The extent of Factor V Leiden thrombophilia in maternal and fetal health. Risk of placenta‐mediated pregnancy complications ‐ a systematic review

Factor V Leiden represents a mutation in the gene coding the production of V factor, being the most common cause for hereditary thrombophilia, affecting up to 50% of the patients with familial thrombophilia. Pregnant women are generally considered a population at risk for developing different associated pathologies potentially leading to premature parturition, or other complications. Existing literature seems to point towards a significant connection between the Factor V Leiden thrombophilia and potential complications, including thromboembolic events, preeclampsia, recurrent pregnancy loss and intrauterine growth restrictions.

Articles published in the past 9 years were sourced on PubMed, using keywords such as “factor V Leiden”, "FVL", "pregnancy". We included systematic reviews, meta-analyses, case-control and retrospective studies. Placenta-mediated pregnancy complications (PMPC), such as recurrent pregnancy loss (RPL), preeclampsia (PE), and intrauterine growth restriction (IUGR) represented the inclusion criteria. Associated pathologies, comparative studies, screening, women with history of IVF and embryo transfer, clinical trials, paternal and fetal mutations were excluded. Bias risk was not assessed, and an abstraction method was used for data synthesis.

21 randomized control trials were selected. Obstetrical outcomes such as RPL, PE, and IUGR were analyzed in connection with the presence of FVL. Bias risk was not assessed. FVL was associated with a higher risk of RPL in Padda J et. al (2021), Hamedi et al. (2020), Jusić A et al. (2018), and Pietropolli A et al. (2014), with a prevalence of 12.6% (OR=2.4), 12.6% (OR=2.37), 7.5% (p=0.021), and 10% (p=0.05). A connection between FVL and preeclampsia was found in Ahmed NA et al. (2019) - 9.6% (OR=18.60), fortified by Li Y et al. (2019) and Fong FM et. al. (2014). FVL had a prevalence of 40% in patients with IUGR in Padda J et al. (2021), while Coriu L et al. (2014) showed similar results, but without statistical significance (OR=1.58, p>0.05).

FVL is associated with higher risk of RPL, preeclampsia and IUGR. However, due to the multifactorial aspects of obstetrical complications, stronger research is recommended for a better understanding in the future.