Systemic Lupus Erythematosus Pregnancies Research Articles

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.

Calcineurin inhibitors experience 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.

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.

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.

Metabolomics profiling reveals low blood tyrosine levels as a metabolic feature of newborns from systemic lupus erythematosus pregnancies.

Pregnancy outcomes of patients with systemic lupus erythematosus (SLE) have improved over the past four decades, leading to an increased desire for pregnancy among this cohort. However, the offspring of patients with SLE still face the risks of preterm birth, low birth weight, learning disabilities, and neurological disorders, while the causes underlying these risks remain unclear. In this study, we analyzed the blood metabolic features of neonates born to 30 SLE patients and 52 healthy control mothers by employing tandem mass spectrometry with the dual aims of identifying the etiology of metabolic features specific to infants born from mothers with SLE and providing new insights into the clinical management of such infants. We found significant differences in serum metabolite levels between infants born from mothers with SLE and those born from mothers without SLE, including 15 metabolites with reduced serum levels. Further analysis revealed a disrupted tyrosine metabolism pathway in the offspring of mothers with SLE. By constructing a composite model incorporating various factors, such as serum tyrosine levels, gestational age, and birth weight, we were able to accurately differentiate between newborns of SLE and non-SLE pregnancies. Our data reveal significant differences in serum concentrations of amino acids and acylcarnitines in newborns born to mothers with SLE. We conclude that the reduction of blood L-tyrosine levels is a feature that is characteristic of adverse neurological outcomes in infants born from mothers with SLE.

Mendelian randomization reveals systemic lupus erythematosus and rheumatoid arthritis and risk of adverse pregnancy outcomes

BackgroundThe effect of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) on adverse pregnancy outcomes is a controversial topic. This study aimed to use Mendelian randomization (MR) analysis to assess the causal relationship between SLE, RA and adverse pregnancy outcomes. MethodsGenetic variants for SLE and RA, as well as adverse pregnancy outcomes, were derived from pooled statistics from large public genome-wide association studies. Several methods, such as inverse variance weighting (IVW), MR-Egger, weighted median and MR-Pleiotropic Residuals Sum and Outliers, were employed to estimate two-sample causality. ResultsGenetic prediction of SLE was associated with higher odds of preterm labour [odds ratio (OR) 1.03, 95 % confidence interval (CI) 1.01–1.05; p = 0.008]. RA was associated with higher odds of preterm labour (OR 1.03, 95 % CI 1.01–1.06; p = 0.009), pre-eclampsia or eclampsia (OR 1.04, 95 % CI 1.01–1.07; p = 0.005), and poor fetal growth (OR 1.08, 95 % CI 1.04–1.12; p = 2.91 × 10−5). The results of bidirectional MR analysis did not indicate that SLE was associated with spontaneous abortion, pre-eclampsia or eclampsia, preterm rupture of membranes, or poor fetal growth (p-value for IVW 0.13–0.97). ConclusionsThis study found a genetic association between SLE and the risk of preterm labour, and highlights the importance of perinatal care and monitoring for patients with SLE. Furthermore, RA was found to be associated with a wide range of adverse outcomes, including preterm labour, pre-eclampsia or eclampsia, and poor fetal growth; as such, there is a need for more intensive therapeutic interventions and prenatal monitoring.

Abstract 16604: Systemic Lupus Erythematosus and Pregnancy: An Analytical Review of Cardiovascular Disease and Obstetric Complications

