Respiratory disease in pregnancy

REVIEW

Respiratory diseasein pregnancySophia Stone

Catherine Nelson-Piercy

AbstractBreathlessness in the absence of an underlying pathology is common in

pregnancy, but serious causes should be excluded depending on symp-

toms. The use of chest X-rays should not be avoided 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 preg-

nancy. It is important to educate women to continue inhaled corticoste-

roid preventer therapy to reduce the risk of attacks. Respiratory

infections are associated with a higher morbidity in pregnancy and should

be treated aggressively.

Women with a chronic respiratory disease should receive pre-preg-

nancy counselling and education, and during pregnancy managed in

a multidisciplinary setting with the respiratory team. Most chronic pulmo-

nary diseases do not alter fertility, and in the majority of cases large

reserves in respiratory function allow a good pregnancy outcome for

fetus and mother. In contrast, 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

Differential diagnoses of breathlessness in pregnancy

Diagnosis Investigations

Physiological Diagnosis by exclusion and typical history

Anaemia Full blood count

Asthma PEFR e response to bronchodilators

Introduction

Severe lung disease leading to respiratory failure is uncommon in

women of child bearing age. However respiratory symptoms are

extremely common in pregnancy both as a result of the effect of

physiological adaptation to pregnancy and partly because of

reduced functional capacity and mobility from diaphragmatic

elevation by the gravid uterus in late gestation. Oxygen

consumption is increased by 20% from early pregnancy, minute

ventilation by 40e50% secondary to tidal volume increase, and

maternal hyperventilation results in a mild fully compensated

respiratory alkalosis (increased arterial pO2 and decreased arte-

rial pCO2, compensatory fall in serum bicarbonate to 18e22

mmol/l; arterial pH 7.44).

Sophia Stone MD MRCOG is a Consultant Obstetrics & Gynaecology at

St Richard’s Hospital, Spitalfield Lane, Chichester, West Sussex

PO19 6SE, UK.

Catherine Nelson-Piercy MA FRCP FRCOG is a Consultant Obstetric

Physician at Guy’s & St Thomas’ Hospitals Trust, London Women’s

Health Services Directorate, 10th Floor e North Wing, St Thomas’

Hospital, Lambeth Palace Road, London SE1 7EH, UK.

OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 14

Respiratory symptoms and signs

The commonest respiratory symptom in pregnancy is breath-

lessness. However this can often be attributed to an increased

awareness of the physiological hyperventilation of pregnancy.

Women most often present in the third trimester but may become

symptomatic at any gestation. Classically physiological breath-

lessness of pregnancy is present at rest or while talking and

paradoxically improves with activity. Table 1 summarises 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 respi-

ratory 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 pulmo-

nary infarction and bronchial breathing þ/� coarse crackles

would suggest consolidation. Absent breath sounds occur with

pneumothorax or extensive collapse.

Investigations

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 proges-

terone-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 ionising radiation

Pulmonary

embolus

Arterial blood gases (YPO2 and YPCO2)/ VQ

scan

Mitral stenosis,

cardiomyopathy

ECG, echocardiogram, chest X-ray

Pneumonia Chest X-ray, sputum culture, serology

Pneumothorax Chest X-ray

Hyperventilation/

anxiety

Arterial blood gases (YPCO2 but not YPO2)

Table 1

� 2009 Published by Elsevier Ltd.

REVIEW

from a chest X-ray is <0.01mGy (<1mRad) and abdominal

shielding will reduce fetal exposure further. The recommenda-

tion in the UK for maximum occupational exposure for a preg-

nant woman is 1mSv (1mGy or 100mrad), and levels below this

have not been shown to cause fetal death or malformation, and

the risk of childhood cancer is very small. Sputum should be sent

for microbiological examination.

Asthma

Asthma is a common chronic inflammatory condition of the lung

airways characterized by episodes of reversible bronchocon-

striction as a result of various stimuli. It affects up to 7% of

women of childbearing age.

