Lupus (2005) 14, 8994

www.lupus-journal.com

PAPER

Pregnancy after lupus nephritis

G Moroni1
and C Ponticelli2
1

Unita Operativa di Nefrologia, IRCCS Ospedale Maggiore Policlinico, Milano; and 2IRCSS Instituto Auxologico Milano

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects primarily women,
commonly in their reproductive years but does not influence fertility. For these reasons, the clinician
has often to face the many problems of pregnancy in patients with SLE including the influence of SLE
on fetal outcome and that of pregnancy on SLE. As there is increasing evidence of an important role of
sex hormones in immunity, the influence of pregnancy on SLE is probably due to the changes in sex
hormone levels during pregnancy that are more important than in any other period of life.
Early reports emphasized a high fetal and maternal risk in particular in patients with lupus
nephritis. However in the same period the prognosis of lupus nephritis was poor, so it was difficult to
know whether pregnancy actually influenced the prognosis of the disease. More recent prospective
studies indicate that pregnancy is safe for the majority of mothers if it is planned when SLE is
quiescent. Instead, although fetal risk has been progressively reduced in the last 40 years, it continues
to be higher than that occurring in pregnancies of healthy women. In particular the presence of
antiphospholipid antibodies considerably worsen the fetal outcome. Lupus (2005) 14, 89 94.
Key words: antiphosholipid antibodies; lupus nephritis; pregnancy

In the early 1960s the results of pregnancies in women

with SLE were discouraging. Fetal survival was poor
and the risk of severe and even life threatening
complications was elevated for mothers.1 As a
consequence, most physicians recommended women
with SLE to avoid pregnancy. During the last decades
the number and the successes of pregnancies in SLE
women has progressively increased for several
reasons.2 Firstly, improvements in therapeutic strategies
for SLE resulted not only in better survival rates but
also better disease control in many patients. Improvements in obstetric and neonatal care permitted the
survival of fetuses delivered many weeks before full
term. Finally, more careful selection of patients based
on identification of the prognostic factors for fetal and
maternal outcome resulted in pregnancy being avoided
in high-risk patients Today, SLE is not considered
per se as a formal contraindication to pregnancy
although there still remain some doubts about the fetal
and maternal risks. In this review we will try to give
an overview of the main problems presented by
pregnancy in SLE patients, based on the reports
published between 1980 and 2003.

Correspondence: Gabriella Moroni, Unita Operativa di Nefrologia e

Dialisi, Ospedale Maggiore IRCCS, Via della Commenda 15 20122
Milano, Italy. E-mail: croff1@policlinico.mi.it
# 2005 Edward Arnold (Publishers) Ltd

Influence of pregnancy on lupus nephritis

The potential impact of pregnancy on lupus activity has
been debated for decades but no consensus has
emerged.
The immunological system during pregnancy
Many changes occur in the immunological system
during pregnancy that allow the mother to avoid an
immune response to the paternal major antigens of
histocompatibility while maintaining the normal
immune response to infections. Although there are no
significant differences in the absolute number of B and
T lymphocytes and NK cells, there is a great deal of
evidence that a switch from Th1 to Th2 response occurs
in pregnancy.3 These immunological changes are
influenced by the increased hormone levels. The
concentration of progesterone and estrogens increases
from four to eight times the level observed in non
pregnant women, although in SLE pregnant patients
hormone levels were found to be lower than in healthy
pregnant women.4 Progesterone stimulates the production by lymphocytes of progesterone-induced
blocking factor that suppresses the proliferation of
lymphocytes through the Th1/Th2 cytokine balance.5
In particular the progesterone-induced blocking factor
10.1191/0961203305lu2066oa

