Pregnancy in women with systemic lupus erythematosus

Authors:
Bonnie L Bermas, MD
Nicole A Smith, MD, MPH
Section Editors:
David S Pisetsky, MD, PhD
Charles J Lockwood, MD, MHCM
Deputy Editor:
Monica Ramirez Curtis, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Aug 2018. | This topic last updated: Jun 08, 2018.

INTRODUCTION — Systemic lupus erythematosus (SLE) predominantly affects women of

childbearing age. Fertility in SLE patients does not appear to be altered by disease itself;
however, a decrease in ovarian reserve can occur in women exposed
to cyclophosphamide.

Pregnancy in women with SLE carries a higher maternal and fetal risk compared with
pregnancy in healthy women. The prognosis for both mother and child is best when SLE
has been quiescent for at least six months prior to the pregnancy. Disease flares during
SLE pregnancy pose challenges with respect to distinguishing physiologic changes related
to pregnancy from disease-related manifestations. Thus, a multidisciplinary approach with
close medical, obstetric, and neonatal monitoring is necessary to optimize both maternal
and fetal outcomes.

This topic review will discuss the major risks associated with pregnancy in SLE patients,
as well as management recommendations. Issues related to menstrual function,
menopause, estrogen replacement therapy, and the use of oral contraceptives in women
with systemic lupus erythematosus are presented separately (see "Menstrual function,
menopause, and hormone replacement therapy in women with systemic lupus
erythematosus" and "Approach to contraception in women with systemic lupus
erythematosus"). Issues related to pregnancy in patients with impaired renal function or
with antiphospholipid syndrome (APS) are also presented elsewhere. (See "Pregnancy in
women with underlying renal disease" and "Management of antiphospholipid syndrome in
pregnant and postpartum women" and "Neonatal lupus: Epidemiology, pathogenesis,
clinical manifestations, and diagnosis".)

PREGNANCY PLANNING — Ideally, disease should be quiescent for six months prior to
systemic lupus erythematosus (SLE) patients attempting conception. Active SLE at the
time of conception is a strong predictor of adverse maternal and obstetrical outcomes [1-
3]. In spite of this risk, the majority of such pregnancies still result in live births. The
following studies are illustrative:
 ●The largest observational study, including 385 pregnant lupus patients with inactive
or mild or moderate disease at conception, found 81 percent of subjects had
uncomplicated pregnancies [4]. After controlling for baseline risk factors such as
lupus anticoagulant, treatment for hypertension, thrombocytopenia, disease flare, or
moderate disease activity at baseline, non-Hispanic white patients had an 8 percent
rate of adverse pregnancy outcomes. However, the study population was limited as it
excluded women with high disease activity, active lupus nephritis, uncontrolled
hypertension, and diabetes.

●A study of 267 pregnancies in a cohort of lupus patients found that women with high
disease activity compared with low disease activity in the first and second trimesters
showed a threefold increase in pregnancy loss (miscarriages and perinatal mortality)
[1]. However, overall there was no statistically significant difference in the number of
live births between the women with high disease activity compared with low disease
activity (77 percent versus 88 percent, respectively).

Our approach to pregnancy planning and management in SLE is generally consistent with
recommendations developed by the European League Against Rheumatism (EULAR) [5].

Preconception evaluation — A preconception assessment is essential in women with

SLE to determine whether pregnancy may pose an unacceptably high maternal or fetal
risk, to initiate interventions to optimize disease activity, and to adjust medications to those
that are least harmful to the fetus.

Women should be advised that discontinuation of medications used to control disease

activity increases the risk of lupus flare and pregnancy complications. Ideally, women
considering conception should be maintained on medications that are compatible with
pregnancy and should continue these medications in pregnancy. Clinical features specific
to pregnancy in the setting of SLE are discussed below. A more general discussion on
preconception care and risk assessment in all women is presented separately. (See "The
preconception office visit".)

Risk assessment — The preconception evaluation in women with SLE should include an
assessment of disease activity and major organ involvement, as well as hypercoagulability
or concurrent medical disorders that may impact pregnancy. Previous obstetric outcomes
should be reviewed, with particular attention paid to history of small for gestational age
fetus, preeclampsia, stillbirth, miscarriage, and preterm birth. An approach to the
assessment of disease activity and severity of SLE is discussed separately.
(See "Overview of the management and prognosis of systemic lupus erythematosus in
adults", section on 'Assessment of disease activity and severity'.)

Patients with evidence of active SLE, especially lupus nephritis, should be advised to defer
pregnancy until the disease is well controlled for at least six months. For those with renal
insufficiency, counseling should include an assessment of the risk of temporary or
permanent decline in renal function. (See "Pregnancy in women with underlying renal
disease".)

