Systemic Lupus Erythematosus Pregnancies Research Articles

Lupus activity and pregnancy outcomes in systemic lupus erythematosus patients undergoing assisted reproductive therapy: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. While pregnancy and hormonal stress can trigger SLE flare-ups, the effects of assisted reproductive therapies (ARTs) on SLE patients are not well defined. We conducted a search of PubMed/Medline, Embase, and CENTRAL until March 20, 2024, to find observational studies assessing the prevalence of SLE flares and pregnancy outcomes following ARTs. Our analysis included random-effects meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for evaluating evidence quality. Five studies involving 237 SLE women who underwent ARTs were eligible. The meta-analysis indicated a prevalence of SLE flares at 17% (95% CI: 10-25%) with moderate-quality evidence. The pooled prevalence of arthritis flares was 7% (95% CI: 0-25%) with low-quality evidence. Successful pregnancy rates were 58% (95% CI: 43-72%), and live birth rates were 96% (95% CI: 83-100%), both with low-quality evidence. Moderate-quality evidence showed pregnancy complications, including preterm premature rupture of membranes (PPROM) at 8% (95% CI: 3-16%), miscarriages at 2% (95% CI: 0-9%), intrauterine fetal demise (IUFD) at 4% (95% CI: 0-11%), and preeclampsia at 7% (95% CI: 1-17%). Low-quality evidence showed preterm labor at 10% (95% CI: 0-32%) and ovarian hyperstimulation syndrome (OHSS) at 2% (95% CI: 0-11%). SLE flares, as well as pregnancy complications such as IUFD, miscarriage, PPROM, and preeclampsia in ART recipients, are equivalent to those in spontaneous conception. This indicates that ART is relatively safe for SLE patients with meticulous pregnancy planning. Key Points •Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. • Pregnancy in women with SLE poses elevated maternal and fetal risks compared to healthy women. • SLE flares and pregnancy complications while receiving ART are equivalent to those in spontaneous conception and ART is relatively safe for SLE patients.

Research Hotspots on Systemic Lupus Erythematosus in Pregnancy Based on Bibliometrics

Objective To explore the research hotspots on systemic lupus erythematosus (SLE) in pregnancy based on the bibliometric analysis of the related articles published from 2018 to 2023 and provide directions for the future research in this field. Methods PubMed,Web of Science,and Embase were searched for the articles on SLE in pregnancy that were published from January 1,2018 to December 31,2023.VOSviewer was used to visualize the high-frequency keywords in the selected articles. Results A total of 266 articles were selected,from which 25 high-frequency keywords were extracted.The bibliometric analysis showed that the available studies about SLE in pregnancy mainly focused on maternal complications,maternal and fetal outcomes,and medications.The studies were limited regarding the predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring. Conclusion Maternal complications,maternal and fetal outcomes,and medications are currently hotspots in the research on SLE in pregnancy,while predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring may become future research directions.

Low-dose aspirin in systemic lupus erythematosus pregnancy: impact on pregnancy outcomes and optimal management

Low-dose aspirin in systemic lupus erythematosus pregnancy: impact on pregnancy outcomes and optimal management

Association Between 25-hydroxyvitamin D Levels and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus.

We evaluated the association of 25-hydroxyvitamin D (25(OH)D) levels with adverse pregnancy outcomes in systemic lupus erythematosus (SLE). The Hopkins Lupus Cohort includes visits of pregnant patients, including assessment of 25(OH)D levels at each visit. We examined the relationship between 25(OH)D levels and adverse pregnancy outcomes (miscarriage, preterm delivery, and small for gestational age). We also used a time-to-event analysis to assess whether time-varying of 25(OH)D levels were associated with time to miscarriage or preterm delivery. In subgroups of patients defined by the average of 25(OH)D levels, we observed significantly different risks of miscarriage (P = 0.0045), preterm delivery (P = 0.0007), and the composite measure of all three adverse pregnancy outcomes (P = 0.011). The highest risks were observed among those with the lowest or highest levels of vitamin D. Nine of 10 pregnant patients with low vitamin D levels during the second trimester resulted in having a premature delivery. The time-to-event model confirmed the same U-shaped association after adjustment for SLE disease activity; however, the increased risk among those with highest levels of vitamin D was not statistically significant. Body mass index did not appear to be a confounding factor. Our study is not able to prove causation, but the results strongly suggest an association of 25(OH)D at both lower and higher levels with adverse pregnancy outcomes. We recommend the monitoring of maternal serum 25(OH)D levels during SLE pregnancies, aiming for the ideal range of 40 to 59 ng/mL.

