Maternal Supraphysiological Hypercholesterolemia: Extra Virgin Olive Oil as a Nutritional Intervention During Pregnancy to Reduce the Impact of This Maternal Condition

HYPOTHESIS: The nutritional supplementation with extra virgin olive oil (EVOO) enriched in polyphenols will improve the lipoprotein profile, the oxidative status and the vascular dysfunction in the mother and the offspring affected by maternal supraphysiological hypercholesterolemia (MSPH).

AIM: To determine the effects of the nutritional supplementation with EVOO during pregnancy on MSPH women, evaluating the lipoprotein profile, lipoprotein function, the oxidative status, and markers of vascular function in the mother and the offspring at birth.

STUDY DESIGN: This is a prospective, longitudinal study that aims to recruit women from week 24th (at moment where most pathological conditions of pregnancy has been diagnosed) to week 27th of gestation. These women will be supplemented with EVOO from the week 28th until term (~12 weeks). Previous studies have established that EVOO supplementation from week 28th until term reduced inflammatory markers in in pregnant women whit gestational diabetes mellitus. An equivalent group of women without EVOO supplementation will be considered as control. The participants will be from the Clínica Universidad de Los Andes (CUA). Recruitment and follow up: Pregnant women that fulfill eligibility according to the inclusion/exclusion criteria will be invited to participate in this study. They will be informed of the details of the study and will be asked to sign an informed consent for the nutritional supplementation and the biological samples donation at end of pregnancy. MPH (pregnancies with maternal physiological hypercholesterolemia or control pregnancies) or MSPH (pregnancies with maternal supraphysiological hypercholesterolemia or pathological pregnancies) will be classified at term of pregnancy according to blood TC levels, obtained by qualified personal of the Department of Obstetrics and Gynecology at CUA, under advisor of the Co- Investigator Dr. Illanes. Study groups: 1) MPH, 2) MPH + EVOO, 3) MSPH and 4) MSPH + EVOO. Inclusion criteria: pregnant women with MPH or MSPH pregnancies, with term pregnancies (≥37-weeks), singleton pregnancies, without fetal malformations, will be considered. Pregnant women with blood TC levels ≤280 mg/dl will be classified as MPH and with TC levels >280 mg/dl will be classified as MSPH. This classification is based on the criteria reported in previous published studies.

Exclusion criteria: Patients with pre-gestational and/or gestational diabetes mellitus, obesity before or during pregnancy or those with pathological conditions (e.g., pre-eclampsia, pregnancy hypertensive syndrome, and growth retardation) will be excluded from the study.

SUPPLEMENTATION: The investigators will supplement the selected women with or without EVOO since week 28th of gestation. However, the classification as MPH or MSPH occur only at birth (≥37-weeks). According to sample size calculation, the estimated sample size is 18 subjects per group. Thus 18 MSPH women supplemented with EVOO and 18 MSPH women not supplemented are required. Considering that MSPH occurs in approximately 32% of the pregnant women (data form the literature), to obtain 36 MSPH women the investigators propose to recruit 120 women in total. Thus, from these 120 women is expected that 36 will be MSPH. The other 84 women will be MPH and will be considered as control of the MSPH women. The 120 women will be randomized, in order of recruitment, one by one as control or EVOO groups. EVOO supplementation: The women randomized to EVOO groups will be supplemented daily with 36 mL (three tablespoons) of EVOO with a concentration of phenolic compounds > 500 mg/kg (this concentration of phenols is non-toxic and highly effective, according to the previous reports). The supplementation will start at week 28th of gestation until the term (≥37-weeks), following the published data of our collaborator Dra. Jawerbaum. EVOO will be indicated to be consumed uncooked and within the main meals as reported. All the needed EVOO for the 12 weeks of protocol will be provided monthly to the participants (to assure the correct quality of EVOO).