Genetic Thrombophilias and Intrauterine Growth Restriction: A Meta-analysis

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


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.


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.


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



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