respiratory disease in pregnancy
TRANSCRIPT
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
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 15
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
� 2009 Published by Elsevier Ltd.
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
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 16
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.
� 2009 Published by Elsevier Ltd.
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 pneumoniaPuerperiumC 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
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 17
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.)
� 2009 Published by Elsevier Ltd.
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 pneumoniaClinical 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
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 18
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.
� 2009 Published by Elsevier Ltd.
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
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 19
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
� 2009 Published by Elsevier Ltd.
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
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 20:1 20
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
� 2009 Published by Elsevier Ltd.
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
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� 2009 Published by Elsevier Ltd.