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