Placental lesions in systemic lupus erythematosus pregnancies associated with small for gestational age infants.

Up to a quarter of pregnant individuals with systemic lupus erythematosus (SLE) have small for gestational age (SGA) infants. We aimed to characterize placental pathology associated with SGA infants in SLE. We retrospectively analyzed SLE deliveries with placental analysis at UCSD from 11/2018-10/2023, comparing SLE pregnancies resulting in SGA to those that did not, and additionally, to matched pregnancies with SGA but without SLE. Placental analysis was available only for 28/70 (40%) SLE deliveries, which had high rates of adverse outcomes (75%). All exhibited at least one histopathologic abnormality. Key findings distinguishing 12 SLE placentas resulting in SGA infants (vs.16 without) included small placental disc for gestational age (100% vs 56%, p= 0.01), placental disc infarct (50% vs 6%, p= 0.02), and increased perivillous fibrin deposition (PVFD, 58% vs 0%, p= 0.001). All seven SLE placentas with increased PVFD resulted in SGA infants. Compared with matched non-SLE pregnancies with SGA (n = 36), the only distinguishing placental lesion was a higher prevalence of increased PVFD in SLE-associated SGA (58% vs 22%, p= 0.03). The higher prevalence of increased PVFD in placentas of SLE-associated SGA may indicate a specific mechanism of placental injury leading to SGA in this context. Thus, its presence, particularly in context of SGA, should prompt providers to screen for an underlying autoimmune disease, including SLE. Systematic placental examination in context of SLE and associated autoimmune diseases could help evaluate responses to existing therapies, comparative studies of novel therapies, and correlation to adverse outcomes.

Azathioprine related alopecia totalis due to NUDT 15 mutation in a pregnant systemic lupus erythematosus patient with successful obstetric outcome.

Azathioprine related alopecia totalis due to NUDT 15 mutation in a pregnant systemic lupus erythematosus patient with successful obstetric outcome.

Systemic Lupus Erythematosus in pregnancy – a multidisciplinary approach to family planning and adverse outcomes prevention

Introduction and purpose Systemic Lupus Erythematosus is a chronic multisystemic autoimmune disease with periods of remissions and flares [1,5,25]. Because of its possible consequences and unpredictability, it is undoubtedly an issue for such patients to decide about pregnancy [3]. The main aim of this review is to present the possible risks of SLE in pregnancy, its general management and current recommendations regarding pregnancy planning and pre-/postnatal care. Review Methods For the review we conducted research of scientific literature from PubMed and books, applying the keywords (below). Consequently, we included in our references above 20 selected articles published between 2017-2024 and 3 chapters of different medical books. All of these were analyzed in terms of their currency and relevance. A brief description of the State of Knowledge SLE mostly affects women at the reproductive age [2, 3,5]. It often requires long-term therapy that aims to achieve and maintain an inactive stage by means of numerous aggressive drugs. Its proper management in gestation is even more challenging than usually, owing to the increased risk of adverse pregnancy outcomes (APO) and higher maternal mortality [1,2,4,5,7]. Therefore, to achieve successful pregnancy, risk stratification, therapy modification and individually adjusted plan of follow-up visits are the most crucial conditions to be met [1,6,7,13]. Summary Considering all the potential complications that may occur in general, the issue of family planning should be raised with every female patient [5,6]. The key to the best outcomes is proper implementation of current strategies and empowering the patient to be an active and aware participant in the decision-making process [1,3,4,6,11].

Single-cell RNA sequencing of peripheral blood mononuclear cells from pregnant women with Systemic lupus erythematosus

Systemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score). Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) was conducted using the 10x Genomics technique. We observed upregulation of genes like CCDC15 and TRBV4-2 in T cells and CMPK2, IFIT1, and OAS2 in monocytes in the SLE-C group. Notably, gene sets related to Cell Cycle and IFN Response showed significant differences between the SLE-C and SLE-NC groups in naïve CD8 T cells. Our comparison of immune cell type ratios and transcriptional patterns between active and inactive SLE during pregnancy sheds light on the single-cell level changes in SLE status during pregnancy, offering insights for future SLE prediction and treatment strategies.

