International Journal of Research and Reports in Gynaecology

Hypertensive disorders of pregnancy and pregnancy-induced hypertension(PIH) are often erroneously often erroneously used interchangeably and in remote past collectively termed "toxemia of pregnancy". This continues to represent a critical global health concern, contributing significantly to maternal and perinatal morbidity and mortality. According to the American College of Obstetricians and Gynecologists (ACOG), these disorders affect approximately 2–8% of pregnancies worldwide, underscoring their clinical relevance. Despite advancements in prenatal care, hypertensive conditions remain a substantial cause of maternal death across both low-resource and high-income settings. Regional data indicate that hypertensive disorders account for approximately 26% of maternal deaths in Latin America and the Caribbean, while in Africa and Asia, they contribute about 9%. Even in high-income countries, where maternal mortality rates have declined considerably due to improvements in obstetric care, 16% of maternal deaths are still attributed to these conditions.

Among the hypertensive disorders of pregnancy, preeclampsia remains the commonest is characterized by new-onset hypertension after 20 weeks of gestation, often accompanied by proteinuria or signs of systemic organ dysfunction and it is associated with adverse outcomes for both mother and fetus. While the precise pathophysiological mechanisms underlying preeclampsia and related hypertensive conditions remain incompletely defined, mounting evidence implicates dysregulated immune and inflammatory responses as central drivers in their development and progression.

One of the prevailing hypotheses posits an imbalance between pro-angiogenic factors (such as vascular endothelial growth factor [VEGF] and placental growth factor [PlGF]) and anti-angiogenic factors (notably soluble fms-like tyrosine kinase-1 [sFlt-1] and soluble endoglin), leading to widespread endothelial dysfunction and impaired placental perfusion. This angiogenic imbalance is believed to be influenced or even triggered by an aberrant maternal immune response to fetal antigens.

Several maternal risk factors have been identified that increase susceptibility to pregnancy-induced hypertension, including extremes of maternal age (particularly under 14 or over 35), a personal or family history of chronic hypertension, preeclampsia, or diabetes, obesity, primigravidity, multiparity, and certain racial/ethnic backgrounds, especially Black and Hispanic populations. Additional risk factors include elevated systolic blood pressure early in pregnancy, high pre-pregnancy body mass index (BMI), a history of smoking, and prior spontaneous abortions or miscarriages.

Increasing attention has been directed toward understanding the immunological landscape of hypertensive pregnancy disorders. In particular, the roles of inflammatory cells (such as macrophages, neutrophils, and T lymphocytes) and their secreted mediators; cytokines (e.g., TNF-α, IL-6, IL-10) and chemokines (e.g., CXCL8, CCL2),have emerged as critical components in the pathogenesis of preeclampsia and other forms of PIH. An exaggerated maternal systemic inflammatory response, coupled with insufficient immune tolerance at the maternal-fetal interface, may contribute to the endothelial injury, placental ischemia, and oxidative stress that characterize these disorders.

This review seeks to provide a mini-comprehensive analysis of the immunopathogenesis of toxemia of pregnancy, with particular emphasis on the interplay between inflammatory cells, cytokines, and chemokines. By elucidating these mechanisms, we aim to enhance our understanding of the disease process and highlight potential avenues for biomarker discovery, risk stratification, and targeted therapeutic interventions.