Objectives: To compare and rank currently available pharmacological interventions for the prevention of recurrent miscarriage (RM) in women with antiphospholipid syndrome (APS).
Methods: A search was performed using PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CNKI, ClinicalTrials.gov, and the UK National Research Register on December 15, 2019. Studies comparing any types of active interventions with placebo/inactive control or another active intervention for the prevention of RM in patients with APS were considered for inclusion. The primary outcomes were efficacy (measured by live birth rate) and acceptability (measured by all-cause discontinuation); secondary outcomes were birthweight, preterm birth, preeclampsia, and intrauterine growth retardation. The protocol of this study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/B9T4E).
Results: In total, 54 randomized controlled trials (RCTs) comprising 4,957 participants were included. Low-molecular-weight heparin (LMWH) alone, aspirin plus LMWH or unfractionated heparin (UFH), aspirin plus LMWH plus intravenous immunoglobulin (IVIG), aspirin plus LMWH plus IVIG plus prednisone were found to be effective pharmacological interventions for increasing live birth rate (ORs ranging between 2.88 to 11.24). In terms of acceptability, no significant difference was found between treatments. In terms of adverse perinatal outcomes, aspirin alone was associated with a higher risk of preterm birth than aspirin plus LMWH (OR 3.92, 95% CI 1.16 to 16.44) and with lower birthweight than LMWH (SMD -808.76, 95% CI -1596.54 to -5.07).
Conclusions: Our findings support the use of low-dose aspirin plus heparin as the first-line treatment for prevention of RM in women with APS, and support the efficacy of hydroxychloroquine, IVIG, and prednisone when added to current treatment regimens. More large-scale, high-quality RCTs are needed to confirm these findings, and new pharmacological options should be further evaluated.
Keywords: Antiphospholipid syndrome; network meta-analysis; pregnancy; recurrent miscarriage; systematic review.