Thrombophilic Polymorphisms and Intrauterine Growth Restriction

Abstract

The relationship between thrombophilic polymorphisms and intrauterine growth restriction remains unclear. Whereas a subset of these polymorphisms have received some attention, others have not. We conducted a case-control study of 493 cases of intrauterine growth restriction (birthweight less than the 10th percentile for gestational age and sex) and 472 controls (greater than the 10th percentile). We also conducted a family study including approximately 250 case trios (affected newborn, mother, and father) for each studied gene. Plasminogen activator inhibitor-1(PAI-1) 4G/5G and Factor XIII Val134Leu variants were compared between maternal and newborn cases and controls. Relative risks for newborn and maternal PAI-1 and Factor XIII genotypes in case trios were estimated using a log-linear model. Transmission of MTHFR C677T and 1298C haplotypes was analyzed in case trios, and the estimated haplotype distribution compared between cases and controls. Finally, we explored pairwise gene-gene interactions between all measured polymorphisms, including Factor V Leiden G1691A and Prothrombin G20210A. PAI-1 and Factor XIII polymorphisms were not associated with an increased risk of intrauterine growth restriction in the case-control analysis, and the case-parent analysis showed no newborn or maternal excess genotype relative risk. No excess transmission of the MTHFR haplotypes was observed in case newborns, and the distribution of MTHFR haplotypes was similar between cases and controls. Some results were suggestive of interactions between genes. Overall, there seems to be little or no indication that thrombophilic genes, at least individually, have an effect on intrauterine growth restriction.