The diagnosis of asthma is a clinical one based on the pres-

ence 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. Recognised triggers include pollen, dust,

animals, infections etc. Confirmation hinges on demonstration of

airflow obstruction varying over short periods of time. The most

recent British Thoracic Society guidelines for the management of

asthma (2008) 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.

Effect of asthma on pregnancy

There have been reports of an association between uncontrolled

asthma and a number of pregnancy complications, including

hyperemesis, vaginal bleeding, hypertension, pre-eclampsia,

complicated labour, congenital malformations, preterm birth,

fetal growth restriction (FGR), low birthweight, and neonatal

hypoxia have been reported, but reassuringly the majority of

pregnancies in women with controlled asthma are not adversely

affected.

Features that increase the probability of asthma

More than one of the following symptoms:

C Wheeze

C Breathlessness

C Chest tightness

C 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

C History of atopic disorder

C Family history of asthma and/or atopic disorder

C Widespread wheeze heard on auscultation of the chest

C Otherwise unexplained low FEV1 or PEF (historical or serial

readings)

C Otherwise unexplained peripheral blood eosinophilia

Table 2


Of greater concern is that many women still stop their medi-

cation at the start of the pregnancy because of (unfounded)

worries regarding the safety profile of these drugs for the fetus,

which can precipitate a deterioration in maternal health.

Effect of pregnancy on asthma

A systematic review has shown that baseline asthma severity

does determine what happens to the course of asthma in preg-

nancy. 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,

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. Non-atopic

patients with asthma tend to have more severe asthma in preg-

nancy 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 hospitalisation. Between 2003 and 2005

there were 5 indirect maternal deaths relating to asthma reported

in the UK, 4 were sudden and unpreventable and a further

woman with asthma and morbid obesity deteriorated throughout

pregnancy and died of respiratory failure soon after a caesarean

section under spinal anaesthesia.

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

toward its pre-pregnancy course within 3 months of delivery.

Management

Pre-pregnancy and antenatal care Pregnancy is an ideal

opportunity to optimise therapy although, ideally this should

occur pre-pregnancy. Women should be advised regarding the

importance and safety of continuing inhalers to maintain good

asthma control. Inhaler techniques should be checked. Pregnant

women must be monitored closely so that any change in course

can be matched by an appropriate change in therapy. 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 chlor-

pheniramine & intranasal beclomethasone, but cetirazine and

loratidine may also be safely used.

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 respi-

ratory team and antenatal anaesthetic review.

Drug therapy in pregnancy is essentially the same as for the

non-pregnant population and should follow the British Thoracic

Society guidelines on the management of asthma. The step-wise

approach illustrated in Figure 1 is recommended. Table 3

summarises guidance of asthma drug use in pregnancy.

Acute asthma attacks should be managed as for the non-

pregnant patient with a low threshold for admission (Table 4).

Multidisciplinary care should include ITU staff early in severe


Summary of step-wise management of asthma

Adapted from the British Thoracic Society Guidelines

Step 1: Mild intermittent asthma

• Inhaled short-acting β2 agonist as required

Step 2: Regular preventer therapy

• Add inhaled steroid 200–800 μg/d appropriate to disease severity

• (400μg/d is appropriate starting dose)

Step 3: Initial add-on therapy

1. add inhaled long-acting β2 agonist (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 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 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

Figure 1 Summary of step-wise management of asthma adapted from the British Thoracic Society Guidelines. 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.

REVIEW

cases. Oxygen is given to maintain saturation 94e98%, and

intravenous rehydration when drinking is impossible.

Continuous fetal monitoring should be instigated. The woman

should be managed in a left lateral position to avoid aorta-

caval compression. A PEF rate of 33e50 per cent best/ pre-

dicted 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.

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 prednis-

olone for >2 weeks prior to the onset of labour require parenteral

hydrocortisone 100 mg 6e8 hourly in labour. Women with

asthma may safely use all forms of pain relief in labour. Ergo-

metrine 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.