Background Cardiovascular disease in pregnant patients with Systemic Lupus Erythematosus (SLE) is not well studied. Our objective is to study the prognostic implications of SLE in pregnancy in terms of cardiovascular disease (CVD) and obstetric complications. Methods A retrospective cohort analysis was conducted using National Inpatient Sample 2016-2020. Cohorts of patients hospitalized for SLE, pregnancy and CVD were identified using respective ICD-10 codes. Multivariate logistic regression analysis was used to assess prognostic outcomes. Results Among 898825 patients hospitalized for SLE, 30845 patients were pregnant. Out of these patients with SLE and pregnancy, 1710 patients had cardiovascular disease (prevalence 5.5%). Mean age for SLE patients with pregnancy and cardiovascular disease was 30 years, 36.7% were white, and 36.4% were African-American. SLE in pregnancy is associated with five folds higher odds of cardiovascular disease (OR 4.8, CI 4.3-5.5, p&lt;0.001). The strongest association of SLE in pregnancy is with pericarditis (OR 77, CI 34.4-172, p&lt;0.001), followed by myocarditis (OR 35, CI 3.9-312, p=0.001), pulmonary hypertension (OR 12.9, CI 8.6-17.5, p&lt;0.001), ischemic heart disease (OR 9.3, CI 6.7-12.8, p&lt;0.001), stroke (OR 9.3, CI 4.8-18, p&lt;0.001) and congestive heart failure (OR 7.7, CI 5.16-11.5, p&lt;0.001). Table 2 outlines the pregnancy outcomes and complications in SLE. SLE is associated with significantly lower odds of live birth (OR 0.35, CI 0.32-0.37, p&lt;0.001). SLE is associated with significantly higher odds of pregnancy complications (Table 2). Conclusion 5.5% of SLE patients with pregnancy have CVD. SLE in pregnancy is associated with five folds higher odds of cardiovascular disease with strongest association to pericarditis, followed by myocarditis, pulmonary hypertension, ischemic heart disease, and stroke. SLE in pregnancy is associated with lower odds of live birth and higher odds of obstetric complications.

The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus.

In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as "active." Patients with lupus low disease activity state (LLDAS) during each of these periods were identified.Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6months of postpartum period. The mean SLEDAI in the 6months postpartum period was significantly higher compared to mean disease activity during pregnancy (p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO- pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO - and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.

Pregnancy and Inflammatory Rheumatological Diseases: A Single-Center Retrospective Cohort Study.

Background Rheumatic diseases pose risks to pregnant women, leading to complications like preterm birth, congenital heart block, and pregnancy loss. These diseases are expected to deteriorate during pregnancy and further in the postpartum period. The impact of these diseases on the pregnancy will add further burden on the patient, fetus, physician, and healthcare system. Advances in diagnosis and treatment have improved outcomes making them similar to that of healthy women, but close follow-up in a multidisciplinary clinic is essential. The objective of this study is to study the outcome of pregnancy in women with rheumatological disease and the behavior of the disease during pregnancy. Methods A retrospective cohort study was conducted in King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia, to compare the outcomes of pregnancy across three rheumatological diseases: Sjogren syndrome (SS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) from 2016 to 2021. A total of 128 pregnancies in 107 women with rheumatological diseases were included in this study. Pregnancy measures and outcomes were investigated by assessing maternal health, fetal health, and pregnancy complications, specifically maternal disease activity, medications to control the disease, infection, preterm birth, birth weight, abortions/stillbirths, mode of delivery, bleeding, preeclampsia, congenital heart block, and neonatal lupus. Results There were 55 patients with RA (63 RA pregnancies), 44 with SLE (54 SLE pregnancies), and eight with primary SS (11 SS pregnancies). In most of the pregnancies (n= 108; 95.58%), the patients were in clinical remission before pregnancy. Lupus nephritis, which was in remission before pregnancy, has been reported in nine (16.67%) out of 54 SLE pregnancies. Vaginal delivery was the most common mode of delivery (n=87; 67.97%). On the other hand, there were 38 cesarean sections (29.69%). Rheumatological disease flares occurred in 10 pregnancies (7.87%). One hundred and twenty-two live births were delivered. Preterm infants were born in 25 pregnancies (20.16%), and 16 (13.22%) of the newborns needed neonatal intensive care unit (NICU) care. Interestingly, congenital heart block (CHB) was found in five (12.2%) neonates out of 41 anti-SS-related antigen A (anti-SSA) positive mothers; one of those five died from heart block. Eleven neonates were delivered with positive serology, and five were diagnosed with neonatal lupus. Conclusion The outcome of pregnancy in patients with rheumatological disease is favorable. A multidisciplinary team approach and close clinical follow-up are the cornerstone for such success. A small dose of prednisolone (5 mg or less) is safe and will not have a negative impact on maternal or fetal health. CHB is a concern for pregnant women with positive anti-SSA.

Maternal and fetal health outcomes in systemic lupus erythematosus pregnancies in the Emirati population: A comparative study.

