Pre-eclampsia
From Wikipedia, the free encyclopedia
| ICD-10 | O11., O13., O14. |
|---|---|
| ICD-9 | 642.4-642.7 |
| DiseasesDB | 10494 |
| MedlinePlus | 000898 |
| eMedicine | med/1905 |
Pre-eclampsia is said to be present when hypertension arises in pregnancy (pregnancy-induced hypertension) in association with significant protein in the urine. (Note: in the U.S. the word is spelled without the hyphen "preeclampsia" and in most other parts of the world with a hyphen "pre-eclampsia.") Its cause remains unclear, although the principal cause appears to be a substance or substances from the placenta causing endothelial dysfunction in the maternal blood vessels.<ref name=DrifeMagowan>Drife JO, Magowan (eds). Clinical Obstetrics and Gynaecology, chapter 39, pp 367-370. ISBN 0-7020-1775-2.</ref> While blood pressure elevation is the most visible symptom 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 at varying times within pregnancy and its progress differs between patients; most cases present pre-term. It has no known cure apart from ending the pregnancy (induction of labor or abortion). It may also present up to 6 weeks post-partum. It is the most common dangerous complication of pregnancy, and it may affect both the mother and the fetus.<ref name=DrifeMagowan/>
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[edit] Diagnosis
Pre-eclampsia is diagnosed when a pregnant woman develops high blood pressure (two separate readings taken at least 6 hours apart of 140/90 or more) and 300 mg of protein in a 24 hour urine sample (proteinuria). 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. It is important to note, however, that 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 provider.
Pre-eclampsia is usually symptomless, 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.
[edit] Appearance
Pre-eclampsia is much more common in the first pregnancy (5-7% of births) and usually becomes evident in the third trimester (and virtually always after the 20th week of pregnancy). It is also more common in women who have preexisting hypertension, diabetes, autoimmune diseases like lupus, various inherited thrombophilias like Factor V Leiden, or renal disease, in women with a family history of pre-eclampsia, and in women with a multiple gestation (twins, triplets and more). The single most significant risk for developing pre-eclampsia is having had pre-eclampsia in a prior pregnancy.
Pre-eclampsia may also occur in the immediate post-partum period or up to 6-8 weeks post-partum. This is referred to as "postpartum pre-eclampsia". The most dangerous time for the mother is the 24-48 hours postpartum and careful attention should be paid to pre-eclampsia signs and symptoms.[citation needed]
[edit] Causes
Pre-eclampsia is thought to be caused by a shallowly implanted placenta which becomes hypoxic, leading to upregulated inflammatory mediators secreted by the placenta and acting on the vascular endothelium. If severe, it 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 fetus and the mother.
Preeclampsia has been described as a disease of theories
- endothelial cell injury
- rejection phenomenon
- 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
- genetic factors <ref name=AMN>Courtney Reynolds, MD, William C. Mabie, MD, & Baha M. Sibai, MD (2006). Preeclampsia. Pregancy - Hypertensive Disorders. Armenian Medical Network. Retrieved on 2006-11-23.</ref>
The current understanding of the disease is as a two-stage process, with a 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, etc. Underlying maternal suceptibility to the damage is likely implicated as well.
[edit] Pathogenesis
Although much research into the causes and mechanism of pre-eclampsia has taken place, its exact pathogenesis remains uncertain. Most studies support the notion of inadequate blood supply to the placenta makes it release particular hormones or chemical agents that, in mothers predisposed to the condition, leads to damage of the endothelium (lining of blood vessels), alterations in metabolism and inflammation.<ref name=DrifeMagowan/>
Studies suggest that hypoxia resulting from inadequate perfusion upregulates sFlt-1, a VEGF and PlGF antagonist, leading to a damaged maternal endothelium and restriction of placental growth.<ref name="JClinInvest2003-Maynard">Maynard S, Min J, Merchan J, Lim K, Li J, Mondal S, Libermann T, Morgan J, Sellke F, Stillman I, Epstein F, Sukhatme V, Karumanchi S (2003). "Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.". J Clin Invest 111 (5): 649-58. PMID 12618519.</ref> In addition, endoglin, a TGF-beta antagonist, is elevated in pregnant women who develop preeclampsia. <ref name="PreE">Venkatesha, S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim KH, Yuan HT, Libermann TA, Stillman IE, Roberts D, D'Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA. (2006). "Soluble endoglin contributes to the pathogenesis of preeclampsia". Nat Med 12 (6): 642-9. PMID 16751767.</ref> Soluble endoglin is likely upregulated by the placenta in response to an upregulation of cell-surface endoglin produced by the maternal immune system, although there is also the potential that sEng is produced by the maternal endothelium. Levels of both sFlt-1 and sEng increase as severity of disease increases, with levels of sEng surpassing levels of sFlt-1 in HELLP syndrome cases.
