Objective: To investigate the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in women with intrauterine fetal death, preeclampsia, preterm delivery, and small for gestational age (SGA) infants.
Methods: In a prospective cohort study, DNA from 2,000 pregnant women were analyzed for MTHFR C677T by DNA microarray (wild-type allele, C; mutant allele, T).
Results: One thousand six hundred seventy-five women completed the study. Of these, 16.6% (278 women with 556 genetic alleles) developed at least one pregnancy complication and were designated study cases. There were 1,397 women (with 2,794 genetic alleles) who served as controls. MTHFR C677T allele frequencies were significantly different between cases and controls (C [wild-type]: 346 of 556 [62%]; T [mutant]: 210 of 556 [38%] compared with C: 1,911 of 2,794 [68%]; T: 883 of 2,794 [32%]; P=.005; odds ratio [OR] 1.23, 95% confidence interval [CI] 1.06-1.42). Genotype distributions were also different between cases and controls (C/T+T/T [abnormal]: 174 of 278 [63%]; C/C [normal]: 104 of 278 [37%] compared with C/T+T/T: 728 of 1,397 [52%]; C/C 669 of 1,397 [48%]; P=.002; OR 1.54, 95% CI 1.18-2.02). The clinical effect of the MTHFR C677T polymorphism was restricted to women with SGA infants (P=.05; OR 1.33, 95% CI 1.00-1.77). No significant differences in genotype distributions were observed among women with intrauterine fetal death, preeclampsia, and preterm delivery.
Conclusion: MTHFR C677T is a genetic marker for identifying women at increased risk of SGA infants.
Level of evidence: II.