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Background: Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins. Objective: To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins. Search Strategy: Electronic databases were searched from inception to January 2022 Selection Criteria: Cohort studies and randomized controlled trials. Data collection and analysis: Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable. Main Results: The analysis included ten studies describing 1,391 women with uteroplacental insufficiency disorders: 703 treated with pravastatin and 688 not treated with statins. Women treated with pravastatin demonstrated significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01-0.87, p = 0.04, I 2 = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23-0.75, p = 0.004, I 2 = 25%). In subgroup analysis, prolongation of pregnancy from study entry to delivery was statistically significant in cohort studies (mean difference 8.93 weeks, 95%CI:4.22-13.95, p = 0.00) but not in randomized control studies. Trends were observed toward a decrease in preeclampsia diagnoses (OR = 0.54, 95%CI:0.27-1.09, p = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09-1.13, p = 0.08, I 2 = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14-212, p = 0.08, I 2 = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R 2 = 1). Conclusion: Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ identifier CRD42020165804 17/2/2020., (Copyright © 2022 Hirsch, Rotem, Ternovsky and Hirsh Raccah.)

Objective: To assess the effect of statin exposure during pregnancy on congenital anomalies and spontaneous abortions. Data sources: Electronic databases were searched from inception to January 2022. Study Eligibility Criteria: Cohort studies and randomized controlled trials (RCTs) evaluate the effect of treatment with statins on congenital anomalies in general and cardiac malformations in particular. Studies evaluating spontaneous abortions were included as a secondary outcome. Study appraisal and synthesis methods: Pooled odds ratio was calculated using a random-effects model and meta-regression was utilized when applicable. Results: Twelve cohort studies and RCTs were included in the analysis. Pregnancy outcomes of 2,447 women that received statins during pregnancy were compared to 897,280 pregnant women who did not. Treatment with statins was not associated with a higher risk of overall congenital anomalies (Odd Ratio = 1.1, CI (0.9-1.3), p = 0.33, I2 = 0%). Yet, cardiac malformations were more prevalent among neonates born to statins users (OR = 1.4, CI (1.1-1.8), p = 0.02, I 2 = 0%). The risk was higher when exposure occurred during the first trimester. This finding was statistically significant in cohort studies, but not in RCTs. Statin treatment was also associated with a higher rate of spontaneous abortions (OR = 1.5, CI (1.1-2.0), p = 0.005, I 2 = 0%). In meta-regression analysis, no significant association between lipophilic statins and the rate of congenital anomalies was found. Conclusion: Overall, treatment with statins during pregnancy was not associated with an increased risk of congenital anomalies. A slight risk elevation for cardiac malformation and spontaneous abortions was seen in cohort studies but not in RCTs. Systematic Review Registration: clinicaltrials.gov, identifier [CRD42020165804 17/2/2020] The meta-analysis was presented online at 42nd annual meeting of SMFM. January 31-5 February 2022., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hirsch, Ternovsky, Zwas, Rotem, Amir and Hirsh Raccah.)