Secondary Prevention of Preeclampsia

Muhammad Ilham Aldika Akbar ^1,2* Roudhona Rosaudyn ³ Khanisyah Gumilar ^2,4 Renuka Shanmugalingam ⁵ Gustaaf Dekker ^1,6,7

• ¹ Faculty of Medicine, Airlangga University, Surabaya, Indonesia
• ² Airlangga University Hospital, Surabaya, East Java, Indonesia
• ³ Dr. Soetomo General Hospital, Surabaya, Indonesia, Surabaya, Indonesia
• ⁴ Graduate Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan
• ⁵ Department of Renal Medicine, Liverpool Hospital, Sydney, Australia, Sidney, Australia
• ⁶ Department Obstetrics & Gynecology, Lyell McEwin Hospital, Adelaide, Australia
• ⁷ University of Adelaide, Adelaide, South Australia, Australia

Preventing preeclampsia (PE) is crucial for the well-being of the mother, fetus, and the neonate with three levels: primary, secondary, and tertiary. Secondary prevention involves pharmacological therapies aimed at stopping the disease's progression before clinical signs. The predominant approach currently employed is the daily administration of low dose Aspirin and calcium. PE is a multifaceted illness characterized by syncytiotrophoblast (STB) stress, leading to endothelial dysfunction and systemic inflammation. Various subtypes of PE, in particular earlyonset PE (EOP) and late-onset PE (LOP), have different pathophysiological pathways leading to STB stress and also different perinatal outcomes. Low-dose Aspirin (LDA) has been shown to be beneficial in lowering the occurrence of EOP, especially when started before 16 weeks of pregnancy. Calcium supplementation is advantageous for women with poor dietary calcium intake, reducing endothelium activation and hypertension. Low molecular weight heparins (LMWH), have pleiotropic effects, besides their anticoagulant effects, LMWH have significant antiinflammatory effects, and have a potential restricted use in patients with history of prior severe placental vasculopathy with or without the maternal preeclamptic syndrome. Pravastatin and other statins have shown positive results in lowering preterm PE and improving outcomes for both the mother and baby. Proton pump inhibitors (PPIs) have shown potential in lowering soluble FMS-like tyrosine kinase-1 (sFlt-1) levels and enhancing endothelial function, but clinical trials have been inconsistent. Metformin, primarily used for improving insulin sensitivity, has potential advantages in decreasing PE incidence due to its anti-inflammatory and vascular properties, particularly in morbidly obese women. Nitric oxide (NO) donors and Larginine have been shown to effectively reduce vascular resistance and improving blood flow to placenta, potentially reducing PE risk. In conclusion, various pharmacological treatments have the