Calcineurin inhibitors in unplanned pregnancies with active lupus disease: A retrospective observational study.

To evaluate the use of calcineurin inhibitors (CNIs), specifically tacrolimus, in unplanned pregnancies with active lupus disease among patients with systemic lupus erythematosus (SLE). The study includes data from pregnancies in women diagnosed with SLE at Gazi University Hospital in Ankara, Türkiye, between January 2010 and July 2022. The study categorized pregnancies into planned and unplanned groups based on lupus nephritis presence, emphasizing the need for inactive lupus disease for at least 6 months before attempting conception in planned pregnancies. The outcomes of pregnancies involving CNIs, particularly tacrolimus, were assessed. In our cohort comprising 632 SLE patients, 39 individuals reported 42 pregnancies. Among the 42 pregnancies, 14 have a history of lupus nephritis. We observed that 8 of 14 patients with a history of lupus nephritis had unplanned pregnancies. Three patients used cyclosporine and 2 used tacrolimus during their pregnancy; their pregnancies were completely healthy, and no lupus flare was observed during their pregnancies. The pregnancy of 2 patients who used azathioprine and 1 last patient who used no immunosuppressive treatment ended in abortion. This study reveals that tacrolimus can be effectively used in unplanned pregnancies with active lupus disease, providing favorable maternal and fetal outcomes. The findings emphasize the importance of considering CNIs, particularly tacrolimus, in the management of SLE pregnancies, even in cases of unplanned pregnancies with a history of lupus nephritis.

Plasma interferon-alpha protein levels during pregnancy are associated with lower birth weight in systemic lupus erythematosus.

Adverse pregnancy outcomes are more common in women with systemic lupus erythematosus (SLE) compared with healthy women, but we lack prognostic biomarkers. Plasma interferon alpha (IFNα) protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFNα, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy. We followed 76 women with SLE prospectively. Protein levels of IFNα were quantified in plasma collected in the 2nd and 3rd trimester with single-molecule array. Positivity for antinuclear and antiphospholipid antibodies was assessed during late pregnancy with multiplexed bead assay. Clinical outcomes included the adverse pregnancy outcomes small for gestational age (SGA), preterm birth, and preeclampsia. During SLE pregnancy, women with SGA infants compared with those without had higher levels of plasma IFNα protein, and IFNα positivity was associated with lower birth weight of the infant. Preterm birth was associated with autoantibodies against chromatin. IFNα protein levels associated positively with autoantibodies against chromatin, Smith/ribonucleoprotein (SmRNP) and RNP, but negatively with phospholipid antibodies. Elevated IFNα protein in plasma of women with SLE is a potential risk factor for lower birth weight of their infants. The association between IFNα and lower birth weight warrants further investigation regarding the pathophysiological role of IFNα during SLE pregnancy.

Modern Management of Pregnancy in Systemic Lupus Erythematosus: From Prenatal Counseling to Postpartum Support.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age. Pregnancy in SLE patients poses unique challenges due to the potential impact on maternal and fetal outcomes. We provide an overview of the management of SLE during pregnancy, including preconception risk stratification and counseling, treatment, and disease activity monitoring. These assessments are critical to minimize maternal and fetal adverse events in pregnant patients with SLE. Disease flares, preeclampsia, antiphospholipid syndrome complications, and maternal mortality are the major risks for a woman with SLE during gestation. Timely treatment of SLE relapse, differentiation of preeclampsia from lupus nephritis, and tailored management for antiphospholipid syndrome are essential for a successful pregnancy. Fetal outcomes include neonatal lupus (NL), preterm birth, cesarean delivery, fetal growth restriction (FGR), and small-for-gestational-age (SGA) infants. We focused on NL, linked to maternal anti-Ro/SS-A and anti-La/SS-B antibodies, which can lead to various manifestations, particularly cardiac abnormalities, in newborns. While there is a common consensus regarding the preventive effect of hydroxychloroquine, the role of echocardiographic monitoring and fluorinated steroid treatment is still debated. Finally, close postpartum monitoring and counseling for subsequent pregnancies are crucial aspects of care.

