Oxidative stress in midpregnancy as a predictor of gestational hypertension and pre-eclampsia

Abstract

Objectives: To explore the relationship between the levels of maternal oxidative stress and glycaemia during pregnancy and to compare the predictive values of 8-epimer of prostaglandin F(2alpha) (8-isoPGF(2alpha)) and mean arterial pressure (MAP) in midpregnancy for the development of hypertensive complications in later pregnancy.

Design: Prospective observational study as an ancillary study to the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study.

Setting: Obstetric clinics and wards of a university teaching hospital in Hong Kong.

Population: Selected women with singleton pregnancies attending the antenatal clinic.

Methods: Pregnant women who met HAPO inclusion criteria were recruited for the study. Glucose tolerance was assessed by a 75-g 2-hour oral glucose tolerance test (OGTT) at 24-32 weeks of gestation. Fasting plasma samples for 8-isoPGF(2alpha) estimation and urine samples for 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) assays were collected and blood pressures measured during the OGTT visit. Random plasma and urine samples were also obtained at 34-37 weeks. Glucose results were unblinded to the attending obstetrician if limits preset under the HAPO protocol were met.

Main outcome measures: Maternal plasma 8-isoPGF(2alpha) and urinary 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) both at the time of OGTT (24-32 weeks) and at 34-37 weeks of gestation. Incidence of pre-eclampsia and gestational hypertension.

Results: Of the 408 women who attended for OGTT at 24-32 weeks, two met the glucose criteria for unblinding and 25 had missing 8-isoPGF(2alpha) values and thus were excluded from analysis. Of the 381 women, 338 (88.7%) attended for random plasma samples at 34-37 weeks. Significant correlations were observed between maternal fasting plasma isoprostane and both fasting (r= 0.20; P < 0.001) and 2-hour (r= 0.39; P < 0.001) plasma glucose levels at the time of OGTT. Gestational hypertension/pre-eclampsia occurred in 17 (4.2%) women, and at the time of OGTT, they had significantly higher fasting plasma 8-isoPGF(2alpha) (P < 0.001), urine 8-isoPGF(2alpha) (P < 0.005) and urine 2,3-dinor 8-isoPGF(2alpha) to creatinine ratios (P < 0.001), as well as higher MAP (P < 0.001) than women who remained normotensive. At 34-37 weeks, only random plasma 8-isoPGF(2alpha) was significantly higher (P < 0.001) among the women with gestational hypertension/pre-eclampsia.

Conclusions: Plasma markers of oxidative stress were positively correlated with plasma glucose at the time of OGTT (24-32 weeks). Women who subsequently developed gestational hypertension/pre-eclampsia had significantly higher plasma and urine markers of oxidative stress at the time of OGTT but only higher plasma markers at 34-37 weeks. Plasma 8-isoPGF(2alpha) appears to be a very good predictor of subsequent gestational hypertension/pre-eclampsia when measured at the time of OGTT, but its ability to discriminate deteriorates as pregnancy advances.