Pregnancy after lupus nephritis

G Moroni and C Ponticelli

90

stimulates the production of soluble factors that favour

the synthesis of prostaglandin E which suppresses the
production of IL2 from T lymphocytes. In contrast,
while in nonpregnant women estrogens stimulate the
T-cell responses and the autoantibodies production,
during pregnancy neither T-cell function nor immunoglobulin production increase. This lack of immune
stimulation by estrogen may be explained by increased
production of immune suppressive factors in pregnancy
that counterbalance the effects of estrogens. These
factors include progesterone, alpha-fetoprotein, human
chorionic gonadotropin, and a pregnancy-specific
b1glycoprotein. Such an interpretation may be
supported by some clinical studies indicating that
pregnancy does not exacerbate clinical lupus activity.6,7
On the other hand, it has been shown that in the murine
lupus model the switch to Th2 response during
pregnancy can enhance the activation of immune
response.5 A possible explanation for this discrepancy
could be that lymphocytes, activated at conception,
become more responsive to Th2 cytokines during
pregnancy.8 Accordingly, pregnancy would not induce
SLE flares unless the disease is already active at the
beginning of pregnancy. These data are in agreement
with those clinical studies9,10 that reported exacerbations of lupus during pregnancy in patients with
active disease.
Renal flares during pregnancy and post partum
A number of clinical studies have evaluated the risk of
flares during pregnancy in SLE patients with conflicting
results. Two prospective controlled studies6,7 reported a
lupus flare rate of 20 and 47%, respectively. In these
studies no difference in the flare rate was seen when
pregnant patients were compared with matched
nonpregnant lupus controls. In contrast, Petri et al.9
and Ruiz-Irastorza et al.10 reported higher flare rate, 60
and 65%, respectively, and found that pregnancy can

exacerbate lupus activity. These discrepancies can be

attributed to several factors: to the different definitions
of SLE flares, the different ethnicities and the different
entry criteria used in these studies. The situation is
even more complicated in patients with lupus nephritis
in whom concomitant morbidity can influence the
outcome of pregnancy. It is well known that renal
insufficiency and arterial hypertension are predictors
of bad outcome of pregnancy whatever the underlying
renal disease.11 In addition, it may be difficult to know
whether an increase in proteinuria and/or the onset of
arterial hypertension should be blamed on pregnancy
itself or to a renal flare. This might partially explain
why the incidence of renal flares during pregnancy or
after delivery in patients with lupus nephritis ranged
between eight and 64% (Table 1) while renal flares
characterized by impairment in renal function ranged
between 0 and 23% of cases. Once again the different
definitions of flares can partly account for these wide
variations. In our unit we used more stringent criteria
to define renal flares. We defined nephritic flare as an
increase in plasma creatinine of at least 30% over the
last value associated with nephritic urinary sediment
and generally increased proteinuria, and a proteinuric
flare as an increase in proteinuria without modification of plasma creatinine. Proteinuria had to increase
by at least 2 g per day if the basal proteinuria was less
than 3.5 g per day, or be doubled if the patient already
had nephrotic proteinuria. We followed 51 pregnancies in 38 women with established lupus nephritis and
observed, four nephritic flares and four proteinuric
flares during pregnancy; and five proteinuric flares in
the post-partum period, the prevalence of renal flares
being 25%. No prospective controlled trial has been
carried out to our knowledge to compare the
prevalence of renal flares in pregnant patients with
lupus nephritis versus nonpregnant lupus nephritis
patients. In our patients the prevalence of renal flares
observed in the period from the diagnosis of lupus

Table 1 Maternal outcome in pregnancies of patients with established lupus nephritis (excluding patients with the onset of lupus nephritis
during pregnancy)
Authors
14

Hayslett and Lynn

Jungers et al.16
Imbasciati et al.19
Oviasu et al.36
Packham et al.20
Julkunen et al.30
Huong et al.31
Moroni et al.12

Legend: N number.
Lupus

N pregnancy
(N women)

SLE flares

SLE activity at pregnancy

onset versus flares

Flares with
renal insuffiency

Deaths

47
26 (14)
22 (19)
53 (25)
47
26 (16)
31 (21)
57 (38)

