Association Between Factor V Leiden Mutation, Small for Gestational Age, and Preterm Birth: A Systematic Review and Meta-Analysis

OBJECTIVE: To estimate the association of a maternal factor V Leiden (FVL) mutation with SGA and preterm birth. DATA SOURCES: We performed a search of PubMed, Embase, Scopus, CINAHL, and the Cochrane Library from inception to April 2016 for cohort and case-control studies of women with FVL mutation and associated outcomes of SGA and preterm birth that included a reference group without FVL mutation. Additional studies were identified from reference lists of relevant research and review articles. STUDY SELECTION: Two authors (JKB, AMO) independently examined the abstracts of the potentially eligible studies, and full texts of eligible studies were retrieved for further evaluation. Disagreements were resolved by consensus. We identified 42 studies suitable for inclusion in the meta-analysis. DATA EXTRACTION: Thirty-two studies evaluated SGA, and 18 studies assessed preterm birth. Study quality was assessed using the Newcastle Ottawa Scale. A random effects model with inverse variance weighting was used to calculate pooled ORs and 95% CIs. Subgroup analyses were performed by study design. DATA SYNTHESIS: The overall OR associating FVL mutation with SGA was significant (OR 1.40, 95% CI 1.18 to 1.67). Analysis of 13 cohort studies resulted in an OR of 1.20 (95% CI 1.03 to 1.41), and data from 19 case-control studies yielded an OR of 1.86 (95% CI 1.35 to 2.56). There was no significant association between FVL mutation and preterm birth (OR 1.17, 95% CI 1.00 to 1.37) when all groups were studied, but the association was significant for case-control studies alone (OR 1.40, 95% CI 1.05 to 1.86). CONCLUSION: There is an increased risk for SGA in pregnancies complicated by FVL mutation in both cohort and case-control study designs. The risk of preterm birth with FVL mutation is less clear, although there is conflicting evidence from cohort and case-control studies regarding the risk of preterm birth associated with FVL mutation.