Lupus (2010) 19, 16651673

http://lup.sagepub.com

LUPUS AROUND THE WORLD

Pregnancy outcome in 396 pregnancies in

patients with SLE in Saudi Arabia
AS Al Arfaj and N Khalil
Division of Rheumatology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

The aim of this study was to examine the pregnancy outcomes in patients with systemic lupus
erythematosus (SLE) and the effect of SLE flare and treatment on pregnancy outcomes.
We performed a retrospective evaluation of all pregnancies occurring in patients with SLE
during the 27-year period from 1980 to 2006. Of the 319 women with SLE planning pregnancy
after SLE onset, 176 (55.2%) conceived resulting in 396 pregnancies. Live births were significantly lower in proportion (70.2% vs. 85.7%) and more likely to end in fetal deaths (29.7%
vs. 14.2%) and preterm births (26.7% vs. 5.8 %) in pregnancies occurring after SLE onset
than in pregnancies occurring before SLE onset (p < 0.0001). With respect to different disease
manifestations, we found that fetal loss was significantly higher in patients with antiphospholipid (aPL) antibodies than without (p < 0.001). Preterm deliveries were significantly
more frequent in patients with lupus nephritis, anti-Ro/SSA antibodies, hypertension, history
of intravenous cyclophosphamide treatment and aPL than those without these features
(p < 0.05). Neonates with intrauterine growth retardation (IUGR) neonates were more
common in hypertensive and Raynauds-positive pregnancies (p < 0.05). SLE flares occurred
in 30.8% pregnancies. There was increased risk of fetal loss, preterm births and IUGR in
pregnancies with SLE exacerbations than without (p < 0.05). Prednisolone was found to
improve the rate of live births, although it was also a predictor of prematurity. The predictors
of pregnancy loss were lupus nephritis (odds ratio (OR) 7.3), aPL (OR 3.9), and SLE flares in
pregnancy (OR 1.9). There was higher risk of preterm deliveries in patients with lupus nephritis (OR 18.9), anti-Ro antibodies (OR 13.9), hypertension (OR 15.7) and SLE flares (OR 2.5).
IUGR was found to be associated with hypertension (OR 37.7), Raynauds (OR 12.3), and
SLE flares (OR 4.2). In conclusion, pregnancies in SLE patients with active lupus nephritis,
anti-Ro/SSA antibodies, aPL, hypertension, Raynauds phenomenon, active disease at conception and SLE exacerbations are at a higher risk of adverse pregnancy outcomes. It is
important to carefully plan pregnancy, and experienced rheumatologists and obstetricians
should monitor SLE patients in pregnancy and postpartum. Lupus (2010) 19, 16651673.
Key words: pregnancy outcome; Saudi Arabia; systemic lupus erythematosus

Introduction
Systemic lupus erythematosus (SLE) is a chronic,
multisystem autoimmune disease aecting in particular women of childbearing age. The impact of
SLE on pregnancy and of pregnancy on maternal
lupus has been reported by several studies but with
variable results. Some reports indicate that there is
an increase in SLE ares during pregnancy,13 and
Correspondence to: Professor Abdurahman Saud Al Arfaj, Division of
Rheumatology, Department of Medicine, College of Medicine, King
Saud University, P.O. Box 34471, Riyadh 11468, Saudi Arabia.
Email: zumaigahoo@yahoo.com
Received 27 February 2010; accepted 17 June 2010
! The Author(s), 2010. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav

others found no dierence in ares between pregnant and non-pregnant patients with SLE 4,5 and
between pregnancies in women with active and
inactive lupus.2,6 The rates of SLE ares in pregnancies have been reported to range from 1368 %,
but rates have been reported to be reduced if pregnancy is delayed until disease is quiescent.25,710
Pregnancies in patients with SLE have been
reported to have higher rates of fetal loss, preterm
delivery, preeclampsia, intrauterine growth retardation (IUGR) and neonatal lupus syndromes.1,7,8,11,12 In addition, the rate of early
pregnancy loss has been reported to be twice that
of non-SLE pregnancies,10 and the rate of preterm
delivery to be 1754%.89,12 Unfavorable pregnancy
10.1177/0961203310378669

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

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1666

outcome has been reported to be associated with

specic factors which include active disease during
pregnancy, renal involvement, hypocomplementemia, and antibodies to Ro/SSA, etc.6,9,12
There are a few reports on pregnancies in SLE
patients from Asia,13 but pregnancy studies in
patients with SLE from the Middle East are negligible. However, a report has been published very
recently from western Saudi Arabia which deals
with pregnancies in a small subset of SLE patients.14
The present study was undertaken to examine the
pregnancy outcomes in a large cohort of patients
with SLE in order to identify the impact of SLE
on pregnancy and of pregnancy on SLE. Our SLE
cohort is an ideal group for the study of pregnancy
outcomes in SLE, as large family sizes are preferred
in the Saudi community, giving an opportunity to
study large number of SLE pregnancies.

