DOI: 10.1111/j.1744-4667.2012.00113.

2012;14:167174

Review

The Obstetrician & Gynaecologist

http://onlinetog.org

Maternal and fetal complications of systemic lupus

erythematosus
Matthew Cauldwell

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


Systemic lupus erythematosus (SLE) is an autoimmune condition

that has multi-organ involvement.
 It is approximately ten times more common in women than in
men and is often diagnosed during the childbearing years.
 SLE is known to increase the risk of spontaneous miscarriage; it
can also cause fetal growth restriction and increased rates of
sudden intrauterine death, pre-eclampsia and preterm delivery.
 Management of women with lupus nephritis can be difficult, as the
disease may mimic and overlap significantly with pre-eclampsia.
 Multidisciplinary management of pregnant women with SLE
ensures optimal surveillance of both mother and fetus.
Learning objectives


To understand how to manage pregnant women with SLE.

 To understand the importance of pre-pregnancy counselling for
women with SLE.

To understand the features and associated risk factors which

increase the chance of adverse pregnancy outcome in women with
SLE.
 To understand which therapies for SLE can be used safely in
pregnancy and while breastfeeding.
 To understand the role of the multidisciplinary team in the care of
women with SLE, particularly those with underlying organ
impairment.
Ethical issues



When should women with SLE be advised against pregnancy?

At what point should termination of pregnancy be considered if
there is deterioration in maternal health in early pregnancy?

Keywords antiphospholipid syndrome / drug therapy / fetal growth

restriction / perinatal complications / pre-conception counselling /

pre-eclampsia / thromboembolism

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

2012 Royal College of Obstetricians and Gynaecologists

most frequently, followed by Asian people.3 The mean age of

diagnosis also varies in the literature, but most women seem to
be diagnosed during the childbearing years.1 The prevalence of
SLE in women of childbearing years is around 1 in 500.

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.

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Maternal and fetal complications of SLE

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

system involvement (Box 2). The presence of anti-Ro/La and

antiphospholipid antibodies should also be determined.
These antibodies are associated with congenital heart block
and neonatal cutaneous lupus syndrome.5 Antiphospholipid
antibodies are present in about 30% of women with SLE and
are associated with arterial and venous thrombosis, recurrent
miscarriage, fetal growth restriction, fetal loss and preterm
delivery due to uteroplacental insufficiency; they require
specific management.
Pre-pregnancy counselling should also include a discussion
regarding medications (see Drug therapy in SLE).
Women should be counselled regarding the possible risks
associated with SLE in pregnancy. They can be reassured that
with quiescent disease, without associated antiphospholipid
syndrome (APS), hypertension or renal involvement the risks
of miscarriage/stillbirth and fetal growth restriction are not
significantly increased compared with background rates and
that adverse outcomes are more likely with the above
complications.10 The risk of miscarriage and stillbirth in
pregnancies complicated by lupus varies in the literature
from 635% and from 022%, respectively.11,12

2012 Royal College of Obstetricians and Gynaecologists

Cauldwell and Nelson-Piercy

Box 2. Investigations for assessment of disease activity in the pre-pregnancy consultation

Organ/system

Complication/manifestation/investigation

Cardiac

 Pulmonary hypertension, valvular heart disease, cardiomyopathy: assess with echocardiography

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.

