a higher incidence of pre-eclampsia. US studies suggest that 11e18% of pregnant women with asthma will have at least one emergency department visit for acute asthma and of these 62% will require hospitalization. Between 2006 and 2008 there were five indirect maternal deaths relating to asthma reported in the UK, one in a woman who was told to stop her course of steroids. The concern is that women stop their medication either of their own accord at the start of the pregnancy or on incorrect medical advice because of worries regarding the safety profile of the drugs for the fetus. There is some evidence that the course of asthma is similar in successive pregnancies. Asthma appears to be significantly less frequent and less severe during the last 4 weeks of pregnancy. Endogenous steroids in labour ensure that acute asthma attacks are very uncommon during labour and delivery. There may be a deterioration post-partum but in the majority, asthma reverts towards its pre-pregnancy course within 3 months of delivery.
Effect of pregnancy on asthma A systematic review has shown that baseline asthma severity does determine what happens to the course of asthma in pregnancy. An early study of 366 pregnancies complicated by asthma, reported worsening asthma in 35%, an improvement in 28%, and unchanged in 33% (approximate rule of thirds,
Features that increase the probability of asthma (from British Thoracic Society Scottish Intercollegiate Guidelines Network 2008; Revised May 2011) More than one of the following symptoms: wheeze, breathlessness, chest tightness and cough, particularly if: C symptoms worse at night and in the early morning C symptoms in response to exercise, allergen exposure and cold air C symptoms after taking aspirin or beta blockers
Management Pre-pregnancy and antenatal care: pregnancy is an ideal opportunity to optimize therapy although, ideally this should occur pre-pregnancy. Current emphasis in the management of asthma is on the prevention of rather than treatment of acute attacks. Women should be advised regarding the importance and safety of continuing inhalers to maintain good asthma control. Inhaler techniques should be checked; spacer devices should be introduced if necessary to improve drug delivery. Pregnant women must be monitored closely so that any change in course can be matched by an appropriate change in therapy. The aim of
History of atopic disorder Family history of asthma and/or atopic disorder Widespread wheeze heard on auscultation of the chest Otherwise unexplained low FEV1 or PEF (historical or serial readings) Otherwise unexplained peripheral blood eosinophilia Table 2
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Use short-acting b2 agonists as normal during pregnancy (B) Use long acting b2 agonists (LABA) as normal during pregnancy (C) Use inhaled steroids as normal during pregnancy (B) Use oral and intravenous theophyllines as normal during pregnancy (C) Check blood levels of theophylline in acute severe asthma and in those critically dependent on therapeutic theophylline levels (D) Use steroid tablets as normal when indicated during pregnancy for severe asthma. Steroid tablets should never be withheld because of pregnancy. Women should be advised that the benefits of treatment with oral steroids outweigh the risks (C) Leukotriene antagonists (LTRA) may be continued in women who have demonstrated significant improvement in asthma control with these agents prior to pregnancy not achievable with other medications. (D) Use chromones as normal during pregnancy (C)
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treatment is complete freedom from symptoms. Allergen and trigger avoidance should be discussed when atopy is also present. Antihistamines and therapy for allergic rhinitis may be safely prescribed. Those with the best safety profile are chlorpheniramine and intranasal beclomethasone, but cetirazine and loratidine may also be safely used. Women who smoke should be advised about the dangers for themselves and their babies and given appropriate support to stop smoking. Women with well controlled asthma may have midwifery-led care. Women with poorly controlled asthma require consultant led antenatal care with fetal surveillance and liaison with respiratory team and antenatal anaesthetic review.
