The association between antiphospholipid antibodies and late fetal loss: A systematic review and meta-analysis

Antiphospholipid syndrome is a chronic autoimmune disease with a high prevalence in females. Published data have identified that antiphospholipid antibodies (APLA) of antiphospholipid syndrome are risk factors for poor pregnancy outcomes, such as recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia. However, the association between APLA and late fetal loss is not fully understood and remains controversial. The aim of this study is to identify and analyze the recent publications to better understand the association between APLA and late fetal loss.

The literature was searched on 31 January 2019 using Ovid, Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) to evaluate the association between APLA and late fetal loss, with articles published before January 2019, according to the PRISMA statement. Without imposing regional restrictions, referenced articles were selected. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model). The between-study heterogeneity was assessed by Q test. Publication bias was assessed by funnel plots.

Nineteen studies (with 10 265 cases) were included in the final analysis. The odds ratio (OR) for the late fetal loss with lupus anticoagulant was 5.02 (95% confidence interval [CI] 2.14-7.89). Seven included studies reported that lupus anticoagulant had a statistically significant association with late fetal loss. The results did not show a statistically significant association between anticardiolipin antibodies and late fetal loss. The pooled odds ratio for the association of anticardiolipin antibodies with late fetal loss was 3.47 (95% CI 0.68-6.26). However, we did find the relation between anticardiolipin antibodies and late fetal loss among cohort studies (OR 2.27, 95% CI 1.20-3.44). Anti-beta2 glycoprotein 1 antibodies (β2GP1) showed a significant association with late fetal loss (OR 3.13, 95% CI 0.75-5.50).

Lupus anticoagulant is strongly associated with late fetal loss in antiphospholipid syndrome patients. However, the association between anticardiolipin antibodies and late fetal loss is inconsistent. There are currently insufficient data to support a significant relation between β2GP1 and late fetal loss.