Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jul;312(1):37-50.
doi: 10.1007/s00404-025-07989-6. Epub 2025 Mar 14.

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

Michail Delis  1 , Elpida Emmanouilidou-Fotoulaki  2 , Christos Chatzakis  3 , Theodoros Theodoridis  4 , Alexandros Sotiriadis  3
Affiliations
Meta-Analysis

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

Michail Delis et al. Arch Gynecol Obstet. 2025 Jul.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

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

Keywords: FVL; Intrauterine Death; Prothrombin; Stillbirth; Thrombophilia.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Flowchart
Fig. 2
Fig. 2
FVL and stillbirth
Fig. 3
Fig. 3
PGM and stillbirth
Fig. 4
Fig. 4
MTHFR, PCD, PSD, ATD and stillbirth
See this image and copyright information in PMC

References

    1. Rey E, Kahn SR, David M, Shrier I (2003) Thrombophilic disorders and fetal loss: a meta-analysis. Lancet Lond Engl 361(9361):901–908. 10.1016/S0140-6736(03)12771-7 - PubMed
    1. Rodger MA, Betancourt MT, Clark P, Lindqvist PG, Dizon-Townson D, Said J et al (2010) The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med 7(6):e1000292. 10.1371/journal.pmed.1000292 - PMC - PubMed
    1. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GDO et al (2006) Thrombophilia in pregnancy: a systematic review. Br J Haematol 132(2):171–196. 10.1111/j.1365-2141.2005.05847.x - PubMed
    1. RCOG [Internet]. [cited 2023 Mar 23]. Late Intrauterine Fetal Death and Stillbirth (Green-top Guideline No. 55). Available from: https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guideline... - PubMed
    1. Management of Stillbirth | ACOG [Internet]. [cited 2023 Mar 23]. Available from: https://www.acog.org/clinical/clinical-guidance/obstetric-care-consensus...

Supplementary concepts

LinkOut - more resources