Increased severity of maternal disease generally correlates with higher maternal and fetal
risk in pregnancy. Thus, recent stroke, cardiac involvement, pulmonary hypertension,
severe interstitial lung disease, and advanced renal insufficiency can be dangerous to both
mother and fetus. Women with these or other worrisome medical conditions should be
counseled carefully by a Maternal Fetal Medicine specialist as to their individual risk
profile, with clear discussion of the morbidity and mortality risks to both mother and fetus
associated with pregnancy. Alternatives such as surrogacy and adoption should be
presented. Should they elect to pursue pregnancy, they should be followed in a
multidisciplinary fashion in a high-risk center [6,7].

Specific maternal antibody status such as antiphospholipid antibodies (aPLs) and

antibodies to Ro/La should be assessed. aPLs may increase obstetric risks such as
recurrent pregnancy loss, stillbirths, and preeclampsia while antibodies
to Ro/La predispose to neonatal lupus (NL) [6]. (See "Neonatal lupus: Epidemiology,
pathogenesis, clinical manifestations, and diagnosis" and "Management of
antiphospholipid syndrome in pregnant and postpartum women".)

Specific laboratory testing — In addition to routine preconception labs (see "The

preconception office visit", section on 'Laboratory assessment'), the following should be
reviewed during the preconception evaluation (see "Overview of the management and
prognosis of systemic lupus erythematosus in adults", section on 'Laboratory evaluation'):

●aPLs: lupus anticoagulant (LA), immunoglobulin G (IgG) and IgM anticardiolipin

(aCL) antibodies, and IgG and IgM anti-beta2-glycoprotein (GP) I antibodies

●Anti-Ro/SSA and anti-La/SSB antibodies

●Renal function (creatinine, urinalysis with urine sediment, spot

urine protein/creatinine ratio)

●Complete blood count (CBC)

●Liver function tests

●Anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies

●Complement (CH50, or C3 and C4)

●Uric acid

Medications — Medications must be reviewed and adjusted prior to conception with the
goal of maintaining disease control with medications with the best safety profile during
pregnancy. Although some medications used to treat SLE are potentially harmful or
contraindicated during pregnancy, there are safe options. Information regarding the use of
immunosuppressive agents in pregnant patients with SLE can be found below, and in a
separate topic (see "Safety of antiinflammatory and immunosuppressive drugs in
rheumatic diseases during pregnancy and lactation"). The most commonly used
medications used to treat patients with SLE are reviewed briefly below.

Recommended during pregnancy

●Hydroxychloroquine – We continue of hydroxychloroquine (HCQ) during pregnancy

in all patients with SLE, unless otherwise contraindicated. Several studies have
demonstrated fewer disease flares and better outcomes in patients continuing HCQ
during pregnancy, with no increase in adverse events or congenital malformations [8-
16]. A randomized trial including 20 consecutive pregnant patients with SLE found no
differences between disease flare rates, but patients in the HCQ group were able to
reduce the prednisone dosage [13]. In addition, the HCQ group had significantly lower
disease activity scores after delivery compared with the placebo group. Findings from
a larger prospective study with 257 pregnancies in 197 women also found that
discontinuation of HCQ during pregnancy was associated with a higher rate of flare
compared with women who either continued HCQ during pregnancy or never took it
[8]. In addition, high disease activity occurred in twice as many pregnancies in which
HCQ was stopped compared with those who continued taking HCQ. The relative
safety of HCQ during pregnancy is discussed in detail separately. (See "Safety of
antiinflammatory and immunosuppressive drugs in rheumatic diseases during
pregnancy and lactation", section on 'Hydroxychloroquine'.)

Additionally, some data suggest a decrease in occurrence of congenital heart block in

at-risk fetuses of mothers with anti-Ro/SSA and anti-LA/SSB antibodies exposed to
HCQ [17]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations,
and diagnosis", section on 'Heart block'.)

●Low-dose aspirin – We initiate low-dose aspirin in all women with SLE, starting from
approximately 12 weeks gestation, to reduce the risk of preeclampsia and its
sequelae (eg, fetal growth restriction), regardless of the presence of antiphospholipid
antibodies (aPLs). This approach is consistent with the recommendation by the
United States Preventive Services Task Force to use low-dose aspirin in women at
high-risk of developing preeclampsia, which includes women with SLE [18].
Recommendations for prophylactic use of low-dose aspirin during pregnancy for
prevention of preeclampsia are discussed in detail separately. (See "Safety of
antiinflammatory and immunosuppressive drugs in rheumatic diseases during
pregnancy and lactation", section on 'NSAIDs' and "Preeclampsia: Prevention".)

Selective use allowed during pregnancy — The following drugs have a reasonable
safety profile during pregnancy, but certain limitations apply to their use. Nonsteroidal
antiinflammatory drugs (NSAIDs), glucocorticoids, azathioprine, and some
antihypertensive medications are included in this category. They each have a small risk of
causing fetal harm, but their use may be acceptable if needed to control manifestations of
SLE during pregnancy.

