Definition
Preeclampsia is defined as gestational blood pressure elevation with proteinuria that develops after 20 weeks' gestation.
In women with preexisting chronic hypertension and proteinuria before 20 weeks' gestation, the preeclampsia can be diagnosed when the blood pressure (BP) is exacerbated BP (systolic >160 mmHg or diastolic >110 mmHg) during the last half of pregnancy or when proteinuria significantly increases.
Preeclampsia is one of four major hypertensive disorders of pregnancy. The other three conditions that comprise these hypertensive complications of pregnancy include gestational hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia.
Wikipedia, Diseases Database, OMIM
Epidemiology
A World Health Organization (WHO) analysis reveals that hypertensive disorders complicate 15% of pregnancies, and are the leading cause of maternal death in Latin America and the Caribbean (25.7%), as well as a major contributor to maternal death in Africa (9.1%) and Asia (9.1%). Although the exact prevalence is unknown, approximately 2-4% of pregnancies (4 million women) are estimated to be complicated by preeclampsia annually; 2% of these women develop eclampsia.
Among nulliparous women, the incidence of preeclampsia is reported to be 5-7%. In the United Kingdom, 15% of maternal deaths are related to preeclampsia-eclampsia syndrome.
Approximately 80% of the world's cases preeclampsia are late onset.
Preterm birth is more common among pregnancies complicated by preeclampsia, which accounts for as many as 15% of preterm deliveries.
High rates of neonatal mortality are reported in the remaining pregnancies complicated by early-onset preeclampsia (11.5%) and eclampsia (30%).
Symptoms and Signs
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.
For more about clinical
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 a health care provider.
"Severe preeclampsia" involves a BP over 160/110, and additional symptoms.
Pre-eclampsia may progress to eclampsia, characterized by the appearance of tonic-clonic seizures. This happens only very rarely, but eclampsia is potentially fatal.
Risk Factors
- Age
Maternal age of younger 20 years and older than 35-40 years are among the clinical risk factors for the development of preeclampsia. The increased incidence of preeclampsia noted among patients older than 35 years probably reflects undiagnosed chronic hypertension with superimposed PIH.
- First time pregnancy
Some research suggests that one's risk of preeclampsia is increased with a first pregnancy with a new partner/husband, however recent research suggests that the key factor in that increased risk is not the new husband, but in fact increased maternal age.
- History
Previous history of preeclampsia, particularly if onset is before the third trimester;
History of chronic high blood pressure, diabetes or kidney disorder;
Family history of the disorder (i.e., a mother, sister, grandmother or aunt who had the disorder).
- BMI
Women with greater than 30% Body mass Index (BMI).
- Mother disease
Polycystic ovarian syndrome;
Lupus or other autoimmune disorders such as rheumatoid arthritis, sarcoidosis or MS.
Complications
Several complications can occur during the course of Preeclampsia, including:
- Fetal and infant mortality and morbidity
- Risk of later cardiovascular disease
- Intergenerational effects.
For more about complication
Pathogenesis
Current concepts regarding the pathophysiology of preeclampsia recognize that preeclampsia is a multisystem disorder characterized by vasoconstriction, metabolic changes, endothelial dysfunction, and activation of the coagulation cascade in conjunction with an inflammatory response. A 2-stage model of preeclampsia has been proposed in which failure of placental vascular remodeling results in reduced placental perfusion and initiates a cascade of events that result in serious maternal illness with the potential for significant perinatal morbidity and death.
Pathophisiology
There are a number of theories trying to explain the origin of preeclampsia, ranging from too much blood flow to too little, from genetics to nutritional problems. Some current theories include:
Preexisting maternal conditions: Mother has undiagnosed high blood pressure or other preexisting problems such as diabetes, lupus, sickle cell disorder, hyperthyroidism, kidney disorder, etc.
Nutritional Problems/Poor Diet: Insufficient protein, excessive protein, not enough fresh fruit and vegetables (antioxidants), among others theories.
High Body Fat: High body fat may actually be the symptom of the tendency to develop this disorder linked to the genetic tendency towards high blood pressure, diabetes and insulin resistance.
Uterine ischemia/ underperfusion: Insufficient blood flow to the uterus.
Hemodynamic vascular injury: Injury to the blood vessels due to too much blood flow.
Endothelial activation and dysfunction: Damage to the lining of the blood vessels that regulates the diameter of the blood vessels keeping fluid and protein inside the blood vessels and keeps blood from clotting.