complements C3 and C4, hypertension (HTN),

Raynauds phenomenon, aPL and lupus ares in
pregnancy. Pregnancies occurring in women who
were previously administered intravenous cyclophosphamide (IV cyclo) were compared with pregnancies in women who did not receive it.
Statistical analysis
Statistical analysis was performed using SPSS
(version 15) and the results are presented as percentages and means. Students t-test was used to
test the dierence in mean values of continuous
variables, and paired t-test was used to compare
groups of SLE patients with dierent characteristics. Multivariate logistic regression analysis was
employed to nd the risk factors for adverse pregnancy outcomes. Odds ratios (ORs) and 95% condence intervals (CIs) were computed. A p-value
<0.05 was considered signicant.

Materials and methods

A retrospective study of all pregnancies in patients
with SLE managed at King Khalid University
Hospital, Riyadh, during the period from 1980
2006 was carried out. SLE was diagnosed according
to 1982 revised criteria of ACR.15 Demographic
data, SLE clinical manifestations and treatment,
maternal SLE status (are or no are), pregnancy
data, its outcome and therapy were recorded
from medical charts. Laboratory data included
complete blood count, urinalysis, antinuclear antibodies (ANA), double stranded (ds) DNA antibodies,
anti-Ro/SSA
antibodies,
anti-La/SSB
antibodies, antiphospholipid antibodies (aPL),
and complements C3 and C4. The pregnancy outcomes retrieved were live births including term and
preterm births, pregnancy loss including miscarriages, stillbirths and neonatal deaths (NND), as
well as gestational age at birth in weeks, infant
birth weight, and IUGR. A are was dened as
onset of new signs of SLE disease activity during
pregnancies in patients previously in remission.
Preterm birth was dened as a live birth occurring
before 37 weeks of gestation, stillbirths as no signs
of life in a fetus delivered after 24 weeks of gestation, and low birth weight as <2.5 kg birth weight
of infant at term.
Pregnancies occurring after the onset of SLE,
were compared with pregnancies occurring before
the onset of SLE. Pregnancy outcome was also
compared between SLE patients with and without
dierent manifestations including lupus nephritis,
anti-Ro/SSA antibodies, anti-La/SSB antibodies,
Lupus

Results
Patient characteristics (after SLE onset)
A total of 566 female SLE patients were seen in
our rheumatology clinics during the 27-year study
period. Among the 556 adult SLE patients identied, 319 were planning for pregnancy and 21 were
menopausal at SLE onset. Out of the 319 women
planning for pregnancy 176 (55.2%) conceived,
resulting in 396 pregnancies, while 143 (44.8%)
could not achieve pregnancy (18 due to primary
infertility). The mean age at SLE onset of the 176
women who achieved pregnancy was 25.6  7.1
years (range 1543 years), and of 143 women
unable to conceive was 32.8  9.2 years (range
1452 years), and the dierence was statistically
signicant (p < 0.0001).
Pregnancy details of 176 pregnant women
Mean age at the time of study was 36.4  7.4 years
(range 1854 years), mean SLE duration was
11.4  5.4 years (range 227 years), and mean
SLE follow-up was 7.4  5.5 years (range 0.322.8
years); 173 were Arabs and three were non-Arabs.
Mean number of pregnancies per patient was
2.3  1.8 (range 112). In 11 (6.3%) women SLE
was diagnosed during pregnancy. All 176 women
were ANA positive, anti-dsDNA was positive in
142 (80.7%), anti-Ro in 39 of 75 tested (52.0%),
anti-La in 17 of 75 tested (22.7%), low C3 in
43 of 121 tested (35.5%), and low C4 in 38 of 107
tested (35.5%) women. Of the 176 women,

