Beruflich Dokumente
Kultur Dokumente
2012;14:167174
Review
MBBS BSc,
a,
* Catherine Nelson-Piercy
FRCP FRCOG
a
Guys and St Thomas NHS Foundation Trust, Maternity Services, St Thomas Hospital, 10th Floor, North Wing, Westminster Bridge Rd, London
SE1 7EH, UK
b
Guys and St Thomas NHS Foundation Trust, London, UK
*Correspondence: Matthew Cauldwell. Email: matthew.cauldwell@imperial.ac.uk
Key content
Please cite this paper as: Cauldwell M, Nelson-Piercy C. Maternal and fetal complications of systemic lupus erythematosus. The Obstetrician & Gynaecologist
2012;14:167174.
Introduction
Systemic lupus erythematosus (SLE) is an idiopathic
autoimmune condition which has multi-organ involvement.
Diagnosis is based on both clinical manifestations and
laboratory indices. The disease course can be sporadic and
unpredictable but is typically characterised by periods of
relapse and remission. This article discusses both the
maternal and fetal complications of SLE and management
of the disease during pregnancy.
Incidence
The literature quotes variable rates of SLE, which may be
due to improvements in diagnostic testing.1 The American
Rheumatism Association first devised a framework for SLE in
1971; this has had several subsequent revisions and the most
recent is outlined in Box 1.2 The disease affects women and
men in a ratio of 10:1. In the UK, population-based studies have
shown that the disease tends to affect Afro-Caribbean people
Pathophysiology
The exact cause of SLE remains unknown, but it has been
proposed that an environmental trigger such as ultraviolet
light or a viral infection; for example, the EpsteinBarr virus,4
combined with a genetic predisposition, forms the basis of
the disease process.5 There is a 25% concordance for SLE
among monozygotic twins.5
The disease is characterised by immune complex
deposition which causes inflammation in vascular beds.
There is polyclonal B-cell activation which is thought to
result in antinuclear antibody production. There is also an
associated impairment of T-cell regulation and deficiencies in
complement which leads to a failure to remove these immune
complexes.
167
Box 1. 1997 update on 1982 American College of Rheumatology classication criteria for systemic lupus
erythematosus2
Criterion
Denition
Malar rash
Discoid rash
Fixed erythema, at or raised, over the malar eminences, tending to spare the nasolabial folds
Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older
lesions
Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation
Oral or nasopharyngeal ulceration, usually painless, observed by physician
Non-erosive arthritis of two or more peripheral joints, with tenderness, swelling or effusion
Pleuritis: convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effusion, or
pericarditis: documented by electrocardiogram or rub or evidence of pericardial effusion
Persistent proteinuria >0.5 g per day or > 3 + if quantication not performed, or
cellular casts: may be red cell, haemoglobin, granular, tubular, or mixed
Seizures: in the absence of offending drugs or known metabolic derangements; e.g. uraemia, ketoacidosis, or electrolyte
imbalance, or
psychosis: in the absence of offending drugs or known metabolic derangements, e.g. uraemia, ketoacidosis, or electrolyte
imbalance
Haemolytic anaemia: with reticulocytosis, or
leucopenia: <4000/mm3 on 2 occasions, or
lymphopenia: <1500/mm3 on 2 occasions, or
thrombocytopenia: <100 000/mm3 in the absence of offending drugs
Anti-DNA: antibody to native DNA in abnormal titre, or
anti-Sm: presence of antibody to Sm nuclear antigen, or
positive nding of antiphospholipid antibodies on:
(i) abnormal serum level of IgG or IgM anticardiolipin antibodies
(ii) positive test result for lupus anticoagulant using a standard method, or
(iii) false-positive test result for 6 months conrmed by Treponema pallidum immobilisation or uorescent
treponemal antibody absorption test
Photosensitivity
Oral ulcers
Arthritis
Pleuritis or pericarditis
Renal disorder
Neurological disorder
Haematological disorder
Immunological disorder
Positive antinuclear
antibody
An abnormal titre of antinuclear antibody by immunouorescence or an equivalent assay at any point in time and in the
absence of drugs
Any combination of four or more of 11 criteria, well documented at any time during a womans history, makes it likely that she has SLE (specicity
and sensitivity are 95% and 75%, respectively).
