One year in review; Authors: D. Zucchi, E. Elefante, D. Schilirò, V. Signorini, F. Trentin, A. Bortoluzzi, C. Tani

One year in review; Authors: D. Zucchi, E. Silvagni, E. Elefante, V. Signorini, C. Cardelli, F. Trentin, D. Schilirò, G. Cascarano, A. Valevich, A. Bortoluzzi, C. Tani

Objectives: To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome. Methods: Pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to the Definition of Remission in SLE (DORIS) criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death. Results: A total of 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. Seventy-three flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking HCQ were less likely to have disease flare, while a history of LN increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on HCQ resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed. Conclusions: Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetric complications in SLE pregnancies.

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

Objective: To analyze complement level variations in systemic lupus erythematosus (SLE) pregnancies, focusing on disease flares and obstetric complications.Methods: SLE pregnancies prospectively followed by multidisciplinary teams from 1987 to 2018 in 2 Italian rheumatology centers were retrospectively analyzed. As reference, pregnancy-modified ranges of normal levels of C3 and C4 were derived from 175 pregnancies from the general obstetric population (GOP), as previously described by our group.Results: Two hundred forty-six pregnancies in 172 patients with SLE were analyzed. Eighty-nine percent were live births. Thirty-five flares were recorded in 30 pregnancies (12.2%) and obstetric complications occurred in 47 pregnancies (19.1%) including 27 pregnancy losses, 11 severely preterm births (2 resulting in perinatal death), and 15 hypertensive disorders. C3 and C4 levels were higher in the GOP than in patients with SLE, at any time point. C3 and C4 levels progressively increased during pregnancy in both GOP and SLE pregnancies without flare and obstetric complications, whereas this physiological increase was not observed in pregnancies with flares or obstetric complications. A significantly higher frequency of low C4 was found in pregnancies with flares (at preconception and in each trimester) and preterm births (at preconception). In multivariate analysis, low C4 at preconception was associated with flares (odds ratio 13.81, 95% CI 3.10-61.43,P< 0.001).Conclusion: Low C4 at preconception was found to be an independent risk factor for SLE flare during pregnancy. Not only C3 and C4 levels but also their variations should be observed, as their failure to increase can be useful to predict risk of complications and suggest closer monitoring.