2012 Royal College of Obstetricians and Gynaecologists

It is important to appreciate that not all pregnancies in women

with SLE need to be considered as high risk. Careful
identification and stratification should take place to allow
women to be managed on an individual basis. Women with
quiescent skin and/or joint disease who have no other underlying
organ impairment and who do not require multidrug therapy or
an incremental increase in their current drug dosage are very
different from those with a history of nephritis/hypertension or
concurrent APS.
Pregnant women with active SLE/lupus nephritis or anti-Ro/
La/antiphospholipid antibodies shouldbe consideredas a higher
risk group and managed in centres with appropriate experience.
Care should be carried out in a multidisciplinary setting where
obstetricians/midwives and physicians/haematologists work
closely together to optimise care. It is difficult to recommend
precisely how often these women should be reviewed, but those
with more active disease need closer monitoring and often
require hospital admission. For those individuals with stable
disease, 4-weekly reviews of disease activity and regular
assessment of fetal growth, blood pressure and proteinuria are
appropriate. For those at particular risk of fetal growth
restriction and/or pre-eclampsia because of active disease or
previous history, more frequent assessment is indicated.
For those women who are anti-Ro/La positive the fetal
heart rate should be monitored and recorded at each visit and
fetal echocardiography assessments made at 1820 and
~28 weeks of gestation.
Careful obstetric management involves an awareness of the
possibility of lupus flare and an understanding of how this
can overlap with normal pregnancy-related changes and with
pre-eclampsia. Pregnancy and SLE-related changes are
summarised in Box 3.

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Maternal and fetal complications of SLE

Box 3. Comparison of pregnancy and SLE-related changes

Features

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

Anaemia of chronic disease

Haemolytic anaemia
Nephritis

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.

Management of SLE flares

The risk of an SLE flare in pregnancy is increased with
active disease in the 36 months prior to conception, with the
majority of flares occurring in the second half of pregnancy.18
Most flares can be managed expectantly with medical
management and adjustments to drug therapy (see Drug
therapy in SLE). The blood pressure should be monitored
closely to detect pregnancy-induced hypertension or preeclampsia and the woman should be screened for proteinuria,
which should be quantified with either a urinary protein:
creatinine ratio (PCR) or 24-hour urine collection.

Distinguishing pre-eclampsia from lupus nephritis

This is, perhaps, the most challenging aspect of obstetric
management. The features of lupus nephritis include
hypertension and proteinuria with or without haematuria
and renal impairment. Lupus nephritis is caused by
autoantibodies which produce immune complexes: these are
deposited in the kidneys and they activate the complement
cascade, causing a generalised inflammatory response.19 The
presence of haematuria or red cell casts as well as a rise in anti-

170

dsDNA titres or a fall in complement levels help to distinguish

this from pre-eclampsia; in addition, lupus disease activity in
non-renal organ systems suggests that a lupus nephritis flare is
more likely. New-onset lupus nephritis without a previous
history of renal involvement is unusual but not impossible.
Despite these distinguishing features the only definitive and
reliable investigation that can be used to distinguish
pre-eclampsia from lupus nephritis is renal biopsy. This
is not generally undertaken during pregnancy because
complications such as bleeding are greatly increased. It may
be appropriate in the first or second trimester if it is felt that the
result is likely to alter management; for example, if there is
concern about underlying lupus nephritis, for which
appropriate treatment with immunosuppressive agents may
allow prolongation of the pregnancy. In cases of lupus nephritis
that fail to respond to increasing dosages of steroids and
azathioprine, and where there is a deterioration of renal
function and/or hypertension, other immunosuppressive
drugs may be considered, such as mycophenolate mofetil or
tacrolimus. Such management decisions should be undertaken
in consultation with nephrologists and rheumatologists, as
there are associated risks (see Drug therapy in SLE).20
Management of blood pressure in lupus nephritis should
follow the same algorithm as for treatment of pregnancyinduced hypertension or pre-eclampsia.21 The blood pressure
should ideally be kept below 140/90 mmHg.22

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

2012 Royal College of Obstetricians and Gynaecologists

Cauldwell and Nelson-Piercy

they should be appropriately counselled regarding this in the

pre-pregnancy period.

Scanning and Doppler ultrasound

There is no definitive guide stipulating the absolute timing of
fetal scans and the frequency between scans in pregnancies
complicated with SLE. It is important for the obstetrician to
be aware of the risks of congenital heart block, fetal growth
restriction and increased rates of preterm delivery and
pre-eclampsia.24 These must all be taken into account when
deciding whether increased fetal scanning is indicated.
Scanning at least every 4 weeks to screen for fetal growth
restriction in those women at risk is generally accepted and
fetal echocardiography referral should be arranged for those
with anti-Ro/La antibodies or if any cardiac abnormalities are
detected on ultrasound scan.
Doppler studies can be used to estimate placental function
and can be an aid to predicting outcomes such as pre-eclampsia
and fetal distress. A uterine artery Doppler should be first
carried out at 20 weeks and repeated 4 weeks later if any
abnormality is found. A raised pulsatility index or diastolic
notching are associated with increased risk for developing
pre-eclampsia, as they can indicate underlying placental
dysfunction. Nevertheless, not all women with an abnormal
uterine artery Doppler will develop complications, so it
is important not to treat abnormal Doppler in isolation.
Second trimester Doppler has been shown to predict late
pregnancy outcome in SLE and/or APS in some25,26 but not
all studies.27