Society guidelines on the management of asthma. The step-wise approach illustrated in Figure 1 is recommended. Mild intermittent asthma is managed with inhaled short-acting ‘reliever’ (b2-agonist) medication as required (Step 1). If usage of a ‘reliever’ (b2-agonist) inhaler exceeds >once/day, regular inhaled anti-inflammatory medication with a steroid ‘preventer’ (e.g. beclomethasone) inhaler [200e800 mg/day] should be commenced. (Step 2). The next step up in therapy is either the addition of a long acting reliever’ b2-agonist (LABA) e.g. Salmeterol, or an increase in the dose of inhaled steroid [800 mg/day].(Step 3). Further steps involve a trial of additional therapies e.g. leukotriene receptor antagonist (see below), slow release oral theophylline or oral b2-agonist. Alternatively the dose of inhaled steroid can be increased to 2000 mg/day. (Step 4). If these measures fail to achieve adequate control then
Drug therapy in pregnancy: is essentially the same as for the non-pregnant population and should follow the British Thoracic
Summary of step-wise management of asthma Step 5: Continuous/frequent use of oral steroids • daily steroid tablet – lowest dose for control • maintain high dose inhaled steroid • consider other drugs to minimise steroid use • refer for specialist care
Step 4: Persistent poor control • Increasing inhaled steroid up to 2000 μg/d • Addition of a 4th drug e.g. SR theophylline, β2 agonist tablet
Step 3: Initial add-on therapy 1. add inhaled long-acting β2agonist (LABA) 2. assess control: • good response – continue LABA •benefit but inadequate – LABA + inhaled steroid to 800 μg/d • no response – Stop LABA and increase inhaled steroid. If control still inadequate institute trial of leukotriene receptor antagonist or SR theophylline
Step 2: Regular preventer therapy • Add inhaled steroid 200–800 μg/d appropriate to disease severity • (400μg/d is appropriate starting dose)
Step 1: Mild intermittent asthma • Inhaled short-acting β2 agonist as required
Adapted from the British Thoracic Society Guidelines
Figure 1 Start treatment at the step most appropriate to initial severity. Regular review to maintain control by stepping up treatment as necessary; stepping down treatment when control is good.
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continuous or frequent use of oral steroids becomes necessary. The lowest dose providing adequate control should be used, if necessary with steroid sparing agents. (Step 5).
hydrocortisone 100 mg 6e8 hourly in labour. Women with asthma may safely use all forms of pain relief in labour. Ergometrine has been reported to cause bronchospasm particularly in association with general anaesthesia, but syntometrine routinely used for active management of the third stage has not been associated with any adverse incidents. In the absence of acute severe asthma, caesarean section is reserved for obstetric indications only. If a caesarean section is required, regional anaesthesia is preferable to general anaesthesia in women with asthma.
Low-dose aspirin: it is important to consider the possibility of ‘aspirin sensitivity’ and severe bronchospasm in a minority of women with asthma. Pregnant women with asthma should be asked about a history of aspirin sensitivity before being advised to take low-dose aspirin. Acute asthma attacks: should be managed as for the nonpregnant patient with a low threshold for admission. The features of acute severe asthma are PEFR 33e50% best/predicted, respiratory rate >25/minute, heart rate > 110/minute, inability to complete sentences in one breath. Multidisciplinary care should be sought with a respiratory physician and obstetrician and early referral to critical care team. Oxygen is given to maintain saturation 94e98%, and intravenous rehydration when drinking is impossible and drug therapy as for the non-pregnant (Table 4). Continuous fetal monitoring should be instigated. The woman should be managed in a left lateral position to avoid aorta-caval compression. A chest X-ray should be performed if there is any clinical suspicion of pneumonia or pneumothorax, or if the woman fails to improve. A PEF rate of 33e50 per cent best/predicted indicates acute severe asthma, <33 per cent is life threatening. Other concerning signs are SpO2<92 per cent, PaO2 <8 kPa with normal PaCO2, silent chest, cyanosis, feeble respiratory effort, hypotension, altered consciousness and exhaustion.
Post-natal care: none of the medications for asthma are contraindicated in breast feeding. Less than 1% of the maternal dose of theophylline is excreted into breast milk. Prednisolone is secreted in breast milk, but milk concentrations of prednisolone are only 5e25% of those in serum and therefore it considered safe to prescribe prednisolone.
