Systemic lupus erythematosus and pregnancy
outcomes: an update and review of the literature
Erica Peart and Megan E.B. Clowse
Purpose of review
This review synthesizes new data from the studies published between 2011 and 2013, with particular
focus on the different information gleaned by various study types.
Recent findings
Population-based cohorts have demonstrated that women with systemic lupus erythematosus (SLE) have
fewer live births and more pregnancy complications, but can have successful live births after having a poor
outcome. A retrospective study suggests that only 4 months, not the traditional 6 months of disease
quiescent SLE prior to pregnancy improves outcomes. Prospective studies identified several novel predictors
of poor pregnancy outcomes, including uterine Doppler and laboratory findings. A prospective study found
great success in transitioning to azathioprine from mycophenolate mofetil prior to pregnancy in patients
with quiet lupus nephritis. Two retrospective analyses suggest that hydroxychloroquine may prevent
congenital heart block in pregnancies exposed to SSA/Ro antibodies. Finally, the initial pregnancy data
for belimumab suggest a high degree of transplacental transfer, but thus far no definitive link between
belimumab and congenital abnormalities.
Summary
Recent studies suggest both novel markers of poor pregnancy outcomes and new approaches to the
management of lupus during pregnancy.
Keywords
belimumab (Benylsta), congenital heart block, glomerulonephritis, lupus nephritis, neonatal lupus,
pregnancy, systemic lupus erythematosus
INTRODUCTION
Treating systemic lupus erythematosus (SLE) during
pregnancy remains challenging for physicians, and
outcomes for both mother and baby can be less than
optimal if the disease is not managed with caution.
Over the past 3 years, published studies have
mapped SLE pregnancy outcomes using a variety
of protocols, including population-based studies,
prospective and retrospective cohorts, case reports,
and open interventional trials. Each protocol type
has associated benefits and pitfalls, which researchers should acknowledge when summarizing their
conclusions and applying results to clinical practice.
Here, we review the overall findings according to
study design, describing how each type of study
contributes to our ability to care for women with
SLE during pregnancy. Given that a single study
cannot address all that we need to know, we have
surveyed multiple studies and multiple study
designs to compile a more complete picture of best
practices.
www.co-rheumatology.com
LUPUS AND PREGNANCY OUTCOMES IN
POPULATION-BASED STUDIES
As they draw from broad administrative cohorts,
population-based studies can amass larger cohorts
of SLE pregnancies then can a single provider. Such
studies enable researchers to estimate rare events, to
compare the target population with a control group
of non-SLE patients, and to identify general outcomes. Moreover, population-based studies may
better represent the general lupus population
because they do not rely on tertiary referral centers.
The main drawback, however, is that the diagnostic
criteria for SLE usually cannot be confirmed; instead,
Duke University Medical Center, Durham, North Carolina, USA
Correspondence to Megan E.B. Clowse, MD, PO Box 3535 Trent Drive,
Durham, NC 27710, USA. Tel: +1 919 681 2045; e-mail: Megan.clowse
@dm.duke.edu
Curr Opin Rheumatol 2014, 26:118–123
DOI:10.1097/BOR.0000000000000030
Volume 26 Number 2 March 2014
Systemic lupus erythematosus and pregnancy outcomes Peart and Clowse
LUPUS AND PREGNANCY OUTCOMES IN
PROSPECTIVE COHORT STUDIES
KEY POINTS
Women with SLE have fewer live births and more
pregnancy complications, but even following a
perinantal loss, they will frequently have successful
pregnancies.
Retrospective studies suggest that 4 months of SLE
quiescence prior to pregnancy is enough to ensure a
safe pregnancy.
Prior and current lupus nephritis are predictors of poor
pregnancy outcome.
HCQ may be successful in preventing CHB.
From monkey studies, we have learned that
belimumab is associated with a high degree of
transplacental transfer, but thus far drug studies in
humans have not shown a definitive link to
congenital abnormalities.
diagnosis is based on coding by the physician.
Although diagnosis may be more reliable in the
hands of a rheumatologist, additional data related
to pregnancy must be gained from labor and delivery
hospital records, and therefore the SLE diagnosis may
rely on the obstetrician. Additionally, these studies
cannot account for disease-related confounders,
medication use, disease activity, and other individual
risk factors.
A recent population-based study by Vinet et al.