●Nonsteroidal antiinflammatory drugs – NSAID use is not strongly associated with

congenital anomalies. However, the use of NSAIDs may impede ovulation or
implantation and is best avoided during a conception cycle. There is conflicting
evidence as to whether exposure to NSAIDs during the first trimester increases the
risk of spontaneous abortion. After the first trimester, NSAIDs may be used until 32
weeks of gestation. As transient oligohydramnios has been reported with daily use
of diclofenac, these medications should be used judiciously. Use of NSAIDs after 32
weeks of gestation may cause premature closure of the ductus arteriosus as well as
other complications, and should be avoided during that time.

●Glucocorticoids – Glucocorticoids are used for a wide range of maternal diseases in

pregnancy. We suggest control of disease with the lowest possible dose
of prednisone, ideally less than 10 mg/day. While there were some reports of
glucocorticoid use during the first trimester being associated with cleft lip, with and
without cleft palate, subsequent studies have failed to consistently demonstrate an
increased risk of this malformation. Maternal and fetal adverse effects of
glucocorticoids are discussed in detail separately. (See "Safety of antiinflammatory
and immunosuppressive drugs in rheumatic diseases during pregnancy and
lactation", section on 'Glucocorticoids'.)

●Azathioprine – Azathioprine is considered relatively safe during pregnancy, but

doses should not exceed 2 mg/kg/day. (See "Safety of antiinflammatory and
immunosuppressive drugs in rheumatic diseases during pregnancy and lactation",
section on 'Azathioprine and 6-mercaptopurine'.)

●Cyclosporine – Limited observations suggest that children exposed in utero to

cyclosporine have normal renal function and blood pressure. The manufacturer
suggests that use in pregnancy should be limited to when maternal benefit outweighs
fetal risk. (See "Safety of antiinflammatory and immunosuppressive drugs in
rheumatic diseases during pregnancy and lactation", section on 'Cyclosporine'.)

●Tacrolimus – A causal relationship between tacrolimus use and birth defects has not
been found, though the number of fetuses exposed in utero has been small. An small
case series of nine pregnant lupus patients reported successful disease maintenance
or control of lupus nephritis flares with tacrolimus [19] (See "Safety of
antiinflammatory and immunosuppressive drugs in rheumatic diseases during
pregnancy and lactation", section on 'Tacrolimus'.)

●Antihypertensive medications – Methyldopa, labetalol, nifedipine,

and hydralazine are the most commonly used antihypertensives in pregnancy. By
 comparison, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
receptor blockers are contraindicated during pregnancy. Diuretics should be used
with caution. Nitroprusside is the agent of last resort for urgent control of refractory
severe hypertension; its use should be limited to a short period of time in an
emergency situation. (See "Management of hypertension in pregnant and postpartum
women"and "Adverse effects of angiotensin converting enzyme inhibitors and
receptor blockers in pregnancy".)

Selective use with caution in pregnancy

●Biologic medications – Data regarding the use of biologic medications such as the
B-cell depleting antibody, rituximab, or the BAFF inhibitor, belimumab, during
pregnancy are limited. There have been case reports of B-cell lymphocytopenia
lasting up to six months in rituximab-exposed infants. Thus, we discourage the use of
these agents during pregnancy. (See "Safety of antiinflammatory and
immunosuppressive drugs in rheumatic diseases during pregnancy and lactation",
section on 'Rituximab'.)

Contraindicated in pregnancy

●Cyclophosphamide – Cyclophosphamide is associated with congenital (or fetal)

malformations and should be avoided during the first 10 weeks of gestation, when the
fetus is most susceptible to teratogens (figure 1). However, in life-threatening clinical
situations, this medication has been used in late pregnancy. (See "Safety of
antiinflammatory and immunosuppressive drugs in rheumatic diseases during
pregnancy and lactation", section on 'Cyclophosphamide'.)

●Mycophenolate mofetil – Congenital anomalies have been reported in infants

exposed to mycophenolate mofetil during pregnancy. This medication should be
avoided during pregnancy. (See "Safety of antiinflammatory and immunosuppressive
drugs in rheumatic diseases during pregnancy and lactation", section on
'Mycophenolate mofetil'.)

Azathioprine or tacrolimus can be substituted for mycophenolate prior to and during

pregnancy, or, alternatively, glucocorticoids may be used at the lowest dose that
controls disease activity. Ideally, this transition in medication should take place six
months prior to conception. (See "Safety of antiinflammatory and immunosuppressive
drugs in rheumatic diseases during pregnancy and lactation", section on 'Azathioprine
and 6-mercaptopurine'.)