24
12
14
6
16
2
5
13

Active 48% Inactive 32%

Active 91% Inactive 27%
Active 100% Inactive 53%
NA
NA
Active/Inactive 8%
NA
Active 39% Inactive 5%

10 (18%)
5 (14%)
5 (23%)
6 (13%)
6 (13%)
0
0
4 (8%)

1
NA
2
0
0
0
0
1

(43%)
(46%)
(64%)
(13%)
(35%)
(8%)
(15%)
(25%)

Pregnancy after lupus nephritis

G Moroni and C Ponticelli

91

nephritis to the beginning of pregnancy was not

significantly different from that observed during
pregnancy and in the six months after delivery.12
Some factors have been reported to be associated
with renal flares during pregnancy or the post-partum
period.
In the early 1960s, Estes and Larson13 underlined
that in pregnant patients with active lupus, the risk of
exacerbations was more than double that in patients
with quiescent disease. Using survey data, Hayslett
and Lynn14 confirmed these results and found that
active lupus at the time of conception was associated
with increased or persistent lupus activity in 48% of
patients. In contrast, if lupus had been in clinical
remission for at least six months prior to pregnancy
only 32% of the patients had relapses during and after
pregnancy. Three other studies have confirmed the
importance of remission of renal disease before
conception for the outcome of lupus nephritis during
pregnancy.15 17 We too observed only one renal flare
out of 20 patients who were in complete remission
of renal disease at the beginning of pregnancy in
comparison with 12 flares in 31 pregnancies in women
with active renal disease.12
The presence of moderate or severe renal insufficiency at conception may increase the risk of severe
hypertension and accelerated decline of renal function.11 The worse the renal function, the poorer the
prognosis. In normotensive patients with a mild but
stable decrease of renal function, the risk of irreversible
progression of renal insufficiency for the mother is low.
If renal function is moderately impaired (serum
creatinine 1.4 3.0 mg/dL) the prognosis is worse, as
about one-third of these patients will have persistent
renal function deterioration. Patients with severe renal
insufficiency are at high risk of poor fetal and maternal
outcome. In women submitted to dialysis the
potential complications include malignant hypertension
and intraperitoneal hemorrhage.18 On the other hand,
severe renal flares can be observed, although more
rarely, even in patients with normal renal function and
complete remission at conception.17,19 The prognosis
of renal flares is good for the majority of cases if a
prompt diagnosis is made and an appropriate therapy is
instituted. As a matter of fact, irreversible renal
insufficiency has been reported to range between 0 to
10%19,20 while arterial hypertension persisted in
another 13% of patients.12
Pregnant women with antiphospholipid antibodies
(aPL) are particularly prone to develop arterial
hypertension favored by the endothelial vascular
damage caused by these antibodies. Another possible
complication in aPL positive pregnant women is the
development of a thrombotic microangiopathy leading
to severe renal failure.21 The renal prognosis may be

poor in these cases although late recovery is possible in

a few patients.
A recent prospective evaluation of 103 pregnancies
in SLE women underlines the fact that the withdrawal
of chloroquine treatment was significantly associated
with the developement of flares during pregnancy.22

