Irena B. King

Elevated Second-Trimester Serum Homocyst(e)ine Levels and Subsequent Risk of Preeclampsia

Objective: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)ine are higher in preeclamptics, as compared with normotensive pregnant women. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. Study Design: We used a prospective nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia (pregnancy-induced hypertension with proteinuria) compared with 56 women who remained normotensive throughout pregnancy. Study subjects were selected from a base population of 3,042 women who provided blood samples at an average gestational age of 16 weeks and later delivered at our center. Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. Results: Approximately 29% of preeclamptics, as compared to 13% of controls had homocyst(e)ine levels ≥5.5 μmol/l (upper decile of distribution of control values). Adjusted for maternal age, parity, and body mass-index, a second trimester elevation of homocyst(e)ine was associated with a 3.2-fold increased risk of preeclampsia (adjusted OR = 3.2; 95% CI 1.1–9.2; p = 0.030). There was evidence of a interaction between maternal adiposity (as indicated by her prepregnancy body mass index) and parity with second trimester elevations in serum homocyst(e)ine. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations (95% CI 2.1–14.1; p = 0.003). Women with a higher prepregnancy body mass index (≥21.4 kg/m2, or upper 50th percentile) and who also had elevated homocyst(e)ine levels, as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia (95% CI 1.4–32.1; p = 0.016). Conclusion: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed to examine the effect of dietary and/or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted.

Vitamin C and the risk of preeclampsia-results from dietary questionnaire and plasma assay

Background. Oxidative stress plays an important role in the pathophysiology of preeclampsia. Methods. In a case-control study of 109 women with preeclampsia and 259 controls, maternal dietary and plasma vitamin C in relation to preeclampsia risk were assessed. Dietary intake during the periconceptional period and pregnancy was ascertained using a semiquantitative food frequency questionnaire. Logistic regression procedures were used to derive odds ratios (OR) and 95% confidence intervals (CI). Plasma ascorbic acid was determined using automated enzymatic procedures. Results. After adjusting for maternal age, parity, prepregnancy body mass index, and energy intake, women who consumed <85 mg of vitamin C daily (below the recommended dietary allowance), as compared with others, experienced a doubling in preeclampsia risk (OR = 2.1; 95% CI = 1.1–3.9). The OR for extreme quartiles of plasma ascorbic acid (<42.5 vs ≥ 63.3 &mgr;mol/liter) was 2.3 (95% CI = 1.1–4.6). Compared with women in the highest quartile, those with plasma ascorbic acid <34.6 &mgr;mol/liter (lowest decile) experienced a 3.8-fold increased risk of preeclampsia (95% CI = 1.7–8.8). Conclusions. Our results, if confirmed, would suggest that current public health efforts to increase intake of fruits and vegetables rich in vitamin C and other antioxidants may reduce the risk of preeclampsia.

Plasma lipid concentrations in preeclamptic and normotensive Peruvian women

Objectives: Dyslipidemia is thought to be of etiological importance in preeclampsia. We studied the relationship between maternal plasma lipid concentrations and risk of preeclampsia. Methods: A total of 125 preeclampsia cases and 179 normotensive control subjects were included in this case‐control study conducted in Lima, Peru, between August 1997 and January 1998. Post‐diagnosis, antepartum plasma lipid profiles were determined by standard enzymatic methods. Logistic regression procedures were used to calculate odds ratios (OR) adjusted for potential confounders. Results: Mean plasma total cholesterol and triglyceride concentrations were, on average, 6% and 21% higher in preeclamptics than controls, respectively. High‐density lipoprotein (HDL) cholesterol concentrations were, on average, 9% lower in cases than controls. After adjusting for maternal age, pre‐pregnancy body mass index, education, parity and other potential confounders, the risk of preeclampsia increased with successively higher quartiles of plasma triglyceride (adjusted OR: 1.00, 1.62, 2.21, 5.00, with the lowest quartile as referent; P‐value for trend <0.001). The association between preeclampsia risk and plasma total cholesterol was much less pronounced. In general, there was an inverse association between preeclampsia risk and HDL cholesterol concentration (adjusted OR: 1.00, 0.41, 0.50, 0.38, with the first quartile as the referent group; P‐value for trend =0.02). Conclusions: These findings suggest that high triglyceride and low HDL cholesterol concentrations are important risk factors for preeclampsia among Peruvian women.