Fetal growth restriction

Since this is common in the context of pregnancies
complicated by hypertension, APS and pre-eclampsia, it is
not surprising that pregnant women with SLE are also at risk
of fetal growth restriction. It may affect nearly one in four
pregnancies with maternal SLE and has been reported as
occurring in as many as 35%, particularly with concurrent
lupus nephritis.28

Congenital heart block

This is associated with maternal anti-Ro/La autoantibodies.
Antibodies cross the placenta and destroy the Purkinje
system. The usual presentation is a fixed fetal bradycardia of
6080 beats per minute on ultrasound scan. It occurs in
23% of fetuses of women with the anti-Ro/La antibody and
there is a recurrence rate of 16% in subsequent pregnancies.
It is associated with significant perinatal morbidity and
mortality, with about half of infants requiring pacing by the
first year of life. Congenital heart block develops between 18
28 weeks of gestation and fetal echocardiography should be
performed around this period to detect it. Hydrops fetalis can
occur in utero and is thought to be due to the degree of
endomyocardial fibrosis and associated myocarditis.

2012 Royal College of Obstetricians and Gynaecologists

Neonatal lupus rash

This forms part of the neonatal lupus erythematosus
spectrum, manifesting as annular inflammatory lesions,
which appear much like lesions of subacute cutaneous SLE.
The lesions are most commonly seen on the face and scalp
and appear typically after ultraviolet exposure in the first
2 weeks of life, but up to 36 months postpartum. The rash
generally appears spontaneously and can persist for up to
6 months postnatally until the neonate clears the maternal
antibodies. It is rare for neonatal cutaneous lupus and
congenital heart block to occur together in the same
individual.29 Skin biopsy shows histopathology and
immunofluoresence typical of that of cutaneous lupus.

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

Drug therapy in SLE

Box 4 lists the majority of the pharmacological agentsused in the
treatment of SLE, their mechanism of action, some of the
contraindications to use and safety in pregnancy and
breastfeeding. Drug therapy is an important consideration, as
it is often necessary to manage women with a combination of
different therapies. This is where the experience of clinicians who
treat pregnant women with SLE on a regular basis is invaluable.
Glucocorticoids, mainly in the form of prednisolone, are
frequently but not exclusively used as one of the first-line
treatments in pregnancy. The dosage used does not vary
greatly between pregnant and non-pregnant patients. The risk
of adverse effects of steroids on the fetus is thought to be low,
with little evidence for congenital malformations or neonatal
adrenal suppression. Prednisolone, methylprednisolone and
hydrocortisone are more efficiently metabolised by placental
enzymes than dexamethasone and betamethasone and
therefore cross the placenta in small amounts only. The
adverse effects of steroids on the mother, however, are more
numerous. These include weight gain, immunosuppression
(and therefore increased risk of infections), acne,
gastrointestinal irritation and, probably the most important
adverse effect in pregnancy, increased glucose intolerance.
Women on moderate to high dosages of steroids should
therefore be screened regularly for gestational diabetes.33

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Maternal and fetal complications of SLE

Box 4. Pharmacological agents used in the treatment of SLE

Drug

Mechanism of
action

Safety in pregnancy and

breastfeeding

When to stop or
to continue

Long-term follow-up
shows no signicant
neurodevelopmental
delay34

May breastfeed safely as

only small amounts
found in breast milk

Continue during
pregnancy

Premature closure of
ductus arteriosus if
taken beyond
32 weeks

Use with caution in rst

and second trimester.
Avoid after 32 weeks of
gestation.35,36 Safe postdelivery provided no renal
involvement
Safe in pregnancy and
breastfeeding, but use at
minimum effective
dose37