Pre-eclampsia
Pre-eclampsia has traditionally been described as the
occurrence of hypertension, edema and proteinuria
after 20 weeks gestation that frequently requires
preterm delivery. The risk of pre-eclampsia is more
elevated in lupus patients (from 13 to 32%)23,24 than in
healthy women (from 3 to 5%).25 Pre-eclampsia is more
likely to occur in patients with renal disease, and/or
arterial hypertension, as well as in women with active
lupus at the beginning of pregnancy, in particular in
those taking more than 30 mg prednisone per day.26 A
high rate of pre-eclampsia has been reported in patients
with well defined antiphospholipid antibody syndrome.27 Although the differential diagnosis between
pre-eclampsia and renal flare is particularly important
as it implies different treatments, the differential
diagnosis can be difficult and in some cases the two
conditions can even coexist. Some laboratory tests can
be useful: a) high or rising levels of anti-DNA
antibodies, anti-C1q antibodies, hypocomplementemia
and activation of the alternative complement pathway are frequently associated with renal flares while
they may be normal in pre-eclampsia; b) in a lupus
flare, proteinuria is associated with an active urinary
sediment (red and white cells and cellular casts)
whereas in pre-eclampsia only proteinuria is present.
Rapid worsening of proteinuria from one day to the
next is more common in pre-eclampsia than in renal
flare. After delivery proteinuria rapidly decreases in
pre-eclampsia while it tends to persist or even to
increase in renal flare; c) thrombocytopenia, elevated
serum levels of liver enzymes and uric acid are more
frequent in pre-eclampsia, while renal flares are often
associated with other clinical signs and symptoms of
SLE. Therefore the best way of detecting SLE activity
during pregnancy is a frequent clinical monitoring of
the patient. Particularly in difficult cases renal biopsy
may provide an accurate diagnosis and allows the
clinicians to take the appropriate therapeutical
decisions.

Influence of lupus nephritis on fetal outcome

A high rate of adverse fetal events can occur in pregnant
women with lupus. These include a high rate of fetal
Lupus

Pregnancy after lupus nephritis

G Moroni and C Ponticelli

92

losses, a high frequency of late miscarriages, premature

delivery and intrauterine growth retardation. Although
progressively reduced during the last 40 years the
incidence of fetal loss in SLE patients is still higher
than in healthy pregnant women. A retrospective casecontrol study comparing the outcome of 481
pregnancies in lupus patients with 356 pregnancies in
blood relatives and 166 controlled pregnancies in best
friends reported a fetal loss in 21% of lupus pregnancies, in 8% of relatives pregnancies and in 14% of
best friends pregnancies.28 In patients with lupus
nephritis fetal losses ranged between eight and 36%,
miscarriages between 4 and 31%, and stillbirths or
neonatal deaths between 4 and 23% (Table 2). While
fetal losses are progressively declining, there is a trend
towards an increased number of pre-term deliveries
that, in a recent study, occurred in more than 70% of
live births.29
There is general agreement that in pregnancies
begun after the diagnosis of SLE, the fetal prognosis
largely depends on disease activity. Fetal loss ranged
between 25 to 57% in patients with active lupus
nephritis at conception versus eight to 12.5% in SLE
women with inactive renal disease at the onset of
pregnancy (Table 2).12,14,15,28,30 Our results are in
agreement. The presence of proteinuria is another risk
factor of fetal loss. The fetal loss ranged between 36
and 38%31 in lupus patients with proteinuria in comparison to 13% of patients without proteinuria.12 All
these observations suggest that the quiescence of renal
disease is a prerequisite for a successful pregnancy and
underline the advisability of avoiding pregnancy in
patients with active lupus nephritis. Impaired renal
function is another strong predictor of poor fetal outcome in SLE patients14 as well as in pregnant women
with other renal diseases.32,33 In patients on regular
dialysis the success rate of pregnancy is less than
50%.18 In contrast, in women with SLE who have had a
kidney transplant the outcome of pregnancy is good
and comparable to that of renal transplant recipients
with other primary renal disease (73% live births in

