Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis

Abstract

STUDY QUESTION Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)? SUMMARY ANSWER Pregnant women with hereditary thrombophilia have an increased risk of RPL, especially for pregnant women with the G1691A mutation of the factor V Leiden (FVL) gene, the G20210A mutation of the prothrombin gene (PGM), and deficiency of protein S (PS). WHAT IS KNOWN ALREADY Prior studies have suggested that pregnant women with hereditary thrombophilia have a higher risk of RPL, however, the results are inconsistent; furthermore, a complete overview is missing. This lack of information is an obstacle to the risk assessment of RPL in pregnant women with hereditary thrombophilia. A comprehensive meta-analysis on the relation between hereditary thrombophilia and the risk of RPL is needed. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis was performed using observational studies published in English before 1 April 2020 to evaluate the relation between hereditary thrombophilia and risk of RPL. PARTICIPANTS/MATERIALS, SETTING, METHODS Relevant studies were identified from PubMed, Web of Science, and EMBASE searches and complemented with perusal of bibliographies of retrieved articles. The exposure of interest was hereditary thrombophilia, including FVL mutation, PGM, deficiency of antithrombin (AT), deficiency of protein C (PC), and deficiency of PS. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were carried out to explore possible sources of heterogeneity and assess the robustness of the results. MAIN RESULTS AND THE ROLE OF CHANCE A total of 89 studies involving 30 254 individuals were included. Results showed that women with FVL mutation (odds ratio (OR): 2.44, 95% CI: 1.96–3.03), PGM (OR: 2.08, 95% CI: 1.61–2.68), or deficiency of PS (OR: 3.45, 95% CI: 1.15–10.35) had higher risks of developing RPL. Compared with the reference group, there was no observed relation between a deficiency in AT or PC and RPL (all P > 0.05). Heterogeneity in the risk estimates of RPL was partially explained by geographic region, definitions of RPL, types of RPL, and controlled confounders. Sensitivity analyses validated the robustness of the findings. LIMITATIONS, REASONS FOR CAUTION Only 39 of the included studies controlled for one or more confounders, and the heterogeneity across all included studies was high. Based on the data available, we cannot determine whether this association is confounded by other potential risk factors of RPL. WIDER IMPLICATIONS OF THE FINDINGS This systematic review and meta-analysis show a possible association between hereditary thrombophilia and an increased risk of RPL, suggesting that testing for hereditary thrombophilia should be considered in individuals with RPL. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Hunan Provincial Key Research and Development Program (Grant number: 2018SK2062) and National Natural Science Foundation Program (Grant number: 81973137). There are no conflicts of interest. REGISTRATION NUMBER N/A.

Thrombophilia Impact on Treatment Decisions, Subsequent Venous or Arterial Thrombosis and Pregnancy-Related Morbidity: A Retrospective Single-Center Cohort Study

“…Although the thrombophilia risk for first VTE is well established [ 51 ], data on the recurrence of VTE are less clear. Multiple reports indicate no association of a positive thrombophilia result with the recurrence of VTE, mostly in low-risk hereditary thrombophilia [ 9 , 10 , 12 ], and heterogeneous results on recurrent pregnancy morbidity [ 52 , 53 , 54 ] with the exception of antiphospholipid antibody syndrome [ 55 ]. However, data on hereditary high-risk thrombophilia are limited and studies including the whole panel of thrombophilia are sparse.…”

Protein S and protein C in preeclamptic pregnant women

“…Other researchers have shown a decrease in the concentration of natural coagulation factors in the development of large obstetric syndromes (preeclampsia, recurrent pregnancy loss) associated with thrombophilia, and thus low values of protein S as an isolated risk factor (13,14), but some previous studies showed no correlation between these factors and protein S levels, which interprets the heterogeneity of the study and requires further randomized evaluation (15,16 ). It is important to point out that we only analysed the levels of coagulation factors from the mother's circulation, not in fetoplacental (umbilical) circulation.…”

Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta‐analysis

“…Recurrent miscarriage (RM) is a disorder of early gestation that affects approximately 1–3% of couples who are expecting a child 1 . It is elusive and can be multifactorial, 2 including embryonal chromosome factor, 3 uterus congenital, 4 endocrine factor, 5 thrombophilia, 6 male‐related factors, 7,8 and environmental factors. Approximately, 50% of patients with RM have no clear cause, 9 which is called idiopathic RM.…”