A Comparison of Obstetric Outcomes in Antiphospholipid Syndrome Among Pregnant Women With Systemic Lupus Erythematosus.

Objective The aim of this study was to evaluate the maternal and perinatal outcomes in systemic lupus erythematosus (SLE) women with antiphospholipid syndrome (APS). Methods This retrospective case-control study was conducted among pregnant women with SLE with and without APS. Group A included SLE patients with APS, whereas group B included pregnant SLE women without APS. Data were expressed as mean ± standard deviation (SD). Frequency and percentage were computed for categorical data. The chi-square test was used to analyze the difference between categorical data. Results Out of 125 cases of SLE, APS was found in 72 (57.6%) women. Almost 95.8% of patients were on treatment (aspirin and enoxaparin) in group A. Preterm delivery (31.89±7.36 versus 34.46±4.97; p=0.021) and termination of pregnancy (18.1% [13/72] versus 5.7% [3/53]; p=0.04) were statistically significant in group A. Among these terminations, second-trimester intrauterine deathis found to be more in group A (SLE with APS)(16.7% [12/72]) as compared to group B(SLE without APS)(5.7% [3/53])with a p-value of 0.05. Perinatal outcomes including NICU admissions (39% [23/59] versus 24% [12/50]; p=0.071) and neonatal death (12.3% [7/57]; p=0.015) were also found to be statistically significant between the two groups. Conclusion APS with SLE is associated with adverse pregnancy outcomes such as preterm birth, termination of pregnancy due to second-trimester fetal loss, more NICU admission, and neonatal deaths when compared to the control group. Hence, pregnancies with APS with SLE require vigilant monitoring and frequent follow-ups to ensure a positive pregnancy outcome.

Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in Systemic Lupus Erythematosus patients.

Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE). We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates). We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, 4 (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, p = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, p = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, p = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, p = 0.04) had significantly more severe flares. In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs. ClinicalTrials.gov, NCT02450396.

P061 A comparative analysis of Systemic Lupus Erythematosus, Rheumatoid arthritis and Juvenile Idiopathic Arthritis pregnancy outcomes: Results from a three-year prospective, case-controlled, single centre study of 183 patients

Abstract Background/Aims Patients with inflammatory rheumatic diseases (IRD) have an increased risk of adverse pregnancy outcomes (APO), although the comparative risk of APO in rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) pregnancies has not been directly compared. Therefore, this study examined pregnancy outcomes (PO) of subjects with RA, JIA, and SLE, who had all received pre-pregnancy counselling to ensure disease control, to identify whether there are any differences in APO between each individual IRD group. Pregnancy outcomes were compared with healthy pregnant subjects lacking IRD, to determine the comparative risk of APO in RA, JIA and SLE pregnancies. Methods A prospective case-controlled study was conducted at University College London Hospital from February 2018 to February 2021. A total of 183 patients were enrolled into the study, consisting of 120 pregnant patients including 60 patients with an IRD (n = 29 RA, n = 12 JIA and n = 19 SLE), 60 pregnant patients without any IRD and 63 non-pregnant patients with IRD (n = 30 RA, n = 12 JIA, n = 21 SLE). Pregnancy outcome data was obtained from all pregnant patients and the individual IRD groups’ outcomes were compared to each other and against outcomes from pregnancies without an IRD. Results Patients were predominantly Caucasian, ranging from 17-45 years of age. Of 111 reported PO, 99.09% (n = 110) resulted in a live birth (n = 27 (100.00%) RA, n = 11 (100.00%) JIA, n = 18 (94.74%) SLE versus n = 54 (100.00%) pregnancies without IRD). Overall, 5.56% (n = 1 SLE pregnancy) resulted in a spontaneous early trimester miscarriage, 6.36% (n = 7) were pre-term births (n = 3 (11.11%) RA, n = 1 (9.09%) JIA, n = 2 (11.11) SLE pregnancies versus n = 1 (1.85%) pregnancy without IRD). No stillbirths/foetal deaths were reported. Only two maternal complications were reported (n = 1 Group B strep infection, n = 1 gestational diabetes in RA pregnancies). In total six foetal complications were observed in four RA (n = 1 each for enlarged kidney, tongue tied, neonatal jaundice and Group B strep infection), n = 1 JIA (tongue tied) and n = 1 SLE (prolapsed cord) pregnancies. In relation to disease activity statuses in pregnancy, the majority of IRD pregnant patients were in remission (n = 42 (73.68%), n = 18 RA, n = 6 JIA and n = 18 SLE), 28 (49.12%) IRD patients had low disease activity (n = 8 RA, n = 2 JIA and n = 18 SLE) and nine (15.79%) had moderate/high disease activity (n = 6 RA, n = 2 JIA and n = 1 SLE). Only two (3.51%) RA patients reported disease flares during pregnancy, whereas no JIA/SLE patients experienced any flares. Conclusion This first prospective case-controlled study of RA, JIA, SLE and healthy pregnancies has identified favourable and comparable PO between IRD pregnancies with good disease control. This study highlights the importance and need for IRD pregnant women to undergo pre-pregnancy counselling and maintenance of disease control during pregnancy to enhance the chances of successful pregnancy outcomes. Disclosure H. Nguyen: None. D.A. Isenberg: Consultancies; AstraZeneca, Merck Serono, Eli Lilly, Servier, Genentech. D.J. Williams: Grants/research support; National Institute for Health Research University College London Hospitals Biomedical Research Centre. I. Giles: Grants/research support; UCB Pharma.