To evaluate adverse pregnancy outcomes in patients with systemic lupus erythematosus (SLE), compare their maternal and fetal outcomes with those of age-matched pregnant women without SLE, and identify factors linked to increased risks of adverse outcomes. Medical records from Tawam Hospital were reviewed retrospectively to identify patients with SLE and a history of pregnancy. Demographics, clinical variables, and maternal and fetal outcomes were obtained. A one-to-one age-matched healthy control group was randomly selected. The outcomes and odd ratios of women with and without SLE were compared, and factors associated with adverse pregnancy outcomes were examined. The outcomes of 78 SLE pregnancies in 39 women were analyzed. Adverse maternal outcomes, such as gestational diabetes mellitus (GDM), occurred in 32% of pregnancies, whereas adverse fetal outcomes, such as low-birth weight and preterm deliveries, occurred in 51% of pregnancies. Pregnant women with SLE had a 5-fold higher risk of GDM, had higher odds of maternal hypertension, and were more likely to deliver through cesarean section than those without SLE. Preterm deliveries and low-birth weight were also more common in SLE pregnancies. Steroid use during pregnancy was significantly associated with an increased risk of GDM development. Lupus nephritis, maternal hypertension, pre-eclampsia, and GDM were linked to preterm deliveries. Pregnant women with SLE were at a higher risk for adverse maternal and fetal outcomes than age-matched pregnant women without SLE. These findings can guide clinical management and emphasize the need for close monitoring of SLE pregnancies.

The prognostic value of neutrophile/lymphocyte ratio and serum chemerin to predict maternal-fetal complications in pregnant systemic lupus erythematosus patients.

Pregnancy in SLE continues to be a challenge. The neutrophil-to-lymphocyte ratio (NLR) and chemerin are predictors of preeclampsia in the general population; however, their role as predictors of maternal-fetal complications in pregnant SLE patients has not been analyzed. To investigate the prognostic value of NLR and serum chemerin, to predict maternal-fetal complications in pregnant SLE patients, and compare both biomarkers among three study groups. Design: Analytical cross-sectional study of cases and controls with the following study groups: systemic lupus erythematosus (SLE), preeclampsia, and healthy. NLR and chemerin serum were determined between 20 and 25weeks of gestation. Patients were evaluated every 4-6weeks until pregnancy resolution. Maternal and fetal outcomes were registered. We employed Receiver Operating Characteristic (ROC) curves to validate prognostic values. Seventy pregnant patients were included: 20 with SLE, 20 with preeclampsia, and 30 healthy pregnant women; NLR values were 4 (2.3-5.6) in SLE, 6 (4.6-9.2) in preeclampsia, and 2.8 (2.1-2.9) in the group of healthy women (p = .0001). Chemerin levels were: 26 (15.3-56.2) in SLE, 96 (37.3-146.2) in preeclampsia, and 24.6ng/mL (15.3-47.4) in the healthy group (p = .007) Maternal complications were observed in 11 (55%), 20 (100%), and 8 (26%) per group, respectively. Thrombocytopenia was the most frequent complication in all pregnant women, followed by hypertensive disorders. Fetal complications were registered in 12 (60%), 16 (80%), and 2 (6.7%), respectively. Congenital malformations and prematurity were the most frequent fetal complications. NLR had good diagnostic accuracy in predicting maternal-fetal complications (AUROC 0.715) p = .015, CI 95% 0.56-0.86, cut-off point level: 2.9, sensitivity 61%, specificity 78%, positive predictive value (PPV) 65%, negative predictive value (NPV) 75%. Regarding chemerin, a cut-off point level >43ng/mL had a sensitivity of 75%, specificity of 72% AUROC 0.75, p = .001, CI 95% 0.61-0.89, PPV 51.7% NPV 87.8%, meaning that 51.7% of patients with chemerin levels >43ng/mL have or will have preeclampsia. The NLR may help predict maternal-fetal complications in SLE pregnancy, constituting a marker of subclinical inflammation. Chemerin levels may be associated with preeclampsia. These biomarkers could improve the care of SLE patients with timely intervention of potential complications during pregnancy.

Diffuse alveolar haemorrhage during pregnancy in systemic lupus erythematosus.

Diffuse alveolar haemorrhage during pregnancy in systemic lupus erythematosus.