Plasma carotenoids, retinol, tocopherols, and lipoproteins in preeclamptic and normotensive pregnant Zimbabwean women

BACKGROUND We examined the relationship between maternal plasma lipoprotein and antioxidant status with risk of preeclampsia among women delivering at Harare Maternity Hospital, Zimbabwe. METHODS One hundred seventy-three pregnant women with preeclampsia and 186 controls were included in a case-control study. Maternal plasma total cholesterol, high-density lipoprotein (HDL), and total triglycerides were measured using enzymatic methods. Plasma carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, beta-cryptoxanthin, zeaxanthin), retinol, and tocopherols (alpha-tocopherol and gamma-tocopherol) were determined using high performance liquid chromatography. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Preeclampsia risk increased with successively higher quartiles of plasma triglyceride (OR: 1.00, 1.70, 2.00, 5.26, with the lowest quartile as referent; P for trend <.001). We noted an inverse association between preeclampsia risk and HDL cholesterol concentrations (OR: 1.00, 0.87, 0.66, 0.68, with the first quartile as the referent group; P for trend =.169), although the trend was not statistically significant. After adjusting for confounders, we noted decreases in preeclampsia risk with increasing concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin, respectively. Women with beta-carotene concentrations in the highest quartile, as compared with those in the lowest quartile experienced a 50% decreased risk of preeclampsia (OR = 0.50, 95% CI 0.25-1.00). There was no clear pattern of preeclampsia risk with lycopene concentrations or with concentrations of gamma- and alpha-tocopherol. CONCLUSIONS Our results are consistent with some, although not all, previous reports. Prospective studies are needed to determine the temporal relationship between observed alterations in lipid and antioxidant concentrations in preeclamptic pregnancies.

Leukocyte selenium, zinc, and copper concentrations in preeclamptic and normotensive pregnant women

Preeclampsia is an important cause of maternal and perinatal mortality worldwide. The etiology of this relatively common medical complication of pregnancy, however, remains unknown. We studied the relationship between maternal leukocyte selenium, zinc, and copper concentrations and the risk of preeclampsia in a large hospital-based case-control study. One hundred seventy-one women with proteinuric pregnancy-induced hypertension (with or without seizures) comprised the case group. Controls were 184 normotensive pregnant women. Leukocytes were separated from blood samples collected during the patients’ postpartum labor and delivery admission. Leukocyte concentrations for the three cations were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations for each cation were reported as micrograms per gram of total protein. Women with preeclampsia had significantly higher median leukocyte selenium concentrations than normotensive controls (3.23 vs 2.80 µg/g total protein, p<0.0001). Median leukocyte zinc concentrations were 31% higher in preeclamptics as compared with controls (179.15 vs 136.44 µg/g total protein, p<0.0001). Although median leukocyte copper concentrations were slightly higher for cases than controls, this difference did not reach statistical significance (17.72 vs 17.00 µg/g total protein, p=0.468). There was evidence of a linear increase in risk of preeclampsia with increasing concentrations of selenium and zinc. The relative risk for preeclampsia was 3.38 (adjusted odds ratio [OR]=3.38, 95% confidence interval [CI]=1.53–7.54) among women in the highest quartile of the control selenium distribution compared with women in the lowest quartile. The corresponding relative risk and 95% CI for preeclampsia was 5.30 (2.45–11.44) for women in the highest quartile of the control zinc distribution compared with women in the lowest quartile. There was no clear pattern of a linear trend in risk with increasing concentration of leukocyte copper concentrations (adjusted for linear trend in risk =0.299). Our results are consistent with some previous reports. Prospective studies are needed to determine whether observed alterations in selenium and zinc concentrations precede preeclampsia or whether the differences may be attributed to preeclampsia-related alterations in maternal and fetal-placental trace metal metabolism.

Risk of Preeclampsia in Relation to Elaidic Acid (Trans Fatty Acid) in Maternal Erythrocytes

Objective: Trans fatty acids, formed by the partial hydrogenation of vegetable oils, are associated with increases in plasma concentrations of cholesterol, triglyceride, lipoprotein (a), and coronary heart disease risk. Trans fatty acids may also increase platelet aggregation and alter eicosanoid biosynthesis. We studied the relation between maternal dietary intake of trans fatty acids and risk of preeclampsia. Methods: Maternal intake of elaidic acid, one of the most abundant dietary trans fatty acids and other fatty acids were estimated using gas-liquid chromatography on erythrocytes from 22 women with preeclampsia and 40 normotensive controls. Fatty acids were expressed as the percentage of total fatty acids in erythrocytes. Logistic regression procedures were used to estimate odds ratios and 95% confidence intervals. Results: Mean levels of elaidic acid were 28% higher among preeclamptics (0.43 ± 0.12) as compared with controls (0.31 ± 0.12; p < 0.001). After adjusting for confounding factors, women with the highest levels of elaidic acid (median = 0.47) were 7.4 times (odds ratio = 7.4; 95% confidence interval 1.4–39.7) more likely to have had their pregnancy complicated by preeclampsia as compared with those women with the lowest levels (median 0.24). Risk of preeclampsia appeared to increase with increasing levels of elaidic acid (p value for linear trend = 0.05). Conclusion: These cross-sectional data suggest that diets high in elaidic acid may be associated with an increased risk of preeclampsia. This hypothesis should be examined in larger longitudinal studies.