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

AS Al Arfaj and N Khalil

1667

73 (41.5%) had a history of lupus nephritis, and

37 of 176 (21.0%) had HTN. Of the 176 women
who conceived, 48 (27.3%) had history of receiving
IV cyclo in the years before pregnancy.
Patient characteristics (before SLE onset)
Among the 459 adult females identied, 324
(70.6%) were planning for pregnancy. Pregnancy
data was available for 247 of these 324 women,
of whom 50 could not achieve any pregnancy,
and the remaining 197 became pregnant resulting
in 925 pregnancies. Mean number of pregnancies
per patient was 4.7  3.3 (range 118), which was
signicantly higher than the corresponding value
in pregnancies after onset of SLE (2.3  1.8;
p < 0.0001).
Pregnancy outcome (after SLE onset)
After SLE onset, 176 women had 396 pregnancies.
Eighty-six women had one pregnancy each, 35
had two each, 21 had three each, 19 had four
each, eight had ve each, three had seven each,
two had eight each and another two had twelve
pregnancies each, resulting in 396 pregnancies.
In the 383 pregnancies with complete data (13 pregnancies excluded from further analysis due to inadequate data), there were 269 (70.2%) live births,

94 (24.5%) miscarriages, 17 (4.4%) stillbirths and

three (0.8%) NND (Figure 1). Thirty women had
one miscarriage each, eight had two each, ve
had three each, four had four each, one woman
had ve and another one woman had twelve miscarriages. There were 176 (73.3%) term and
64 (26.7%) preterm births among 240 live births,
and 60 (25.0%) of 240 live births were complicated
by IUGR. Mean gestational age at delivery was
36.5  3.2 weeks (range 2542 weeks), and mean
birth weight of infants was 2.47  0.79 kg (range
0.6603.9 kg).
Pregnancy outcome (before SLE onset)
Before SLE onset, 197 women had 925 pregnancies.
Among 925 pregnancies, 793 (85.7%) were live
births, 104 (11.2%) were miscarriages, 25 (2.7%)
were stillbirths and three (0.3%) were NND. Live
births were term deliveries in 747 (94.2%) and preterm in 46 pregnancies (5.8%) (Figure 1).
Comparative pregnancy outcome (before and after
SLE onset)
The proportion of pregnancies ending in live
birth was signicantly lower among women after
acquiring SLE (70.2%) than in women before
SLE (85.7%) (p < 0.0001). The proportion of

94.2

100
90

85.7

80

73.3

70.2

Percentage

70

Before SLE onset

After SLE onset

60
50
40

26.7
24.5

30
20

11.2
2.7 4.4

10

5.8
0.3 0.8

0
Live
births

Miscarriages

Still
births

Neonatal
deaths

Term
births

Preterm
births

Figure 1 Pregnancy outcome before and after SLE onset.

Lupus

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

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1668

miscarriages was signicantly higher in pregnancies

conceived after SLE onset (24.5%) than before SLE
(11.2%) (p < 0.0001). Overall fetal death was twice
as likely in SLE pregnancies (29.7%) than in pregnancies before SLE (14.2%) (p < 0.0001). Preterm
births were signicantly more prevalent in postSLE live births (26.7%) than in pregnancies conceived before SLE diagnosis (5.8%) (p < 0.0001).
Pregnancy outcome in patients with and without
lupus nephritis
There was a smaller proportion of live births in
patients with lupus nephritis (65.4%) compared
with those without (73.5%), and the proportion of
miscarriages was higher in lupus nephritis patients

Table 1

(28.8%) compared with patients with no lupus

nephritis (21.7%), though this was not signicant
statistically (p > 0.05). However, preterm births
were signicantly more common in lupus nephritis
patients (36.4%) than in SLE patients with no
renal disease (21.1%) (p 0.010) (Table 1). Renal
disease was active at the time of conception in
44 (28.8%) and quiescent in 109 (71.2%) of the
153 lupus nephritis pregnancies. Compared with
quiescent renal disease, active lupus nephritis at conception signicantly raised the rate of pregnancy
loss (p < 0.001) and of preterm deliveries
(p 0.014) (Table 2). IUGR outcome was not
aected by the state of renal disease at conception
(p 0.333).

Comparison of pregnancy outcomes in different SLE characteristics, SLE flares and different therapies
Pregnancy Outcomes

SLE characteristics
Nephritis
Yes
No
Anti-Roc
Pos
Neg
Anti-La c
Pos
Neg
HTN
Yes
No
Raynauds
Pos
Neg
IV CYC
Givenz
Not Given
aPL
Yes
No
SLE flares
Yes
No
Therapy
PSL
PSL HCQ
PSL AZA
PSL AZA HCQ
None

No. of pregnancies

Miscarriage

Stillbirths

Neonatal deaths

Live births

Live births
Preterm Term

n 383

n (%)

n (%)

n (%)

n (%)

n (%)

n (%)

p-value

n (%)

p-value

153
230

44 (28.8)
50 (21.7)

8 (5.2)
9 (3.9)

1 (0.7)
2 (0.9)

100 (65.4)
169 (73.5)

32 (36.4)
32 (21.1)

