Maternal and Neonatal Outcome of Preeclamptic Pregnancies: The Potential Roles of Factor v Leiden Mutation and 5,10 Methylenetetrahydrofolate Reductase

Abstract

Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.

High frequency of methylenetetrahydrofolate reductase 677TT genotype in Hungarian HELLP syndrome patients determined by quantitative real-time PCR

“…We had similar findings in our previous study of 120 pre-eclamptic women in 2000. 7 In the present study, however, there was a substantial difference between the incidence of MTHFR 677TT genotype among HELLP syndrome patients compared to the other two study groups.…”

“…The severe pre-eclamptic and HELLP syndrome patients were diagnosed according to the recommendations of the ACOG. 7 Briefly, patients in the severe PE group had systolic BP4160 mm Hg and diastolic BP 490 mm Hg with significant proteinuria and intrauterine growth restriction (IUGR). IUGR was diagnosed in neonates when their birth weight was below 10 percentile for gestational age by weight based on Hungarian population tables.…”

“…[1][2][3][4][5][6][7] It is a major cause of maternal and perinatal mortality. PE can be complicated by haemolysis, elevated liver enzymes and low platelets, called HELLP syndrome, named by Weinstein in 1982.…”

“…The same holds true for HELLP syndrome that occurs in about 24% of all PE pregnancies. 7 Family studies have shown that the genetic factor plays a role in the development of PE. Dekker and Sibai 9 found that placental ischaemia, oxidative stress and maternal-fetal immune maladaptation are the key elements in pathophysiology.…”

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

“…Most recently, the meta-analysis by Xia et al (95) reported that the TT genotype compared with the CC and CT genotypes carried a significantly greater risk of preeclampsia (by 76%) among Asian women only, whereas in Caucasian women this increased risk was not evident. It is worth noting however that a much greater number of large-scale studies in this area have been conducted within Asian populations with far fewer studies conducted in Caucasian populations; a factor that limits Sohda et al (87) 425 Japan 2·5 (1·3, 4·8) Grandone et al (88) 225 Italy 1·8 (1·0, 3·5) Kupferminc (96) 144 Israel 2·9 (1·0, 8·5) Powers et al (97) 237 Caucasian women 1·28 (0·58, 2·79) Kobashi et al (98) 316 Japan 0·68 (0·30, 1·55) Laivuori et al (99) 216 Finland 0·50 (0·14, 1·77) Rigo et al (100) 221 Caucasian women 1·13 (0·38, 3·37) Morrison et al (101) 404 Scotland 1·00 (0·55, 1·82) Prasmusinto et al (102) 112 Germany and Croatia 0·28 (0·03, 2·47) Pegoraro et al (103) 609 South African (Black) 0·62 (0·06, 6·90) Perez-Mutul et al (91) 325 Mexico 0·94 (0·59, 1·49) Williams et al (104) 304 Peru 1·6 (0·7, 3·8) Yilmaz et al (105) 111 Turkey 0·84 (0·26, 2·67) Also-Rallo et al (79) 165 Spain 0·73 (0·31, 1·76) Hernandez-Diaz et al (86) 154 USA/Canada 3·0 (1·2, 7·7) Stiefel et al (106) 584 Spain 0·92 (0·50, 1·71) the extent to which different populations can be compared. An additional limitation is that genotype-driven recruitment is generally not undertaken in these studies, a feature that is reflected by the relatively small numbers of pregnant women with the TT genotype being investigated and these raised the concern that many such studies may be statistically underpowered.…”