Endothelial nitric oxide synthase gene influences the risk of pre-eclampsia, the recurrence of negative pregnancy events, and the maternal-fetal flow.

OBJECTIVES: Pre-eclampsia is associated with vascular endothelial dysfunction, adverse pregnancy outcome and cardiovascular disease in later life. An inadequate nitric oxide availability related to polymorphisms in the endothelial nitric oxide synthase gene (eNOS) might predispose to the disease. METHODS: We investigated the role of eNOS T-786C, G894T and 4a4b polymorphisms in predisposing to both pre-eclampsia and the recurrence of negative pregnancy events, per se and in the presence of angiotensin-converting enzyme (ACE) DD genotype, and investigated their influence on maternal-fetal flow in 106 non-thrombophilic women with a history of pre-eclampsia, compared with 106 women with a history of normal pregnancy. RESULTS: No association between eNOS polymorphisms and predisposition to pre-eclampsia was found; nevertheless, the contemporary presence of eNOS 894TT and -786CC genotypes represented a susceptibility factor to the disease. In 48 out of 106 women, documented complications (pre-eclampsia and fetal growth restriction) were present in the current pregnancy. The eNOS 894TT genotype influenced the risk of recurrence of negative events (odds ratio = 5.45), particularly in contemporary women homozygous for both eNOS 894TT and ACE DD genotypes (odds ratio = 11.4). Throughout the pregnancy, a progressive alteration of maternal-fetal flow indices was found in women carrying the eNOS 894TT genotype, and this effect was strengthened in women with the contemporary presence of the ACE DD genotype. CONCLUSIONS: An original finding is the increased risk of pre-eclampsia and recurrence of pregnancy negative events, probably by modulating the maternal-fetal flow, in women homozygous for the eNOS 894T allele previously analyzed for the ACE I/D polymorphism.

Lack of concordance between the 75-g and 100-g glucose load tests for the diagnosis of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is common and can have a substantial impact on fetal growth, birth weight, and morbidity. The American Diabetes Association recommends GDM testing with either a 3-h, 100-g glucose load (100 g) (criteria according to Am J Obstet Gynecol 1982;144:768-73) or a 2-h, 75-g glucose load (75g). We investigated the comparability of the 75 g and the 100g tests in the diagnosis of GDM. METHODS: From January 1997 to December 1999, in 1061 consecutive Caucasian nonobese and nondiabetic pregnant women who attended the Maternal-Fetal Medicine Unit, we performed GDM testing with a 75-g load during 2 periods of pregnancy: early (16-20 weeks) and late (26-30 weeks). Because we assumed there would be few GBM cases in women with a 1-h plasma glucose <1300 mg/L in the 75 g test, we did not retest these women. We retested the remaining women with possible or diagnosed GDM with a 100-g load within a week. RESULTS: GDM was diagnosed in 41 of 227 women with the 100-g load and 15 of 227 with the 75-g load (11 concordant); the kappa index was 0.21. At 26-31 weeks of pregnancy, 484 of 976 women (49.9%) underwent both tests. GDM was diagnosed in 60 of 484 woman with the 100-g load and in 26 of 484 with the 75-g load (13 concordant); the kappa index was 0.18. CONCLUSIONS: Among women with possible GDM in both early and late periods of pregnancy, there was only weak diagnostic agreement between results determined with 75-g and 100-g glucose loads.