56
120

0.010*

28 (31.8)
32 (21.1)

0.355

105
72

24 (21.8)
13 (18.1)

1 (0.9)
3 (4.2)

2 (1.9)
0 (0.0)

78 (74.3)
56 (77.8)

18 (26.1)
5 (9.6)

51
47

0.012*

12 (17.4)
8 (15.4)

0.311

30
148

8 (26.7)
41 (27.7)

0 (0.0)
4 (2.7)

1 (3.3)
0 (0.0)

21 (70.0)
103 (69.6)

6 (33.3)
14 (14.9)

12
80

5 (27.8)
11 (11.7)

0.128

79
304

20 (25.3)
74 (24.3)

7 (8.9)
10 (3.3)

1 (1.3)
2 (0.7)

51 (64.6)
218 (71.7)

23 (48.9)
41 (21.2)

24
152

0.000*

21 (44.6)
39 (20.2)

0.010*

57
326

20 (35.1)
74 (22.7)

2 (3.5)
15 (4.6)

0 (0.0)
3 (0.9)

35 (61.4)
234 (71.8)

10 (32.3)
54 (25.8)

21
155

0.660

13 (41.9)
47 (22.4)

0.020*

90
293

21 (23.3)
73 (24.9)

7 (7.8)
10 (3.4)

1 (1.1)
2 (0.7)

61 (67.8)
208 (70.9)

20 (40.8)
44 (23.0)

29
147

0.001*

16 (32.7)
44 (23.0)

0.520

205
178

63 (30.7)
31 (17.4)

13 (6.3)
4 (2.2)

1 (0.5)
2 (1.1)

128 (62.4)y*
141 (79.2)y

32 (27.6)
32 (25.8)

84
92

0.757

30 (25.9)
30 (24.2)

0.767

118
265

35 (29.7)
59 (22.3)

10 (8.5)
7 (2.6)

2 (1.7)
1 (0.4)

71 (60.2)y*
198 (74.7)y

25 (39.7)
39 (22.0)

38
138

0.003*

24 (38.1)
36 (20.3)

0.003*

222
69
30
8
54

38
23
10
2
21

11
1
3
0
2

2
0
0
0
1

171
45
17
6
30

52
8
2
0
2

104
32
12
4
24

0.011*

38
12
3
1
6

0.902

(17.1)
(33.3)
(33.3)
(25.0)
(38.9)

(4.9)
(1.4)
(10.0)
(0.0)
(3.7)

(0.9)
(0.0)
(0.0)
(0.0)
(1.9)

(77.0)*
(65.2)
(56.7)
(75.0)
(55.6)

(32.0)
(20.0)
(14.3)
(0.0)
(7.7)

IUGR

0.129

(24.4)
(30.0)
(21.4)
(25.0)
(23.1)

* significant p-value (<0.05,) c no data for some pregnancies, no data for 29 live births regarding term/preterm and IUGR, z given before
pregnancies.
aPL antiphospholipid antibodies, AZA azathioprine, HCQ hydroxychloroquine, HTN hypertension, IUGR intrauterine growth retardation, PSL prednisolone, IV cyclo intravenous cyclophosphamide.
(p > 0.05 for live births between different SLE characteristics except aPL, flares), y p-value significant (aPL p < 0.001; SLE flare p 0.004); PSL
vs. none.
Lupus

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

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1669

Table 2 Pregnancy outcomes in SLE patients with active and

quiescent lupus nephritis
Pregnancy outcome
Live births
Pregnancy loss
Term live births
Preterm live
births
IUGR
No IUGR

Active LN
(n 44) n (%)

Quiescent LN
(n 109) n (%)

18 (40.9)
26 (59.1)
n 18
7 (38.9)
11 (61.1)

82 (75.2)
27 (24.8)
n 70 c
49 (70.0)
21 (30.0)

0.014*

4 (22.2)
14 (77.8)

24 (34.3)
46 (65.7)

0.333

p-Value

<0.001*

* significant p-value (<0.05); c No data for 12 live births regarding

term/preterm/IUGR.
LN lupus nephritis, IUGR intrauterine growth retardation.

