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Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

ABSTRACT: Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12-20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0-12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3-11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0-34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy.

SUBMITTER: Tedeschi SK

PROVIDER: S-EPMC5343667 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

Tedeschi Sara K SK Guan Hongshu H Fine Alexander A Costenbader Karen H KH Bermas Bonnie B

Clinical rheumatology 20160511 7

Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital ...[more]

PMID: 27166627

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Project description:BackgroundPregnant women with systemic lupus erythematosus (SLE) have increased risk of adverse outcomes including disease flare, spontaneous abortion, preeclampsia/eclampsia, premature birth and maternal death. However, pregnancy outcomes among adolescents and young women with SLE have not been well-explored. Our objective was to compare risk of adverse pregnancy outcomes in adolescents and young women with SLE to risk among peers without SLE.MethodsWe studied the 2000-2011 Nationwide Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) to estimate the prevalence of adverse pregnancy outcomes in women with SLE aged ≤ 21 years at time of delivery. Outcomes were compared to peers without SLE by using multivariate logistic regression to calculate odds ratios and risk differences. Additionally, differences in length of stay and total charges per hospitalization were described.ResultsThere were 8,791,391 unique pregnancies, of which 4002 occurred in young women with SLE. After adjustment for age, race, insurance type and quartile of median income based on patient ZIP code individuals with SLE had increased odds of pre-eclampsia/eclampsia (OR 3.2, 95% CI 2.3-4.6), maternal death (OR 80, 95% CI 10-604), preterm birth (OR 2.7, 95% CI 2-3.7), spontaneous abortion (OR 5.1, 95% CI 2.8-9.6), and induced abortion (OR 30, 95% CI 14-63). The increase in risk among women with SLE was greatest for preterm birth (RD 11%, 95% CI 6-16), pre-eclampsia/eclampsia (RD 9%, 95% CI 5-13), and spontaneous abortion (RD 4%, 95% CI 0.9-6). Risk difference for induced abortion was 2% with 95% CI 0.6-4, while the difference in risk for maternal death did not reach statistical significance (RD 0.4, 95% CI -0.4-1).ConclusionsAdolescents and young women with SLE experience increased risk of adverse, pregnancy-specific outcomes as compared to their peers, including pre-eclampsia/eclampsia, maternal death, preterm birth, spontaneous abortion, and induced abortion. Additionally, length of stay and total charges for hospitalization are increased.

Project description:BackgroundEffectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE.MethodsThe GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis.ResultsWe identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01).ConclusionsOur preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.

Project description:COVID-19 vaccination has been shown to be safe in patients with systemic lupus erythematosus (SLE), but data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking. We investigated COVID-19 vaccination-related AEs in pregnant SLE patients from the COVAD study, a global esurvey involving 157 collaborators from 106 countries. A total of 9201 complete responses were extracted. Among 6787 (73.8%) women, we identified 70 (1.1%) who were exposed to at least one COVID-19 vaccine dose during pregnancy, 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women. Health-related quality of life and physical function was recorded using PROMIS. Age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs or change in the status of their autoimmune disease. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved after a median of 3 (IQR: 2.5-5.0) days. All patients reported good to excellent health status. No adverse pregnancy outcomes were reported. Importantly, none of the patients reported thrombotic events post-vaccination, which provides reassurance in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or the antiphospholipid syndrome, a considerable portion of SLE patients. Our findings provide reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and highrisk pregnancies due to their background autoimmune disease. The risk/benefit ration of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.

Project description:ObjectiveTo completely and quantifiably determine the effect of systemic lupus erythematosus (SLE) on pregnancy outcomes in a Chinese cohort.DesignA retrospective cohort study.SettingData were collected at a tertiary medical centre located in Shanghai, China, from September 2011 to May 2017.ParticipantsWe assigned 338 pregnant women with SLE to the study cohort and 1014 randomly selected pregnant women without SLE (three for every woman with SLE) to a comparison cohort. The relevant medical records of all pregnant women were retrospectively reviewed. Cases of multiple pregnancy and cases in which an artificial abortion was performed for personal reasons were excluded.Primary and secondary outcome measuresMaternal and fetal outcomes were primary outcomes, and management of antenatal care was the secondary outcome.ResultsThe risks of pregnancy-induced hypertension (OR 2.68, 95% CI 1.75 to 4.09), pre-eclampsia (OR 3.13, 95% CI 1.95 to 5.03) and premature rupture of membranes (OR 2.53, 95% CI 1.46 to 4.40) were significantly different between women with and without SLE. Gestational diabetes was negatively associated with SLE in pregnant women (OR 0.49, 95% CI 0.28 to 0.85). Pregnant women with SLE displayed significantly higher rates of fetal loss (OR 10.23, 95% CI 5.08 to 20.59), including spontaneous abortion (OR 4.42, 95% CI 1.52 to 12.80), therapeutic abortion (OR 16.57, 95% CI 5.80 to 47.35) and stillbirth (OR 13.25, 95% CI 1.49 to 118.11), and a higher risk of preterm birth (OR 3.15, 95% CI 2.21 to 4.50), intrauterine growth restriction (OR 2.20, 95% CI 1.35 to 3.58), a child who was small for the gestational age (OR 1.86, 95% CI 1.11 to 3.13), a caesarean section (OR 4.73, 95% CI 3.30 to 6.80) or a neonatal intensive care unit admission (OR 3.48, 95% CI 2.21 to 5.48) than women in the non-SLE population after adjusting for confounding factors.ConclusionsIn this study, SLE significantly increased the risk of adverse pregnancy outcomes. Therefore, a preconception assessment and close antenatal monitoring by both rheumatologists and obstetricians should be performed in pregnant women with SLE.

Dataset Information

Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

Publications

Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

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