It is important to note that both sFlt-1 and sEng are upregulated in all pregnant women to some extent, supporting the idea that hypertensive disease in pregnancy is a normal pregnancy adaptation gone awry. As natural killer cells are intimately involved in placentation and as placentation involves a degree of maternal tolerance for a foreign placenta which requires maternal resources for its support, it is not surprising that the maternal immune system might respond more negatively to the arrival of placentae under certain circumstances, such as a placenta which is more invasive than normal. Initial maternal rejection of the placental cytotrophoblasts may be the cause of the inadequately remodeled spiral arteries in those cases of preeclampsia associated with shallow implantation, leading to downstream hypoxia and the appearance of maternal symptoms in response to upregulated sFlt-1 and sEng. (See parent-offspring conflict.)
It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop preeclampsia. These findings have given rise to the hypothesis that preeclampsia is a disease process by which a placental lesion such as hypoxia allows increased fetal material into maternal circulation that leads to an inflammatory response and endothelial damage ultimately resulting in preeclampsia and eclampsia..<ref name="Holzgreve2002">Hahn S, Holzgreve W (2002). "Fetal cells and cell-free fetal DNA in maternal blood: new insights into pre-eclampsia". Hum Reprod 8 (6): 501-8. PMID 12498420.</ref>
[edit] Differential Diagnosis
Preeclampsia-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome. It must always be considered a possibility in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when preexisting disease such as hypertension is present. <ref name=AMN1>Preeclampsia-Eclampsia. Diagnosis and management of pre-eclampsia and eclampsia. Armenian Medical Network (2003). Retrieved on 2005-11-23.</ref>
[edit] Complications
Eclampsia complicates 1 in 2000 maternities in the United Kingdom and carries a maternal mortality of 2 per cent. The HELLP syndrome is commoner, probably about 1 in 500 maternities, but may be as dangerous as eclampsia itself. These two major maternal crises can present unheralded by prodromal signs of pre-eclampsia.
Cerebral haemorrhage is a lesion that can kill women with pre-eclampsia or eclampsia. In that cerebral haemorrhage is a known complication of severe hypertension in other contexts, it must be assumed that this is a major predisposing factor in this situation, although this has not been proved. Adult respiratory distress syndrome appears to have become more common, it is not known whether this is a consequence of modern methods of respiratory support rather than of the disease itself.
[edit] Therapy
The only known treatment for eclampsia or advancing preeclampsia is 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. In some cases women with preeclampsia or eclampsia can be stabilized temporarily with magnesium sulphate intravenously to forestall seizures while steroid injections are administered to promote fetal lung maturation. Evidence for the use of magnesium sulphate came from the international MAGPIE atudy. When induced delivery needs to take place before 37 weeks gestation, it is accepted that there are additional risks to the baby from premature birth that will require additional monitoring and care.
