The goal of this clinical trial is to evaluate whether hydroxytyrosol supplementation (10 mg/day for 4 weeks) is effective in improving inflammatory and oxidative stress markers in pregnant women diagnosed with hypertensive disorders of pregnancy (including preeclampsia, chronic hypertension, and gestational hypertension). The main questions it aims to answer are:

1. Does hydroxytyrosol supplementation reduce neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR)?
2. Does hydroxytyrosol supplementation lower systolic and/or diastolic blood pressure?
3. Does hydroxytyrosol supplementation increase superoxide dismutase (SOD) levels?

Researchers will compare a group receiving hydroxytyrosol supplementation to a standard care control group to see if hydroxytyrosol produces superior anti-inflammatory and antioxidant effects.

Participants will:

• Take hydroxytyrosol 10 mg orally once daily for 4 weeks (intervention group) or receive standard antenatal care without hydroxytyrosol (control group).
• Undergo laboratory testing (NLR, MLR, SOD) before and after the intervention.
• Have their blood pressure monitored regularly throughout the study period.

Hypertensive disorders of pregnancy, including preeclampsia, chronic hypertension, and gestational hypertension, are major contributors to maternal and perinatal morbidity and mortality worldwide. Oxidative stress and systemic inflammation play critical roles in the pathophysiology of HDP. Biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and superoxide dismutase (SOD) have been associated with the severity and progression of these conditions.

Hydroxytyrosol, a polyphenol compound found in olives, has demonstrated potent antioxidant and anti-inflammatory properties in both in vitro and in vivo studies. Its potential therapeutic role in cardiovascular and metabolic diseases suggests a possible benefit in hypertensive pregnancies, though clinical evidence in this population remains limited.

This randomized controlled trial aims to evaluate the effectiveness of hydroxytyrosol supplementation (10 mg/day for 4 weeks) in improving markers of systemic inflammation and oxidative stress among pregnant women with HDP. A total of eligible pregnant women diagnosed with preeclampsia, chronic hypertension, or gestational hypertension will be randomly assigned to receive either hydroxytyrosol supplementation in addition to standard antenatal care (intervention group), or standard antenatal care alone (control group).

The primary outcome measures include changes in NLR and MLR after 4 weeks of supplementation. Secondary outcomes include changes in systolic and diastolic blood pressure, NLR and MLR levels, and serum SOD levels. All participants will undergo baseline and post-intervention laboratory testing and blood pressure monitoring.

The results of this study are expected to provide clinical insight into the potential role of hydroxytyrosol as a supportive therapeutic agent in managing hypertensive disorders during pregnancy, potentially improving maternal outcomes through modulation of oxidative stress and inflammatory response.

Inclusion Criteria:

1. Singleton pregnancy with a live intrauterine fetus

2. Gestational age over 24 weeks. Gestational age is confirmed based on:

   • Last Menstrual Period (LMP)
   • First trimester ultrasound biometry

3. Belongs to the Hypertensive Disorders of Pregnancy group, with the following criteria:

   • Gestational hypertension and preeclampsia according to ACOG 2018 criteria
   • Chronic hypertension according to ACOG 2019 criteria
   • Superimposed preeclampsia according to ACOG 2018 criteria

Exclusion Criteria:

1. Pregnancy with infection, including chronic infections such as tuberculosis (TB), HIV, or hepatitis B
2. Pregnancy with other complications (e.g., diabetes mellitus, heart disease, kidney disease, liver disease, malignancy, autoimmune disorders)
3. Refusal to participate in the study

Female

This study uses identical capsules for hydroxytyrosol and placebo to maintain masking of all parties.