lupus patients versus 76% in control patients).34 There

is litte information about the impact of hypertension on
fetal loss. However, there is some evidence that
hypertension can increase the risk for perinatal
morbidity and mortality.35 Oviasu et al.36 reported a
fetal loss in 29% of hypertensive patients vs. 13% in
normotensive SLE mothers. In our experience fetal
loss occurred in 70% of cases when the mother was
hypertensive and in 27% of cases when the mother was
normotensive.12
Some 20 years ago it was pointed out that the
presence of aPL in pregnant women was associated
with a high risk of repeated miscarriages and of
unexpected intrauterine deaths in the second and third
trimester.20,37 These data have been confirmed by more
recent reports. A review of 10 studies of 554 women
with SLE found that fetal loss ranged from 39 to 59% in
patients with aPL vs. 16 20% in those without such
antibodies, 36% in patients with lupus anticoagulant vs.
13% in negative patients and 39% in patients with
anticardiolipin antibodies vs. 18% in negative
patients.38 Packham et al.20 reported a fetal loss in
53% of pregnancies in patients with lupus nephritis
and aPL versus 14% in aPL negative patients. Our
results are in agreement: in a multivariate analysis of
70 pregnancies in patients with lupus nephritis, aPL
emerged as an independent predictor of fetal loss. We
observed a fetal loss in 13% of aPL negative patients
versus 83% of patients with aPL.12 Two studies did not
find any correlation between the presence of aPL and
fetal outcome29,36 but the number of aPL positive
patients evaluated was low. Fetal losses have been
attributed to thrombosis of the uteroplacental vessels
and placental infarction. However, these thrombosis
are not present in all cases in a sufficient degree to
account for pregnancy loss. Recent studies have
underlined that aPL decrease the placental hormone
production and trophoblast intercellular fusion and
invasion. These data may suggest that some obstetrical
complications are the consequence of trophoblast
dysfunction induced by aPL.39

Table 2 Fetal outcome in pregnancies of patients with established lupus nephritis (excluding patients with the onset of lupus nephritis
during pregnancy)
Authors

N pregnancy
(N women)

Therapeutic
abortion N

Fetal loss

SLE activity versus

fetal loss

Miscarriages
N

Stillbirths
N

Premature
deliveries N

Full term
deliveries N

Hayslett and Lynn14

Jungers et al.16
Imbasciati et al.19
Oviasu et al.36
Packham et al.20
Julkunen et al.30
Huong et al.31
Moroni et al.12

47
26
22
53
47
26
31
57

9
3
2
6
/
2
0
6

11 (24%)
4 (17%)
8 (36%)
9 (19%)
14 (30%)
2 (8%)
7 (22.5%)
18 (35%)

Active 36% Inactive 12.5%

Active 25% Inactive 9%
NA
NA
LAC 53% LAC 2 15%
Active/inactive 8%
Active 33% Inactive 7%
Active 57% Inactive 10%

6
3
3
8
8
1
5
16

5 (11%)
1 (4%)
5 (23%)
1 (2%)
6 (13%)
1 (4%)
2 (6.5%)
2 (4%)

1
2
9
10
13
6
18
10

35
17
5
28
20
16
6
23

N number.
Lupus

(14)
(19)
(25)
(16)
(21)
(38)

(13%)
(13%)
(13%)
(17%)
(17%)
(4%)
(126%)
(31%)

(2%)
(9%)
(41%)
(21%)
(28%)
(25%)
(58%)
(20%)

(74%)
(74%)
(23%)
(60%)
(42%)
(67%)
(19.5%)
(45%)

Pregnancy after lupus nephritis

G Moroni and C Ponticelli

Prematurity is a constant hazard in lupus pregnancy.

The preterm delivery rate in lupus nephritis pregnancies
is extremely wide ranging from 3 to 74% of live
births.14,29 The variable definition of preterm delivery
in different studies may partly account for this
discrepancy. Intrauterine growth retardation occurs in
10 to 30% of cases.20,30 Arterial hypertension emerged
as an important predictor of premature delivery and
of intrauterine growth retardation in many studies.
Rahman et al.40 and Cortes-Hernandez et al.22 found
that maternal arterial hypertension was an independent
predictor for premature delivery. Other authors
reported an association of prematurity with a prednisone dose of more than 20 mg per day, with aPL
positivity, with pre-eclampsia and with premature
rupture of membranes.19,31 In a recent study the presence of antibodies directed against protein S was
significantly correlated with prematurity and intrauterine growth retardation in pregnancies of SLE
patients.41 Nowadays, however, in experienced hands,
perinatal and postpartum deaths are becoming less and
less frequent.