[1] followed 1334 women with SLE through the
Quebec administrative databases and determined
that women with SLE have fewer live births than
the general population: over a 9-year period, 559
live births occurred among the SLE patients
compared with the 708 that would have been
expected in the general population [standardized
incidence ratio 0.79; 95% confidence interval (CI)
0.73–0.86]. Another Canadian study reviewed 95
SLE pregnancies and found that when compared
with the general population mothers with SLE
experienced more complications during pregnancy, including preeclampsia and eclamsia [odds
ratio (OR) 2.16; 95% CI 1.10–4.21], C-section (OR
3.47; 95% CI 1.67–7.22), prematurity (OR 6.17
95% CI 3.28–11.58), and postpartum infection.
Interestingly, this study [2] did not show an
increased risk for congenital defects in patients
with SLE. An optimistic finding from a population-based study [3 ] in New South Wales,
Australia, which looked at 675 women with SLE
and 1058 deliveries, suggested that women whose
first pregnancies result in perinatal death can
nevertheless expect a live birth in subsequent
pregnancies.
&
Prospective cohort studies follow a collection of
women with SLE through pregnancy. Such research
provides accurate, real-time estimations of disease
activity, laboratory data, and medication details,
which can be correlated with pregnancy outcomes
without the potential for bias introduced by knowing the outcomes when recording the predictors.
However, such studies are often based on small,
selective cohorts in tertiary referral centers; it is
therefore difficult to determine whether the data
collected are generalizable, given the limited number of participants, and whether the patients seen in
this type of center represent the general lupus population. Additionally, this method may under-report
pregnancy losses. A loss may occur before a woman
is enrolled in the cohort, meaning she might have
had a prior unsuccessful pregnancy, which was
not reported.
One recent prospective cohort study identified
risk factors for preterm birth and adverse pregnancy
outcomes in SLE. Clowse et al. [4 ] tracked 40 pregnancies in 39 women with mild-to-moderate SLE
disease, finding biomarkers that correlated with
preterm delivery including ferritin, oestradiol, and
uric acid (all checked at mid-gestation).
&
LUPUS AND PREGNANCY OUTCOMES IN
RETROSPECTIVE COHORT STUDIES
Retrospective studies typically involve a collection
of pregnancies from a single center, which allows a
larger cohort and more accurate assessment of the
pregnancy loss rate. In such protocols, however,
researchers know the pregnancy outcomes before
they document each patient’s specific lupus symptoms, medications, and other potential confounding factors. This introduces recall bias, which may
result in less reliable findings.
A recent retrospective study from Korea, based
on 183 pregnancies in 143 SLE patients between
1998 and 2010, found no association between poor
pregnancy outcomes and lupus nephritis. It did,
however, confirm that the risk of preterm birth
and pregnancy loss increases with the presence of
antiphospholipid antibodies and lupus activity at
conception. Additionally, through Receiver operating characteristic curve analysis, the authors found
that 4 months of SLE stability prior to conception
meaningfully decreased the risk of pregnancy loss,
premature birth, and intrauterine growth restriction
[5]. A second retrospective study, which encompassed 65 SLE pregnancies between 2002 and
2011 in Turkey, evaluated uterine artery Doppler
in predicting adverse pregnancy outcomes in SLE. In
this series, clinicians preformed uterine artery
1040-8711 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Doppler as part of the standard care for women with
high-risk pregnancies. Because fetal loss, fetal
growth restriction, and preeclampsia are placentaassociated problems, abnormalities in uteroplacental circulation may suggest adverse outcomes. Of
the 65 pregnancies, 13 (20%) had abnormal uterine
artery Doppler studies. When these pregnancies
were compared with pregnancies with normal Doppler studies, 23 vs. 0% resulted in a fetal loss, 69.2 vs.
5.7% resulted in fetal growth restriction and/or
preeclampsia, and 69.2 vs. 17.3% had a preterm
delivery (P < 0.001). This study [6] indicates that
uterine artery Doppler, known to be helpful in
identifying poor placentas, may also be useful in
SLE. Another retrospective cohort following 111 SLE
pregnancies and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores observed that
severe flares were associated with poor fetal outcomes, and full-term pregnancies were more common in patients without disease flares. Specifically,
the rate of fetal loss in the active SLE group (17%)
was significantly higher than that in the inactive
group (2%) (P ¼ 0.047). Preeclampsia/eclampsia
(OR ¼ 8.04, 95% CI: 2.00–32.34) and active SLE
(OR ¼ 19.9, 95% CI: 2.38–166.27) were associated
with preterm birth [7].
women with prior lupus nephritis are currently managed with long-term mycophenolate mofetil (MMF).