●Methotrexate – Methotrexate is teratogenic and should not be used during

pregnancy. (See "Safety of antiinflammatory and immunosuppressive drugs in
rheumatic diseases during pregnancy and lactation", section on 'Methotrexate'.)
 ●Leflunomide – Pregnancy should be deferred for two years after discontinuation of
leflunomide (or a washout procedure should be employed), since this drug can
remain detectable in the serum for up to two years. (See "Safety of antiinflammatory
and immunosuppressive drugs in rheumatic diseases during pregnancy and
lactation".)

Ideally conception should only be attempted in a state of disease remission or stable

disease on medications compatible with pregnancy. However, if pregnancy occurs during
a period of disease activity, medications will need to be adjusted for fetal and maternal
safety.

SPECIFIC CONSIDERATIONS DURING PREGNANCY

Exacerbation of SLE — Although it is generally accepted that pregnancy and the

postpartum period are associated with a higher rate of systemic lupus erythematosus
(SLE) disease flares, widely variable rates have been reported ranging from 25 to 60
percent [3,7,20,21]. Some of this variation may be attributed to the heterogeneous study
designs, diverse patient and control groups, and different definitions of flares used in the
studies. For comparison, the background rate of flare of SLE is approximately 30 percent
per year.

The following factors are associated with an increased risk of SLE flare during pregnancy
[1,8,22-24]:

●Active disease during the six months prior to conception

●A history of lupus nephritis

●Discontinuation of hydroxychloroquine (HCQ)

●Primigravidas

Impact of lupus on pregnancy — Pregnancy in the setting of SLE is associated with a

higher risk of complications compared with healthy women. The largest study to evaluate
maternal and pregnancy complications associated with SLE included 13,555 pregnancies
[25]. Women with SLE also had a two- to fourfold increased rate of obstetric complications
including preterm labor, unplanned cesarean delivery, fetal growth restriction,
preeclampsia, and eclampsia. Patients with SLE also had a significantly higher risk of
thrombosis, infection, thrombocytopenia, and transfusion. This study also reported that
maternal mortality was 20-fold higher among women with SLE; however, mortality
amongst similar-aged SLE patients who were not pregnant was even higher. Another
study found that increased rates of hypertension during pregnancy, preterm delivery,
unplanned cesarean delivery, postpartum hemorrhage, and maternal venous
thromboembolism were all more frequent in women with SLE compared with pregnancies
of women without SLE [26].
Several predictors of adverse pregnancy outcomes among women with SLE have been
identified and include active disease, use of antihypertensives, prior lupus nephritis, the
presence of antiphospholipid antibodies (aPLs), and thrombocytopenia [4,27]. Moreover,
primigravidas are at higher risk for pregnancy complications [24].

Preeclampsia — Preeclampsia is one of the most frequent complications of pregnancy in

SLE, occurring in 16 to 30 percent of women with SLE, compared with 4.6 percent of
pregnancies in the general obstetric population [3,28-30]. Risk factors for preeclampsia in
women with SLE are the same as those in healthy women and are discussed separately
(see "Preeclampsia: Clinical features and diagnosis", section on 'Risk factors'). Additional
risk factors for preeclampsia that are specific to SLE patients include an active or prior
history of lupus nephritis, declining complement levels, and thrombocytopenia. The data
on whether aPLs predispose to preeclampsia is unclear, although some studies suggest
an association [28,31].

Preterm birth — Preterm birth is the most common obstetric complication in women with
SLE. Rates of preterm birth from 15 to 50 percent are reported, with increased incidence in
women with lupus nephritis or high disease activity. This compares with 12 percent of
pregnancies in the general United States obstetric population [1,23,28]. In women with
SLE, the majority of preterm births are medically indicated due to preeclampsia or
maternal SLE activity [32]. The presence of lupus nephritis and active disease are the
strongest predictors for early delivery [20,29,33]. The rates of preterm birth are likely better
among women without such risk factors [4]. In addition to disease activity, other factors
contributing to higher rates of preterm births include superimposed preeclampsia,
intrauterine growth restriction, and likely higher rates of abruption, and exposure to
glucocorticoids.

Fetal complications — Fetal complications during pregnancy in patients with SLE include
miscarriage, stillbirth, growth restriction, neonatal lupus (NL) syndromes, and
complications of prematurity.

●Fetal loss – Historically, significantly elevated rates of both early and late
pregnancy loss have been seen in women with SLE. Many contemporary studies
group all losses from the embryonic stage (up to 9 to 10 weeks gestation) to stillbirth
(fetal death at 20 or more weeks) under the term “fetal loss,” making it challenging to
interpret the risk of early miscarriage versus later fetal death.

The effect of SLE on embryonic losses is controversial, with a possible slight increase
in risk. Women with SLE are at increased risk of fetal death beyond 10 weeks,
particularly in the presence of active SLE, lupus nephritis, and antiphospholipid
syndrome (APS). Overall, fetal loss rates amongst SLE patients have been declining
over the last decades, with increased rates of livebirths [1,33,34]. A large
observational cohort of patients with inactive lupus or mild to moderate disease
activity at conception found that 5 percent of pregnancies ended in fetal or neonatal
 death [4]. For comparison, the population risk of miscarriage at less than 20 weeks
gestation ranges from 8 to 20 percent [35,36].

