Absence of association of thrombophilia polymorphisms with intrauterine growth restriction.
BACKGROUND
Previous data have demonstrated associations between thrombophilia polymorphisms in pregnant women and an increased risk of intrauterine growth restriction in their offspring, but this finding remains uncertain.


METHODS
We performed a hospital-based case-control study and a family-based study including 493 newborns with intrauterine growth restriction (defined by birth weight below the 10th percentile for gestational age and sex according to Canadian norms) and 472 controls (with birth weight at or above the 10th percentile). We determined the presence or absence in newborns and their parents of the following polymorphisms: methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, factor V Leiden G1691A, and prothrombin G20210A. Mothers were interviewed to obtain information on other risk factors for intrauterine growth restriction.


RESULTS
The risk of intrauterine growth restriction was not increased among mothers carrying a polymorphism associated with thrombophilia. In the case-control study, the odds ratios associated with two copies of the variant, after adjustment for newborn genotype and other risk factors, were 1.55 for MTHFR C677T (95 percent confidence interval, 0.83 to 2.90) and 0.49 for MTHFR A1298C (95 percent confidence interval, 0.25 to 0.93); heterozygotes for factor V Leiden had an odds ratio of 1.18 (95 percent confidence interval, 0.54 to 2.55), and heterozygotes for prothrombin G20210A had an odds ratio of 0.92 (95 percent confidence interval, 0.36 to 2.35). These polymorphisms in the newborn were not associated with an increased risk. Newborns who were homozygous for the MTHFR C677T variant had a decreased risk of intrauterine growth restriction (odds ratio after adjustment for mother's genotype and other confounders, 0.52 [95 percent confidence interval, 0.29 to 0.94]). The results of the family-based study supported those of the case-control study.


CONCLUSIONS
Our findings do not indicate that there are associations between maternal or newborn polymorphisms associated with thrombophilia and an increased risk of intrauterine growth restriction.
Infante-Rivard
Claire
C
Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Canada. claire.infante-rivard@mcgill.ca
Rivard
Georges-Etienne
GE
Yotov
Wagner V
WV
Génin
Emmanuelle
E
Guiguet
Marguerite
M
Weinberg
Clarice
C
Gauthier
Robert
R
Feoli-Fonseca
Juan Carlos
JC
D000328:Adult; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D005165:Factor V / Q000235:genetics; D005220:Fathers; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009035:Mothers; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000503:physiopathology*; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D004247:DNA; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)