A known teratogen, MMF results in congenital
anomalies in up to with up to 25% of live births
[9]. A recent prospective study evaluated the effect
of switching from MMF to AZA in patients with a
history of lupus nephritis counseled for pregnancy
from a single center between 2000 and 2010. All
women had prior biopsy-proven lupus nephritis,
were on maintenance with AZA or MMF, had quiet
SLE (SLEDAI < 5), and were in renal remission. Of the
54 participants who met all qualifying criteria, 23
were being treated with MMF and 31 with AZA.
Patients receiving MMF were tapered off that therapy
and shifted to AZA, which was maintained for the
duration of the pregnancy. MMF was tapered by
500 mg/day every 4 weeks until 500 mg/day was
reached then patients were transferred to AZA
(2 mg /kg) and MMF was discontinued. Of the women
who switched from MMF to AZA, three (13%) developed a renal flare prepregnancy; of those who maintained remission, 89% conceived. Remarkably, no
women experienced a renal flare during pregnancy,
but two had mild lupus nephritis postpartum.
Adverse pregnancy outcomes were associated with
increased prednisone dose, SLE activity, and
maternal age. Overall, this study [10 ] reported that
patients with quiescent lupus nephritis who either
switched from MMF to AZA or remained on AZA for
pregnancy developed renal flares only rarely and had
favorable pregnancy outcomes.
&&
LUPUS NEPHRITIS
Two recent studies, one prospective and one retrospective, have shed new, and encouraging, light on
our ability to obtain positive pregnancy outcomes
despite a patient’s history of lupus nephritis. The
retrospective study, which included 95 pregnancies
in 92 women between 2005 and 2009, found that
both previous lupus nephritis and active lupus
nephritis at conception were predictors for adverse
maternal outcomes, but that neither appeared to
impact pregnancy outcomes. All pregnancies were
divided into two groups according to whether the
woman had previously experienced lupus nephritis:
60 in the nonnephritis group compared with 35
with prior nephritis. Among women with prior
nephritis, 25.7% had active lupus at conception,
and 74.2% were taking azathioprine (AZA); among
women without prior nephritis, the numbers were
6.6 and 31.6%, respectively. Women with prior
nephritis also had significantly more renal flares
(45.7 vs. 6.6%, P < 0.0001). Despite this, the rates
of live birth, preterm birth, preeclampsia, and infant
birth weight were the same in both groups [8].
Because of the limited number of therapies
approved for the treatment during pregnancy, the
clinical management of patients with a history
of lupus nephritis can be challenging for rheumatologists. AZA is probably the safest immunosuppressant during gestation, but many non-pregnant
120
www.co-rheumatology.com
Lupus-associated congenital heart block
The rate of congenital heart block (CHB) in babies
exposed to SSA/Ro and/or SSB/La antibodies is
1–2%, but increases to up to 20% if the mother
has previously delivered an infant with neonatal
lupus. Complete heart block can be devastating
for these babies: over 60% require a pacemaker
(and recurrent changes as the child grows), 10% will
develop cardiomyopathy late after birth despite
pacemaker placement, and their 10-year mortality
rate is 20–35% [11]. Atrioventricular block develops
due to an inflammatory immune reaction to antiRo/La antibodies among the fetal cardiocytes, leading to fibrosis of the cardiac conduction system [11].
Currently, there is no consensus about how to prevent the occurrence of CHB in patients with SSA
and/or SSB antibodies, although there have been
multiple studies on the topic with various therapies.
There is consensus regarding the poor prognostic factors associated with neonatal CHB. In a
retrospective multicenter study involving 175
fetuses with second and third-degree atrioventricular block, researchers identified several variables
associated with neonatal death: detection of CHB
Volume 26 Number 2 March 2014
at gestational age less than 20 weeks, ventricular rate
less than 50 bpm, fetal hydrops, and impaired left
ventricular function. The study [12] also suggested
that administration of fluorinated steroids for
women with a fetus in second-degree heart block
may prevent progression to complete heart block
in some infants. A retrospective database study
reviewed the outcomes of cardiac neonatal lupus
in 325 offspring from 297 mothers enrolled in the
Research Registry for Neonatal Lupus, which was
started in 1994. This registry includes families with
documented positive anti-Ro/La antibodies and at
least one offspring with some form of neonatal
lupus. According to the database study, the primary
risk factors for mortality (either in utero or after
birth) were changes on the fetal echocardiogram
showing hydrops, carditis, or endocardialfibroelastosis, as well as maternal diagnosis of SLE or
Sjogren’s syndrome. This study [13] also suggested
that third-degree heart block might be prevented in
some infants by treating second-degree heart block
with fluorinated steroids.
