Inherited thrombophilias and stillbirth: a systematic review and meta- analysis

The association between inherited thrombophilias and stillbirth has been long investigated but the estimated risk remains unknown. The aim of our study is to summarize available data on the effect of Factor V Leiden, Prothrombin G20210A and MTHFR mutation, Protein S, Protein C and Anithrombin deficiency on the prevalence of stillbirth.

We conducted a systematic review and meta- analysis of all relevant available PubMed, Embase and Cochrane studies until February 2024. A sensitivity analysis of only prospective and retrospective studies was performed.

Based on 31 included studies, Factor V Leiden and Prothrombin G202110A mutations, significantly rise the prevalence of stillbirth with a pooled OR 2.35 (95% CI 1.74-3.17) and 2.62 (95% CI 1.79-3.84), respectively. This positive correlation did not change in the sensitivity analysis. Positive correlation was also found between Antithrombin deficiency and stillbirth with a pooled OR 3.97 (95% CI 1.50-10.48). No statistically significant relationship was found between stillbirth and MTHFR mutation or Protein C and Protein S deficiency according to the random effects model.

Our findings suggest that in the presence of certain inherited thrombophilias, the occurrence of intrauterine fetal death is significantly more prevalent.