Practice points (BTS recommendations): C
C
Acute asthma. C Acute severe asthma in pregnancy is an emergency and should be treated vigorously in hospital. C Give drug therapy including corticosteroids for acute asthma as for the non-pregnant patient C Deliver oxygen to maintain saturation 94e98%, re-hydrate and instigate continuous fetal monitoring
Delivery: acute attacks of asthma are very rare in labour due to endogenous steroid production. Prostaglandin E2 for induction of labour does not cause bronchoconstriction and may be used. Prostaglandin F2a should be used only in extreme circumstances and with caution since it may precipitate an acute asthma attack. Likewise aspirin and non-steroidal anti-inflammatory drugs should generally be avoided. Encourage women to continue their regular medication in labour. Women taking >7.5 mg prednisolone for >2 weeks prior to the onset of labour require parenteral
In labour C Advise women that acute asthma is rare in labour C Advise women to continue their usual asthma medications in labour C In the absence of acute severe asthma, reserve caesarean section for the usual obstetric indications C If anaesthesia is required, regional blockade is preferable C Women receiving steroid tablets at a dose exceeding prednisolone 7.5 mg per day for more than two weeks prior to delivery should receive parenteral hydrocortisone 100 mg 6-8 hourly during labour C Use prostaglandin F2a with extreme caution in women with asthma because of the risk of inducing bronchoconstriction
Treatment of acute asthma (British Thoracic Society Guidelines) Oxygen
Give high flow oxygen
b2 agonist bronchodilators Ipratropium bromide
High-dose inhaled b2 agonists by oxygendriven nebulizer Add nebulized ipratropium bromide (0.5 mg 4 e6 hourly) if poor response to bronchodilators or severe acute asthma Systemic corticosteroids (i.v. hydrocortisone 100 mg and/or oral prednisolone 40e50 mg daily) in all cases for at least 5 days or until recovery Consider single dose i.v. Magnesium sulphate (1.2e2 g infusion over 20 minutes) or i.v. b2 agonist, or i.v. aminophylline Routine antibiotics are not recommended
Steroid therapy
Other therapies
Puerperium C Encourage women with asthma to breast feed C Use asthma medications as normal during lactation
Respiratory tract infections Pneumonia occurs in the pregnant population with a frequency equal to that in the general population.
Table 4
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Counsel women with asthma to continue their medication in pregnancy For women with poorly controlled asthma during pregnancy there should be close liaison between the respiratory physician and obstetrician
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Effects of pregnancy on pneumonia Pneumonia in pregnancy is often more virulent and mortality is higher. There is an increased risk of serious maternal complications including respiratory failure. The spectrum of pathogens is similar to that in the non-pregnant population and the management does not differ. Co-existing maternal disease including asthma and anaemia and immunosuppressive therapy increase the risk of contracting pneumonia.
number of severe cases was significantly less, the earlier oseltamivir was started after onset of symptoms. Severe and moderate cases occurred in all trimesters but the highest numbers were seen in the third trimester. Neonatal outcome was poor if the women delivered during a severe illness. Six women died e all were women who developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. Hence recommendations are that pregnant women with confirmed, probable, or suspected H1N1 virus should receive a 5 day course of antiviral treatment ideally from within 48 hours of symptom onset. Oseltamivir should be considered the preferred treatment for pregnant women because its higher systemic absorption might suppress influenza viral loads more effectively in sites other than the respiratory system (e.g., placenta) and might provide better protection against mother-child transmission. Pregnant women in close contact with a confirmed, probable, or suspected case should receive a 10-day course of prophylaxis with zanamivir or oseltamivir.
Effect of pneumonia on pregnancy Severe pneumonia may precipitate preterm delivery and result in low birthweight infants. Bacterial pneumonia Community acquired pneumonia is most commonly caused by streptococcus pneumoniae, haemophilus influenzae and mycoplasma pneumoniae. Clinical features: women may present with cough, fever, rigours, breathlessness and pleuritic pain. Signs include fever, purulent sputum, coarse crackles on auscultation and signs of consolidation. Diagnosis may be confirmed with a chest X-ray but radiographic changes lag behind the clinical picture. Blood and sputum cultures should be taken. Bacterial pneumonia is associated with a raised white blood cell count although mycoplasma pneumonia is not. Knowledge of the increased mycoplasma activity in the community during an epidemic period may help guide the clinician to the increased likelihood of mycoplasma infection. Mycoplasma and chlamydial pneumonias are diagnosed on serological assays with complement fixation tests.