As available treatments have limited success,
prevention of neonatal CHB may be the key to
managing this disease process. Two recent nonrandomized retrospective studies evaluated the
use of hydroxychloroquine (HCQ) (200–400 mg)
throughout pregnancy for the prevention of CHB
in mothers with SSA or SSB antibodies. In a review of
33 pregnancies with anti-Ro antibodies, Tunks et al.
[14 ] found that when the mother was treated with
HCQ, 93% of fetuses maintained normal conduction, compared with 63% in the untreated group
(OR, 0.14; P ¼ 0.09). Another study involved 257
pregnancies among three cohorts of women (from
the United States, the United Kingsdom, and
France) who had previously delivered infants with
neonatal lupus. During gestation, 40 fetuses were
exposed to HCQ and 217 were not. Among those
with HCQ exposure, 7.5% developed second or
third-degree CHB; among those without HCQ
exposure, the number rose to 21.2% (P < 0.01).
When the results of the study [15 ] were adjusted
for other risk factors for heart block, HCQ remained
significantly protective (OR 0.23, P ¼ 0.037).
In a database study following a French registry of
autoimmune CHB, researchers reviewed 84 subsequent pregnancies. All women had previously
given birth to a baby with CHB and presented with
antibodies to SSA or SSB. Subsequent pregnancies
were complicated by CHB in 20.2% of cases; the
occurrence rate of CHB was 26.9% in fetuses who
were not exposed to HCQ (14 of 52 cases) compared
with 9.4% in those exposed to HCQ (three of 32
cases; P ¼ 0.052) [16]. Figure 1 [14 ,15 ] shows the
results of the three recent studies looking at HCQ in
&
&&
&
&&
Percentage of pregnancies resulting in
congenital heart block
Systemic lupus erythematosus and pregnancy outcomes Peart and Clowse
Effect of treatment with hydroxychloroquine and risk
of cardiac neonatal lupus
40%
35%
30%
25%
20%
15%
FIGURE 1. Compares the results of three different studies
using hydroxychloroquine during SLE pregnancies and the
risk of congenital heart block in those who received the
treatment and those who did not. The Tunks et al. [14 ] and
Izmirly et al. [15 ] studies were retrospective cohorts, and
the results published by Levesque were based on database
review. SLE, systemic lupus erythematosus.
&
&&
SLE pregnancies, and how it impacts the risk of
cardiac neonatal lupus. These studies suggest that
HCQ may help prevent CHB in fetuses at risk for
neonatal lupus.
Two open-label interventional trials studied the
effect of Intravenous immunoglobulin (IVIG) on
prevention of CHB. In an American study that
followed 20 women with SSA autoantibodies and
a previous child with CHB or neonatal lupus,
mothers were treated with IVIG (400 mg/kg) every
3 weeks between weeks 12 to 24 of gestation. The
primary outcome was the development of second or
third-degree CHB. Three of the fetuses developed
advanced CHB, which was the endpoint of the
study. By reaching the endpoint, the study [17]
concluded that low-dose IVIG does not prevent or
reduce the reoccurrence of CHB. A similar European
multicenter prospective study followed 22 women
(24 pregnancies) who had a previous pregnancy
complicated by CHB and who tested positive for
SSA and/ or SSB antibodies. Fifteen of the patients
received IVIG at a dose comparable to that in the
American study [18], with similar results: 20% of the
babies developed advanced CHB despite treatment
with IVIG. Unfortunately, both studies demonstrated that the use of IVIG does not affect the
reoccurrence rate of CHB in SLE pregnancies.
Belimumab (benlysta) and pregnancy
With addition of belimumab to the clinical repertoire of treatment options for patients with SLE,
questions regarding its gestational safety have
emerged. Belimumab is a pregnancy category C
drug, and according to the manufacture should be
1040-8711 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
used during pregnancy only if the potential benefit
to the mother justifies the potential risk to the fetus.
If the physician and the patient decide the risk is too
great and elect to stop therapy, the patient is advised
to wait at least 4 months after the final treatment
before attempting to conceive.