●Fetal growth restriction – About 10 to 30 percent of pregnancies in women with

SLE are complicated by fetal growth restriction and small-for-gestational-age babies
compared with about 10 percent of pregnancies in the general obstetric population
[20,23,37]. As with the other complications, the risk is higher in the presence of active
disease, hypertension, and lupus nephritis. Lower birth weight at every gestational
age is also more prevalent in women with SLE [26].

●Neonatal lupus – NL is a passively transferred autoimmune disease that occurs in

some babies born to mothers with anti-Ro/SSA or anti-LA/SSB antibodies, who may
or may not carry the diagnosis of SLE or Sjögren’s. The major manifestations of NL
are either cutaneous or cardiac, but other manifestations of NL include hematologic
and hepatic abnormalities.

The most serious complication in the neonate is congenital complete heart block,
which occurs in approximately 2 percent of children born to primigravid women
with anti-Ro/SSA antibodies [38]. In women who have had a child with congenital
complete heart block, the risk of complete heart block increases to approximately 16
to 18 percent for subsequent pregnancies, or 10 to 15 percent when a previous infant
had cutaneous NL [39-41]. Data suggest that congenital heart block may occur more
frequently in the setting of anti-Ro52, as opposed to anti-Ro60 or anti-La antibodies;
however, at this time, neonatal surveillance should not be altered by antibody type,
and Ro antibody differentiation is not routinely performed to guide obstetric care [42].
The pathogenesis, clinical manifestations, screening, prevention, and treatment of NL
are discussed separately. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical
manifestations, and diagnosis" and "Congenital third degree (complete)
atrioventricular block".)

SLE does not appear to confer risks for other identifiable congenital abnormalities [43,44].
Some studies have found that learning disabilities may be more frequent in children,
particularly sons, of SLE mothers, but more studies are needed to confirm this [45,46].

Special considerations

Lupus nephritis — Women with active lupus nephritis should be encouraged to delay
pregnancy until the disease is inactive for at least six months to optimize maternal
outcomes. As discussed above, a previous history of lupus nephritis or active lupus
nephritis during pregnancy is associated with higher rates of maternal and fetal
complications. The following examples are illustrative:

●An observational study with 193 pregnancies of 104 women with SLE, among which
81 occurred in the presence of active renal disease, found that low birth weight was
observed more frequently in pregnancies with renal disease [22]. The presence of
 active renal disease during pregnancy was also associated with an increased
frequency of pregnancy-induced hypertension and lupus flares.

●Another retrospective study of 95 pregnancies among women with SLE found that a
previous history of lupus nephritis was a predictor for adverse maternal outcomes
[23]. Pregnancies of women with previous nephritis were associated with a higher risk
of maternal complications (88 percent versus 43 percent, respectively) and a higher
rate of flares (54 percent versus 25 percent, respectively), most of which were renal
flares. However, most renal flares in this cohort were not severe, responded to high
doses of prednisone, and did not lead to pregnancy loss.

●A retrospective study of 90 pregnancies among 58 lupus patients found significantly

lower rates of preeclampsia, preterm birth, and pregnancy loss among women with
lupus nephritis in remission compared with women with active lupus nephritis (35, 30,
and 25 percent versus 57, 52, and 35 percent, respectively) [33].

Thus, these women require careful monitoring during pregnancy, and may require
medication to control their disease. A detailed discussion of pregnancy in women with
underlying renal disease is presented separately (see "Pregnancy in women with
underlying renal disease"), and the approach to therapy of a flare of lupus during
pregnancy is discussed below. (See 'Management during pregnancy' below.)

Women with SLE who have received renal transplants have pregnancy outcomes that are
similar to those of other transplant recipients [47]. Management of pregnancy following
renal transplantation is discussed separately. (See "Pregnancy in women with underlying
renal disease", section on 'Pregnancy in the renal transplant recipient'.)

Presence of antiphospholipid antibodies — aPLs are present in about a quarter to a

half of patients with SLE; however, few patients develop thrombotic or obstetric
complications related to APS.

Pregnant women with SLE who have an obstetric history suggestive of APS (fetal death
after 10 weeks or three or more consecutive miscarriages, or premature birth <34 weeks
due to preeclampsia or placental insufficiency) or unexplained venous or arterial
thrombotic event, should be tested for the presence of aPLs (ie, lupus anticoagulant [LA],
immunoglobulin G [IgG] and IgM anticardiolipin [aCL] antibodies; and IgG and IgM anti-
beta2-glycoprotein [GP] I). The clinical manifestations, diagnosis, and management of
women with aPL who are contemplating pregnancy or who are pregnant are discussed in
more detail separately. (See "Management of antiphospholipid syndrome in pregnant and
postpartum women" and "Diagnosis of antiphospholipid syndrome".)