Maternal varicella pneumonia: pneumonia can occur in up to 10% of pregnant women with chickenpox and severity increases with gestation. Mortality rates of 20e45% in the pre-antiviral era have fallen to 3e14% with antiviral therapy and improved intensive care. However, between 1985 and 2005 there were nine indirect maternal deaths and one late maternal death reported in the UK as complications of maternal varicella pneumonia, suggesting a case fatality rate of less than 1% but a rate five times higher in pregnancy than in the non-pregnant adult. A live attenuated vaccine is available in the USA and should be offered to non-immune women pre-pregnancy. Women should be asked about previous chickenpox infection before they are prescribed steroids in pregnancy, and those found not to be immune should be given VZIG. Table 5 summarizes the RCOG management guidance. Those women who do develop clinical varicella should be treated with acyclovir and intravenous therapy may be necessary. Maternal and neonatal morbidity and mortality in cases of maternal varicella pneumonia justifies the use of i.v. acyclovir. A study has suggested that later gestational age (perhaps because of increased immunosuppression) at the onset of varicella pneumonia is a significant risk factor for maternal mortality. Anyone with varicella should be examined at a distance from the antenatal clinic and ward to minimize exposure to other pregnant women.
Management: supportive measures include oxygen administration and rehydration especially in the presence of fever. Chest physiotherapy will help clear secretions and aid oxygenation. Oral antibiotic therapy should be commenced for community acquired bacterial infections. Betalactam and macrolide antibiotics are safe in pregnancy. Oral amoxicillin (500 mg e 1 g t.d.s.) and clarithromycin (500 mg b d) are current recommended strategies. For severe community acquired or hospital acquired infections, intravenous cefuroxime and clarithromycin should be used. Tetracyclines cause discolouration of the teeth in the fetus and should be avoided after 20 weeks’ gestation. Viral pneumonia Seasonal influenza epidemics and previous influenza pandemics have shown that pregnant women generally are at higher risk for influenza-associated morbidity and mortality compared with women who are not pregnant. Influenza vaccination can reduce the prevalence of hospitalizations among pregnant women during influenza season and is not contraindicated in pregnancy. Influenza vaccination administered in pregnancy has also been shown to confer immunity to the neonate.
Pneumocystis pneumonia (PCP) e in association with HIV: is the most common opportunistic infection in patients progressing to acquired immunodeficiency syndrome (AIDS). It should be suspected in the presence of profound hypoxia out of proportion to the chest X-ray findings and bronchoscopy should be considered. Treatment is with high-dose cotrimoxazole (Septrin) (þ/ pentamidine), usually contraindicated in pregnancy because of theoretical risks of neonatal kernicterus or haemolysis except in the presence of PCP. Those women presenting with a PaO2<9.3 kPa or SpO2<92% should receive a course of prednisolone (40 mg twice daily for 5 days then once daily for 5 days, then 20 mg daily for 10 days). Women with HIV and a past history of PCP or CD4 þ cell count of <200 cells/ml considering pregnancy, should receive prophylactic cotrimoxazole.
Novel influenza A (H1N1) virus in pregnancy: the most frequently reported symptoms among non-pregnant patients with swine fever have been fever, cough, and sore throat. Review of the known cases in the USA during the 2009 pandemic demonstrated that compared with non-pregnant cases, pregnant women had a higher hospitalization rate, and mortality rate. The
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without delay. The usual drugs are rifampicin (no proven adverse fetal effects but risk of maternal hepatotoxicity), isoniazid (in combination with pyridoxine 50 mg/d to reduce the risk of peripheral neuritis), pyrazinamide and ethambutol for 2 months followed by 4 months of isniazid and rifampicin. Directly observed therapy is recommended. Liver function should be monitored monthly. In the event that the transaminases more than double, all antituberculous chemotherapy should be temporarily withdrawn and then individual agents introduced in a step-wise fashion while liver function tests are monitored closely. Since rifampicin induces the enzyme cytochrome P450, vitamin K should be given to the mother in the same way it is given to mothers receiving enzyme-inducing antiepileptic drugs. After delivery the neonate should be given prophylactic isoniazid treatment if the mother is sputum positive and vaccinated as soon as possible. Breastfeeding is not contraindicated since very little of the drugs are excreted in breast milk. However, if the mother has newly diagnosed, untreated, active TB she should be separated from her infant regardless of mode of infant feeding because of aerosol spread. In women co-infected with HIV, the timing of ART initiation and regimen needs to take into account potential maternal and fetal toxicities when concomitantly treating TB. Latent TB may be reactivated by HIV and although there is some debate whether latent TB should be treated in pregnancy or deferred until post-partum, in the presence of HIV, isoniazid preventative therapy is recommended in pregnancy despite the risk of hepatotoxicity. UKOSS (UK Obstetric Surveillance System) recently carried out a national descriptive study reporting a minimum incidence estimate of 4.2 per 100 000 maternities in the UK. The study confirmed that the disease appeared to be limited in the UK to ethnic minority women, most commonly recent immigrants. Extrapulmonary disease (at sites such as lymph nodes, bone, liver, spleen, bone marrow, caecum, nervous system and eye) was as common as pulmonary disease in pregnancy with a greater delay in diagnosis. There was one case fatality. Two additional deaths were identified in the most recent CEMACH report; of these, two were from tuberculous meningitis and one in a woman with HIV. Globally, TB incident cases have risen to 9.4 million in 2008. TB is one of the leading causes of non-obstetric maternal mortality with an estimated one-third of deaths occurring in women of child-bearing age.