Immunological Activation: The immune system believes that damage has occurred to the blood vessel and in trying to fix the "injury" actually makes the problem worse (like scar tissue) and augments the process.
Oxidative stress: Candidate placental mediators for maternal endothelial dysfunction in preeclampsia, include products of oxidative stress, released into the maternal circulation, for example Xanthine oxidase.
Insufficient Magnesium Oxide and B6: involved mostly in pathogenesis of eclampsia, magnesium stabilizes vascular smooth muscles and helps regulate vascular tone
Magnesium for seizure prophylaxis in patients with mild preeclampsia.
Magnesium sulphate for the management of preeclampsia
Prostacyclin/thromboxane imbalance (ASA): Disruption of the balance of the hormones that maintain the diameter of the blood vessels.
Prostacyclin/thromboxane early changes in pregnancies that are complicated by preeclampsia
Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis
Calcium deficiency: Calcium helps maintain vasodilation, so a deficiency would impair the function of vasodilation (see above).
Serum calcium, magnesium and uric acid in preeclampsia and normal pregnancy
We can focus our attention on some particular topics, that we find as the subject of various recent studies:
- GENETIC ASPECTS: there are studies of candidate genes that, thus far, have very much reflected the pathophysiological research interests of the investigators. The multifaceted nature of PE and the difficulties of accurate phenotyping require the accumulation of a large, very carefully phenotyped, database.
What is the place of genetics in the pathogenesis of pre-eclampsia?
One of the studied genes is the AGTR gene, the one who codes for the Angiotensin II receptor.
Angiotensin II (AII) acts as a growth factor in local systems, mediating diverse effects such as cellular proliferation and apoptosis. These effects are controlled through two main receptor subtypes: AGTR1 and AGTR2.
The study doesn’t evidence a significant difference in haplotype frequency between preeclamptic and normotensive women, but identifies two novel polymorphisms in AGTR2: there was evidence for a significant increase in the frequency of one haplotype in women with preeclampsia.
Haplotypes of the angiotensin II receptor genes AGTR1 and AGTR2 in women with normotensive pregnancy and women with preeclampsia
Another important American study concerns the Soluble fms-like tyrosine kinase 1: it reports that mRNA expression of placental sFlt1 in patients with preeclampsia is higher than in normotensive term pregnancies, and, in fact, the average serum level of sFlt1 was almost five times higher in patients with severe preeclampsia than in normotensive pregnant women.
Excess (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia through his various interactions:
- sFlt1 is known to antagonize the proangiogenic molecules VEGF and PlGF by binding to them and preventing their interaction with their cell-surface receptors, Flt1 and KDR, so in preeclampsia excess sFlt1 causes widespread endothelial dysfunction, decreasing levels of unbound VEGF and PlGF;
- endogenous sFlt1 gives also antiangiogenic properties to the serum of preeclamptic patients, for the reduction of VEGF and PlGF.
- it significantly reduces VEGF- and PlGF-induced vasodilation in patients with severe preeclampsia, so it might oppose physiologic vasorelaxation, thus contributing to hypertension.
- sFlt1 induces glomerular endotheliosis: glomerular enlargement with occlusion of the capillary loops by swelling and hypertrophy of endocapillary cells; in this way it contributes to proteinuria.
Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia
Maternal serum placental growth factor and soluble fms-like tyrosine kinase 1 as early predictors of preeclampsia
Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women
Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia
- IRON STATUS: In preeclamptic women, serum iron concentration, ferritin, and percent saturation of transferrin are higher than in control subjects, whereas unsaturated iron-binding capacity and apotransferrin levels are significantly lower.
Released iron species in preeclampsia may contribute to the etiology of the disease, because it exacerbates lipid peroxidation and endothelial cell injury; iron free radicals are released from ischaemic placenta, so this connection between mother and fetus may contribute to pre eclampsia etiology.
Routine investigation of serum iron status of pregnant women, as part of antenatal checkup, may help in the establishment of diagnosis of pre eclampsia before appearance of its clinical manifestation.
Abnormal iron parameters in the pregnancy syndrome preeclampsia
Alteration in iron status in pre eclampsia
Iron status and body iron are sometimes decreased in physiological pregnancies, and have to be monitored because women may need an iron supplementation.
Anyway, there is no increased frequency of preeclampsia in women taking iron supplements.
An expedient seems to be the schedule of somministration: daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation.
Iron and pregnancy—a delicate balance
Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation
References
Pubmed
emedicine
Wikipedia
Medline Plus
OMIM
Authors:
Pozzi Giada, Schirò Matteo
