From Epidemiology to Therapeutics: A Holistic Review of Preeclampsia’s Burden, Mechanisms, Risks, and Innovations View PDF

^*Dabbakuti Kranthi Kumar
Medicine, Kamineni Academy Of Medical Sciences And Research Centre, Hyderabad, Telangana, India
Mrithini Pon Balakrishnan
Medicine, Government Sivagangai Medical College, Sivagangai, Tamil Nadu, India
Sakshi Satish
Medicine, Sapthagiri NPS University, Bengaluru, India
Venugopala Krithivasan Pushparajan
Medicine, Vydehi Institute Of Medical Science And Research Centre, Whitefield, Bengaluru, India

^*Corresponding Author:

Dabbakuti Kranthi Kumar
Medicine, Kamineni Academy Of Medical Sciences And Research Centre, Hyderabad, Telangana, India

Published on: 2026-03-20

Abstract

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide, yet its complex pathophysiology and heterogeneous clinical presentation continue to challenge early diagnosis and effective management. Despite decades of research, significant gaps persist in translating mechanistic insights into universally effective therapies, particularly for high-risk populations in resource-limited settings. This review addresses the urgent need to consolidate recent advances in preeclampsia research, bridging fundamental science with clinical applications to improve outcomes. The review synthesizes critical insights into the multifactorial origins of preeclampsia, emphasizing the central role of placental dysfunction, angiogenic imbalance, and systemic inflammation. It evaluates current diagnostic tools, including the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio, alongside evidence-based interventions such as lowdose aspirin, statins, and optimized antihypertensive regimens. Regional disparities in prevalence and outcomes are analyzed, highlighting the disproportionate burden in low- and middle-income countries. Emerging therapeutic strategies targeting oxidative stress, immune dysregulation, and genetic susceptibility are critically appraised. The review also explores innovative approaches like personalized risk assessment, while underscoring the limitations of existing treatments. Clinical studies comparing drug efficacy (e.g., nicardipine vs labetalol) and preventive measures (e.g., 150 mg aspirin) are systematically reviewed to guide practice. Finally, the interplay between preeclampsia and long-term maternal cardiovascular health is examined, reinforcing the need for postpartum surveillance. Future research must prioritize large-scale trials to validate novel biomarkers and therapies across diverse populations, with particular attention to implementation in resourceconstrained settings. Investigations into fetal microchimerism and epigenetic modifiers could unlock new preventive strategies, while artificial intelligence integration may revolutionize early-risk prediction models. Multidisciplinary collaborations are essential to develop standardized protocols for screening, management, and postpartum follow-up. By addressing these priorities, the field can mitigate the global burden of preeclampsia and its lifelong health consequences.

Keywords

Angiogenic factors, Biomarkers, Hypertensive disorders of pregnancy, Maternal-fetal outcomes, Pathophysiology, Prevention strategies, Therapeutic innovations

Introduction

Preeclampsia is a complex pregnancy-related disorder characterized by hypertension and often accompanied by proteinuria [1-3]. It poses significant risks to both maternal and fetal health, contributing to a considerable burden of morbidity and mortality worldwide. It is characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, often leading to severe complications if untreated [4- 6]. The pathogenesis of preeclampsia involves a multifaceted interplay of genetic, molecular, and environmental factors, with the placenta playing a central role [7-9]. Despite its prevalence, the only definitive treatment remains the delivery of the fetus and placenta, which can result in preterm birth and associated neonatal complications. Recent research has focused on understanding the underlying mechanisms, risk factors, and potential therapeutic innovations to improve outcomes for affected women and their infants [10-12]. This article aims to provide a comprehensive overview of epidemiology, mechanisms, risk factors, and recent innovations in the management of preeclampsia.

The epidemiology of preeclampsia underscores its significant contribution to maternal and perinatal morbidity and mortality worldwide, positioning it as a critical public health concern [13]. Its prevalence is influenced by a complex interplay of risk factors, including socioeconomic determinants, which have been explored to better understand the etiology and potential avenues for prevention [10]. The condition’s burden extends beyond pregnancy, with evidence linking preeclampsia to increased long-term cardiovascular risks, highlighting the importance of understanding its pathophysiology for effective management [14]. Mechanistically, preeclampsia involves intricate pathophysiological processes. The comprehensive reviews emphasize the role of abnormal placental development, endothelial dysfunction, and immune maladaptation as central to its onset [15]. These mechanisms contribute to the clinical manifestations observed, such as hypertension and organ damage, by disrupting normal vascular and placental functions [15]. Additionally, the condition shares common pathways with other vascular and metabolic disorders, including insulin resistance, which may exacerbate disease severity and influence therapeutic strategies [16].

The risk factors associated with preeclampsia are multifaceted, encompassing both maternal and environmental components. Factors such as chronic kidney disease and metabolic disturbances have been identified as significant contributors, further complicating the clinical picture and emphasizing the need for holistic risk assessment [10, 17]. The association between preeclampsia and subsequent cardiovascular disease suggests shared pathogenic pathways, including vascular remodeling impairments and chronic inflammation [14]. Recent advances in predicting and preventing preeclampsia focus on identifying biomarkers and understanding underlying mechanisms to enable early intervention [10]. Innovations in therapeutics are increasingly targeting the molecular pathways involved in endothelial dysfunction and immune regulation, aiming to mitigate disease progression and improve outcomes [15]. The integration of mechanistic insights with clinical strategies holds promise for reducing the global burden of preeclampsia and its long-term sequelae.

In summary, the literature highlights preeclampsia as a multifactorial disorder with significant epidemiological impact, driven by complex pathophysiological mechanisms involving placental, vascular, and metabolic factors [18-20]. Advances in understanding these mechanisms are paving the way for improved predictive tools and targeted therapies, ultimately aiming to lessen their burden on maternal and fetal health [10, 14, 15].