Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis

Abstract

Background: To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. Methods: In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. Findings: Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47–0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55–2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35–4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74–3·58]; I2=0%), preterm birth (2·65 [1·87–3·77]; I2=0%), and pre-eclampsia (5·86 [3·41–10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96–4·33]; I2=21%) and pre-eclampsia (2·32 [1·40–3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27–0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44–5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29–2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. Interpretation: We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. Funding: None.