If a caesarean section is required, regional anaesthesia is

preferable to general anaesthesia in women with asthma.

Post-natal care None of the medications for asthma are contra-

indicated in breastfeeding. 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.


A summary of the BTS guidelines on drug use inpregnancy

C Use short acting b2 agonists as normal during pregnancy (B).

C Use long acting b2 agonists (LABA) as normal during pregnancy (C).

C Use inhaled steroids as normal during pregnancy (B).

C Use oral and intravenous theophyllines as normal during preg-

nancy (C).

C Check blood levels of theophylline in acute severe asthma and in

those critically dependent on therapeutic theophylline levels (D).

C 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).

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).

C Use chromones as normal during pregnancy (C).

Table 3

Practice points (BTS recommendations)

C Counsel women with asthma to continue their medication in

pregnancy

Acute asthmaC Give drug therapy including corticosteroids for acute asthma

as for the non-pregnant patient.

C For women with poorly controlled asthma during pregnancy

there should be close liaison between the respiratory physi-

cian and obstetrician

C Acute severe asthma in pregnancy is an emergency and should

be treated vigorously in hospital. Deliver oxygen to maintain

saturation 94e98%, re-hydrate and instigate continuous fetal

monitoring

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 pred-

nisolone 7.5 mg per day for more than two weeks prior to

delivery should receive parenteral hydrocortisone 100 mg 6e8

hourly during labour

REVIEW

Respiratory tract infections

Pneumonia occurs in the pregnant population with a frequency

equal to that in the general population.

C Use prostaglandin F2a with extreme caution in women with

asthma because of the risk of inducing bronchoconstriction
Effects of pregnancy on pneumonia
PuerperiumC Encourage women with asthma to breast feed

C Use asthma medications as normal during lactation

Pneumonia in pregnancy is often more virulent and mortality is

higher. There is an increased risk of serious maternal complica-

tions including respiratory failure. The spectrum of pathogens is

similar to that in the non-pregnant population and the manage-

ment does not differ. Co-existing maternal disease including

asthma and anaemia and immunosuppressive therapy increase

the risk of contracting pneumonia.

Effect of pneumonia on pregnancy

Severe pneumonia may precipitate preterm delivery and result in

low birthweight infants.

Treatment of acute asthma (British Thoracic SocietyGuidelines)

Oxygen Give high flow oxygen

b2 agonist

bronchodilators

High dose inhaled b2 agonists by oxygen-

driven nebuliser

Ipratropium

bromide

Add nebulised ipratropium bromide (0.5 mg

4e6 hrly) if poor response to bronchodilators

or severe acute asthma

Steroid therapy Systemic steroids (40e50 mg daily) in all

cases for at least 5 days or until recovery

Other therapies Consider single dose i.v. Magnesium sulphate

(1.2e2 g infusion over 20 mins)

Routine antibiotics are not recommended

Table 4


Bacterial pneumonia

Community acquired pneumonia is most commonly caused by

streptococcus pneumoniae, haemophilus influenzae and myco-

plasma pneumoniae.

Clinical features Women may present with cough, fever, rigors,

breathlessness and pleuritic pain. Signs include fever, purulent

sputum, coarse crackles on auscultation and signs of consolida-

tion. Diagnosis may be confirmed with a chest X-ray. Blood and

sputum cultures should be taken. Bacterial pneumonia is asso-

ciated 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 diag-

nosed on serological assays with complement fixation tests.

Management Supportive measures include oxygen administra-

tion and rehydration especially in the presence of fever. Chest

physiotherapy will help clear secretions and aid oxygenation.

Oral antiobiotic therapy should be commenced for community

acquired bacterial infections. Betalactam and macrolide antibi-

otics are safe in pregnancy. Oral amoxicillin (500 mg-1 g t.d.s.)


