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Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis

Affiliation
Department of Obstetrics & Gynecology ,Shaare Zedek Medical Center ,Affiliated with the Hebrew University School of Medicine ,Jerusalem ,Israel
Hirsch, Ayala;
Affiliation
Department of Obstetrics & Gynecology ,Shaare Zedek Medical Center ,Affiliated with the Hebrew University School of Medicine ,Jerusalem ,Israel
Rotem, Reut;
Affiliation
Division of Clinical Pharmacy ,Institute for Drug Research ,School of Pharmacy ,Faculty of Medicine ,Hebrew University of Jerusalem ,Jerusalem ,Israel
Ternovsky, Natali;
Affiliation
Division of Clinical Pharmacy ,Institute for Drug Research ,School of Pharmacy ,Faculty of Medicine ,Hebrew University of Jerusalem ,Jerusalem ,Israel
Hirsh Raccah, Bruria

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.

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License Holder: Copyright © 2022 Hirsch, Rotem, Ternovsky and Hirsh Raccah.

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