Pre-pregnancy counselling
This should form the first part of management for women
with an established diagnosis of SLE, as conception in a
period of quiescence has been shown to reduce the likelihood
of a flare of their disease during pregnancy.6 Fertility is not
thought to be reduced in women with SLE7 unless there is
concurrent ovarian failure associated with the use of high
cumulative dosages of cyclophosphamide, particularly in
older women,8 or unless there is end-stage renal failure
(chronic kidney disease stage 5) associated with lupus
nephritis, which can cause amenorrhoea. Non-steroidal
anti-inflammatory drugs (NSAIDs) can cause infertility by
means of inhibition of cyclooxygenase, which controls
ovulation, known as luteinised unruptured follicle
syndrome.9 Women who have been investigated for
infertility without any obvious cause but who regularly take
NSAIDs should be advised to stop taking these medications
and use alternative analgesia, as fertility may resume.
During the pre-pregnancy consultation the woman should
be assessed for disease activity and the presence of any organ-
168
Complication/manifestation/investigation
Cardiac
Respiratory
Pulmonary brosis: may need to consider chest X-ray, CT, lung function tests if there is underlying restrictive respiratory
involvement
Renal
Urine dipstick and protein:creatinine ratio to screen for and to quantify any underlying proteinuria.
Document and quantify presence of haematuria, hypertension and/or renal impairment (lupus nephritis)
Renal function tests to assess pre-existing renal dysfunction
Haematology/
immunology
Thrombosis: assessment of risk and need for anticoagulation. Full blood count to determine any anaemia, neutropenia or
thrombocytopenia
Autoantibody prole: antiphospholipid (aPL), anticardiolipin (aCL), lupus anticoagulant (LA), anti-dsDNA and anti-Ro/antiLa antibodies, complement C3/C4 levels
CT = computed tomography
Obstetric management
Perhaps the most difficult discussions concern when to
advise women not to conceive or when to terminate a
pregnancy. Of great concern are women with SLE and
associated pulmonary arterial hypertension who wish to
conceive: maternal mortality rates have been quoted as being
as high as 40%, but recent data have shown that this rate is
~33%.13 The point prevalence of pulmonary arterial
hypertension in patients with lupus is 4.2%, with most cases
being defined as mild (systolic pulmonary arterial
pressure <40 mmHg).14 This was determined for a nonpregnant cohort of patients, but the mean age was 41 years,
highlighting the importance of selectively screening women for
underlying pulmonary arterial hypertension prior to
pregnancy. Women should also be advised not to conceive
during a period of active disease, particularly with lupus
nephritis, because of worse maternal and fetal outcomes.15 In
very general terms, women with SLE have two to four-fold
higher rates of complications compared with those without
the disease: this includes pre-eclampsia, preterm delivery and
fetal growth restriction, all of which are discussed in this
article.5,10,16
Termination of pregnancy or preterm delivery should be
considered in the presence of uncontrolled hypertension and/
or worsening renal function despite optimal pharmacological
therapy. This may be related to a flare of lupus nephritis
or severe early-onset pre-eclampsia, particularly if there is
associated APS. In active lupus nephritis with worsening
renal function, increasing proteinuria and hypertension,
it may be necessary to use such treatments as
cyclophosphamide and mycophenolate mofetil, which are
associated with congenital malformations if used in the first
trimester, in which case appropriate counselling should be
offered.
169
Pregnancy-related
Lupus activity
Anaemia
Physiological haemodilution
Iron deciency
Pre-eclampsia
Physiological increase of baseline proteinuria
related to pregnancy or withdrawal of ACE inhibitors
Mechanical arthralgia/effusion
Gestational
HELLP syndrome
Pre-eclampsia
Melasma
Facial blushing
Eclampsia
Proteinuria
Joint swelling/pain
Thrombocytopenia
Facial rash
Seizure
Inammatory synovitis
Immune thrombocytopenia
APS
Malar rash
Neuropsychiatric lupus
Cerebral vein thrombosis (APS)
ACE = angiotensin-converting enzyme; HELLP = haemolysis, elevated liver enzymes, low platelet count; APS = antiphospholipid syndrome
Risk of thromboembolism
Women should be individually assessed for risk of
thromboembolism. Ideally, this should be done at the earliest
opportunity: it can be done as part of pre-pregnancy assessment
and counselling. Risk of thromboembolism and the possible
need for thromboprophylaxis should be reassessed in such
circumstances as admission to hospital for a lupus flare.17
Particular care is needed in women with concurrent APS, who
have a higher risk of a thromboembolic event. Women who have
had a previous venous thromboembolism (some of whom may
be on long-term warfarin) should receive thromboprophylaxis
with low molecular weight heparin throughout pregnancy and
for 6 weeks postpartum or until converted back to warfarin.
