Authored by Abanoub Gabra*
Abstract
Hypertensive disorders of pregnancy are among the most common medical problems during pregnancy and they are associated with significant mortality and morbidity rate. Low dose Aspirin is already approved by many societies like ACOG and WHO to be used as prophylaxis for preeclampsia in high-risk patients. Recent studies showed a possible reduction in the incidence of preeclampsia and intrauterine growth restriction for high-risk mothers who taking LMWH during pregnancy. Although, the published evidence supporting LMWH is characterized by profound heterogeneity and inconsistency in terms of selection criteria and treatment regimens. Antepartum treatment with a combination of LMWH with low-dose ASA is endorsed by the American College of Chest Physicians and The American College of Obstetricians and Gynecologists for treatment of Antiphospholipid syndrome during pregnancy. WHO recommends Calcium as the first nutritional supplementation to prevent preeclampsia among population with low calcium in the diet. Folic acid and statins showed possible reduction in incidence of preeclampsia in high-risk patients but there is a need for further studies to confirm that. Dietary and lifestyle interventions have the potential to reduce the risk of preeclampsia. Both Metformin and vascular endothelial growth factors has promising preventive role that has been found through recent studies.
Keywords: Preeclampsia; Prevention; Hypertensive disorders of pregnancy
Introduction
Hypertensive disorders of pregnancy are among the most common medical problems during pregnancy and they are associated with significant mortality and morbidity rate [1]. They affect 4 % of pregnant women and may cause serious complications like stroke, heart failure, and renal failure [2]. Those diseases are among the top 6 causes of maternal mortality in the USA being responsible for 10% of maternal deaths [3]. They should be considered as a syndrome rather than a single disease entity [4]. Highest mortality rates were found to be related to eclampsia, HELLP syndrome, hemorrhage, delayed diagnosis [5]. The incidence may be affected by parity, socioeconomic level, race, and environmental factors [6]. African Americans have a high incidence of preeclampsia, eclampsia, related maternal mortality [5]. Their incidence has been dramatically increased recently with significant health burden in terms of affection of both mother and fetus health [3]. Having standardized health care for those patients is associated with a significant reduction in both mortality and morbidity [7,8].
Many societies contribute to Classifying hypertensive disorders of pregnancy in order to determine proper management lines and timelines for each category.
Chronic hypertension is defined as systolic BP of 140 or greater Or diastolic BP of 90 or greater Or both on 2 separate occasions at least 4 hours apart, This condition is diagnosed at or before 20 gestational weeks or already documented before pregnancy [9]. However, ACOG suggests that gestational hypertension or earlyonset preeclampsia should be considered if 1st trimester BP measures are within normal range [10]. Gestational hypertension is defined as elevated BP above 140/90 mmHg after 20 weeks at two separate occasions 6 hours apart in the absence of features of severe preeclampsia [11]. Severe gestational hypertension is defined by sustained elevated BP at more than or equal 160/110mmHg [12]. SOMANZ defines preeclampsia with severe features as a unique condition of pregnancy with multisystem effects involving liver, kidney and hematological parameters [13]. ACOG criteria for diagnosis include new-onset hypertension after 20 weeks associated with new-onset proteinuria (>300 mg/24 hours urine collection) [14]. In absence of proteinuria, diagnosis can be made upon presence of gestational hypertension plus any of the following: low platelet count less than 100.000/cc, creatinine level more than 1.1 (double the baseline creatinine level in absence of other renal problem), raised liver enzymes (double baseline), pulmonary edema, visual or cerebral symptoms [15].
Low dose Aspirin is already approved by many societies like ACOG and WHO to be used as prophylaxis for preeclampsia in high-risk patients. In this article, we are going beyond Aspirin to know more updates about other possible prophylactic measures of preeclampsia including Low molecular weight heparin, Calcium, vitamin D, Arginine, statins, and Folic acid.
Pathogenesis
The pathogenesis of preeclampsia is not completely understood despite extensive researches focused on it [16,17]. Placental ischemia remains the most accepted theory that was postulated to explain the pathogenesis of preeclampsia because delivery of the fetoplacental unit remains the main curative line of treatment [17,18]. In addition to that, placental ischemia also explains other complications e.g. IUGR and oligohydramnios. Also, it explains a higher incidence of disease in patients with chronic hypertension, DM and autoimmune diseases. Placental ischemia may explain the effectiveness of both low dose Aspirin and Low molecular weight heparin [19,20]. In normal pregnancy, invasion of uterine arteries to cytotrophoblast causes their transformation from epithelial to endothelial cells with low resistance pressure allowing enough blood supply to fetus through a process called ‘’pseudovasculogenesis’’ [18]. Cytotrophoblast cells initiate migration of extra villous trophoblast to decidua of uterus and invade partially myometrium inducing remodeling of spiral arteries [16]. 2-stage theory has been hypothesized recently to understand this pathology [17,21]. The first stage is abnormal events during embryogenesis of trophoblast which contribute to fetoplacental oxidative distress and abnormal release of antiangiogenetic factors in maternal circulation and subsequent multisystem endothelial dysfunction [17,22]. Abnormal remodeling of spiral arteries and early immunologically mediated events are considered major causes of those events [18]. Moreover, trophoblast fails to adequately invade uterine wall and spiral arteries so subsequently vascular resistance in this area could not be decreased to allow adequate placental transfusion [23]. Also, the failure of obliteration of tunica media of myometrium vessels contributes to inability of placenta to accommodate enough blood supply due to lack of thinning of those vessels [17]. This leads to excessive secretion of sFlt-1 (soluble-fms like tyrosine kinase-1) and soluble endoglin [24]. sFlt-1 binds in the blood to both the vascular endothelial growth factor (VEGF) and the placental growth factor (PLGF). Both sFlt-1 and low VEGF/PLGF play a major role in the development of systematic hypertension [21,24]. Later on, maternal syndrome may occur in terms of vascular endothelial dysfunction, intravascular hypercoagulability, and vasospasm leading to multiple systems dysfunctions [21]. Abnormal vascular changes in placenta are confirmed by histopathological examination of postpartum specimens of placenta which showed vascular infarcts and sclerosis of arterioles [17]. Immunological maternal reaction towards fetal and paternal derived Antigens may also contribute, which is considered a certain type of immunological intolerance [25]. Immunological theory is supported by high serum level of cell-free fetal DNA. This theory has been also postulated to understand pathogenesis of hyperemesis gravidarum [26,27]. Recently genetic factors were found to contribute to preeclampsia; Angiotensinogen gene T235 and Leiden factor deficiency were found to be associated with disease [28]. Also, the higher incidence of preeclampsia was found in trisomy 13 pregnancy than pregnancy with normal karyotyping [29,30]. Interestingly, the gene for sFlt-1 which is known for contributing to preeclampsia is also encoded in chromosome 13q [31].
To read more about this article.....Open access Journal of Gynecology & Womens Health
Please follow the URL to access more information about this article
To know more about our Journals....Iris Publishers
No comments:
Post a Comment