No evidence for lipid peroxidation in severe preeclampsia.

OBJECTIVE: This study was undertaken to address the role of oxidative stress in preeclampsia. STUDY DESIGN: We measured urinary 8,12-iso-iPF(2alpha)-VI, a chemically stable, free-radical catalyzed product, in a case control study of severe preeclampsia nested within the trial of Calcium for Preeclampsia Prevention. Cases included 29 women who developed severe preeclampsia and from whom urine had been obtained 10 to 20 weeks before the diagnosis of preeclampsia, 3 to 9 weeks before, and 1 day before through delivery. Controls did not develop hypertension or proteinuria and were matched to cases by center, gestational age at each of 3 corresponding urine collections, and date of enrollment. RESULTS: Urinary 8,12-iso -iPF(2alpha)-VI did not differ significantly between cases and controls before or at diagnosis of preeclampsia, nor did it vary with gestational age. CONCLUSIONS: These results call into question the importance of oxidative stress in the disease and the biochemical rationale for clinical trials of antioxidants to prevent and treat preeclampsia.

Ethnicity, nutrition, and birth outcomes in nulliparous women.

OBJECTIVE: Ethnic differences in birth outcomes are well established, but it is not clear whether differences in nutrition may partly explain unaccounted differences in birth outcomes. Our purpose was to evaluate the relationship of nutrition to ethnic differences in birth outcomes. STUDY DESIGN: This was a multicenter, prospective study of 4589 healthy nulliparous women who were enrolled in the Calcium for Preeclampsia Prevention trial conducted from 1992 to 1995. Main outcome measures were birth weight, gestational age at delivery, preterm birth, and small for gestational age birth after the data were controlled for maternal characteristics and intake of total calories, protein, carbohydrate, fat, and 13 vitamin and mineral constituents that were obtained from a 24-hour recall at 13 to 21 weeks' gestation. RESULTS: Black and non-Hispanic white women differed significantly in birth outcomes, with odds ratios of 2.06 (95% confidence interval, 1.48-2.86) for small for gestational age and 1.38 (95% confidence interval, 0.98-1.95) for preterm birth, after adjustment for maternal characteristics. These odds ratios were hardly changed by the further adjustment for all nutritional variables, even though there were substantial nutritional differences between black and white women. Differences in birth outcomes between Hispanic and non-Hispanic white women were small. Hispanic women who spoke only Spanish were better nourished than those Hispanic women who spoke English, but this had only a modest effect on birth outcomes. CONCLUSION: Nutritional variation among women in the United States does not appear to have a significant role in the explanation of ethnic differences in birth outcomes.

Nutrient intake and hypertensive disorders of pregnancy: Evidence from a large prospective cohort.

OBJECTIVE: The objective of this analysis was to prospectively determine the effects of nutrient intakes on the incidences of preeclampsia and pregnancy-associated hypertension among women enrolled in the Calcium for Preeclampsia Prevention study. STUDY DESIGN: This was a prospective observational cohort study of women in a randomized clinical trial that included women seeking prenatal care at university medical centers and affiliated clinics and hospitals in 5 US communities. A total of 4589 nulliparous women were recruited between 13 and 21 weeks' gestation. Preeclampsia and pregnancy-associated hypertension were the main outcome measures. RESULTS: Preeclampsia was noted in 326 (7.6%) of the 4314 women with known pregnancy outcomes followed up until > or =20 weeks' gestation, and pregnancy-associated hypertension was noted in 747 (17.3%). As previously reported, there was no significant difference in these outcomes between cohorts randomly assigned to supplementation with calcium or placebo. By means of logistic regression a baseline risk model was constructed for preeclampsia and pregnancy-associated hypertension. After adjustment for treatment and clinical site, body mass index >26 kg/m(2) and race were significantly associated with an increased risk of preeclampsia. Body mass index > or =35 kg/m(2), race, and never smoking were significantly associated with an increased risk of pregnancy-associated hypertension. After adjustment for baseline risks, none of the 28 nutritional factors analyzed were significantly related to either preeclampsia or pregnancy-associated hypertension. CONCLUSION: We found no evidence in this study for a significant association of hypertensive disorders of pregnancy with any of the 23 nutrients measured.

Should the definition of preeclampsia include a rise in diastolic blood pressure of >/=15 mm Hg to a level <90 mm Hg in association with proteinuria?

OBJECTIVE: This study was undertaken to compare baseline characteristics and pregnancy outcomes between normotensive women who did and those who did not have a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria. STUDY DESIGN: We studied 4302 healthy nulliparous women from the Calcium for Preeclampsia Prevention trial who were delivered at >/=20 weeks' gestation. We selected as the study group normotensive women who developed proteinuria within 7 days of a rise in diastolic blood pressure of >/=15 mm Hg with respect to baseline on 2 occasions 4 to 168 hours apart. Baseline blood pressure was the mean of measurements at 2 clinic visits before 22 weeks' gestation. Other normotensive women used for comparison were those who did not develop gestational hypertension or a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria. RESULTS: Except for greater weight (P <.001), body mass index (P <.001), and systolic blood pressure (P =.05) the baseline characteristics of the 82 women with a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria did not differ significantly from those of the other normotensive women. Although they had a greater rate of weight gain (P <.005), larger babies (P =.06), and a 2-fold increase in abdominal delivery (P <.001), there was little other evidence of adverse pregnancy outcomes among these women. CONCLUSION: During normotensive pregnancy a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria appears to be benign and is not a useful clinical construct.

