Abstract

BackgroundWomen with systemic lupus erythematosus (SLE) are known to have more difficulty in achieving a successful pregnancy than healthy women. They have a higher risk for adverse pregnancy outcomes (APOs) including preterm birth (PB), low birth weight (LBW). (1,2). Many reports revealed that these APOs are related to uncontrolled high disease activity (3,4). Therefore, it is important for SLE women who hope to conceive to control disease activity strictly. However, it is not clear to what extent disease activity should be strictly controlled, including serum parameters such as complement levels and anti-dsDNA antibodies.ObjectivesThe purpose of this study was to determine whether disease activity parameters at conception could be a risk factor for PB or LBW among APOs in patients with SLE.MethodsDisease activity parameters including SLEDAI score, LLDAS achievement rate, serum complement levels (C3, C4, CH50), and anti-dsDNA antibody titer were retrospectively collected from medical records. We then collected information related to each APOs (PB and LBW), and analyzed the association with disease activity parameters.ResultsThe subjects were 60 pregnancies of 45 patients. As for a comprehensive disease activity index at conception, SLEDAI score or the rate of LLDAS achievement became risk factors for PB (both of p<0.01, Table 1), and SLEDAI score was also a risk factor for LBW (P=0.04, Table 1). Analysis of immunological disease activity parameters showed that low C3 or high titer of anti-dsDNA antibody were risk factors for PB (P=0.03 and 0.01, respectively, Table 1). In the logistic regression analysis of PB, the cut-off levels of C3 and anti-dsDNA antibody were 62 mg/dl and 5.4 IU/ml, respectively (Figure 1 [1]-A, [1]-D). The risk of PB was significantly higher in the cases with low serum C3 and high anti-dsDNA antibody titer at conception (P=0.02).Similarly, low C3 or CH50 were risk factors for LBW (P=0.02 and 0.03, respectively, Table 1). Logistic regression analysis for LBW showed the cut-off level of C3 as 87 mg/dl, and CH50 as 41.8 IU/ml (Figure 1 [2]-A, [2]-C). Cases with low C3 and low CH50 were at higher risk for LBW (P=0.03).Table 1.Association between disease activity parameters and PB or LBWPreterm birth (PB)Low birth weight (LBW)PB (+)(n = 14)PB (-)(n = 46)P valueLBW (+)(n = 23)LBW (-)(n = 37)P value Achievement of LLDAS, n (%)##5 (41.7)30 (71.4)0.0912 (63.2)23 (65.7)1.00 Achievement of LLDAS without a glucocorticoid dose, n (%)##5 (41.7)37 (88.1)< 0.01*13 (68.4)29 (82.9)0.31 SLEDAI score#3.5±2.91.1±1.3<0.01*2.3±2.11.3±2.00.04* C3, mg/dl#77.3±19.094.7±21.20.03*80.5±16.396.7±22.70.02* C4, mg/dl#16.1±9.019.2±6.30.1617.6±6.319.1±7.40.56 CH50, IU/ml#37.3±10.641.1±8.50.1736.5±6.642.2±9.70.03* Anti-dsDNA antibody, IU/ml#32.5±68.55.5±11.10.01*20.7±55.87.0±12.20.34(Values are presented as mean ± standard deviation or number (%). #Wilcoxon rank sum test; ##Fisher’s exact test; *P < 0.05.)Figure 1.Logistic regression analysis of cut-off value of PB and LBW for C3, C4, CH50 and anti-dsDNA antibody.(ROC curves based on logistic regression analysis of cut-off levels for disease activity parameters, including C3, C4, CH50, and anti-dsDNA antibody titer. [1] showed ROC curves for PB, and [2] showed those for LBW.)ConclusionWe revealed that disease activity parameters of SLE at coception are strongly associated with negative pregnancy outcomes; PB and LBW. These include low serum C3 and CH50 levels and high anti-dsDNA antibody titers. In particular, low serum complement is a risk factor for both PB and LBW. Therefore, it is important to strictly control these disease activity parameters at conception in women with SLE.

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