Study selection and data extraction
Two investigators (A.H. and N.T.) independently identified and extracted articles for potential inclusion, using the Rayyan QCRI web application for systematic reviews. Disagreements were resolved by referral to a third reviewer (B.H.R.). The full texts of the resulting references were retrieved and analysed. If more than one study published data from the same cohort, we included the report with the higher quality according to the Risk of bias In Non-randomized Studies of Interventions (ROBINS-I) tool (Newcastle-Ottawa Quality Assessment Scale- NOS) to avoid overlap.
Exposure to statins during pregnancy was defined as exposure to any dose and in any trimester of pregnancy. Pregnancies that were defined as high risk for future development of uteroplacental insufficiency disorder and those that had developed uteroplacental insufficiency disorders were included. The spectrum of uteroplacental insufficiency disorders included: preeclampsia, early-onset IUGR (<28w), and obstetrical antiphospholipid syndrome. Multiple pregnancies were excluded in patient-level data to avoid bias. The primary outcome included prolongation of pregnancy from study entry to delivery. The secondary outcomes included neonatal outcomes such as admission to the neonatal intensive care unit (NICU), birth weight and neonatal death, and the maternal occurrence of a new diagnosis of preeclampsia. Neonatal death was defined as stillbirth or death in the first month of life. Data were extracted from the included studies by a single reviewer and subsequently evaluated by the second reviewer. For studies that did not report the outcomes, we contacted the authors and requested the missing data.