OA24 Age-associated T-bet+ B cells in healthy and autoimmune pregnancy

Abstract Background/Aims Inflammatory rheumatic diseases (IRD), including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), affect females of reproductive age and are characterised by loss of immune tolerance and an increased burden of adverse pregnancy outcomes (APO). Mechanisms by which IRD may affect immune adaptations of healthy pregnancy to maintain host and fetal defence whilst tolerating male fetal antigens are poorly characterised. This study aimed to investigate B cell subpopulations in healthy and IRD in pregnancy, with a focus on IgD-CD27- (double negative, DN) T-bet+ B cells, considered pathogenic in IRD. Given disparate relationships between disease activity and risk of APO in SLE and RA pregnancy, the objective of this pilot study was to determine if pregnancy alters the frequency and/or the phenotype of DN T-bet+ B cells in IRD compared with healthy control pregnancies. Methods Peripheral blood mononuclear cells were obtained from IRD pregnancy (SLE n = 5; RA n = 8), IRD non-pregnancy (SLE n = 12; RA n = 10), and healthy pregnant (n = 8) people at University College London Hospital by informed consent. Cells were analysed by flow cytometry to identify B cell subpopulations and their expression of multiple markers including T-bet, IFN-γR, TLR7, TLR9, Ki67, CD38 and CD19 was assessed. Results There were no significant differences in B cell subpopulations, categorised based on the expression of IgD and CD27, between the cohorts. In healthy pregnancy, the median frequency (%) of CD19+T-bet+, IgD-CD27+T-bet+, DNT-bet+ cells was 5, 1.3 and 2, respectively. In contrast, the median frequency of CD19+T-bet+ cells was significantly elevated in SLE pregnancy at 13% compared with 5% (p < 0.05) in healthy pregnancy[GI3] [RV4] . Similarly, the median frequency of DNT-bet+ B cells was elevated in SLE pregnancy at 6% compared with 2% (p = 0.009) in healthy pregnancy. RA pregnancy, but not SLE pregnancy, had significantly lower frequency of Ki67+ DN T-bet+ cells compared to non-pregnant RA (p=0.04) and SLE (p=0.07). ROC analysis demonstrated that for both RA (p = 0.016, AUC = 0.84, 95% CI [0.65, 1.00]) and SLE (p = 0.015, AUC=0.88) the frequency of DN T-bet+ Ki67+ B cells can discriminate between pregnancy and non-pregnancy samples. In pooled analysis (n = 43), but not in single cohorts, DN T-bet+ cells had significantly high TLR7 and TLR9 expression. High frequencies of CD19hi DN T-bet+ cells were found but were unaffected by pregnancy. Clustering revealed canonical DN T-bet+ clusters and CD38hi T-bet+ clusters enriched in SLE and pregnancy-altered. Conclusion We have immunophenotyped B cell populations in healthy pregnancy and identified different patterns of alteration in frequency and proliferation of DNTbet+ cells in IRD compared with healthy pregnancy that are disease specific. This pilot study reveals previously unrecognized immunological changes in disease pregnancy warranting further larger studies of their mechanistic basis and clinical relevance. Disclosure S. Benton: None. C. Raine: None. K. Shah: None. S. Luong: None. A. Venkatkrishnan: None. M. Leandro: None. M. Castelino: None. D. Sen: None. D.A. Isenberg: None. A. Akbar: None. I. Giles: Grants/research support; IG has received an unrestricted research grant, travel and speaker fees from UCB Pharma. V.R. Reddy: None.

