Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)

A Randomized, Clinical Trial of Antioxidants to Prevent Preeclampsia:

Preeclampsia is the leading cause of maternal morbidity, as well as perinatal morbidity and mortality. Once the diagnosis has been established, therapy other than delivery has not been successful except to prolong pregnancy minimally (at some risk to mother and infant). Prevention efforts to reduce or eliminate preeclampsia are directed at the pathophysiology of the disorder prior to clinically evident preeclampsia and before irreversible changes have occurred.

This double-masked, placebo-controlled trial of 10,000 subjects is designed to evaluate the effects of antioxidant therapy in preventing serious complications associated with pregnancy-related hypertension in low risk, nulliparous women who begin treatment at 9-16 weeks gestation. The hypothesis being tested is that antioxidant therapy initiated prior to 16 weeks gestation will reduce the frequency of serious maternal and infant complications associated with pregnancy-related hypertension.

After randomization, subjects will receive either 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo daily. They will be seen for monthly pill counts and to assess side effects, weight, blood pressure, and urine for protein. Blood and urine are collected at 24 and 32 weeks' gestation.

An Observational Cohort Study to Predict Preeclampsia:

A prospective, cohort study has been designed to complement the randomized, controlled, trial (RCT) and will test various biochemical and biophysical markers for ability to predict preeclampsia in 4,000 of the women who are enrolled in the RCT and are between 9 and 12 weeks gestation. These subjects will have additional procedures including a CBC and uterine artery Doppler.

RCT Inclusion Criteria:

• Gestational age 9 -16 weeks
• Singleton pregnancy
• Nulliparous

Observational Inclusion Criteria:

• Women randomized to the RCT
• Gestational age 9 - 12 wks

Exclusion criteria

RCT and Observational:

• BP >= 135/85
• Proteinuria
• History or current use of anti-hypertensive medication or diuretics
• Use of vitamins C > 150 mg and/or E > 75 IU per day
• Pregestational diabetes
• Current pregnancy is a result of in vitro fertilization
• Regular use of platelet active drugs or non-steroidal anti-inflammatory drugs (NSAIDS)
• Known fetal abnormalities
• Documented uterine bleeding within a week of screening
• Uterine malformations
• History of medical complications
• Illicit drug or alcohol abuse during current pregnancy
• Intent to deliver elsewhere
• Participating in another interventional study