Drug treatment in pregnant women

with lupus nephritis
The aim of the treatment is to maintain renal disease
quiescent during and after pregnancy and to improve
the outcome of the fetus. The immunosuppressive
treatment given at the beginning of pregnancy should
usually be continued. Corticosteroids and azathioprine
can be used during pregnancy, but cyclophosphamide
and methotrexate are teratogenic and should be stopped
respectively six months and three months before
conception.30 The use of hydroxychloroquine (HCQ)
during pregnancy remains controversial. It has been
demonstrated that HCQ passes through the placenta,
with cord blood concentrations nearly identical to those
found in maternal blood. However, the successes of
pregnancies were similar in 154 women taking HCQ
and in their untreated control (88% live births in HCQ
versus 84% in controls). Three malformations were
observed in the HCQ group versus four in the control
group.42 Although more data are necessary to confirm
the safety of HCQ during pregnancy, these results seem
to suggest that this drug may be maintained during
pregnancy. Two different therapeutic approaches have
been proposed to prevent renal flares during pregnancy:
i) administration of a minimum dosage of prednisone
(.10 mg/day) to all SLE patients who become
pregnant, irrespective of the activity of the disease;2
ii) the administration of high-dose steroids (80 mg/day
prednisone or equivalent) for a few days before and
after delivery to reduce the exacerbation rate during

post-partum.12,36 With the first approach, in a prospective study, the rate of SLE reactivation was 60%, a
rate similar to that observed in studies in which the
therapy was not modified during pregnancy.2 With
the second approach a reduction of flares during the
puerperium was reported by some authors,2,43 but not
by others.44 At any rate, whenever a flare occurs it
should be treated agressively with high doses of
corticosteroids plus azathioprine if needed. There is
general agreement that pregnant women with severe
hypertension should receive pharmacological treatment.35 Alfa-methyldopa, hydralazine and labetalol
have a long record of safety in pregnancy, while
calcium channel blockers and angiotensin-converting
enzyme inhibitors are contraindicated because of their
potential teratogenicity. Randomized controlled trials
showed that the fetal outcome of pregnancies in aPL
positive mothers has significantly improved since the
demonstration that low dose aspirin and heparin
markedly reduced the fetal wastage rate.45,56
In summary, in pregnant women with renal SLE the
fetal and maternal outcome is strongly correlated with
lupus activity, kidney function and the presence of aPL
at the time of conception.10 The probabilities of
favorable fetal and renal outcomes are good in women
with stable and prolonged remission of SLE, normal
renal function, normal blood pressure and negative
aPL. On the contrary, the risk of fetal loss and/or
kidney function deterioration is elevated in patients
with active SLE and/or renal insufficiency. To prevent
renal complications a reinforcement of prednisone for a
few days before the estimated delivery and for a week
after delivery or miscarriage with rapid tapering to
maintenance levels may be suggested. However no
randomized trial has dealt with this particular problem.
Planning pregnancy during the phases of quiescent
renal disease, careful monitoring of blood pressure,
renal function and urinalysis, and treatment with
heparin and low dose aspirin in women with positive
aPL are the prerequisites for successful pregnancies in
patients with lupus nephritis.

93

Acknowledgements
This study was supported by the grant Project in
glomerulonephritis in memory of Pippo Neglia.

References
1 Ellis FA, Bereston ES. Lupus erythematosus associated with pregnancy
and menopause. Arch Dermatol Siphil Dis 1952; 65: 170 176.
2 Mintz G, Niz J, Guttierez G, Garcia A, Karchmer S. Prospective study of
pregnancy in systemic lupus erythematosus. Results of a multidisciplinary approach. J Rheumatol 1986; 13: 732739.
Lupus