Pregnancy outcome in SLE patients with and without

anti-Ro, anti-La antibodies, low C3/C4, HTN and
Raynauds phenomenon
Live births and pregnancy losses were not signicantly dierent among these groups. Preterm deliveries were signicantly more frequent in anti-Ro
antibody-positive SLE patients (26.1%) than
in anti-Ro antibody-negative patients (9.6%)
(p 0.012) and in hypertensive pregnancies
(48.9%) compared with normotensive pregnancies
(21.2%) (p < 0.001). IUGR was found to be significantly more frequent in hypertensive pregnancies
(p 0.010) and Raynauds-positive pregnancies
(p 0.020). Anti-La antibodies and low levels of
complements C3 and C4 did not aect pregnancy
outcomes in our study (p > 0.05) (Table 1).
Pregnancy outcome in patients with and without
history of IV cyclo treatment
Of the 319 women of reproductive age, 99 had
received IV cyclo and 220 had not. Of the 99 receiving IV cyclo, 51 (51.5%) could not achieve pregnancy and 48 conceived (48.5%). Of the 220 women
who had not received IV cyclo, 92 (41.8%) could
not achieve pregnancy and 128 conceived (58.2%).
The infertility rate among women receiving IV
cyclo (51.5%) was higher than the infertility rate
among women not receiving IV cyclo (41.8%).
However, the dierence was not statistically significant (p 0.1083). There was no dierence in rates
of fetal loss/live births and IUGR between those
with a history of IV cyclo and those without
(p > 0.05); however, patients with history of IV
cyclo had signicantly more preterm births
(p 0.001) than those who had not received
it (Table 1).

Pregnancy outcome in SLE patients with and

without aPL
The rate of pregnancy loss was signicantly much
higher in pregnancies with aPL antibodies (77 of
205, 37.5%) compared with pregnancies without
(37 of 178, 20.7%) (p < 0.001). There was no
eect of these antibodies on length of gestation,
as the rate of preterm pregnancies among these
groups did not dier (p > 0.05). There was no evidence of association of aPL with IUGR (Table 1).
SLE flares in pregnancies and pregnancy outcome
There were 118 (30.8%) SLE ares during pregnancies. The most frequent were mild ares including
malar and discoid rash seen in 35 pregnancies
(29.7%) and severe ares including renal ares
(nephrotic syndrome) in 35 (29.7%), followed by
arthralgias and arthritis in 27 (22.9%), hematological in 11 (9.3%), oral ulcers in nine (7.6%), and
pulmonary HTN, preeclampsia leading to coma in
pregnancy in one patient. Among those who had
renal ares, lupus nephritis class III progressed
to class IV in two pregnancies. One patient with
renal disease and preeclampsia developed uncontrolled HTN post-cesarean section and died due
to active SLE. Four patients were admitted to
either Intensive Care Unit (ICU), Medical ICU,
or Surgical ICU post miscarriage and post delivery
for shortness of breath, toxic epidermal necrolysis
and raised jugular venous pressure. The rate of
pregnancy loss of 39.8% (47 of 118 pregnancies)
found in the presence of lupus ares was found to
be signicantly higher than the rate of 25.3% (67 of
265 pregnancies) in the absence of lupus ares
(p 0.004). There were increased preterm births
(39.7% vs. 22.0%) and IUGR neonates (38.1 vs.
20.3%) in pregnancies with SLE exacerbations
than without (p < 0.05) (Table 1).
Therapy in pregnancies and pregnancy outcome
All medications were discontinued upon conrmation of pregnancy in 54 (14.1%) pregnancies. In 222
(57.9%) pregnancies patients received prednisolone
(PSL) alone and in 69 (18.0%) pregnancies PSL
was combined with hydroxychloroquine (HCQ).
In 30 (7.8%) pregnancies PSL was prescribed
with azathioprine (AZA) and in eight (2.1%) pregnancies PSL was prescribed with AZA and HCQ
(Table 1). Patients with aPL syndrome and previous history of miscarriages were also given aspirin
and enoxaparin. Patients who received therapy
fared signicantly better in terms of live birth outcome (72.6%) compared with those who did not
Lupus

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

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1670

(55.6%) (p < 0.05). However, live births were more

frequently preterm (32.0%) when PSL was used
compared with no treatment (7.7%) (p 0.011).
There was no inuence of therapy on IUGR outcome. HCQ was received by patients in 161 pregnancies before conception (Table 3). It was stopped
in 84 and continued in 77 pregnancies on conrmation of pregnancy. It was observed that HCQ did
not aect the rate of pregnancy loss, preterm deliveries or IUGR (p > 0.05). However, the rate of SLE
ares was signicantly reduced in pregnancies on
HCQ (14.3%) compared with pregnancies where
HCQ was stopped (47.6%) (p < 0.001).

p 0.039) and SLE ares (OR 2.5; 95% CI 1.44.6;

p 0.003) (Table 4). History of IV cyclo was not found
to be a predictor of prematurity by multiple regression
analysis, despite being associated by univariate analysis (Table 1). The predictors of IUGR were found to be
anti-La antibodies (OR 11.5; 95% CI 1.1115.2;
p 0.038), HTN (OR 37.7; 95% CI 3.6189.7;
p 0.002), Raynauds phenomenon (OR 12.3; 95%
CI 2.269.7; p 0.005) and SLE ares in pregnancy
(OR 4.2; 95% CI 1.313.1; p 0.015) (Table 4). The
odds of having live births (OR 2.7; 95% CI 1.44.9;
p 0.002) and prematurity (OR 5.7; 95% CI 1.325.1;
p 0.022) were raised with the use of PSL in pregnancy (Table 5).