It is unclear whether women with aPLs without an APS diagnosis are at increased risk of
pregnancy loss [48]. Issues associated with the presence of these autoantibodies in
pregnant women and the management of such patients is discussed separately.
(See "Management of antiphospholipid syndrome in pregnant and postpartum women",
section on 'aPL alone'.)

Presence of anti-Ro and anti-La antibodies — As mentioned above, a fetus exposed

to anti-Ro/SSA and/oranti-La/SSB antibodies is at an increased risk of developing
congenital complete heart block or NL (see 'Fetal complications' above). In most cases,
congenital heart block develops between 18 and 24 weeks of gestation. Thus, in some
centers, women who have antibodies to Ro/SSA and/or La/SSB undergo increased fetal
surveillance for heart block, with differing surveillance protocols at different sites. While
there is no therapeutic intervention proven to prevent progression, early detection allows
for increased monitoring. The monitoring and management of congenital heart block
associated with neonatal lupus is discussed in detail separately. (See "Neonatal lupus:
Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Heart
block' and "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and
diagnosis", section on 'Fetal surveillance for heart block' and "Neonatal lupus:
Management and outcomes", section on 'In utero management'.)

HCQ use during pregnancy has been associated with reduced rates of congenital heart
block [49,50]. (See "Neonatal lupus: Management and outcomes", section on 'Prevention
of NL in subsequent pregnancies'.)

Women with anti-Ro/SSA and anti-La/SSB may have detectable amounts of these
antibodies in breast milk, but there is no evidence that NL results from breast feeding
[51].

MANAGEMENT DURING PREGNANCY — Management of pregnant women with

systemic lupus erythematosus (SLE) should involve close collaboration between a
rheumatologist and an obstetrician experienced in caring for high-risk mothers. An
approach to monitoring pregnant women with SLE as well as treating active SLE during
pregnancy is presented below.

Monitoring SLE activity — Women should be assessed by a rheumatologist for disease

activity at least once each trimester, and more frequently if they have active SLE. The
schedule for monitoring includes:

Initial evaluation — At the first visit after (or at which) pregnancy is confirmed, the
following investigations are recommended [52]:

●Physical examination, including blood pressure

●Renal function (creatinine, urinalysis, spot urine protein/creatinine ratio)

●Complete blood count (CBC)

●Liver function tests

 ●Anti-Ro/SSA and anti-La/SSB antibodies

●Lupus anticoagulant (LA) and anticardiolipin antibody (aCL) assays

●Anti-double stranded DNA (dsDNA) antibodies

●Complement (CH50, or C3 and C4)

●Serum uric acid

Some physiological changes of pregnancy may overlap with features of active SLE,
making differentiation difficult. As an example, laboratory findings that may be observed
during a normal pregnancy include mild anemia, mild thrombocytopenia, elevated
erythrocyte sedimentation rate (ESR), and proteinuria. Protein excretion increases in the
course of normal pregnancy, but should remain below 300 mg/24 hours. A baseline 24-
hour urine collection can be helpful in distinguishing lupus flare from preeclampsia and
normal changes later in pregnancy (see 'Preeclampsia versus lupus nephritis' below).
Also, during normal pregnancy, complement levels may rise by 10 to 50 percent, and may
appear to remain normal despite active SLE. Thus, the trend of complement levels is
generally more informative than the actual value.

Thus, laboratory testing must be interpreted in the clinical context and women who show
evidence of increased serologic activity but who remain asymptomatic should be
monitored more closely. We do not initiate therapy for serologic findings alone.

Laboratory testing — In addition to a physical examination with blood pressure testing,

the following laboratory tests are recommended at regular intervals during pregnancy:

●CBC

●Creatinine

●Urinalysis with examination of urinary sediment

●Spot urine protein/creatinine ratio or 24-hour urine collection

The following laboratory tests should be performed in patients with active disease or who
have previously manifested changes in these levels with a flare:

●Anti-dsDNA antibodies

●Complement (CH50, or C3 and C4)

Ordering additional laboratory tests such as liver function tests and serum uric acid should
be guided by the clinical presentation. The frequency of laboratory testing is individualized
and varies with disease activity. Patients with stable disease should ideally undergo
laboratory testing each trimester, but those with active lupus will require more frequent
testing.

