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Updates on lupus and pregnancy.

ABSTRACT: This review focuses on events subsequent to planning a pregnancy and addresses three components of concern for women with systemic lupus erythematosus: maternal, placental, and fetal. Flare rates are generally low for patients who are clinically stable at conception. For patients who have never had renal disease, there is no frm evidence that they will develop active renal disease simply due to being pregnant. For patients who begin pregnancy with an abnormal creatinine (> 2 mg/dl is ill advised), risks include hypertension, preeclampsia, high rate of fetal loss, and possible further deterioration of renal function. Discontinuation of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and mycophenalate is mandatory. Elevated levels of sVEGF-1 may be a harbinger of preeclampsia. For patients with anti-phospholipid antibodies detected in the frst trimester of pregnancy, the lupus anticoagulant per se may be the strongest predictor of pregnancy complications. For women with anti-SSA/Ro antibodies the risk of having a child with congenital heart block is 2% which rises to a recurrence rate of 18%. Information on current approaches to prevention and treatment of heart complications of neonatal lupus is provided.

SUBMITTER: Buyon JP

PROVIDER: S-EPMC3904228 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Updates on lupus and pregnancy.

Buyon Jill P JP

Bulletin of the NYU hospital for joint diseases 20090101 3

This review focuses on events subsequent to planning a pregnancy and addresses three components of concern for women with systemic lupus erythematosus: maternal, placental, and fetal. Flare rates are generally low for patients who are clinically stable at conception. For patients who have never had renal disease, there is no frm evidence that they will develop active renal disease simply due to being pregnant. For patients who begin pregnancy with an abnormal creatinine (> 2 mg/dl is ill advised ...[more]

PMID: 19852749

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Project description:Because systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern.To identify predictors of adverse pregnancy outcomes (APOs) in patients with inactive or stable active SLE.Prospective cohort.Multicenter.385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study. Exclusion criteria were urinary protein-creatinine ratio greater than 1000 mg/g, creatinine level greater than 1.2 mg/dL, prednisone use greater than 20 mg/d, and multifetal pregnancy.APOs included fetal or neonatal death; birth before 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age (SGA) neonate (birthweight below the fifth percentile). Disease activity was assessed with the Systemic Lupus Erythematosus Pregnancy Disease Activity Index and the Physician's Global Assessment (PGA).APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death occurred in 4%, neonatal death occurred in 1%, preterm delivery occurred in 9%, and SGA neonate occurred in 10%. Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of lupus anticoagulant (LAC) (odds ratio [OR], 8.32 [CI, 3.59 to 19.26]), antihypertensive use (OR, 7.05 [CI, 3.05 to 16.31]), PGA score greater than 1 (OR, 4.02 [CI, 1.84 to 8.82]), and low platelet count (OR, 1.33 [CI, 1.09 to 1.63] per decrease of 50 × 109 cells/L). Non-Hispanic white race was protective (OR, 0.45 [CI, 0.24 to 0.84]). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who either were LAC-positive or were LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and fetal or neonatal mortality was 22.0%.Patients with high disease activity were excluded.In pregnant patients with inactive or stable mild/moderate SLE, severe flares are infrequent and, absent specific risk factors, outcomes are favorable.National Institutes of Health.

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.

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Updates on lupus and pregnancy.

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Updates on lupus and pregnancy.

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