Aetiology

Pre-eclampsia is associated with a failure of normal trophoblast invasion, leading to maladaptation of maternal spiral arterioles, and is associated with hyperplacentation disorders such as diabetes, hydatidiform mole, and multiple pregnancy.[7][8]​​[9]

There are numerous risk factors that increase the probability and severity of pre-eclampsia, including nulliparity, previous maternal history or family history, body mass index >30, maternal age >40 years, multiple (twin) pregnancy, sub-fertility, gestational hypertension, pre-existing diabetes, polycystic ovary syndrome, autoimmune disease, renal disease, pre-existing cardiovascular disease and chronic hypertension, an interval of 10 years or more since a previous pregnancy, and high-altitude residence.[1][10] However, these risk factors do not account for all cases and complications such as eclampsia, HELLP syndrome (a subtype of severe pre-eclampsia characterised by haemolysis [H], elevated liver enzymes [EL], and low platelets [LP]), and fetal growth restriction.

Pathophysiology

Pre-eclampsia is caused by an initial placental trigger and a maternal systemic response.[8]​ It is associated with failure of normal trophoblast invasion, leading to maladaptation of maternal spiral arterioles.[7] Maternal arterioles are the source of the blood supply to the fetus. Maladaptation of these vessels can interfere with normal villous development, leading to placental insufficiency and, consequently, fetal growth restriction. The pathophysiology of insufficient trophoblastic invasion is likely to be multifactorial, with genetics, immunology, and endothelial dysfunction each having roles. The extent and specificity with which placental gene expression changes in pre-eclampsia remains to be fully understood.[11] Raised levels of pro-inflammatory and anti-angiogenic cytokines in the maternal circulation may contribute to placental vasoconstriction and subsequent hypoxia.[12][13]

The maternal systemic response results in vasoconstriction and capillary leaking, leading to hypertension and complications such as:

  • Cerebral vascular dysregulation and oedema

  • Liver vascular dysregulation and oedema

  • Pulmonary oedema.

Although clinical manifestation does not occur until after 20 weeks' gestation, abnormal physiological changes can occur from early in the first trimester.[14] This is suggested by the presence of various biomarkers, such as:

  • Pregnancy-associated plasma protein A

  • ADAM12 (a disintegrin and metalloproteinase 12)

  • Placental growth factor

  • Soluble endoglin

  • Soluble fms-like tyrosine kinase 1 (sFlt-1).[12]

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