Current available data about the safety of belimumab are scant, based only on an unpublished
preclinical monkey study and on accidental pregnancies that have occurred during drug trials. The
monkey study [19] demonstrated that belimumab
can cross the placenta, therefore, exposing the fetus
to this agent. Human pregnancy data are currently
limited to unintended pregnancies that occurred
during the manufacture’s placebo-controlled phase
2 and 3 studies. In these studies, patients received
belimumab and standard therapy for SLE (corticosteroids, immunosuppressives, antimalarials,
NSAIDs, or a combination thereof); when each pregnancy was discovered, the belimumab treatment was
stopped immediately, and the patient was removed
from the trial. At this time, 83 pregnancies that
occurred during these trials have known outcomes:
24% elective terminations, 27.7% spontaneous abortions, and 42% live births. Of the three congenital
anomalies (rate of 3.6%) that developed in these
pregnancies, one was a chromosomal translocation
also found in the mother, and thus was unrelated to
belimumab [20]. A pregnancy registry is currently
being administered by the maker of belimumab;
through this avenue, we may further gain insight
into the safety of the drug during pregnancy.
CONCLUSION
Because of the rarity and sensitivity of pregnancies
in women with SLE, it is not currently possible to
conduct the gold-standard studies that usually
determine the treatment: randomized clinical trials.
Therefore, we are left to interpret the available
imperfect data to guide our therapeutic recommendations. Studies conducted in the last 3 years
include population-based cohorts, prospective
single-center and multicenter cohorts, retrospective
studies, and even small interventional trials. The
population-based cohorts have demonstrated that
women with SLE have fewer live births and more
pregnancy complications, but that even following a
perinatal loss, they can often have successful pregnancies. The prospective cohorts have identified
new predictors of pregnancy complications, and a
retrospective study has suggested that 4 months –
not, as previously reported, 6 months – of SLE
quiescence is enough to ensure a safe pregnancy.
Another retrospective cohort suggested that uterine
Doppler used mid-pregnancy could predict pregnancy outcomes. One prospective study identified
122
www.co-rheumatology.com
both prior and current lupus nephritis as predictors
of poor pregnancy outcome, yet a retrospective
analysis demonstrated that transferring women
from MMF to AZA prior to conception could lead
to successful pregnancies. Recent cohort studies of
pregnancies at risk for CHB identified several cardiac
changes associated with neonatal mortality and
suggested that treatment of second-degree heart
block with fluorinated steroids might prevent progression to third-degree block in some infants.
Although recent open-label interventional trials of
IVIG to prevent CHB failed to meet their goals, two
retrospective analyses of prospectively collected
data suggest that HCQ may be successful in preventing CHB. Initial information regarding belimumab’s
safety in pregnancy comes from a preclinical
monkey study and from data on accidental pregnancies that have occurred during human drug
studies. From the monkey study, we have learned
that there is a high degree of transplacental transfer,
but so far the drug studies in humans, although
admittedly limited in scope, have established no
definitive link between belimumab and congenital
abnormalities. These data are available from the
maker of belimumab, but have not been published
in the medical literature.
A wide range of new information about lupus
pregnancy has emerged during the last several years,
and it is imperative that we interpret this information
appropriately, taking into account the strengths and
limitations of different study protocols. Although
large population-based studies provide broad information, they often remain short on details; on the
contrary, single-center prospective cohorts provide
great detail, but are often limited both in power and
generalizability. Only by combining these data sources are we able to find the best approach to managing
pregnancy in women with SLE.
Acknowledgements
None.
Conflicts of interest
M.E.B.C is a consultant for UCB, no other conflicts of
interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
&
of special interest
&& of outstanding interest
1. Vinet E, Labrecque J, Pineau CA, et al. A population-based assessment of live
births in women with systemic lupus erythematosus. Ann Rheum Dis 2012;
71:557–559; Epub 2011/11/16.
2. Barnabe C, Faris PD, Quan H. Canadian pregnancy outcomes in rheumatoid
arthritis and systemic lupus erythematosus. Int J Rheumatol 2011;
2011:345727; Epub 2011/10/27.
Systemic lupus erythematosus and pregnancy outcomes Peart and Clowse
3. Shand AW, Algert CS, March L, Roberts CL. Second pregnancy outcomes
&
for women with systemic lupus erythematosus. Ann Rheum Dis 2013;
72:547–551; Epub 2012/07/04.
