AUTHOR=Hirsch Ayala , Rotem Reut , Ternovsky Natali , Hirsh Raccah Bruria 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1021548

DOI=10.3389/fphar.2022.1021548

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objective:</bold> To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins.</p><p><bold>Search Strategy:</bold> Electronic databases were searched from inception to January 2022</p><p><bold>Selection Criteria:</bold> Cohort studies and randomized controlled trials.</p><p><bold>Data collection and analysis:</bold> Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable.</p><p><bold>Main Results:</bold> 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, <italic>p</italic> = 0.04, I<sup>2</sup> = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23–0.75, <italic>p</italic> = 0.004, I<sup>2</sup> = 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, <italic>p</italic> = 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, <italic>p</italic> = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09–1.13, <italic>p</italic> = 0.08, I<sup>2</sup> = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14–212, <italic>p</italic> = 0.08, I<sup>2</sup> = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R<sup>2</sup> = 1).</p><p><bold>Conclusion:</bold> Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies.</p><p><bold>Systematic Review Registration:</bold><ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.crd.york.ac.uk/prospero/">https://www.crd.york.ac.uk/prospero/</ext-link> identifier CRD42020165804 17/2/2020.</p>