Preeclampsia
Overview
Pre-eclampsia (US: preeclampsia, priːɛ'klæmpsia, from Greek eklampsia, to shine forth, term used by Hippocrates to suggest a sudden development) is a medical condition where hypertension arises in pregnancy (pregnancy-induced hypertension) in association with significant amounts of protein in the urine. Because pre-eclampsia refers to a set of symptoms rather than any causative factor, it is established that there are many different causes for the syndrome. It also appears likely that there is a substance or substances from the placenta that may cause endothelial dysfunction in the maternal blood vessels of susceptible women. While blood pressure elevation is the most visible sign of the disease, it involves generalized damage to the maternal endothelium and kidneys and liver, with the release of vasopressive factors only secondary to the original damage. Pre-eclampsia may develop from 20 weeks gestation (it is considered early onset before 32 weeks, which is associated with increased morbidity) and its progress differs among patients; most cases are diagnosed pre-term. Apart from abortion, Caesarean section, or induction of labor, and therefore delivery of the placenta, there is no known cure. It may also occur up to six weeks post-partum. It is the most common of the dangerous pregnancy complications; it may affect both the mother and the fetus.
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. This theory emphasizes the role of the maternal immune system, and refers to evidence suggesting a lack of established immunological tolerance to 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 fetus." 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, preeclampsia progresses to fulminant pre-eclampsia, with headaches, visual disturbances, and epigastric pain, and further to 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 preeclampsia 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
- genetic factors
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.
Diagnosis
Pre-eclampsia is diagnosed when a pregnant woman develops high blood pressure (two separate readings taken at least 4 hours apart of 140/90 or more) and 300 mg of protein in a 24-hour urine sample (proteinuria). A rise in baseline BP of 30 systolic or 15 diastolic, while not meeting the absolute criteria of 140/90 is still considered important to note but no longer diagnostic. Swelling, or edema, (especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia, but in current medical practice only hypertension and proteinuria are necessary for a diagnosis. However, pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant and should be reported to your health-care provider. Although eclampsia is potentially fatal, pre-eclampsia is often asymptomatic, hence its detection depends on signs or investigations. Nonetheless, one symptom is crucially important because it is so often misinterpreted. The epigastric pain, which reflects hepatic involvement and is typical of the HELLP syndrome, may easily be confused with heartburn, a very common problem of pregnancy. However, it is not burning in quality, does not spread upwards towards the throat, is associated with hepatic tenderness, may radiate through to the back, and is not relieved by giving antacids. It is often very severe, described by sufferers as the worst pain that they have ever experienced. Affected women are not uncommonly referred to general surgeons as suffering from an acute abdomen, for example acute cholecystitis. In general, none of the signs of pre-eclampsia is specific; even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Diagnosis, therefore, depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression after delivery. Some women develop high blood pressure without the proteinuria (protein in urine); this is called Pregnancy-induced hypertension (PIH) or gestational hypertension. Both pre-eclampsia and PIH are regarded as very serious conditions and require careful monitoring of mother and baby.
Treatment
The only known treatments for eclampsia or advancing pre-eclampsia are abortion or delivery, either by induction or Caesarean section. However, post-partum pre-eclampsia may occur up to 6 weeks following delivery even if symptoms were not present during the pregnancy. Post-partum pre-eclampsia is dangerous to the health of the mother since she may ignore or dismiss symptoms as simple post-delivery headaches and edema. Hypertension can sometimes be controlled with anti-hypertensive medication, but any effect this might have on the progress of the underlying disease is unknown. Many studies have also suggested the importance of a woman's immunological tolerance to her baby's father, whose genes are present in the young fetus and its placenta and which may pose a challenge to her immune system. As the theory is gaining support, researchers are increasingly recognizing the importance of a woman's continued exposure to her partner's semen as early as several years before conception. One study published in the American Journal of Obstetrics and Gynecology involved several hundreds of women and found that "women with a short period of cohabitation (less than 4 months) who used barrier methods for contraception had a substantially elevated risk for the development of pre-eclampsia compared with women with more than 12 months of cohabitation before conception." The study was also statistically significant at a desired 99.6% confidence level. Results from research conducted in the past two decades strongly suggest the importance of repeated exposure to the father's semen throughout the full length of the pregnancy due to the immune-modulating effects of key factors in semen. Women with underlying inflammatory disorders such as chronic hypertension or autoimmune diseases would likely benefit from aggressive treatment of those conditions prior to conception, tamping down the overactive immune system. Women with thrombophilias including Factor V Leiden may have a small increased risk of preeclampsia. While early studies suggest anticoagulant medication may prevent preeclampsia in women with thrombophilia these studies need to be confirmed before being adopted in clinical practice.