Analysis of predictors of adverse pregnancy outcome

by multiple regression analysis
Factors that were analyzed to identify the predictors of adverse pregnancy outcome (pregnancy loss,
preterm births, IUGR) included lupus nephritis,
anti-Ro and anti-La antibodies, C3, C4, HTN,
Raynauds phenomenon, history of IV cyclo therapy, aPL antibodies and SLE ares in pregnancy.
Among these, lupus nephritis (OR 7.3; 95% CI 1.2
42.1; p 0.027), aPL antibodies (OR 3.9; 95% CI
1.113.5; p 0.033) and SLE ares (OR 1.9; 95%
CI 1.23.1; p 0.004) were found to be the predictors of fetal loss (miscarriages, stillbirths and neonatal deaths) in patients with SLE. The remaining
factors were not associated with pregnancy loss
(p > 0.05) (Table 4). Though lupus nephritis was
found to be associated with pregnancy loss by multivariate analysis, we did not nd this association
by univariate analysis (Table 1). The predictors of
preterm delivery in our SLE patients were lupus
nephritis (OR 18.9; 95% CI 1.6125.9; p 0.020),
anti-Ro antibodies (OR 13.9; 95% CI 1.1116.4;
p 0.046), HTN (OR 15.7; 95% CI 1.2115.1;
Table 3 Pregnancy outcomes in SLE patients in relation to
hydroxychloroquine therapy in pregnancy
Variable
SLE Flares
No SLE Flares
Live births
Pregnancy Loss
Term Live births
Preterm Live births
IUGR
No IUGR

HCQ continued
(n 77) n (%)

HCQ stopped
(n 84) n (%)

11 (14.3)
66 (85.7)
51 (66.2)
26 (33.8)
n 44c
36 (81.8)
8 (18.2)
13 (29.5)
31 (70.5)

40 (47.6)
44 (52.4)
55 (65.5)
29 (34.5)
n 52c
36 (69.2)
16 (30.8)
15 (28.8)
37 (71.2)

p-value

<0.001*
0.908
0.159
0.941

*Significant p-value (<0.05); c no data for some live births regarding term/preterm/IUGR.
IUGR intrauterine growth retardation, HCQ hydroxychloroquine.
Lupus

Discussion
SLE can be detrimental to pregnancy and may
cause adverse pregnancy outcomes. Conversely,
pregnancy can cause ares of lupus disease activity.
As a result of advances in the understanding of the
pregnancy-lupus interaction and better therapeutic
options, pregnancy outcomes have improved over
the last few years. However, several studies have
shown that maternal and fetal complications still
occur.
In our study, the live birth rate among women
conceiving after a diagnosis of SLE was lower and
pregnancy loss and preterm births were more
common than in women before development of
SLE. This nding is in agreement with previous
reports.7,16 The rate of pregnancy loss in our
patients after SLE diagnosis was twice that in
patients before SLE diagnosis, similar to previous
reports.10 The mean number of pregnancies was
signicantly higher in our patients in pregnancies
occurring before SLE onset than in pregnancies
occurring after SLE onset.16 The rate of miscarriages of 24.5% in our cohort of patients with
SLE is similar to that found in other studies,
which have reported rates ranging from 824% in
SLE patients compared with 8% in the general
population.6,7,9,13,1720 Reported incidences for preterm delivery in SLE pregnancies range from
1754%.8,9,12 The preterm birth rate in SLE pregnancies in our study was 26.7% and was almost
vefold higher than that in pregnancies before
SLE diagnosis.
Several studies have suggested that nephritis
may contribute to adverse maternal and fetal outcomes.21,22 We did not nd association of pregnancy
loss with lupus nephritis by univariate analysis, but
the risk of pregnancy loss was found to be increased

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

AS Al Arfaj and N Khalil

1671

Table 4 Relation of pregnancy outcomes with different SLE features, SLE flares and therapy by multivariate regression analysis

SLE characteristics
Lupus nephritis
Anti-Ro antibodies
Anti-La antibodies
C3
C4
HTN
Raynauds
IV cyclo
aPL
SLE flares in pregnancy