OA22 Pregnancy in connective tissue diseases: a 30 year follow-up study of 465 pregnancies from a Spanish monocentric registry

Abstract Background/Aims Pregnancy in patients with connective tissue diseases (CTDs) are known to be at high risk for the occurrence of adverse pregnancy outcomes. We aimed to evaluate pregnancy outcomes in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS) and undifferentiated connective tissue disease (UCTD). Methods A retrospective and descriptive study was conducted from 1990 to 2020. All data were collected from the medical records of women of childbearing age with SLE, SSc, SS and UTCD enrolled in our clinic at the time of their pregnancy and childbirth. The obstetric, maternal and fetal outcomes were collected and compared regarding diagnosis and adverse outcomes. Results The study group included 295 patients: 125 patients (42%) with SLE; 50 patients (17%) with SSc; 80 patients (27%) with pSS; 40 patients (14%) with UCTD. A total of 465 pregnancies were registered. The mean age at delivery was 31.5±8.5 years and the mean duration of disease was 7.2±5.6 years. Pregnancy loss occurred in 21% of patients, live births in 66% of pregnancies, preterm delivery in 8%, postpartum haemorrhage in 6%, preeclampsia in 5%, placental abnormalities in 4%, ectopic pregnancy in 3%, and premature rupture of membranes in 2%. Treatment with hydroxychloroquine (HCQ) was received in 115 pregnancies in SLE (59%), 21 pregnancies in SSc (24%) 62 pregnancies in pSS (52%) and 32 pregnancies in UCTD (49%). Exposure to corticosteroids and biologics during pregnancy was 23 (18.4%), 6 (12%), 15 (19%) and 3 (7.5%), respectively. Patients with SLE had a higher risk of fetal morbidity, including abortion (p = 0.03), mean abortion rate (p = 0.03), preeclampsia (p = 0.04), ectopic pregnancy (p = 0.03), preterm delivery (p = 0.02) and postpartum haemorrhage (p = 0.01) than patients without SLE. The multivariate model found an association between unfavourable pregnancy outcomes and disease activity (OR 2.4; 95% CI 1.3-7.2; p 0.003), whilst HCQ during pregnancy (OR 0.23; 95% CI 0.03-0.82) had a protective effect. Conclusion 66% of pregnancies in patients with autoimmune diseases resulted in live births. Patients with SLE had higher rates of fetal and maternal morbidity than SSc, pSS and UCTD. Disease activity was associated with unfavourable pregnancy outcomes. Exposure to HCQ had a protective effect during pregnancy. Disclosure C. Sieiro Santos: None. P. Pérez García: None. J. Ordas Martínez: None. C. Álvarez Castro: None. E. Díez Álvarez: None.

Comparing pregnancy outcomes in patients with Systemic Lupus Erythematosus (SLE) and Undifferentiated Connective Tissue Disease (UCTD): a descriptive cohort study