A summary of RCOG Green top guideline 13 Chickenpox in pregnancy Significant exposure to a non-immune pregnant woman: VZIG as soon as possible, up to 10 days after contact. May require a second dose of VZIG after 3 weeks if further exposure. Clinical varicella after 20 weeks gestation: oral acyclovir (800 mg five times a day for 7 days) if within 24 hours of the onset of the rash. Refer immediately if: chest symptoms, neurological symptoms, haemorrhagic rash or bleeding, a dense rash þ/ mucosal lesions. Consider hospital (multidisciplinary) assessment if: significant immunosuppression, taking corticosteroids, smokers, chronic lung disease, or are in the latter half of pregnancy Delivery during a viraemic period: maternal risks of bleeding, thrombocytopenia, disseminated intravascular coagulation and hepatitis; fetal risk of varicella transmission with significant morbidity and mortality. Aim to avoid delivery and provide supportive treatment and intravenous acyclovir - however, delivery may be required in women to facilitate assisted ventilation in cases complicated by respiratory failure. Anaesthesia: general anaesthesia may exacerbate varicella pneumonia; spinal anaesthesia has a theoretical risk of transmitting the virus from skins lesions to CNS. Therefore epidural anaesthesia may be safer because dura is not penetrated. A site free of cutaneous lesions should be chosen for needle placement. Table 5
Tuberculosis (TB) Mycobacterium tuberculosis characteristically causes caseating granulomas with the lungs as the primary site. The patient is often asymptomatic but typically can present with a cough, haemoptysis, weight loss and night sweats. The diagnosis is confirmed with sputum examination for acid-fast bacilli (ZiehleNeelsen stain). Culture of the organism takes about 6 weeks. If there is no sputum, washings from bronchoscopy must be obtained. The Mantoux test (0.1 ml of 10 tuberculin units of purified protein derivative of MBTB) is not affected by pregnancy. Newer diagnostic blood tests include interferon gamma release assays such as the enzyme-linked immunospot assays (ELISPOT) and QuantiFERON e TB. These blood tests can distinguish latent TB from BCG. They have greater specificity for diagnosing latent rather than active TB. Although pregnancy and TB appear to have little effect on each other, treatment should not be delayed. Congenital TB with infection via the umbilical vein or amniotic fluid is rare. One prospective study found that there were no significant differences in pregnancy complications compared with matched healthy controls except if women started TB treatment late in pregnancy with associated higher neonatal mortality and extreme prematurity. The WHO recommends that the treatment of TB in pregnant women should be the same as that in nonpregnant women, except that streptomycin should be avoided because of fetal ototoxicity. The advice of a respiratory physician must be sought and pregnant mothers with TB should be treated
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Aspiration pneumonia This complication of gastric regurgitation most commonly occurs during induction for general anaesthesia in late pregnancy or in the event of an excessively high regional block. Increased intraabdominal pressure, delayed gastric emptying and reduced gastro-oesophageal sphincter tone contribute to the risk and in consequence feeding in labour was discouraged in the past. However, a recent trial (RCT) suggested that despite the rising incidence of obesity in the UK, a light diet in labour did not confer an increased risk of aspiration pneumonia. Ranitidine, an H2 antagonist, which reduces gastric acid secretion and an antacid to neutralize the gastric acid are routinely prescribed for women in labour with risk factors for caesarean section or before an elective procedure.