Pregnancy loss/live births

Preterm/term Live births

IUGR/No IUGR

OR; p-Value
(95% CI)

OR; p-Value
(95% CI)

OR; p-Value
(95% CI)

7.252; 0.027*
(1.24842.149)
1.051; 0.934
(0.3213.438)
1.016; 0.980
(0.2993.450)
0.978; 0.943
(0.5331.794)
0.877; 0.679
(0.4721.632)
3.002; 0.231
(0.49718.143)
1.076; 0.931
(0.2045.669)
0.276; 0.094
(0.0611.245)
3.878; 0.033*
(1.11413.5)
1.956; 0.004*
(1.2343.102)

18.878; 0.020*
(1.577125.964)
13.996; 0.046*
(1.051116.429)
0.726; 0.815
(0.05010.585)
1.011; 0.977
(0.4772.145)
0.636; 0.289
(0.2761.467)
15.735; 0.039*
(1.151115.146)
5.368; 0.413
(0.096100.154)
2.780; 0.505
(0.13756.536)
2.725; 0.427
(0.23032.315)
2.481; 0.003*
(1.3504.560)

0.905; 0.912
(0.1545.307)
0.356; 0.376
(0.0363.511)
11.477; 0.038*
(1.144115.153)
0.667; 0.781
(0.03811.561)
1.463; 0.403
(0.5993.575)
37.712; 0.002*
(3.649189.728)
12.273; 0.005*
(2.16069.731)
0.699; 0.775
(0.0608.149)
0.444; 0.297
(0.0962.046)
4.156; 0.015*
(1.31713.113)

*Significant p-value (<0.05).

aPL antiphospholipid antibodies, CI confidence interval, HTN hypertension, IUGR intrauterine growth retardation, IV cyclo intravenous cyclophosphamide, OR odds ratio.

Table 5 Relation of pregnancy outcomes in SLE patients with different treatment regimens by multivariate regression analysis
Therapy

PSL

PSL HCQ

PSL AZA

PSL AZA HCQ

Pregnancy outcomes

OR; p-value
(95% CI)

OR; p-value
(95% CI)

OR; p-value
(95% CI)

OR; p-value
(95% CI)

2.682; 0.002*
(1.4414.992)
5.691; 0.022*
(1.29025.113)
2.608; 0.094
(0.8508.007)

1.500; 2.77
(0.7233.114)
4.308; 0.068
(0.89920.632)
0.573; 0.438
(0.1402.343)

1.046; 0.922
(0.4252.573)
1.091; 0.946
(0.08913.347)
1.100; 0.920
(0.1727.029)

2.400; 0.309
(0.44412.980)
2.400; 0.507
(0.18131.883)
5.500; 0.082
(0.80437.609)

Live births/
Pregnancy loss
Term/Preterm live births
IUGR/No IUGR

OR odds ratio, CI confidence interval,*significant p-value (<0.05).

AZA azathioprine, HCQ hydroxychloroquine, IUGR intrauterine growth retardation, PSL prednisolone.

in lupus nephritis patients when multiple regression

analysis was used. Prematurity was more prevalent
in our lupus nephritis patients (36.4%) than in SLE
pregnancies without nephritis (21.1%), which is in
accordance with previous reports.23 In our study
renal disease was clinically inactive in 71.2%, while
28.8% had active renal disease at the time of conception and were on cytotoxic therapy, and some
others had ares during pregnancies. It has been
proposed that SLE patients with quiescent renal disease do not have adverse pregnancy outcomes,24 and
our results support this nding. We found adverse
pregnancy outcomes associated with active renal
disease at conception and not quiescent renal disease. On account of this we found higher rate of

miscarriages in lupus nephritis patients compared

with those without. To optimize pregnancy outcomes in nephritis patients, conceptions should
occur during disease quiescence. Although we
found previous use of IV cyclo to be associated
with preterm deliveries by univariate analysis, the
odds of having this association were not signicant
in the multivariate model. It is likely that the
increased incidence of preterm delivery in patients
with previous treatment with IV cyclo is due to
aggressive maternal renal disease requiring this therapy. Aggressive maternal renal disease is also associated with increased maternal blood pressure, poor
fetal growth and preeclampsia, all of which may
contribute to iatrogenic preterm delivery.25
Lupus