A Summary of RCOG Green top guideline 13

Chickenpox in pregnancy

Significant exposure to a non-immune pregnant woman: VZIG as

REVIEW

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.

soon as possible, up to 10 days after contact. May require a second

dose of VZIG after 3 weeks if further exposure.
Viral pneumonia
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 e however, delivery

may be required in women to facilitate assisted ventilation in cases

complicated by respiratory failure.

Anaesthesia: General anaesthesia may exacerbate varicella pneu-

monia; 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

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 hospitalisations among pregnant women

during influenza season and is not contraindicated in pregnancy.

Novel influenza A (H1N1) virus in pregnancy The most

frequently reported symptoms among nonpregnant patients with

swine fever have been fever, cough, and sore throat. The Center

for Disease Control and Prevention (USA) recently reported 20

cases of pregnant women (median age 26 years). Three were

hospitalised. All suffered symptoms of acute febrile respiratory

illness; one developed ARDS and died. They concluded 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.

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, sug-

gesting a case fatality rate of less than 1% but a rate five times

higher in pregnancy than in the nonpregnant adult. Table 5

summarises the RCOG management guidance.

Pneumocystis pneumonia (PCP) -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 co-trimoxazole (Sep-

trin) þ/� pentamidine, usually contra-indicated in pregnancy

because of theoretical risks of neonatal kernicterus or haemol-

ysis except in the presence of PCP. Women with HIV and a past

history of PCP or CD4þ cell count of <200 cells/ml considering

pregnancy, should receive prophylactic Septrin or nebulised

pentamidine.

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 (Ziehl-

Neelsen stain). Although pregnancy and TB have little effect on

each other, treatment should not be delayed and involves pro-

longed courses of multiple chemotherapeutic agents at the advice

of the respiratory physicians. 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 /or ethambutol.

Liver function should be monitored monthly. Streptomycin is

associated with eighth nerve damage and should be avoided.

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 breastmilk.

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 pregnany 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.


REVIEW

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 intra-

abdominal pressure, delayed gastric emptying and reduced gas-

tro-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 neutralise the gastric acid are

routinely prescribed for women in labour with risk factors for

caesarean section or before an elective procedure.

Cystic fibrosis

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 adult-

hood. CF is characterised by the production of very thick and

sticky mucus. About 90 percent 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

Practice points

C Pneumonia in pregnancy is often more virulent therefore treat

aggressively

C All non-immune pregnant women exposed to varicella should

be given zoster immunoglobulin (ZIG) as soon as possible

C Clinical varicella should be treated with acyclovir if within 24

hours of the onset of the rash and after 20 weeks gestation

C H1 N1 influenza should be treated as in the non-pregnant with

oseltamivir

C Risk of TB should be assessed at booking especially in

immigrant women


delivery in the unwell. Women with CF are at an increased risk of

developing gestational diabetes.

Effect of pregnancy on CF

Pregnancy does not affect disease severity or cause deterioration.

Maternal mortality is no greater than non-pregnant age-matched

women with CF except in the presence of pulmonary hyperten-

sion, 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.

Management

Fetal Pre-pregnancy genetic counselling should include a risk esti-

mate 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.

Maternal Women with CF benefit from a pre-pregnancy assess-

ment. Women with mild disease may be reassured that preg-

nancy 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% is a relative

contra-indication to pregnancy.

Screening for diabetes and baseline lung function tests as well

as dietary supplementation, enzyme supplements, chest physio-

therapy are important. Infective chest exacerbations should be

treated aggressively with antibiotic therapy.

There is no contraindication to vaginal delivery but a pro-

longed second stage should be avoided because of the risk of

pneumothoraces. General anaesthesia should be avoided. There

is no contra-indication to breast feeding but women may need to

continue nutritional supplements post-natally.

Bronchiectasis

Bronchiectasis is a sequel of cystic fibrosis, pneumonia, and rarer

causes such as Kartagener’s syndrome. It is characterised 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 deterio-

rate 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.