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The main maternal morbidity in CF pregnancies includes: poor maternal weight gain e even those without pancreatic insufficiency are often underweight at the onset of pregnancy and have difficulty gaining weight during pregnancy; deterioration in lung function with worsening dyspnoea, exercise tolerance and oxygen saturation e although there is usually loss of lung function during pregnancy, this is regained following delivery; pulmonary infective exacerbations; congestive cardiac failure.
Practice points C
C
C
C
C
Pneumonia in pregnancy is often more virulent therefore treat aggressively All non-immune pregnant women exposed to varicella should be given zoster immunoglobulin (ZIG) as soon as possible Clinical varicella should be treated with acyclovir if within 24 hours of the onset of the rash and after 20 weeks gestation H1 N1 influenza should be treated as in the non-pregnant with oseltamivir Risk of TB should be assessed at booking especially in immigrant women
Management Fetal: pre-pregnancy genetic counselling should include a risk estimate of a child born with CF of 2e2.5% if the carrier status of the father is unknown (based on UK carrier status of 1 in 25) and 50% if the father is heterozygous for the gene. During pregnancy, fetal surveillance to detect early signs of growth restriction is essential.
Cystic fibrosis Maternal: women with CF benefit from a pre-pregnancy assessment. Women with mild disease may be reassured that pregnancy is safe. For more severe cases, liaisons between a CF centre and an obstetrician with a special interest in CF can be planned ahead of the pregnancy. The presence of pulmonary hypertension, cor pulmonale or FEV1 <30e40% are contraindications to pregnancy. Since Burkholderia cepacia may be associated with rapid deterioration in lung function, recent acquisition or declining lung function in the presence of this organism may also be a contraindication to pregnancy. Screening for diabetes and baseline lung function tests as well as dietary supplementation, enzyme supplements, chest physiotherapy are important. Infective chest exacerbations should be treated aggressively with antibiotic therapy. There is no contraindication to vaginal delivery but a prolonged second stage should be avoided because of the risk of pneumothoraces. General anaesthesia should be avoided. There is no contra-indication to breastfeeding but women may need to continue nutritional supplements post-natally.
Cystic fibrosis (CF) is an autosomal-recessive disorder affecting the body’s exocrine glands, including the pancreas, sweat glands, and lungs. It has a carrier frequency of 1 in 25 in Caucasians. A gene deletion in 70% causes a defect in the CF transmembrane conductance regulator protein resulting in impaired movement of water and electrolytes across epithelial surfaces. Improvements in treatment have allowed survival to adulthood and pregnancy. The clinical entity varies, depending on severity and presence of infections. Some milder cases are not diagnosed until adulthood. CF is characterized by the production of very thick and sticky mucus. About 90% of cases involve the lungs with recurrent or persistent infections, development of bronchiectasis and respiratory failure. The ducts leading from the pancreas become obstructed causing pancreatic insufficiency, diabetes and malnutrition. Almost always, a productive cough is present, and patients often appear barrel-chested. Recurrent respiratory, gastrointestinal, and nutritional problems result in frequent hospital admissions. Effect of CF on pregnancy Malnutrition þ/or thickened cervical mucus may impair female fertility. Men are usually sterile. Most series of pregnancies in women with CF have shown that with careful planning and monitoring by a dedicated team, pregnancy outcomes are favourable. Commonly reported adverse events are fetal growth restriction and prematurity which includes iatrogenic early delivery in the unwell. Women with CF are at an increased risk of developing gestational diabetes. In a recent series of 20 pregnancies in women with CF, adverse fetal outcomes were significantly higher in women with an FEV1 <60% and/or pre-pregnancy BMI <20. Gestational diabetes occurred in 43%.