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

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1672

In our patients, anti-Ro antibodies and HTN

were found to be associated with prematurity,
which is in accordance with previous reports.12,26
We found HTN and Raynauds phenomena to be
associated with IUGR. One-quarter of our live
births born to SLE mothers were aected by
IUGR. Studies have shown that the main factors
contributing to the increased rate of IUGR in
patients with SLE are HTN, preeclampsia and
low complement levels,6,19,27 and other studies
have shown a relationship between Raynauds phenomenon and IUGR.12 The association between
Raynauds and IUGR may reect increased maternal vasculitis and subsequent poor placentation.
Although anti-La/SSB antibody was not found to
be associated with IUGR by univariate analysis, it
was found to be a predictor of IUGR by multivariate analysis. This suggests the prognostic value of
this antibody in SLE pregnancies. Few studies have
shown association of anti-La antibody with spontaneous abortions.17 Our study did not nd correlation between low complement levels and adverse
pregnancy outcomes, which is in contrast to previous reports showing an association of low complement levels with IUGR.28 In normal pregnancy,
complement levels gradually rise; a decline of
these levels occurs during the course of pregnancy
in some patients with SLE. This decline in levels
may not represent decreases in the overall synthesis
of complement. Low complement levels can be
normal in pregnancy, and therefore are a poor
indicator of disease are.
Studies have demonstrated that the fertility rate
in SLE is usually unaected and comparable with
that found in the general population.29 Factors
such as renal failure, use of high-dose steroids
and previous treatment with IV cyclo predispose
some women with SLE to lower fertility.30,31
Seventeen women in our study who reproduced
developed sustained amenorrhea for a period ranging between 640 months, induced by IV cyclo. IV
cyclo did not contribute signicantly to a higher
infertility rate in our group of patients, although
the proportion of women unable to conceive was
slightly elevated in the cohort treated with IV cyclo
(51.5%) than in women not treated with IV cyclo
(41.8%).
The association of aPL antibodies and fetal loss
has been well documented. The literature indicates
that presence of these antibodies is associated with
almost twofold increase in fetal loss compared with
fetal loss in aPL-negative SLE patients.6,32,33 Our
ndings are similar to these reports, and by multivariate analysis we found aPL to be a strong predictor of fetal loss.
Lupus

Some 118 pregnancies (30.8%) were complicated

by lupus ares. This is consistent with reported
are rates ranging from 1368% and also up to
75% in patients with active disease at time of conception.25,710,28 The literature shows that renal
ares occur in 5% of patients with quiescent renal
disease compared with 39% of patients with active
renal disease.32 The most frequent ares manifested
in our women with SLE ranged from mild symptoms including rash and arthralgia, to severe ares
including nephrotic syndrome and worsening of
renal disease. Most studies have shown that lupus
tends to are during pregnancy and after pregnancy; in some patients ares were mild such as
arthritis, constitutional and cutaneous manifestations, and in others they were more serious problems aecting the kidneys and central nervous
system.6,9,17,34 Lupus are in pregnancy was
found to be related to adverse pregnancy outcomes
including pregnancy loss, preterm delivery and
IUGR in our patients, consistent with previous
reports.8 This was the strongest predictor of all
the adverse pregnancy outcomes among the characteristics we compared. Treatment in pregnancy
with PSL was found to be correlated with higher
incidence of live births compared with pregnancies
receiving no treatment; however, it was also a predictor of prematurity in neonates, similar to previous reports.6,8,28 Multivariate regression analysis
conrmed the association of PSL with prematurity.
The continuation of HCQ treatment during pregnancy did not cause any adverse pregnancy outcomes in our patients and also reduced lupus
ares in pregnancy. Our ndings are consistent
with prior reports which have demonstrated that
cessation of HCQ treatment during pregnancy
increases the degree of lupus activity.35
Our ndings suggest that pregnant women with
active SLE remain at a high risk of pregnancy loss
(spontaneous miscarriages, stillbirths, NNDs), preterm births, IUGR, low birthweight neonates, and
SLE ares during pregnancy and in puerperium.
Lupus nephritis, anti-Ro, anti-La and aPL antibodies, HTN, Raynauds phenomenon and SLE ares
in pregnancy are the predictors of adverse pregnancy outcomes.
Our study includes data over a 27-year period,
during which management of SLE and pregnancy
have changed. Progress made in maternal disease
control and improvements in obstetrical care have
contributed to better fetal outcomes. Owing to this,
pregnancy outcomes in our patients may have
improved in the later years of the study compared
with the earlier years. We conclude that in order to
achieve favorable pregnancy outcomes it is essential

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

AS Al Arfaj and N Khalil

1673

that disease activity remains in control at the time

of conception, and that pregnancy is managed by
experienced rheumatologists and obstetricians.

Funding
This research received no specic grant from any
funding agency in the public, commercial, or notfor-prot sectors.

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Lupus

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