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

Crosses placenta but

fetal liver lacks
enzyme to convert
to active metabolite

No cases of congenital
abnormalities

Does not cross

placenta

Mycophenolate
mofetil (MMF)

Immunosuppressive
agentprevents
cell proliferation
and inhibits
lymphocyte
function
Antimetabolite.
Inhibits cellmediated immunity
Inhibitor of purine
synthesis

Neural tube defects if

used in early
pregnancy
Associated with
miscarriage and
congenital
malformations36

Contraindicated in
pregnancy. No data on
effects in breastfeeding
Avoid in pregnancy and in
breastfeeding

Cyclophosphamide

Alkylating agent

Crosses placenta and

is excreted in breast
milk

Teratogenic. Increased
rates of miscarriage
and congenital
abnormalities36

Excreted in breast milk, so

should be avoided
altogether in pregnancy

Ciclosporin

T-cell mediated
response prevents
formation of
interleukin-2

Crosses placenta and

found in fetal
blood

Treatment used extensively

in transplant patients and
autoimmune disease.
Breastfeeding probably
safe

Hydroxychloroquine

Disrupts lysosome
presentation and
the processing of
antigens

Does cross placenta

Main problems
reported:
prematurity and low
birthweight38 but
this may relate to
underlying disease
No increase in
congenital
abnormalities39

Methotrexate

Crosses placenta and

is excreted in breast
milk

Other immunosuppressant agents that are frequently

used and are generally considered safe during
pregnancy include azathioprine and hydroxychloroquine.
There is no indication to discontinue them during
pregnancy.
It is also worth noting that several drugs can cause a
lupus-like syndrome. The most common of these are

172

Withdrawal in nonpregnant patients may

precipitate are, so safe
to continue. May
breastfeed safely

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

hydralazine, procainamide, quinidine, isoniazid, diltiazem

and minocycline. The pathophysiology of drug-induced
lupus is not completely understood, but in the case of
hydralazine it is thought to be caused by the formation of
antinuclear antibodies to H1 and the H3H4 complex
(antihistone). However, these drugs do not cause disease
flare in women with established lupus.

2012 Royal College of Obstetricians and Gynaecologists

Cauldwell and Nelson-Piercy

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.

References
1 Uramoto KM, Michet CJ Jr, Thumboo J, Sunku J, OFallon WM, Gabriel
SE. Trends in incidence and mortality of systemic lupus erythematosus,
19501992. Arthritis Rheum 1999;42:4650 [http://dx.doi.org/
10.1002/1529-0131(199901)42:1<46::AID-ANR6>3.0.CO;2-2].
2 American College of Rheumatology. Update of the American College
of Rheumatology Revised Criteria for Classication of Systemic Lupus
Erythematosus. Atlanta: ACR; 1997.
3 Johnson AE, Gordon C, Palmer RG, Bacon PA. The prevalence and
incidence of systemic lupus erythematosus in Birmingham, England.
Relationship to ethnicity and country of birth. Arthritis Rheum
1995;38:5518 [http://dx.doi.org/10.1002/art.1780380415].
4 Ulff-Mller CJ, Nielsen NM, Rostgaard K, Hjalgrim H, Frisch M.
EpsteinBarr virus-associated infectious mononucleosis and risk of
systemic lupus erythematosus. Rheumatology (Oxf) 2010;49:170612
[http://dx.doi.org/10.1093/rheumatology/keq148].
5 Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med
2008;358:92939 [http://dx.doi.org/10.1056/NEJMra071297].
6 Mackillop LH, Germain SJ, Nelson-Piercy C. Systemic lupus
erythematosus. BMJ 2007;335:933 [http://dx.doi.org/10.1136/
bmj.39358.519491.AD].
7 Silva CAA, Leal MM, Leone C, Simone VP, Takuiti AD, Saito MI.
Gonadal function in adolescents and young women with juvenile
systemic lupus erythematosus. Lupus 2002;11:41925 [http://dx.doi.
org/10.1191/0961203302lu219oa].
8 Langevitz P, Klein L, Pras M, Many A. The effect of cyclophosphamide
pulses on fertility in patients with lupus nephritis. Am J Reprod
Immunol 1992;28:1578.

