Objective: Genetic polymorphisms associated with vascular diseases have been proposed to be involved in the pathogenesis of late unexplained intrauterine fetal death (IUFD). The Nos3 gene is known to regulate vascular tone via the endothelial nitric oxide synthase/nitric oxide pathway. Study design: In a multicenter case-control study, we evaluated two Nos3 polymorphisms (exon 7 Glu298Asp and a 27 bp-repeat in intron 4) in 92 women with IUFD and 92 healthy control women. Results: The investigated Nos3 polymorphisms were not associated with the occurrence of IUFD. In the subgroup of pregnancies affected by IUFD, women with at least one mutant allele of the Nos3 intron 4 polymorphism were diagnosed with IUFD at a significantly earlier gestational age (31.8 [standard deviation (SD) = 4.9] weeks versus 34.6 [SD=4.8] weeks, p=0.02) and showed a significantly reduced birth weight (2113 g [SD = 1028] versus 1571 g [SD = 568], p = 0.03). Conclusion: We are the first to report on Nos3 polymorphisms and IUFD. While not being associated with the incidence of IUFD overall, the intron 4 Nos3 polymorphism might modulate the timing of IUFD in affected pregnancies.
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