BackgroundFemales diagnosed with systemic lupus erythematosus (SLE) face an elevated risk of adverse pregnancy outcomes (APOs). However, the evidence regarding whether a similar association exists in patients with undifferentiated connective tissue disease (UCTD) is inconclusive. MethodsWe conducted a retrospective review (2006–2019) of pregnancy outcomes among patients with SLE (n = 51) and UCTD (n = 20) within our institution. We examined the occurrence of various APOs, encompassing miscarriage, stillbirth, termination, preterm birth, pre-eclampsia, eclampsia, HELLP syndrome, intrauterine growth restriction, abruption placentae, congenital heart block, or other cardiac abnormalities. ResultsThe mean age at pregnancy was 35 ± 7.0 years for patients with SLE and 35 ± 6.8 years for those with UCTD (p = 0.349). The proportion of Caucasian women was 47% in SLE and 80% in UCTD. Pregnancies in both groups were planned (81% in SLE and 77% in UCTD), and patients presented with inactive disease at conception (96% in SLE and 89% in UCTD). Hydroxychloroquine at conception was utilized by 86% of women with SLE, in contrast to 36% in the UCTD group. Both, SLE and UCTD cohorts exhibited low rates of disease flares during pregnancy and/or puerperium (14% vs. 10%). The incidence of APOs was 15.6% in SLE patients compared to 5% in those with UCTD (Risk difference 19.5%; 95% confidence interval: −3.9 to 43.1; p = 0.4237). ConclusionOur study underscores the importance of strategic pregnancy planning and the maintenance of appropriate treatment throughout pregnancy to ensure optimal disease management and minimize adverse outcomes in both SLE and UCTD pregnancies.

Predictive Factors for the Common Adverse Maternal and Fetal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus.

This study aimed to evaluate the outcomes of pregnancy in patients with systemic lupus erythematosus (SLE). It focused on identifying clinical and laboratory markers that could predict the common adverse pregnancy outcomes (APOs) after 20 weeks of gestation, namely preeclampsia (PE) and preterm birth (PTB) in them. Pregnant SLE women who delivered at the study center from 2010 to 2023 were retrospectively analyzed. Categorical variables were evaluated using the chi-square test or Fisher's exact test, while continuous variables underwent Mann-Whitney U testing. Stepwise regression was used to assess the predictors of pregnancy outcomes. The study enrolled 445 pregnancies in 408 women diagnosed with SLE. Of these, 202 pregnancies (45.4%) resulted in at least one APO. Disease flare-ups, hypertension, and proteinuria during the first trimester were primary predictors of at least one APO and PTB. The most frequently recorded maternal adverse outcome was PE (14.6%), while PTB accounted for 32.6% of fetal adverse outcomes. Multivariate regression analysis identified hypertension, history of PE, associated antiphospholipid syndrome (APS), proteinuria, and low serum C4 in the first trimester as independent risk factors for PE. Regular follow-ups at our center correlated with lower risks of APOs, PE, and PTB. APS also emerged as a risk factor for PTB, whereas the use of hydroxychloroquine (HCQ) during pregnancy seemed to protect against PTB. For pregnancies complicated by SLE, we recommend early pregnancy screening for proteinuria-even in the absence of lupus nephritis-as well as continued use of HCQ and routine prenatal care throughout pregnancy.

Platelet ındices as potential biomarkers of perinatal outcomes in women with SLE during pregnancy.

This study aimed to assess the platelet parameters and their prognostic value for perinatal outcomes in pregnant women with systemic lupus erythematosus (SLE). This retrospective study involved 180 participants, 90 pregnant women with SLE and 90 healthy pregnant women. Clinical and demographic variables including routine first-trimester neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet parameters such as platelet distribution width (PDW), mean platelet volume (MPV), plateletcrit (PCT) were compared between the groups. The perinatal outcomes of the whole study group were also compared. SLE patients had lower leukocyte (p = 0.001), lymphocyte (p = 0.001) and platelet counts (p = 0.018), higher PDW (p = 0.002), MPV (p = 0.001), NLR (p = 0.008) and PLR (p = 0.015) and lower PCT (p = 0.015) than the control group. The groups had no significant difference in hemoglobin levels (p = 0.936). SLE patients had higher rates of cesarean section (p = 0.002), small for gestational age (SGA) (p = 0.019) and stillbirth (p = 0.017) and lower birth weight (p = 0.001) than the control group. PCT was a significant predictor of stillbirth with a cut-off value of 0.21, sensitivity of 64.3% and specificity of 83.3% (AUC: 0.843, p < 0.001). Pregnant women with SLE have altered platelet parameters and increased inflammatory markers compared to healthy pregnant women. PCT is a simple and useful marker for predicting stillbirth risk in SLE pregnancies.

Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy

BackgroundLymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.MethodsRepeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren’s syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.ResultsWomen with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment.ConclusionLymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.