Abstract

Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.

Highlights

  • Reactive oxygen species (ROS) are molecules produced from the reduction of molecular oxygen, generated as by-products of aerobic respiration and metabolism

  • As part of a larger study following up women with hypertensive pregnancies (GH, PE, and essential hypertension (EH) without superimposed PE), the aims of this present study were to address the specific questions of whether or not markers of oxidative stress are still raised in maternal blood at 6 weeks postpartum and whether their concentrations differ between the hypertensive states

  • OXIDATIVE STRESS MARKER (TBARS) At 6 weeks postpartum, there were no statistically-significant differences in the median maternal thiobarbituric acid reactive substances (TBARS) concentration between the hypertensive pregnancy groups: PE 7.6 [IQR 6.1–8.7]; gestational hypertension (GH) 7.3 [5.8–8.6] and EH without PE, 10.5 [7.2–12.4] μM

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Summary

Introduction

Reactive oxygen species (ROS) are molecules produced from the reduction of molecular oxygen, generated as by-products of aerobic respiration and metabolism. The successful completion of spiral artery remodeling at around 10–12 weeks’ gestation, results in unplugging of these vessels, which have been transformed into flaccid conduits with no resistance, enabling uteroplacental blood to flow unimpeded (Pijnenborg et al, 1991, 2006). This restoration of blood flow results in a rapid rise in the tissue oxygen tension which triggers the production of human chorionic gonadotrophin (hCG) and enzymes such as P-450 cytochrome aromatase, involved in the synthesis of oestrogens (Jauniaux et al, 2006); this gives rise to acceleration of placental tissue growth

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