Bronchiectasis Bronchiectasis is a sequelae of cystic fibrosis, pneumonias, and rarer causes such as Kartagener’s syndrome. It is characterized by irreversibly dilated damaged bronchi predisposing to persistently infected mucus and bacterial infections. A cough productive of large amounts of sputum is characteristic. The condition is uncommon in child-bearing years but is associated with fetal growth restriction in pregnancy. Women should be managed jointly with respiratory physicians. Their condition can deteriorate in pregnancy. Hence close attention to postural drainage and physiotherapy is important as is regular sputum culture and intermittent or continuous antibiotic therapy for chest infections þ/ bronchodilators. As in CF, the presence of pulmonary hypertension and/or hypoxaemia adversely affects prognosis.
Effect of pregnancy on CF Pregnancy does not appear to influence the long-term course of disease and is not associated with a shortened survival or more rapid decline in lung function. Maternal mortality is no greater than non-pregnant age-matched women with CF except in the presence of pulmonary hypertension, cyanosis, arterial hypoxaemia (oxygen saturation <90%), moderate/severe lung disease (FEV1 <60% predicted) and/or malnutrition when both maternal and fetal outcome are poor. The last CEMACH reported one death from CF in a woman with severe disease.
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Pulmonary arterial hypertension Although mortality rate remains high (>50%), advances in the management of this condition have meant that successful pregnancies are reported in those with well controlled PAH and in those long-term responders to calcium channel blockers.
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disease remains unknown. The disease most commonly involves granuloma formation in the lungs. Other commonly involved organ systems include the lymph nodes (especially the intrathoracic nodes); the skin; the eyes; the liver; the heart; and the nervous, musculoskeletal, renal, and endocrine systems. The course of sarcoidosis is variable, ranging from self-limited acute disease to a chronic debilitating disease that may result in death. Spontaneous remissions occur in nearly two thirds of patients, but 10e30% of patients have a more chronic or progressive course. Because sarcoidosis can involve any organ system, the clinical presentation is often variable. Many patients are asymptomatic but there may be chest symptoms. Other features include erythema nodosum, anterior uveitis, hypercalcaemia, arthropathy, fever or CNS symptoms.
However, case series are small and the general recommendation is to avoid pregnancy in the presence of PAH.
Cystic fibrosis lung transplant recipients Although the physiological changes of pregnancy are generally well tolerated by lung þ/ heart transplant(s) recipients, the risk of allograft rejection during and after pregnancy is significant. These patients must be counselled pre-pregnancy of the impact of pregnancy on survival, citing a 50% 5-year mortality rate. An adequate level of immunosuppression must be maintained in pregnancy. A multidisciplinary team, involving maternofetal medicine, respiratory and transplant medicine specialists, anaesthetists, neonatologists, geneticists, and social service, is crucial to the care of these patients. The management plan should be individualized according to the status of the mother, the fetus, and the allograft. Of a series of 10 pregnancies in 10 women with CF lung transplant recipients, five with a long stable interval of >3 years between transplant and the pregnancy had favourable outcomes; the remaining five had preterm deliveries. All 10 sadly showed progressive decline in lung function and all died of chronic rejection within 38 months of delivery.
Effect of pregnancy on sarcoidosis: sarcoidosis either improves or remains the same in pregnancy. There is a tendency to relapse in the puerperium. This is not a contraindication to pregnancy except in severely affected cases. Factors indicating a poor prognosis include parenchymal lesions on chest radiograph, advanced radiographic staging, advanced maternal age, low inflammatory activity, requirement for drugs other than steroids, and presence of extrapulmonary sarcoidosis.
Practice points on cystic fibrosis C C
C C C
Effect of sarcoidosis on pregnancy: sarcoidosis does not adversely affect pregnancy and is not transmitted to the fetus. There is one report of sarcoid granulomata found in the placenta of one patient.
Joint care with a CF centre Specialist dietary advice and nutritional supplements should be sought ideally pre-pregnancy, fat soluble vitamins should be continued in pregnancy Screen for gestational diabetes Infective exacerbations should be treated aggressively Avoid prolonged pushing in second stage of labour
Management: ideally, patients require evaluation before pregnancy to establish chronicity, baseline pulmonary function, inflammatory activity, staging, and response to treatment. Systemic steroids should be continued in pregnancy. Angiotensin converting enzyme levels, used as a marker of disease activity, are unreliable in pregnancy. Women should be advised to avoid vitamin D because of the risk of hypercalcaemia. Intravenous hydrocortisone should be administered in labour in women taking >7.5 mg daily of prednisolone.
