Maternal-Fetal Flow, Negative Events, and Preeclampsia

Abstract

Abstract-The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (Pϭ0.0002) and allele frequency (PϽ0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (Pϭ0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. Key Words: angiotensin-converting enzyme Ⅲ polymorphism Ⅲ preeclampsia Ⅲ pregnancy T he risk for an adverse pregnancy outcome in women who have previously had preeclampsia is markedly higher (from 20% to 40%) 1,2 in comparison to women with history of normal pregnancy, but the mechanisms involved have not yet been identified. The maternal syndrome of preeclampsia (PE) and the fetal syndrome of fetal growth restriction (FGR) during the latter half of pregnancy are believed to result from impaired placentation in early gestation. 3,4 Deficient placentation is characterized by inadequate trophoblast invasion into the maternal spiral arteries and a failure to develop lowresistance uteroplacental circulation. 3 Doppler ultrasonographic studies of uteroplacental 5 and fetal umbilical circulation 6 have shown that high impedance to flow is associated with subsequent PE, FGR, and related complications.Previous experimental studies 7 suggested that the "physiological remodeling" of spiral arteries throughout pregnancy is mediated by the renin-angiotensin system (RAS), which is one of the main factors regulating blood pressure, and fluid and electrolyte balance. 8 Throughout normal pregnancy, the RAS is stimulated; plasma renin activity, angiotensinogen, angiotensin II, and aldosterone levels are all increased. 9 At the same time, pregnancy induces a refractoriness to the pressor effects of angiotensin II. 10 In patients with PE, a significant association between the T235 molecular variant of the angiotensinogen (AGT) gene, ...

Low-Molecular-Weight Heparin Lowers the Recurrence Rate of Preeclampsia and Restores the Physiological Vascular Changes in Angiotensin-Converting Enzyme DD Women

“…13 In these women, we observed Ϸ2-fold higher percentage of recurrence rate of preeclampsia in comparison to those carrying the ID and II genotypes. In the present study, the pattern of maternal uteroplacental circulation in the control group was comparable to that observed in the DD women in our previous study.…”

“…In the present study, the pattern of maternal uteroplacental circulation in the control group was comparable to that observed in the DD women in our previous study. 13 To date, in vitro and in vivo studies indicate that ACE interferes with hemostasis through different mechanisms, including an influence on fibrinolysis, platelet aggregation, and blood clotting activation. 18 Thrombophilia has been reported to be a condition predisposing to adverse pregnancy outcomes, such as preeclampsia; 19 during pregnancy, marked changes in hemostasis take place and ACE DD genotype has been proposed as a new thrombophilic factor influencing pregnancy negative events.…”

“…18 Thrombophilia has been reported to be a condition predisposing to adverse pregnancy outcomes, such as preeclampsia; 19 during pregnancy, marked changes in hemostasis take place and ACE DD genotype has been proposed as a new thrombophilic factor influencing pregnancy negative events. 13 Moreover, the renin-angiotensin system, in addition to the well-known vasomotor functions, is involved in key events of the inflammatory process, 20 by increasing vascular permeability and contributing to the recruitment of inflammatory cells. 21 Regarding hemostasis, several reactions are modulated by the renin-angiotensin system, and evidence exists for an association between the ACE DD genotype and increased risk of thrombotic events.…”

“…13 All women underwent 24-hour automated blood pressure monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36. The 24-hour, awake, sleep average systolic, and awake-sleep blood pressure differences (percentage changes) were calculated for each woman.…”

“…In our previous studies, we reported that the angiotensinconverting enzyme (ACE) DD genotype affects the recurrence of an adverse pregnancy outcome and uteroplacental and umbilical flow in women with history of preeclampsia, in whom classic thrombophilia was excluded, 13 and that DD genotype represents a predictive marker for fetal loss. 14 ACE is involved in key events of hemostasis and of inflammatory process 15 related to preeclampsia, in addition to its involvement in modulating vascular tone and smooth muscle cell proliferation.…”