Genetic Thrombophilias and Intrauterine Growth Restriction: A Meta-analysis

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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

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