Restrictive & fibrotic lung diseases Restrictive ventilatory defects are characterized by a reduction in lung volumes and an increase in the ratio of FEV1 to forced vital capacity (FVC) which occur when lung expansion is limited. This may be because of alterations in the lung parenchyma or abnormalities in the pleura, chest wall, or neuromuscular apparatus. The majority of pulmonary diseases do not alter fertility. A large reserve in respiratory function allows both fetus and mother to survive without compromise in most cases. FVC of >1 l or 50% of predicted FVC has been suggested as a cut off for successful pregnancies and although more severe cases can negotiate pregnancy, patients with severe restrictive lung disease should be advised against it and to consider a therapeutic termination. In addition, the associated polycythaemia confers an added thrombotic risk. Women with an associated kyphoscoliosis are often delivered preterm because of deterioration in lung function. Mode of delivery tends to be caesarean section because of abnormal fetal presentation due to associated bony pelvic abnormalities. Each case should be assessed individually.
Wegener’s granulomatosis This is a rare form of systemic vasculitis in which necrotizing granulomatous lesions affect the upper respiratory tract, lungs and kidneys. Without treatment the condition has a poor prognosis. Remission may be achieved with prednisolone and cyclophosphamide. Conclusions from 43 published cases suggest 65% of Wegener’s will flare during pregnancy and post-partum but this risk is halved when the disease is in remission at conception. It is impossible to predict flares in pregnancy. Antineutrophil cytoplasmic antibody (ANCA) titres are markers of disease activity. Despite the teratogenic risk, the pregnancies in which flares were treated with cyclophosphamide had better outcomes and there are good data to support the safe use of cyclophosphamide beyond the first trimester of pregnancy. It is associated with a 7% rate of fetal growth restriction and transient cytopenias after birth.
Conclusion
Sarcoidosis Sarcoidosis is characterized by non-caseating epithelioid granulomas that may affect any organ system. The aetiology of the
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Breathlessness in the absence of an underlying pathology is common in pregnancy especially in the 2nd and 3rd trimesters. The use of chest X-rays when underlying disease is suspected
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Byrne BMP, Crowley PA, Carrington D. Chicken pox in pregnancy. Green top guideline No 13. RCOG, 2007. Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009; 374: 451e8. Knight M, Kurinczuk JJ, Nelson-Piercy C, Spark P, Brocklehurst P on behalf of UKOSS. Tuberculosis in pregnancy in the UK. BJOG 2009; 116: 584e8. Mnyani CN, McIntyre JA. Tuberculosis in pregnancy. BJOG 2011; 118: 226e31. Murphy VE, Namazy JA, Powell H, et al. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG 2011; 118: 1314e23. Nelson-Piercy C. Respiratory disease. In: Nelson-Piercy C, ed. Handbook of obstetric medicine. 4th edn. London: Informa Healthcare, 2010. Schatz M, Dombrowski MP. Clinical practice. Asthma in pregnancy. N Engl J Med 2009; 360: 1862e9. Soh MH, Hart HH, Bass E, Wilkinson L. Pregnancy complicating Wegener’s granulomatosis. Obstet Med 2009; 2: 77e80. Wu DW, Wilt J, Restaino S. Pregnancy after thoracic organ transplantation. Semin Perinatol 2007; 31: 354e62.
should not be avoided in pregnancy and most drugs can be used safely in pregnancy. It is important that women with a chronic respiratory disease should receive pre-pregnancy counselling and education regarding the risks of pregnancy and the importance of continuing medications. It also provides an opportunity to optimize their condition and so reduce adverse pregnancy outcomes. Women should be managed in a multidisciplinary setting with regular review by chest physicians and access to chest physiotherapy if necessary. Liaison with obstetric anaesthetists in the antenatal period will optimize care at delivery with regard to pain relief and reduce anaesthetic risks. Respiratory diseases complicated by pulmonary hypertension and cor pulmonale have a poor prognosis in pregnancy. A
FURTHER READING British Thoracic Society: guidelines for the management of community acquired pneumonia. Thorax 2009; 64(suppl. III). British Thoracic Society: Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma 2008, revised Jan 2012.
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