Pregnancy outcomes in healthy nulliparas who developed hypertension. Calcium for Preeclampsia Prevention Study Group.

OBJECTIVE: To determine maternal and perinatal outcomes in nulliparas with pregnancy-associated hypertension or preeclampsia. METHODS: We conducted (and reported elsewhere) a randomized, double-masked, placebo-controlled trial calcium supplementation of 4589 healthy nulliparas assigned at 13-21 weeks' gestation. This well-defined and characterized data set provided an opportunity to detail more precisely adverse maternal, fetal, and newborn outcomes in women who developed hypertension among a prospective series of healthy nulliparas. RESULTS: Of 4302 women observed to or beyond 20 weeks' gestation, 1073 (24.9%) developed mild or severe pregnancy-associated hypertension or preeclampsia. One hundred sixteen women of the 1073 with hypertension (10.8%) and 336 of the 3229 without hypertension (10.4%) were delivered before 37 weeks' gestation. Fetal and neonatal mortality were similar in those groups; however, selected maternal and newborn morbidities were significantly greater in women with hypertension. Significantly increased maternal morbidities included increased cesarean deliveries, abruptio placentae, and acute renal dysfunction; and significantly increased perinatal morbidities included respiratory distress syndrome, ventilatory support, and fetal growth restriction. Adverse outcomes were highest in women with severe pregnancy-associated hypertension or preeclampsia. CONCLUSION: Hypertension, especially severe hypertension, was associated with an appreciable increase in important maternal and perinatal morbidity but not perinatal mortality.

The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women. Calcium for Preeclampsia Prevention (CPEP) Study Group.

OBJECTIVE: The study's aim was to determine whether healthy nulliparous women with abnormal glucose tolerance during pregnancy are at increased risk for development of pregnancy-associated hypertension or preeclampsia. STUDY DESIGN: A series of 4589 healthy nulliparous women from 5 university centers were evaluated prospectively to determine whether calcium supplementation would prevent preeclampsia. Pregnancy-associated hypertension was a diastolic blood pressure > or = 90 mm Hg on 2 occasions 4 hours to 1 week apart. Pregnancy-associated proteinuria was proteinuria > or = 1+ by dipstick testing on 2 occasions 4 hours to 1 week apart, proteinuria > or = 300 mg/24 h, a protein to creatinine ratio of > or = 0.35, or a single dipstick measurement of > or = 2+. Preeclampsia was defined as pregnancy-associated hypertension and pregnancy-associated proteinuria documented within 7 days of each other. Normal glucose tolerance was a plasma glucose level < 140 mg/dL 1 hour after a 50-g oral glucose challenge. Abnormal glucose tolerance was a plasma glucose level > or = 140 mg/dL 1 hour after a 50-g oral glucose challenge followed by a 3-hour 100-g oral glucose tolerance test yielding < 2 abnormal values. Gestational diabetes mellitus was a plasma glucose level > or = 200 mg/dL 1 hour after a 50-g oral glucose challenge in the absence of an oral glucose tolerance test or > or = 2 abnormal plasma glucose values in a 3-hour 100-g oral glucose tolerance test (> or = 105 mg/dL fasting, > or = 190 mg/dL at 1 hour, > or = 165 mg/dL at 2 hours, or > or = 145 mg/dL at 3 hours). For purposes of this study women with preeclampsia were excluded from the category of pregnancy-associated hypertension. RESULTS: Calcium supplementation did not prevent pregnancy-associated hypertension or preeclampsia. Of 3689 women with complete glucose testing data, 227 (6%) had abnormal glucose tolerance and 81 (2%) had gestational diabetes mellitus. Compared with women with normal glucose tolerance, women with abnormal glucose tolerance were significantly older, had greater body mass index, and were more likely to be white non-Hispanic, to smoke, and to have private medical insurance. Among women with gestational diabetes mellitus, after adjustment for clinical center the relative risks of preeclampsia and of all hypertensive disorders were increased (relative risk 1.67, 95% confidence interval 0.92-3.05, and relative risk 1.54, 95% confidence interval 1.28-2.11, respectively). Risk ratios were not substantially reduced after further adjustment for race and body mass index (odds ratios 1.41 and 1.48, respectively). Even within the normal range, multivariate analysis demonstrated that the level of plasma glucose 1 hour after a 50-g oral glucose challenge was an important predictor of preeclampsia. CONCLUSION: Even within the normal range, the level of plasma glucose 1 hour after a 50-g oral glucose challenge was positively correlated with the likelihood of preeclampsia. Women with gestational diabetes mellitus were at increased risk for hypertensive disorders during pregnancy after adjustment for clinical center, race, and body mass index, although the increase was not statistically significant. These findings suggest that insulin resistance may play a role in the pathogenesis of the hypertensive disorders of pregnancy.

Trial of Calcium for Preeclampsia Prevention (CPEP): rationale, design, and methods.

The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods.