Randomised trial of pravastatin versus placebo for the prevention of high blood pressure in pregnancy

INTERVENTION: All women attending for the routine risk assessment for Down's syndrome at 11‐13 weeks will be screened for pre‐eclampsia. Women will then be classified as high­ and low risk for pre­‐eclampsia based on the combination of maternal history, biophysical findings (mean arterial blood pressure and uterine artery Dopplers) and biochemical factor (PlGF). Patients found to be at high risk of developing pre‐­eclampsia will receive information regarding the implications of this finding and will be offered the option of participating in a randomised study of pravastatin vs. placebo. Informed and written consent will be sought from those agreeing to participate in the study. Study participants have an equal chance of being allocated into one of the two groups ‐ pravastatin 20mg or placebo. The investigators, participants, and clinicians will not be aware of the treatment assignments. The participants will take one tablet daily from randomisation (11‐14 weeks) until 36 weeks’ gestation or earlier in the event of preterm delivery. Follow­‐up clinical visits for all participants will be carried out at 19‐24 weeks, 30‐34 weeks and at 36 weeks. At these visits, a routine fetal scan, measurements of uterine artery Doppler, blood pressure, maternal blood levels of PlGF will be carried out. Trial participants will be telephoned at 16 weeks and 28 weeks to address concerns and enquire about side effects and compliance with medication. They will also be followed up by a further telephone interview 30 days after the last dose of medication. Data on pregnancy and neonatal outcomes will be collected from the hospital maternity records or their general practitioners. In the event that the neonates are admitted to Special Care Baby Unit (SCBU)/Neonatal Intensive Care Unit (NICU), additional neonatal outcomes will be collected from the discharge summary of SCBU/NICU. CONDITION: Pre‐eclampsia ; Pregnancy and Childbirth PRIMARY OUTCOME: Incidence of preterm pre‐­eclampsia (PE) < 37 weeks SECONDARY OUTCOME: 1. Incidence of early‐PE (<34 weeks) and total PE (at any gestation); 2. Neonatal birthweight below the 3rd, 5th and 10th centile; 3. Stillbirth or neonatal death due to any cause; 4. Stillbirth or neonatal death ascribed to PE or fetal growth restriction ; 5. Stillbirth or neonatal death in association with maternal or neonatal bleeding; 6. Rate of neonatal intensive care unit admission; 7. Composite measure of neonatal mortality and morbidity; 8. Placental abruption (clinically or on placental examination); 9. Spontaneous preterm delivery <34 weeks and <37 weeks INCLUSION CRITERIA: 1. Age > 18 years 2. Singleton pregnancies 3. Live fetus at 11‐13 weeks' of gestation 4. High‐risk for preterm‐PE at 11‐13 weeks by the algorithm combining maternal history and characteristics, biophysical findings (mean arterial pressure and uterine artery Dopplers) and biochemical factors (placental growth factor) 5. English or Spanish speaking (otherwise interpreters will be used) 6. Informed and written consent