Postpartum laboratory testing — Some women will experience exacerbations of SLE in

the postpartum period. Those who have had active disease at conception and those with
significant end-organ damage are at greater risk of disease flares in the postpartum period
compared with women with inactive disease [53]. Thus, periodic assessment of disease
activity is warranted postpartum. The following laboratory tests are recommended at one
month following an uncomplicated delivery [52]:

●Urinalysis, urine protein/urine creatinine ratio

●Renal function if the urinalysis is abnormal

●CBC

We also check the following laboratory tests in patients with severe disease or in those in
whom the anti-dsDNA and complement levels correlate well with disease activity:

●Anti-dsDNA

●Complement (CH50, or C3 and C4)

Treatment of postpartum women with active SLE is the same as that of nonpregnant
women. Some medications used for the management of active SLE are not compatible
with breastfeeding; thus, breastfeeding women will require thoughtful discussions with their
clinicians as to the risks and benefits of various treatment approaches. Medication safety
in pregnancy differs in many instances from medication safety in lactation.
(See 'Breastfeeding' below.)

Maternal-fetal monitoring — The optimal monitoring schedule to ensure maternal and

fetal health during pregnancy is not known. Women with risk factors or poor prognostic
indicators will require more frequent monitoring. In addition to routine prenatal care, fetal
monitoring for women with SLE includes:

●First-trimester ultrasound evaluation to establish the estimated date of delivery. A

fetal anatomic survey is performed at approximately 18 weeks of gestation.

●Ultrasound evaluation for fetal growth and placental insufficiency in the third
trimester. Frequency of surveillance for fetal growth will depend upon maternal and
fetal wellbeing, but typically will be performed approximately every four weeks. More
frequent monitoring, including Doppler velocimetry, is also recommended if growth
restriction or placental insufficiency is suspected. (See "Fetal growth restriction:
Evaluation and management", section on 'Pregnancy management'.)
 ●Fetal testing with nonstress tests and/or biophysical profile during the final four to six
weeks of pregnancy is indicated in most women with lupus, with individual
surveillance plans based on fetal and maternal assessment. (See "Overview of
antepartum fetal surveillance".)

●In patients with positive anti-Ro/SSA and/or anti-La/SSB antibodies, increased

surveillance for congenital heart block is recommended. (See "Neonatal lupus:
Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Fetal
surveillance for heart block' and 'Presence of anti-Ro and anti-La antibodies' above.)

Preeclampsia — Women with SLE are at higher risk of preeclampsia than the general
population. These patients require additional vigilance, as the presentation of
hypertension, proteinuria, or end-organ dysfunction after 20 weeks of gestation is
concerning for development of preeclampsia. Severe, early-onset growth restriction is
similarly concerning for developing preeclampsia. While preeclampsia presenting later in
pregnancy can often be managed expectantly, in pre-and peri-viable gestations, delivery is
indicated to prevent catastrophic maternal complications. For this reason, early diagnosis
is essential.

In women at elevated risk of preeclampsia, including all women with SLE, low-
dose aspirin has been shown to reduce the risk of disease by approximately 24 percent
when initiated between 12 to 16 weeks gestation [18] (see "Preeclampsia: Prevention",
section on 'Candidates' and 'Recommended during pregnancy' above). Preeclampsia in
women with antiphospholipid syndrome (APS) is discussed separately. (See "Management
of antiphospholipid syndrome in pregnant and postpartum women".)

Preeclampsia versus lupus nephritis — Differentiating preeclampsia from lupus

nephritis or a lupus flare can be challenging. Lupus nephritis flares during pregnancy can
mimic preeclampsia, presenting with increasing proteinuria, hypertension,
thrombocytopenia, and a deterioration in renal function. Active lupus nephritis and
preeclampsia can also occur at the same time. Evidence of lupus activity in other organs
can sometimes help distinguish SLE from preeclampsia.

Laboratory testing may be, but is not always, useful in distinguishing preeclampsia from
nephritis or a lupus flare:

●Lupus nephritis is often associated with proteinuria and/or an active urine sediment
(red and white cells and cellular casts), whereas only proteinuria is seen in
preeclampsia.

●Flares of SLE are likely to be associated with low or decreasing complement levels
and increased titers of anti-dsDNA antibodies; by comparison, complement levels are
usually, but not always, normal or increased in preeclampsia [54-56].
 ●Thrombocytopenia, elevated serum levels of liver enzymes and an elevated or rising
level of uric acid are more prominent in preeclampsia than lupus nephritis. However,
thrombocytopenia may also be seen in association with antiphospholipid antibodies
(aPLs), thrombotic thrombocytopenic purpura, and immune thrombocytopenia, each
of which may complicate pregnancy in women with SLE.

The onset of these overlapping symptoms before 20 weeks of gestation is more consistent
with lupus nephritis. Renal biopsy could help differentiate the two conditions, but the higher
risk of complications during pregnancy limits the use in pregnancy. (See "Acute kidney
injury in pregnancy".)

