http://lup.sagepub.com
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
1666
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,
1667
94.2
100
90
85.7
80
73.3
70.2
Percentage
70
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
1668
Table 1
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
1669
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*
1670
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
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
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)
Table 5 Relation of pregnancy outcomes in SLE patients with different treatment regimens by multivariate regression analysis
Therapy
PSL
PSL HCQ
PSL AZA
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
1672
1673
Funding
This research received no specic grant from any
funding agency in the public, commercial, or notfor-prot sectors.
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