170
Fetal management
SLE also confers greater risks to the fetus and there needs to
be an awareness of the fetal problems that can develop. It is
generally associated with increased rates of miscarriage,10
although what must be taken into account is that many
women with SLE also have APS.23 However, it is generally
thought that women with SLE without APS have an increased
rate of miscarriage, possibly related to disease activity, and
Preterm delivery
This is more common in pregnancies complicated by SLE30
and is often compounded by obstetric intervention and a
tendency to deliver once the fetus is mature. Review of the
literature suggests that the most common indication for
delivery is pre-eclampsia, followed by fetal distress and fetal
growth restriction. Premature rupture of membranes is also
regarded as being more frequent in pregnancies complicated
by SLE; rates vary and are generally quoted as ~20%.31
Interestingly, this risk does not appear to be related to disease
status or serology, although women on steroid treatment
appear to have a greater risk.32
171
Mechanism of
action
When to stop or
to continue
Long-term follow-up
shows no signicant
neurodevelopmental
delay34
Continue during
pregnancy
Premature closure of
ductus arteriosus if
taken beyond
32 weeks
Ideally, discontinue
prior to
conception
Placental transfer
Effects on fetus
Betamethasone and
dexamethasone
cross placenta
readily.
Prednisolone and
hydrocortisone
cross less well
Yes
Corticosteroids
Anti-inammatory
and
immunosuppressive
Non-steroidal antiinammatory
drugs
Inhibit
cyclooxygenase
Azathioprine
No cases of congenital
abnormalities
Mycophenolate
mofetil (MMF)
Immunosuppressive
agentprevents
cell proliferation
and inhibits
lymphocyte
function
Antimetabolite.
Inhibits cellmediated immunity
Inhibitor of purine
synthesis
Contraindicated in
pregnancy. No data on
effects in breastfeeding
Avoid in pregnancy and in
breastfeeding
Cyclophosphamide
Alkylating agent
Teratogenic. Increased
rates of miscarriage
and congenital
abnormalities36
Ciclosporin
T-cell mediated
response prevents
formation of
interleukin-2
Hydroxychloroquine
Disrupts lysosome
presentation and
the processing of
antigens
Main problems
reported:
prematurity and low
birthweight38 but
this may relate to
underlying disease
No increase in
congenital
abnormalities39
Methotrexate
172
Do not stop
without
guidance from
rheumatology
staff. Safe to
continue
Stop prior to
conception
Stop (change to
azathioprine)
prior to
conception but
seek guidance
from
rheumatology
staff
Stop prior to
conception but
in a woman with
are consult
rheumatology
staff
Seek advice from
rheumatology/
nephrology staff
regarding usage
Continue
throughout
pregnancy, do
not withdraw
Postpartum care
This includes:
ongoing management and treatment of any underlying
pregnancy-induced hypertension
a risk assessment and prophylaxis regimen for thrombosis,
particularly in women with APS or who have a previous
history of thrombosis or nephrotic syndrome
advice regarding contraception and on avoiding estrogencontaining preparations, as these increase the risk of a flare
vigilance concerning the increased risk of lupus flare in the
postpartum period.
Conclusion
The management of SLE and pregnancy should be
undertaken in a multidisciplinary setting. Labelling all
pregnancies in women with SLE as high risk is not helpful
or appropriate as those with quiescent disease will, in many
cases, have uncomplicated pregnancies. For women who have
active disease in pregnancy, are at risk of neonatal lupus or
who have lupus nephritis or APS and therefore require closer
monitoring because of increased risks of maternal and fetal
adverse outcome, more intensive surveillance by an expert
team is important. The involvement of obstetricians and
physicians with experience of managing SLE in pregnancy
improves the outcome for the mother and fetus.
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