Treating active SLE — The treatment of active SLE during pregnancy is guided by the
severity and degree of organ involvement, similar to patients in the non-pregnant state.
Treatment should not be withheld due to pregnancy; however, some medications used to
treat SLE may cross the placenta and cause fetal harm. Thus, the risks and benefits of
treatment during pregnancy must be weighed against the risk of SLE activity having a
deleterious effect on the mother and the fetus. The most commonly used medications
used to treat patients with SLE are reviewed above (see 'Medications' above). The use of
immunosuppressive drugs during pregnancy is discussed in detail separately. (See "Safety
of antiinflammatory and immunosuppressive drugs in rheumatic diseases during
pregnancy and lactation".)

A detailed discussion regarding the treatment of active lupus is presented separately.

(See "Overview of the management and prognosis of systemic lupus erythematosus in
adults", section on 'Pharmacologic therapies'.)

Lupus nephritis in pregnancy requires special consideration because of its potential

morbidity and possible confusion with preeclampsia. (See 'Lupus nephritis' above
and 'Preeclampsia versus lupus nephritis' above.)

BREASTFEEDING — Breast feeding is encouraged for most women with systemic lupus
erythematosus (SLE). The safety of medications in lactation sometimes differs, and their
use should be discussed on an individual level and specific risks reviewed.

Hydroxychloroquine (HCQ), prednisone, cyclosporine, azathioprine, and tacrolimus are

considered compatible with breast feeding. Methotrexate in low or intermittent doses is
also considered compatible with breast feeding. Limited information on biologics
or leflunomide is available. Cyclophosphamide is contraindicated in lactation. Premature or
ill infants may be at increased risk of some medication exposures. Biologics, given their
large size, are unlikely to be transferred into breast milk in significant concentration;
however, data on their safety in lactation are limited. Detailed information regarding
compatibility of medications with lactation is provided by the United States National Library
of Medicine (LactMed drug and lactation database) [57]. A more detailed discussion on the
use of immunosuppressive drugs during lactation can be found elsewhere. (See "Safety of
antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy
and lactation".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines

from selected countries and regions around the world are provided separately.
(See "Society guideline links: Systemic lupus erythematosus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: Lupus and pregnancy (The

Basics)" and "Patient education: Lupus and kidney disease (The Basics)")

●Beyond the Basics topic (see "Patient education: Systemic lupus erythematosus and
pregnancy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Ideally, all pregnancies in women with systemic lupus erythematosus (SLE) should
be planned during periods of disease quiescence for at least six months prior to
conception. Active SLE at the time of conception is a strong predictor of adverse
maternal and obstetrical outcomes. In spite of this risk, the majority of such
pregnancies still result in live births. (See 'Introduction' above and 'Pregnancy
planning' above.)

●A preconception assessment is essential in women with SLE to determine whether

pregnancy may pose an unacceptably high maternal or fetal risk, to initiate
interventions to optimize disease activity, and to adjust medications to those with the
best safety profile during pregnancy. (See 'Preconception evaluation' above
and 'Specific laboratory testing' above and 'Medications' above.)

●Women who are primigravidas and women with a history of lupus nephritis or active
nephritis are at highest risk of flare. Higher rates of complications such as
preeclampsia, preterm birth, fetal loss, growth restriction, neonatal lupus (NL)
syndromes, and prematurity are seen in lupus pregnancy. (See 'Exacerbation of
 SLE' above and 'Impact of lupus on pregnancy' above and 'Fetal complications' above
and 'Special considerations' above.)

●Management of pregnant women with SLE should involve close collaboration

between a rheumatologist and an obstetrician experienced in caring for high risk
mothers. Periodic assessment for disease activity should occur throughout pregnancy
and the postpartum period. (See 'Management during pregnancy' above
and 'Monitoring SLE activity' above.)

●For all pregnant women with SLE, we suggest continuation of hydroxychloroquine to

reduce the risk of SLE flares (Grade 2C). (See 'Recommended during
pregnancy' above.)

●Women with SLE are at higher risk of preeclampsia than the general population.
Recommendations for prophylactic use of low-dose aspirin for preeclampsia is
discussed in detail separately. Lupus nephritis flares during pregnancy can mimic
preeclampsia, and differentiating one from the other can be challenging.
(See 'Preeclampsia' above and 'Recommended during pregnancy' above.)

●Women with risk factors or poor prognostic indicators may require more frequent
maternal-fetal monitoring. In patients with positive anti-Ro/SSA and/or anti-
La/SSB antibodies, increased surveillance for congenital heart block is appropriate.
(See 'Maternal-fetal monitoring' above.)

●The treatment of active SLE during pregnancy is guided by the severity and degree
of organ involvement, similar to patients in the non-pregnant state. Treatment should
not be withheld due to pregnancy; however, some medications used to treat SLE may
cross the placenta and cause fetal harm. Thus, the risks and benefits of treatment
during pregnancy must be weighed against the risk of SLE activity having a
deleterious effect on the mother and the fetus. (See 'Treating active SLE' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Peter

Schur, MD, who contributed to an earlier version of this topic review.