2022 Chinese guideline for the management of pregnancy and reproduction in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a prevalent autoimmune disease predominantly affecting women of childbearing age, presents ongoing challenges despite notable advances in diagnosis and treatment. Although survival rates for SLE patients have significantly improved, pregnancy continues to pose a considerable obstacle. Addressing this critical need for enhanced reproductive and prenatal care, there is a pressing imperative to establish standardized protocols for peri-gestational monitoring and treatment in SLE patients. This guideline is jointly sponsored by the National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), the Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR), and the Chinese Research Committee of Pregnancy and Reproduction in Autoimmune Rheumatic Diseases (CHOPARD). Thirteen pertinent clinical questions have been generated through several rounds of rigorous clinical and methodological expert discussions and selections for a comprehensive understanding of key aspects in this domain. Guided by thorough examination of research evidence and expert perspectives, the formulated recommendations aim to optimize pregnancy success rates, reduce maternal and infant mortality rates, and ultimately enhance the overall well-being of SLE patients.

Preconception clinical factors related to adverse pregnancy outcomes in patients with systemic lupus erythematosus or primary Sjögren’s syndrome: a retrospective cohort study

ObjectiveTo identify preconception clinical factors associated with adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) or primary Sjögren’s syndrome (pSS).MethodsA single-centre, retrospective cohort study was conducted, which...

Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus

BackgroundAn increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.MethodsRepeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.ResultsWomen with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.ConclusionOur results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.

Optimizing Patient Care: A Systematic Review of Multidisciplinary Approaches for SLE Management.

Systemic lupus erythematosus (SLE) is characterized by multisystemic clinical manifestations ranging from a relatively mild involvement to potentially life-threatening complications. Due to this complexity, a multidisciplinary (MD) approach is the best strategy for optimizing patients' care. The main aim of this systematic literature review (SLR) was to scrutinize the published data regarding the MD approach for the management of SLE patients. The secondary objective was to evaluate the outcomes of the MD approach in SLE patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. We performed an SLR to retrieve articles available in English or Italian listed in PubMed, Embase, Cinahl, and Cochrane Library concerning the MD approach used in observational studies and clinical trials. Four independent reviewers performed the study selection and data collection. Of 5451 abstracts evaluated, 19 studies were included in the SLR. The MD approach was most frequently described in the context of SLE pregnancy, reported in 10 papers. MD teams were composed of a rheumatologist, except for one cohort study; a gynecologist; a psychologist; a nurse; and other health professionals. MD approaches had a positive impact on pregnancy-related complications and disease flares and improved SLE psychological impact. Although international recommendations advise an MD approach for managing SLE, our review highlighted the paucity of data supporting this strategy, with most of the available evidence on the management of SLE during pregnancy.

Implications of the accuracy of diagnostic algorithms for systemic lupus on our understanding of racial disparities in pregnancy outcomes.

Disparities in pregnancy outcomes among women with SLE remain understudied, with few available racially diverse datasets. We sought to identify disparities between Black and White women in pregnancy outcomes within academic institutions in the United States. Using the Common Data Model electronic medical record (EMR)-based datasets within the Carolinas Collaborative, we identified women with pregnancy delivery data (2014-2019) and ≥1 SLE International Classification of Diseases 9 or 10 code (ICD9/10) code. From this dataset, we identified four cohorts of SLE pregnancies, three based on EMR-based algorithms and one confirmed with chart review. We compared the pregnancy outcomes identified in each of these cohorts for Black and White women. Of 172 pregnancies in women with ≥1 SLE ICD9/10 code, 49% had confirmed SLE. Adverse pregnancy outcomes occurred in 40% of pregnancies in women with ≥1 ICD9/10 SLE code and 52% of pregnancies with confirmed SLE. SLE was frequently over-diagnosed in women who were White, resulting in 40-75% lower rates of adverse pregnancy outcomes in EMR-derived vs confirmed SLE cohorts. Over-diagnosis was less common for Black women with pregnancy outcomes 12-20% lower in EMR-derived vs confirmed SLE cohorts. Black women had higher rates of adverse pregnancy outcomes than White women in the EMR-derived, but not the confirmed cohorts. EMR-derived cohorts of pregnancies in women who are Black, but not White, provided accurate estimations of pregnancy outcomes. The data from the confirmed SLE pregnancies suggest that all women with SLE, regardless of race, referred to academic centres remain at very high risk for adverse pregnancy outcome.