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 counseled pre-pregnancy of the impact of

pregnancy on survival, citing a 50% 5-year mortality rate. An


REVIEW

adequate level of immunosuppression must be maintained in

pregnancy. A multi-disciplinary team, involving maternofetal

medicine, respiratory and transplant medicine, anaesthetics,

neonatology, genetics, 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 trans-

plant recipients, 5 with a long stable interval of >3 years between

transplant and the pregnancy had favourable outcomes, the

remaining 5 had preterm deliveries. All 10 sadly showed

progressive decline in lung function and all died of chronic

rejection within 38 months of delivery.

Restrictive & fibrotic lung diseases

Restrictive ventilatory defects are characterised 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 appa-

ratus. The majority of pulmonary diseases do not alter fertility. A

large reserve in respiratory function allows fetus and mother to

survive without compromise in most cases. FVC of > 1 litre 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 consider a therapeutic termi-

nation. In addition the associated polycythaemia confers an

added thrombotic risk. Women with an associated kyphosco-

liosis 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.

Sarcoidosis

Sarcoidosis is characterized by non-caseating epithelioid granu-

lomas that may affect any organ system. The aetiology of the

disease remains unknown. The disease most commonly involves

granuloma formation in the lungs. Other commonly involved

organ systems include the lymph nodes (especially the intra-

thoracic nodes); skin; eyes; liver; heart; and nervous, musculo-

skeletal, 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

Practice points on cystic fibrosis

C Joint care with a CF centre

C Specialist dietary advice and nutritional supplements should

be sought ideally pre-pregnancy

C The risk of Gestational Diabetes is increased

C Infective exacerbations should be treated aggressively

C Avoid prolonged pushing in second stage of labour


are asymptomatic but there may be chest symptoms. Other

features include erythema nodosum, anterior uveitis, hyper-

calcaemia, arthropathy, fever or CNS symptoms.

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 extra pulmonary sarcoidosis.

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.

Management Ideally patients require evaluation before preg-

nancy 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.

Wegener’s granulomatosis

This is a rare form of systemic vasculitis in which necrotising

granulomatous lesions affect the upper respiratory tract, lungs

and kidneys. Without treatment the condition has a poor prog-

nosis. Remission may be achieved with prednisolone and

cyclophosphamide. Conclusions from 43 published cases suggest

65% of Wegener’s will flare during pregnancy & 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 but their reliability in pregnancy has not been evaluated.

Despite the teratogenic risk, the pregnancies in which flares were

treated with cyclophosphamide had better outcomes and there is

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

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

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 opti-

mise 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 physio-

therapy if necessary. Liaison with obstetric anaesthetists in the


REVIEW

antenatal period will optimise 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 2001; 56(Suppl. IV). 2004; 59: 364e366

(update).

British Thoracic Society, Scottish Intercollegiate Guidelines Network.

British guideline on the management of asthma. Thorax 2008;

63(Suppl. IV): iv1e121. 2009 (update).

Byrne BMP, Crowley PA, Carrington D. Chicken pox in pregnancy. Green

top guideline No 13. RCOG, 2007.


De Swiet M. Respiratory disease. In: de Swiet M, ed. Medical disorders in

obstetric practice. 4th edn. London: Blackwell Science Ltd, 2002: 1e28.

Fonseca V, Davis M, Wing R. Novel Influenza A (H1N1) virus infections in

three pregnant women in United States AprileMay 2009. MMWR 2009;

58: 497e500.

Knight M, Kurinczuk JJ, Nelson-Piercy C, Spark P, Brocklehurst P, UKOSS.

Tuberculosis in pregnancy in the UK. BJOG 2009; 116: 584e8.

Nelson-Piercy C. Respiratory disease. In: Nelson-Piercy C, ed. Handbook of

obstetric medicine. 3rd edn. London: Informa Healthcare, 2006: 65e90.

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.


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Respiratory disease in pregnancy