Genetic thrombophilias and intrauterine growth restriction: a meta-analysis.
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.


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


METHODS
III.
Facco
Francesca
F
From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University School of Medicine, Chicago, Illinois.
You
Whitney
W
Grobman
William
W
D005165:Factor V / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011247:Pregnancy; D011516:Prothrombin / Q000235:genetics; D019851:Thrombophilia / Q000150:complications / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)