Pregnancy after lupus nephritis

G Moroni and C Ponticelli

94
3 Saito S, Sakai M, Sasaki Y, Tanebe K, Tsuda H, Michimata T.
Quantitative analysis of pheripheral blood Th0, Th1, Th2 and the
Th1:Th2 cell ratio during normal human pregnancy and pre-eclampsia.
Clin Exp Immunol 1999; 117: 550 555.
4 Doria A, Cutolo M, Ghirardello A et al. Steroid hormones and disease
activity during pregnancy in systemic lupus erythematosus. Arthritis
Rheum 2002; 47: 202 209.
5 Formby B. Immunologic response in pregnancy. Its role in endocrine
disorders of pregnancy and influence on the course of maternal autoimmune
diseases. Endocrinol Metab Clin North Am 1995; 24: 187205.
6 Lockshin MD, Reinitz E, Druzin ML, Murrmann M, Estes D. Lupus
pregnancy. Case-control prospective study demonstrating absence
of lupus exacerbation during or after pregnancy. Am J Med 1984; 77:
893898.
7 Urowitz MB, Gladman DD, Farewell VT, Stewart J, McDonald J. Lupus
and pregnancy studies. Arthritis Rheum 1993; 36: 13921397.
8 Singh AK. Lupus nephritis and the anti-phospholipid antibody
syndrome in pregnancy. Kidney Int 2000; 58: 22402254.
9 Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy. The
Hopkins lupus pregnancy center experience. Arthritis Rheum 1991; 34:
15381545.
10 Ruiz-Irastorza G, Lima F, Alves J et al. Increased rate of lupus flare
during pregnancy and the puerperium, a prospective study of 78
pregnancies. Br J Rheumatol 1996; 35: 133138.
11 Jones DC, Hayslett JP. Outcome of pregnancy in women with moderate
or severe renal insufficiency. N Engl J Med 1996; 335: 226232.
12 Moroni G, Quaglini S, Banfi G et al. Pregnancy in lupus nephritis. Am J
Kidney Dis 2002; 40: 713 720.
13 Estes ZD, Larson DL. Systemic lupus erythematosus and pregnancy.
Clin Obstet Gynecol 1965; 8: 307 321.
14 Hayslett JP, Lynn RI. Effect of pregnancy in patients with lupus
nephropathy. Kidney Int 1980; 18: 207220.
15 Zulman J, Tala N, Hoffman GS, Epstein WWV. Problems associated with
the management of pregnancies in patients with systemic lupus
erythematosus. J Rheumatol 1980; 7: 3749.
16 Jungers P, Dougados M, Pelissler C et al. Lupus nephropathy and
pregnancy. Report of 104 cases in 36 patients. Arch Intern Med 1982;
142: 771 776.
17 Bobrie G, Liote F, Houiller P, Grunfeld GP, Jungers P. Pregnancy in lupus
nephritis and related disorders. Am J Kidney Dis 1987; 9: 339343.
18 Gafter V. Successful pregnancies in women on regular hemodialysis
treatment. Israel Journal of Medical Science 1990; 26: 266 270.
19 Imbasciati E, Surian M, Bottino S et al. Lupus nephropathy and
pregnancy. A study of 26 pregnancies in patients with systemic lupus
erythematosus and nephritis. Nephron 1984; 36: 4651.
20 Packham DK, Lam SS, Nicholls K, Fairley KF, Kincaid-Smith PS.
Lupus nephritis and pregnancy. Q J Med 1992; 83: 315 324.
21 Kincaid-Smith P, Fairley KF, Kloss M. Lupus anticoagulant associated
with renal thrombotic microangiopathy and pregnancy-related renal
failure. Q J Med 1988; 69: 795 815.
22 Cortes-Hernandez J, Ordi-Ros J, Pares F, Casellas M, Castillo M,
Vilarde Tarres M. Clinical predictors of fetal and maternal outcome in
systemic lupus erythematosus a prospective study of 103 pregnancies.
Rheumatology 2002; 41: 643 650.
23 Lockshin MD. Pregnancy does not cause SLE to worsen. Arthritis
Rheum 1989; 32: 665 670.