2012 Royal College of Obstetricians and Gynaecologists

9 Stone M, Khamashta MA, Nelson-Piercy C. Non-steroidal antiinammatory drugs and reversible female infertility: is there a link?
Drug Safety 2002;25:54551 [http://dx.doi.org/10.2165/00002018200225080-00001].
10 Clowse ME, Jamison M, Myers E, James AH. A national study of
complications of lupus in pregnancy. Am J Obstet Gynecol
2008;199:127e16.
11 Mintz G, Niz J, Gutierrez G, Garcia-Alonso A, Karchmer S. Prospective
study of pregnancy in systemic lupus erythematosus. Results of a
multidisciplinary approach. J Rheumatol 1986;13:7329.
12 Nossent HC, Swaak TJ. Systemic lupus erythematosus. VI. Analysis
of the interrelationship with pregnancy. J Rheumatol 1990;
17:7716.
13 Bdard E, Dimopoulos K, Gatzoulis MA. Has there been any progress
made on pregnancy outcomes among women with pulmonary artery
hypertension? Eur Heart J 2009;3:25665.
14 Prabu A, Patel K, Yee CS, Nightingale P, Situnayake RD, Thickett DR,
Townend JN, Gordon C. Prevalence and risk factors for pulmonary
arterial hypertension in patients with lupus. Rheumatology (Oxf)
2009;48:150611 [http://dx.doi.org/10.1093/rheumatology/kep203].
15 Gladman DD, Tandon A, Ibanez D, Urowitz MB. The effect of lupus
nephritis on pregnancy outcome and fetal and maternal
complications. J Rheumatol 2010;37:7548 [http://dx.doi.org/
10.3899/jrheum.090872].
16 Bramham K, Hunt BJ, Bewley S, Germain S, Calatayud I, Khamashta
MA, et al. Pregnancy outcomes in systemic lupus erythematosus with
and without previous nephritis. J Rheumatol 2011;38:190613
[http://dx.doi.org/10.3899/jrheum.100997].
17 Royal College of Obstetricians and Gynaecologists. Green Top
Guideline No. 37a. Reducing the Risk of Thrombosis and Embolism
During Pregnancy and the Puerperium. London: RCOG; 2009
[www.rcog.org.uk/les/rcog-corp/GTG37aReducingRiskThrombosis.pdf].
18 Clowse ME, Magder LS, Witter F, Petri M. The impact of increased
lupus activity on obstetric outcomes. Arthritis Rheum 2005;52:
51421 [http://dx.doi.org/10.1002/art.20864].
19 Grande JP. Mechanisms of progression of renal damage in lupus
nephritis: pathogenesis of renal scarring. Lupus 1998;7:60410
[http://dx.doi.org/10.1191/096120398678920721].
20 Kainz A, Harabacz I, Cowlrick IS, Gadgil SD, Hagiwara D. Review of the
course and outcome of 100 pregnancies in 84 women treated with
tacrolimus. Transplantation 2000;70:171821 [http://dx.doi.org/
10.1097/00007890-200012270-00010].
21 National Institute for Health and Clinical Excellence. Clinical Guideline
107. Hypertension in Pregnancy. The Management of Hypertensive
Disorders in Pregnancy. London: NICE; 2010 [www.nice.org.uk/
nicemedia/live/13098/50418/50418.pdf].
22 Davison JM, Nelson-Piercy C, Kehoe S, Baker P, editors . Renal Disease
in Pregnancy. London: RCOG Press; 2008.
23 Oshiro BT, Silver RM, Scott JR, Yu H, Branch DW. Antiphospholipid
antibodies and fetal death. Obstet Gynecol 1996;87:48993 [http://
dx.doi.org/10.1016/0029-7844(95)00498-X].
24 Clark CA, Spitzer KA, Nadler JN, Laskin CA. Preterm deliveries in
women with systemic lupus erythematosus. J Rheumatol
2003;30:212732.
25 Guzman E, Schulman H, Bracero L, Rochleson B, Farmakides G, Coury
A. Uterine-umbilical artery Doppler velocimetry in pregnant women
with systemic lupus erythematosus. J Ultrasound Med 1992;11:
27581.
26 Le Thi Huong D, Wechsler B, Vauthier-Brouzes D, Duhaut P, Costedoat
N, Andreu MR, et al. The second trimester Doppler ultrasound
examination is the best predictor of late pregnancy outcome in
systemic lupus erythematosus and/or the antiphospholipid syndrome.
Rheumatology (Oxf) 2006;45:3328 [http://dx.doi.org/10.1093/
rheumatology/kei159].
27 Bramham K, Hunt BJ, Germain S, Calatayud I, Khamashta M, Bewley S,
Nelson-Piercy C. Pregnancy outcome in different clinical phenotypes of