Studies into supplementation with antioxidant vitamins C and E found no change in preeclampsia rates.<ref name="NEJM2006-Rumbold">Rumbold A, Crowther C, Haslam R, Dekker G, Robinson J (2006). "Vitamins C and E and the risks of preeclampsia and perinatal complications.". N Engl J Med 354 (17): 1796-806. PMID 16641396.</ref> Drs. Padayatty and Levine with NIH in a "Letter to the Editor" stated that the studies and another "Letter to the Editor" overlooked a key reason for the lack of vitamin C on the prevention of preeclampsia. Because plasma ascorbate concentrations were not reported, we estimated them from known data, the placebo and treatment groups in the study probably had similar plasma and tissue ascorbate concentrations. Doses of 1 g per day have little effect on plasma or intracellular ascorbate concentrations.<ref name="Padayatta”>Padayatty SJ, Levine M. (2006). "Vitamin C and E and the Prevention of Preeclampsia - Letter" (PDF). NEJM 355 (10): 1065-1066.</ref> Calcium supplementation in women with low-calcium diets found no change in preeclampsia rates but did find a decrease in the rate of severe preeclamptic complications.<ref name="AmJObstetGynecol2006-Villar">Villar J, Abdel-Aleem H, Merialdi M, Mathai M, Ali M, Zavaleta N, Purwar M, Hofmeyr J, Nguyen T, Campódonico L, Landoulsi S, Carroli G, Lindheimer M (2006). "World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women.". Am J Obstet Gynecol 194 (3): 639-49. PMID 16522392.</ref> Aspirin supplementation is still being evaluated as to dosage, timing, and population and may provide a slight preventative benefit in some women, however significant research has been done on aspirin and the results thus far are unimpressive.<ref name="Cochrane2004-Duley">Duley L, Henderson-Smart D, Knight M, King J (2004). "Antiplatelet agents for preventing pre-eclampsia and its complications.". Cochrane Database Syst Rev (1): CD004659. PMID 14974075.</ref> There is insufficient evidence to recommend either exercise<ref name="Cochrane2006-Meher-exercise">Meher S, Duley L (Apr 19 2006). "Exercise or other physical activity for preventing pre-eclampsia and its complications.". Cochrane Database Syst Rev (2): CD005942. PMID 16625645.</ref> or bedrest<ref name="Cochrane2006-Meher-rest">Meher S, Duley L (Apr 19 2006). "Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure.". Cochrane Database Syst Rev (2): CD005939. PMID 16625644.</ref> as treatments. Studies of protein/calorie supplementation have found no effect on preeclampsia rates, and dietary protein restriction does not appear to increase preeclampsia rates.<ref name="Cochrane2003-Kramer">Kramer M, Kakuma R (2003). "Energy and protein intake in pregnancy.". Cochrane Database Syst Rev (4): CD000032. PMID 14583907.</ref>
[edit] Effects of smoking
Several types of "Smoker’s Paradoxes" have been observed where smoking appears to have specific beneficial effects, such as less frequent repeated revascularization after percutaneous coronary intervention (PCI).<ref name="cohen">Cohen, David J., Michel Doucet, Donald E. Cutlip, Kalon K.L. Ho, Jeffrey J. Popma, Richard E. Kuntz (2001). "Impact of Smoking on Clinical and Angiographic Restenosis After Percutaneous Coronary Intervention". Circulation 104: 773. PMID 11502701. Retrieved on 2006-11-06.</ref> Smoking may also interfere with development of preeclampsia.<ref>Lain, Kristine Y., Robert W. Powers, Marijane A. Krohn, Roberta B. Ness, William R. Crombleholme,James M. Roberts (November 1991). "Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure". American Journal of Obstetrics and Gynecology 181 (5): 908-14. PMID: 11422156. Retrieved on 2006-11-06.</ref> A plausible mechanism of action may be the nicotine in tobacco smoke acting as an anti-inflammatory agent and interfering with the disease process.<ref name="sciam">Lisa Melton (June 2006). "Body Blazes". Scientific American: p.24.</ref>
[edit] See also
[edit] Reference
[edit] Footnotes
<references />
[edit] External links
- Preeclampsia Foundation - U.S. based organisation which promotes research, raises awareness and provides individual support.
- Action on Preeclampsia - U.K. based organisation. Working with the Preeclampsia Foundation to form an International Preeclampsia Alliance.
- Australian Action on Pre-eclampsia
- Hellp Syndrome Society - Based in U.S. with worldwide membership.
es:Preeclampsia fr:Pré-éclampsie id:pre-eclampsia nl:Pre-eclampsie nn:Preeklampsi
