Comparison of treatments for the prevention of fetal growth restriction in obstetric antiphospholipid syndrome: a systematic review and network meta-analysis

Women with criteria and non-criteria obstetric antiphospholipid syndrome (APS) carry an increased risk of pregnancy complications, including fetal growth restriction (FGR). The management of obstetric APS traditionally involves clinicians, obstetricians and gynaecologists; however, the most appropriate prophylactic treatment strategy for FGR prevention in APS is still debated. We performed a systematic review and network meta-analysis (NetMA) to summarize current evidence on pharmacological treatments for the prevention of FGR in APS. We searched PubMed and Embase from inception until July 2020, for randomized controlled trials and prospective studies on pregnant women with criteria or non-criteria obstetric APS. NetMA using a frequentist framework were conducted for the primary outcome (FGR) and for secondary outcomes (fetal or neonatal death and preterm birth). Adverse events were narratively summarised. Out of 1124 citations, we included eight studies on 395 pregnant patients with obstetric APS treated with low-dose aspirin (LDA) + unfractionated heparin (UFH) (n = 132 patients), LDA (n = 115), LDA + low molecular weight heparin (n = 100), LDA + corticosteroids (n = 29), LDA + UFH + intravenous immunoglobulin (n = 7), or untreated (n = 12). No difference among treatments emerged in terms of FGR prevention, but estimates were largely imprecise, and most studies were at high/unclear risk of bias. An increased risk of fetal or neonatal death was found for LDA monotherapy as compared to LDA + heparin, and for no treatment as compared to LDA + corticosteroids. The risk of preterm birth was higher for LDA + UFH + IVIg as compared to LDA or LDA + heparin, and for LDA + corticosteroids as compared to LDA or LDA + LMWH. No treatment was associated with an increased risk of bleeding, thrombocytopenia or osteopenia.