Pre-eclampsia - Causes

Causes

The pre-eclampsia syndrome is thought in many cases to be caused by a shallowly implanted placenta which becomes hypoxic, leading to an immune reaction characterized by secretion of upregulated inflammatory mediators from the placenta, and acting on the vascular endothelium. The shallow implantation is thought to stem from the maternal immune system's response to the placenta and refers to evidence suggesting a lack of established immunological tolerance in pregnancy. This results in an immune response against paternal antigens from the fetus and its placenta. In some cases of pre-eclampsia it is thought that the mother lacks the receptors for the proteins the placenta is using to downregulate the maternal immune system's response to it. This view is also consistent with evidence showing many miscarriages to be an immunological disorder where the mother's immune system "unleashes a destructive attack on the tissues of the developing child".

In many cases of the pre-eclampsia syndrome, however, the maternal response to the placenta appears to have allowed for normal implantation. It is possible that women with higher baseline levels of inflammation stemming from underlying conditions such as chronic hypertension or autoimmune disease may have less tolerance for the inflammatory burden of pregnancy.

If severe, pre-eclampsia progresses to fulminant pre-eclampsia, with headaches, visual disturbances, and epigastric pain, and further to the HELLP syndrome and eclampsia. Placental abruption is associated with hypertensive pregnancies. These are life-threatening conditions for both the developing baby and the mother.

Many theories have attempted to explain why pre-eclampsia arises, and have linked the syndrome to the presence of the following:

• endothelial cell injury
• immune rejection of the placenta
• compromised placental perfusion
• altered vascular reactivity
• imbalance between prostacyclin and thromboxane
• decreased glomerular filtration rate with retention of salt and water
• decreased intravascular volume
• increased central nervous system irritability
• disseminated intravascular coagulation
• uterine muscle stretch (ischemia)
• dietary factors, including vitamin deficiency
• Hughes syndrome
• genetic factors
• air pollution
• obesity
• unfamiliar sperm theory
• Thyroid dysfunction: Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, has been estimated to increase the risk of pre-eclampsia with an odds ratio of 1.7.

The current understanding of the syndrome is as a two-stage process, with a highly variable first stage which predisposes the placenta to hypoxia, followed by the release of soluble factors which result in many of the other observed phenomena. Many of the older theories can be subsumed under this umbrella, as the soluble factors have been shown to cause, for example, endothelial cell injury, altered vascular reactivity, the classic lesion of glomerular endotheliosis, decreased intravascular volume, inflammation, etc. Underlying maternal susceptibility to the damage is likely implicated as well...