Repurposing Pravastatin as a Heme Oxygenase-1 Inducer for the Prevention of Preterm Delivery: A Literature Review

Abstract

ABSTRACT
Preterm delivery is a leading cause of neonatal morbidity and mortality globally, with limited effective preventative therapies. A substantial body of evidence implicates intrauterine inflammation and oxidative stress as a central pathological mechanism. This review aims to synthesize the extensive literature on repurposing pravastatin, a widely used HMG-CoA reductase inhibitor, as a potential therapeutic agent to prevent preterm delivery by inducing the potent cytoprotective enzyme, Heme Oxygenase-1 (HO-1). An exhaustive bibliographic exploration was executed through the PubMed, Scopus, and Semantic Scholar repositories encompassing scholarly works published prior to September 2025. The search strategy included keywords such as "pravastatin," "statins," "heme oxygenase-1," "HO-1," "preterm delivery," "preterm birth," "preeclampsia," and "placental insufficiency." The review included peer-reviewed preclinical studies, clinical trials, meta-analyses, and foundational scientific reviews relevant to the mechanism and application of pravastatin in pregnancy. Heme Oxygenase-1 constitutes a pivotal stress-responsive enzyme that functions as a formidable intrinsic safeguard against cytopathic damage by virtue of its profound anti-inflammatory, antioxidative, and vasorelaxant attributes. Its role in maintaining a healthy pregnancy, particularly in placental function and uterine quiescence, is well-established. Conversely, deficient HO-1 activity is strongly associated with adverse pregnancy outcomes. Pravastatin has proven to be a robust inducer of HO-1, primarily acting through the Nrf2 signaling pathway. A significant body of preclinical evidence and animal models demonstrates that pravastatin can mitigate inflammation, reverse vascular dysfunction, and prevent adverse pregnancy outcomes, including inflammation-induced preterm birth. Crucially, the historical safety concerns regarding statin use in pregnancy have been largely allayed for hydrophilic pravastatin, with numerous recent, large-scale studies and clinical trials confirming its favorable safety profile. While clinical trials have primarily focused on preeclampsia prevention, they have provided invaluable safety data and clear evidence of pravastatin's biological activity in pregnant women. Repositioning pravastatin as a selective activator of the HO-1 axis constitutes an exceptionally auspicious and mechanistically coherent approach toward the prophylaxis of preterm parturition. The confluence of robust preclinical justification and an affirming clinical safety record furnishes a persuasive impetus for the commencement of extensive, randomized controlled investigations meticulously structured to ascertain its effectiveness in mitigating preterm birth among high-risk cohorts.