Retrospective study demonstrating good pregnancy outcomes in women with
lupus who had a prior poor pregnancy outcome.
4. Clowse ME, Wallace DJ, Weisman M, et al. Predictors of preterm birth in
&
patients with mild systemic lupus erythematosus. Ann Rheum Dis 2013;
72:1536–1539; Epub 2013/01/31.
Identifies mid-pregnancy predictors of preterm birth, including estradiol, uric acid,
and ferritin.
5. Ko HS, Ahn HY, Jang DG, et al. Pregnancy outcomes and appropriate timing
of pregnancy in 183 pregnancies in Korean patients with SLE. Int J Med Sci
2011; 8:577–583; Epub 2011/10/25.
6. Madazli R, Yuksel MA, Oncul M, et al. Obstetric outcomes and prognostic
factors of lupus pregnancies. Arch Gynecol Obstet 2013; Epub 2013/06/
29.
7. Liu J, Zhao Y, Song Y, et al. Pregnancy in women with systemic lupus
erythematosus: a retrospective study of 111 pregnancies in Chinese women.
J Matern Fetal Neonatal Med 2011; 25:261–266; Epub 2011/04/21.
8. Saavedra MA, Cruz-Reyes C, Vera-Lastra O, et al. Impact of previous lupus
nephritis on maternal and fetal outcomes during pregnancy. Clin Rheumatol
2012; 31:813–819; Epub 2012/01/27.
9. Sifontis NM, Coscia LA, Constantinescu S, et al. Pregnancy outcomes in solid
organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 2006; 82:1698–1702.
10. Fischer-Betz R, Specker C, Brinks R, et al. Low risk of renal flares and negative
&&
outcomes in women with lupus nephritis conceiving after switching from
mycophenolate mofetil to azathioprine. Rheumatology (Oxford) 2013;
52:1070–1076; Epub 2013/02/06.
A prospective study that showed great success in transitioning women with
quiescent lupus nephritis from MMF to AZA prior to conception.
11. Ostensen M. Intravenous immunoglobulin does not prevent recurrence of
congenital heart block in children of SSA/Ro-positive mothers. Arthritis
Rheum 2010; 62:911–914; Epub 2010/02/05.
12. Eliasson H, Sonesson SE, Sharland G, et al. Isolated atrioventricular block in
the fetus: a retrospective, multinational, multicenter study of 175 patients.
Circulation 2011; 124:1919–1926; Epub 2011/10/12.
13. Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with
mortality and morbidity in a multiracial/ethnic registry of anti-SSA/Ro-associated
cardiac neonatal lupus. Circulation 2011; 124:1927–1935; Epub 2011/10/
05.
14. Tunks RD, Clowse ME, Miller SG, et al. Maternal autoantibody levels in
&
congenital heart block and potential prophylaxis with antiinflammatory agents.
Am J Obstet Gynecol 2013; 208:64e1–64e7; Epub 2012/10/16.
A nonrandomized prospective study that found a lower risk of CHB in women who
took low-dose prednisone or HCQ during pregnancy.
15. Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydro&&
xychloroquine is associated with a reduced risk of recurrent anti-SSA/
Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation
2012; 126:76–82; Epub 2012/05/26.
An analysis of several cohorts that identified HCQ as a protective agent against
CHB.
16. Levesque K. French Cohort Study of 141 Cases of Autoimmune Congenital
Heart Block. ACR Abstract Supplement: 2012 October 2012. Report No.:
Contract No.: 1649.
17. Friedman DM, Llanos C, Izmirly PM, et al. Evaluation of fetuses in a study of
intravenous immunoglobulin as preventive therapy for congenital heart block:
results of a multicenter, prospective, open-label clinical trial. Arthritis Rheum
2010; 62:1138–1146; Epub 2010/04/15.
18. Pisoni CN, Brucato A, Ruffatti A, et al. Failure of intravenous immunoglobulin to
prevent congenital heart block: findings of a multicenter, prospective, observational study. Arthritis Rheum 2010; 62:1147–1152; Epub 2010/02/05.
19. Auyeung-Kim DJ, Devalaraja MN, Migone TS, et al. Developmental and peripostnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator. Reprod Toxicol 2009;
28:443–455; Epub 2009/07/28.
20. GlaxoSmithKline. Use of Intravenous (IV) Benlysta in Pregnant Patients with
Systemic Lupus Erythematosus (SLE) 2013.
1040-8711 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins