Genetic thrombophilias and intrauterine growth restriction: a meta-analysis

Abstract

Objective: To estimate the relationship between inherited thrombophilias and intrauterine growth restriction (IUGR) using meta-analytic techniques.

Methods: A literature review identified case-control and cohort studies evaluating the relationship between IUGR and the following thrombophilias: homozygous or heterozygous factor V Leiden or prothrombin (PT) G20210A mutations and homozygous methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Using mixed effects and random-effects models, the association between thrombophilias and IUGR was explored. Publication bias was assessed with funnel plots and corrected for with Duval and Tweedie's trim-and-fill method.

Results: The following number of related studies were found: studies evaluating relationships between factor V Leiden mutation and IUGR, 12 case-control and four cohort; between PT mutation and IUGR, 11 case-control and 0 cohort; and between MTHFR C677T homozygosity and IUGR, 10 case-control and two cohort. The overall summary odds ratio (OR) for the association between factor V Leiden and IUGR was significant (OR 1.23, 95% confidence interval [CI] 1.04-1.44); however, this was mainly driven by the positive association seen in the case-control studies (OR 1.91, 95% CI 1.17-3.12). The association between PT and IUGR was only explored in case-control studies yielding a summary OR that was not significant (OR 1.52, 95% CI 0.98-2.35). The overall summary OR for the association between MTHFR and IUGR was not significant (OR 1.01, 95% CI 0.88-1.17), but was significant for the case-control studies alone (OR 1.35, 95% CI 1.04-1.75). For both factor V Leiden and MTHFR mutations, a funnel-plot analysis of the case-control studies suggests publication bias. When the trim-and fill-method was used to correct for the publication bias, these summary estimates were no longer significant.

Conclusion: The association between inherited thrombophilias and IUGR can only be discerned in case-control studies and seems to be largely because of publication bias.

Level of evidence: III.