Pre-eclampsia is a serious condition that typically affects pregnant women after the 20th week of pregnancy, characterized by high blood pressure and damage to organs such as the kidneys and liver. Currently, treatment options are limited, which has prompted researchers to explore alternative approaches. One such promising alternative is dietary nitrate found in vegetables like beetroot, as nitrate can be converted into nitric oxide in the body, which helps lower blood pressure. This study aims to determine the acute effects of nitrate-rich beetroot juice on blood pressure, several blood and salivary markers in pregnant women with pre-eclampsia and healthy pregnant. Furthermore, the study will assess fetal blood flow using Doppler ultrasound. We want to understand the kinetics of nitrate and nitric oxide metabolites and assess the temporal dependency of the hypotensive response. Through this investigation, we seek evidence of nitrate-enriched beetroot juice as an adjunct therapy in managing pre-eclampsia.

The study will include women diagnosed with early-onset preeclampsia and a healthy pregnancy, in accordance with the guidelines of the American College of Obstetricians and Gynecologists. Participants will be required to sign informed consent forms following a detailed explanation of the study. Four groups will be formed, with twenty-four pregnant women randomly assigned to each group using a free online program. In each group (early-onset preeclampsia), twenty-four pregnant women will receive nitrate-enriched beet juice (Beet It®, James White, UK), while another twenty-four pregnant women will receive an equivalent amount of placebo juice. Additionally, the same division applies to the group of healthy pregnant women, with six healthy pregnant women receiving the nitrate-enriched beet juice and six healthy pregnant women receiving the placebo. The study will begin in the morning, between 7:30 a.m. and 8:30 a.m., following a standardized, low-nitrate breakfast provided by the hospital. Participants will be instructed to avoid nitrate-rich foods the night before and will receive guidance from the project team and the hospital's nutrition service. The hospital's nutrition team will supervise dietary procedures. Ambulatory blood pressure monitoring will be performed at time -30 minutes (before juice or placebo intake), 0 hours, 3 hours, and 6 hours after juice or placebo intake. Saliva samples will be collected to assess nitrate reductase activity, and blood samples will be drawn to measure nitrate, nitrite, and nitrosothiol (nitric oxide metabolites), as well as to perform biochemical analyses of oxidative stress. Doppler ultrasound and Doppler velocimetry evaluation will be conducted at the peak action time of nitrate, which is estimated to occur three hours post-ingestion, based on previous research.

1. Pre-eclampsia pregnat women

   Inclusion Criteria:

   • Pregnant women at or beyond the 20th week of gestation.
   • Hospitalized at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto.
   • Diagnosed with early-onset pre-eclampsia confirmed by a medical professional.
   • Capacity to provide written informed consent for study participation.

   Exclusion Criteria:

   • Multiple pregnancies.
   • Uncontrolled arterial hypertension (Systolic Blood Pressure > 160 mmHg or Diastolic Blood Pressure > 100 mmHg).
   • Pregnant women with a body mass index > 40 kg/m²
   • Severe gestational complications.
   • History of food allergy with hypersensitivity to beetroot.
   • Smokers.
   • Chronic alcohol consumption.
   • Medications such as non-steroidal anti-inflammatory drugs, nasal decongestants, users of proton pump inhibitors and H2 receptor antagonists or any other medication that interferes with stomach pH.
   • Diagnosis of renal or hepatic disease affecting nitrate metabolism.
   • Cardiac conditions such as moderate to severe congestive heart failure and coronary artery disease.
   • Pre-existing type 1 or type 2 diabetes.

2. Healthy Pregnant Women

Inclusion Criteria:

• Healthy pregnant women at or beyond the 20th week of gestation.
• Absence of pre-eclampsia diagnosis or other obstetric complications.
• Willingness and ability to remain admitted at the Clinical Research Unit for the - period required by the study.
• Capacity to provide written informed consent for study participation.

Exclusion Criteria:

- The same exclusion criteria from Pre-eclampsia group apply.

We will provide access to individual de-identified participant data and related study documents upon request from qualified researchers, subject to certain criteria, conditions, and exceptions.