173

Maternal and fetal complications of SLE

28

29
30

31

32

33

34

antiphospholipid syndrome. Lupus 2010;19:5864 [http://dx.doi.org/

10.1177/0961203309347794].
Lima F, Buchanan NM, Khamashta MA. Obstetric outcomes in
systemic lupus erythematosus. Semin Arthritis Rheum 1995;25:
18492 [http://dx.doi.org/10.1016/S0049-0172(95)80030-1].
Lee LA. The clinical spectrum of neonatal lupus. Arch Dermatol Res
2009;301:10710 [http://dx.doi.org/10.1007/s00403-008-0896-4].
Yasmeen S, Wilkins EE, Field NT. Pregnancy outcomes in women with
systemic lupus erythematosus. J Matern Fetal Med 2001;10:916
[http://dx.doi.org/10.1080/jmf.10.2.91.96].
Clowse MEB, Jamison M, Myers E, James AH. A national study of the
complications of lupus in pregnancy. Am J Obstet Gynecol
2008;199:127.
Chakravarty E, Colon I, Langen E, Nix D, El-Saved Y, Genovese M,
Druzin M. Factors that predict prematurity and pre-eclampsia in
pregnancies that are complicated by systemic lupus erythematosus.
Am J Obstet Gynecol 2005;192:18971904 [http://dx.doi.org/
10.1016/j.ajog.2005.02.063].
Yildirim Y, Tinar S, Oner RS, Kaya B, Toz E. Gestational diabetes
mellitus in patients receiving long-term corticosteroid therapy during
pregnancy. J Perinat Med 2006;34:2804 [http://dx.doi.org/10.1515/
JPM.2006.053].
Vohr Br, Wright LL. Neurodevelopmental delay and functional
outcomes of extremely low birth weight infants in National Insititute

174

35

36

37

38

39

of Child Health and Human Development Research Network.

Pediatrics 2000;105:121626 [http://dx.doi.org/10.1542/
peds.105.6.1216].
Li DK, Liu L, Odouli R. Exposure to non steroidal anti-inammatory
drugs during pregnancy and the risk of miscarriage: population based
cohort study. Br Med J 2003;237:36873 [http://dx.doi.org/10.1136/
bmj.327.7411.368].
Ostensen M, Khamashta M, Lockshin M. Anti-inammatory and
immunosuppressive drugs and reproduction. Arthritis Res Ther
2006;8:20928 [http://dx.doi.org/10.1186/ar1957].
Sau A, Clarke S, Bass J, Marinaki A, Nelson-Piercy C. Azathioprine and
breast feeding: is it safe? BJOG 2007;114:498501 [http://dx.doi.org/
10.1111/j.1471-0528.2006.01232.x].
Bar Oz B, Hackman R, Einarson T, Koren G. Pregnancy outcome
after cyclosporine therapy during pregnancy: a meta-analysis.
Transplantation 2001;71:1051 [http://dx.doi.org/10.1097/00007890200104270-00006].
Clowse ME, Magder L, Witter F. Hydroxychloroquine in lupus
pregnancy. Arthritis Rheum 2006;54:36407 [http://dx.doi.org/
10.1002/art.22159].

2012 Royal College of Obstetricians and Gynaecologists