Characteristics of the studies
The studies were published between 2016 and 2021 and originated from the United States (n=2), Indonesia (n=2), Serbia (n=2), UK (n=1), Spain (n=1), Greece (n=1), and multicentre over Europe (n=1). Four were cohort studies and six RCTs . Studies included women with uteroplacental insufficiency defined as early onset of preeclampsia between gestational age 24 and 31 weeks or high risk for developing preeclampsia. This risk was defined in two studies as a history of severe preeclampsia in a prior pregnancy that required delivery before 34 weeks gestation. In another study, as a history of previous preeclampsia and birth before 37 weeks of gestation or at least two main risk factors for preeclampsia. One study selected women with at least 20% risk for developing preeclampsia based on the presence of minimally 2 independent clinical risk factors or abnormal doppler velocimetry index. and another selected women with high risk for preeclampsia based on a survival-time model of Bayes theorem . Two studies defined uteroplacental insufficiency as a pregnancy with an obstetric antiphospholipid syndrome that developed preeclampsia or IUGR associated with abnormal placental Dopplers. An additional study defined a pregnancy with uteroplacental deficiency as having a past poor obstetric history and abnormal placental Dopplers. Abnormal placental Dopplers was defined as uterine artery pulsatility index above the 95th percentile. One study also included the early onset of IUGR, diagnosed earlier than 28 weeks of pregnancy.
Although the search algorithm included all types of statins, only pravastatin was used in the studies included. The dosage of pravastatin differed between studies: 40 mg in five studies, 20 mg in four studies and 10 mg in one study. The comparator treatment included aspirin together with low molecular weight heparin in two studies, aspirin alone in one study, placebo in four studies and no treatment in two studies. Most studies initiated treatment with pravastatin in the second trimester, but in two studies a minority of the patients were diagnosed and started treatment in their third trimester and one large RCT included only women in their late third trimester. Table 1 shows a summary of the key characteristics of the included trials.