Lupus

24 Burkett G. Lupus nephropathy and pregnancy. Clin Obstet Gynecol

1985; 28: 310 323.
25 Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia.
Lancet 2001; 357: 5356.
26 Lockshin MD, Qamar T, Druzin ML. Hazards of lupus pregnancy.
J Rheumatol 1987; 14: 214 217.
27 Branch DW, Andres R, Digre KB, Rote NS, Scott JR. The association of
aPL with severe preeclampsia. Obstet Gynecol 1989; 73: 541545.
28 Petri M, Allbritton J. Fetal outcome in lupus pregnancy: a retrospective
case control study of the Hopkins lupus cohort. J Rheumatol 1993; 20:
650 656.
29 Houng LT, Wechsler B, Vauther-Brouzes D, Beautifils H, Lefebvre G,
Piette JC. Pregnancy in past or present lupus nephritis: a study of 32
pregnancies from a single center. An Rheum Dis 2001; 60: 599604.
30 Julkunen H. Renal lupus in pregnancy. Scand J Rheumatol 1998; 27:
80 83.
31 Huong DT, Wechsler B, Piette JC, Bletry O, Godeau P. Pregnancy and its
outcome in systemic lupus erythematosus. Q J Med 1994; 87: 721729.
32 Imbasciati E, Ponticelli C. Pregnancy and renal disease. Predictors for
fetal and maternal outcome. Am J Nephrol 1991; 11: 353 362.
33 Hou SH, Grossman SD, Madias NE. Pregnancy in women with renal
disease and moderate renal insufficiency. Am J Med 1985; 78: 185194.
34 McGrory CH, McCloskey LJ, DeHoratius RJ, Dunn SR, Moritz MJ,
Armenti VT. Pregnancy outcome in female renal recipients: a
comparison of systemic lupus erythematosus with other diagnoses. Am
J Transplant 2003; 3: 3542.
35 Sibai BM. Diagnosis and management of chronic hypertension in
pregnancy. Obstet Gynecol 1992; 78: 451461.
36 Oviasu E, Hicks J, Cameron JS. The outcome of pregnancy in women
with lupus nephritis. Lupus 1991; 1: 19 25.
37 Prentice R, Gatenby PA, Loblay RH, Shearman RP, Kronenberg H. Baste
Lupus anticoagulant in pregnancy. Lancet 1984; 2: 464.
38 McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical
importance of aPL. Adv Immunol 1991; 49: 193.
39 Caruso A, De Carolis S, Di Simone N. APL in obstetrics: new
complexity sites of action. Hum Reprod Update 1999; 5: 267 276.
40 Rahman P, Gladman DD, Urowitz MB. Clinical predictors of fetal
outcome in systemic lupus erythematosus. J Rheumatol 1998; 25:
15261530.
41 Bertolaccini ML, Sanna G, Ralhan S et al. Antibodies directed to
protein S in patients with systemic lupus erythematosus: prevalence and
clinical significance. Thromb Haemost 2003; 90: 636 641.
42 Costedoat-Chalumeau N, Amoura Z, Duhaut P, Huong DLT et al. Safety
of hydroxychloroquine in pregnant patients with connective tissue
diseses. Arthritis Rheum 2003; 48: 32173211.
43 McGee, Makowski EL. Systemic lupus erythematosus in pregnancy.
Am J Obstet Gynec 1970; 107: 10081012.
44 Khamashata MA, Hughes GR. Pregnancy in systemic lupus
erythematosus. Curr Opin Rheumatol 1996; 8: 424 429.
45 Kutteh WH, Ermel LD. A clinical trial of the treatment of
antiphspholipid antibody associated recurrent pregnancy loss with
lower dose heparin and aspirin. Am J Reprod 1996; 4: 402 407.
46 Rai R, Cohen H, Dave M, and Reagan L. Randomized controlled trial of
aspirin plus heparin in pregnant women with recurrent miscarriage
associated with phospholipid antibodies (or aPL). BMJ 1997; 314:
253 257.

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