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      Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) is Improving: Results from a Case Control Study and Literature Review

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          Abstract

          Objectives

          For women who suffer from systemic lupus erythematosus (SLE), pregnancy can be a concern, placing the mother and fetus at risk. Our objectives were to assess the risk of adverse pregnancy outcome, disease flares, fertility rate, and co-morbidities in SLE women compared to healthy controls. We also systematically reviewed the literature available on pregnancy outcome in SLE to compare our results to other published data. Our hypothesis was that pregnancy outcome in SLE is improving over time.

          Methods

          A case-control study comparing self-report of the above-mentioned parameters in SLE (N=108) vs healthy controls or patients with non-inflammatory musculoskeletal (MSK) disorders (N=134) was performed. Data were collected using a self-administered questionnaire. Proportions, means and odds ratios were calculated. We searched and quantified the literature on pregnancy outcome, lupus reactivation and fertility rate. Data were summarized and presented in mean % ± SEM and median % with interquartile range (IQR).

          Results

          Gynecological history, fertility rate and age at first pregnancy in SLE patients were comparable to controls. Eighteen percent of SLE patients reported a flare and 18% reported an improvement of symptoms during pregnancy. Twenty-four percent of lupus patients had at least one preterm delivery vs 5% in controls (OR =8.32, p = 0.0008), however other pregnancy outcomes (miscarriage, therapeutic abortion, stillbirth and neonatal death rate) did not differ between the groups. Thyroid problems were reported to be more likely in SLE patients (p = 0.02), but the prevalence of other co-morbidities was similar to controls. A literature review demonstrated that fertility was not affected in SLE patients. Lupus reactivations are common during pregnancy (36.5% ± SEM 3.3%). Most agreed that SLE pregnancies had more fetal loss (19.5% ± SEM 1.6%) and preterm births (25.5% ± SEM 2.2%) when compared to the general population. Over time, the rate of SLE peripartum flares has improved (p = 0.002) and the proportion of pregnancies resulting in live birth has increased (p = 0.024). The frequency of fetal death has not significantly changed. Our findings from the case-control study were, in general, consistent with the literature including the frequency of fetal death, neonatal death, live births and pregnancy rate.

          Conclusion

          Prematurity (25.5% ± SEM 2.2%) and fetal death (19.5% ± SEM 1.6%) in SLE pregnancy are still a concern. However, new strategies with respect to pregnancy timing and multidisciplinary care have improved maternal and fetal outcome in SLE.

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          Most cited references 101

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          Combined oral contraceptives in women with systemic lupus erythematosus.

          Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable. Copyright 2005 Massachusetts Medical Society.
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            Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy.

            To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus. Controlled, retrospective clinical study. Government referral-based research hospital. Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls. Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses. Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy. Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: or = 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients. Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide.
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              Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies.

              Our aim was to assess the outcome of pregnancy in a cohort of patients with SLE and to evaluate clinical and laboratory markers for fetal outcome and maternal flares. Sixty patients with 103 pregnancies were evaluated prospectively between 1984 and 1999. There were 68 live births, 15 spontaneous abortions, 12 stillbirths and eight therapeutic abortions. Of liveborn infant births, 19 were premature, 24 had suffered intrauterine growth restriction and one had neonatal lupus. Maternal lupus flares occurred in 33% of pregnancies, mostly in the second trimester (26%) and in the post-partum period (51%). Flares during pregnancy showed a statistically significant association with discontinuation of chloroquine treatment, a history of more than three flares before gestation, and a SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score of >or=5 in these flares. Antiphospholipid antibodies, C3 hypocomplementaemia and hypertension during pregnancy were significantly associated with fetal loss, prematurity and intrauterine growth restriction. Patients with more active SLE and those with aPL antibodies and hypertension should be monitored and managed carefully during pregnancy.
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                Author and article information

                Journal
                Open Rheumatol J
                TORJ
                The Open Rheumatology Journal
                Bentham Open
                1874-3129
                31 December 2008
                2008
                : 2
                : 89-98
                Affiliations
                Department of Medicine, The University of Western Ontario, London, ON, Canada
                Author notes
                [* ]Address correspondence to this author at St. Joseph’s Health Centre, 268 Grosvenor St., London, Ontario, N6A 4V2, Canada; Tel: 519-646-6332; Fax: 519-646-6334; E-mail: janet.pope@ 123456sjhc.london.on.ca
                Article
                TORJ-2-89
                10.2174/1874312900802010089
                2627535
                19156224
                © Yuen et al.; Licensee Bentham Open.

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                Categories
                Article

                Rheumatology

                systemic lupus erythematosus (sle), case-control., pregnancy outcome

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