Homocysteine and Cellular Fibronectin are Increased in Preeclampsia,not Transient Hypertension of Pregnancy

Objective. The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction.

Methods. We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls.

Results. Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9±14.1 μg/mL versus 10.9±5.4 and 10.1±6.2 μg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3±2.5 μM versus 5.5±2.2 and 5.4±3.4 μM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine.

Conclusions. The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.     

Utility of a Single Plasma Fibronectin Level for the Prediction of Preeclampsia

Previous studies have indicated that repeated maternal plasma fibronectin (FN) levels may aid in the prediction of preeclampsia. To investigate the development of a preeclampsia screening test, avoiding the requirement for repeated maternal blood samples throughout pregnancy, we examined the efficacy of a single screening plasma FN level for the prediction of preeclampsia. Total plasma FN levels were determined between 24 and 32 weeks' gestation in 115 normotensive patients, and cellular FN was determined in a subgroup of 81 of these patients. Among nulliparas (n = 76) total plasma FN values were significantly (P = 0.007) greater in patients (n = 13) who subsequently developed preeclampsia (median = 370, range 130-1104 μg/ml) than among those who remained nonpreeclamptic (median = 283, range 80-490 μg/ml). Based on maximization of the receiver/operator curve, a cut-off plasma FN value of 300 μg/ml was selected as a positive screen in the nulliparous group, resulting in a sensitivity of 85%, specificity of 60%, positive predictive value of 31% and a negative predictive value of 95%. Eleven of the thirteen nulliparous preeclamptics had positive plasma FN screens prior to onset of disease, with increased plasma FN occurring 8-14 weeks prior to the clinical onset of preeclampsia. There were no significant differences in cellular FN values between the nulliparous preeclamptics (median = 3.40, range 2.80–4-20 μg/ml) and nonpreeclamptics (median = 3.30, range 2.40-5.20 μg/ml; P = 0.41). Due to the low incidence of preeclampsia in the multiparous patients in our study (2.6%), measurements of neither total plasma nor cellular FN were found to be of value as a screening test in this group. These results indicate the potential value of a single maternal plasma FN screen at 24-32 weeks' gestation for predicting preeclampsia in nulliparous women.     

Prioritisation of Tests for the Prediction of Preeclampsia Complications: A Delphi Survey

Background: Preeclampsia is associated with several maternal and fetal complications. Numerous tests—including patient history, physical examination findings, and laboratory investigations—are used to predict such complications in women with preeclampsia. At present, there are no robust systematic reviews or large studies examining the accuracy of tests that could predict complications in women with preeclampsia. Objective: To identify the tests (which include items of history, examination, and investigations) that are clinically relevant in predicting maternal and fetal complications in women with preeclampsia. Methods: A two-generational Delphi method was used to prioritize the clinically relevant tests that are considered helpful in predicting the maternal and fetal complications of preeclampsia. Results: Blood pressure was rated as the best predictor of complications with mean score (± SD) of 4.7 (± 0.47), followed by proteinuria 4.6 (± 0.5) and liver function tests 4.5 (± 0.52). Conclusion: The list of tests that have been identified and prioritized will form the basis for future systematic reviews of the literature in this field.     

Markers for Presymptomatic Prediction of Preeclampsia and Intrauterine Growth Restriction

Preeclampsia and intrauterine growth restriction are both characterized by placental malfunction. The pathological processes of abnormal trophoblast invasion, partial absence of maternal spiral artery modification, increased apoptosis of trophoblast cells, and placental ischemia are all associated with the release of specific molecules. These proteins, as well as cell‐free fetal DNA and RNA might be detected in the maternal peripheral circulation, quantified, and used for early identification and prediction of preeclampsia and intrauterine growth restriction, prior to the appearance of the clinical symptoms. As preeclampsia and intrauterine growth restriction are associated with increased maternal, perinatal, and neonatal morbidity and mortality, early identification of these pregnancy associated complications will permit the design of appropriate preventive measures. In this review a variety of factors reported to be useful as potential markers for early detection of pregnancies at increased risk will be discussed. Molecules associated with the establishment of the placenta and essential in fetal–maternal interactions, like interleukin 2‐receptor, insulinlike growth factor‐1, and insulinlike growth factor binding protein‐1, placenta growth factor, hepatocyte growth factor, inhibin A, activin A, and human chorionic gonadotrophin seem to be the most likely candidates for presymptomatic markers for preeclampsia and/or intrauterine growth restriction. Detection and discrimination of these molecules through the placental RNA in maternal plasma based strategy has become a realistic option.     

Prediction and Prevention of Preeclampsia

Preeclampsia increases maternal and perinatal morbidity and mortality rates. Much research has been done to identify unique screening tests that would predict the risk of developing preeclampsia before the classic symptoms appear. The possible use of a screening test with high predictive accuracy in patients with high-risk or low-risk of preeclampsia remains to be investigated. At present, the search for additional tests continues. There is growing interest in the use of combinations of tests. Effective primary prevention is not possible because the causes are still unknown, but to identify and to modify susceptible risk factors might decrease the frequency of preeclampsia. A community guideline improves the screening and early detection of preeclampsia, and uniforms the referral thresholds and assessment procedures. Secondary prevention with calcium supplementation and aspirin administration during pregnancy are beneficial in low calcium intake women and in the patient at a very high risk of developing severe early onset disease. Lifestyle choices, dietary nutritional measures (antioxidant as vitamin C, vitamin E, lycopene, selenium, zinc, magnesium and the mitochondrial antioxidants nicotine, coenzyme Q₁₀ and melatonin; and other dietary nutritional measures as low dietary salt, omega 3 fatty acids, folic acid, garlic, nutritional advice, protein and energy supplementation, isocaloric balanced protein and protein and energy restriction for obese women) and others drugs; have not shown benefits or there is insufficient evidence to recommend clinical use. Proper antenatal care and timed delivery are of utmost importance in tertiary prevention.     

Prediction of Preeclampsia and Delivery of Small for Gestational Age Babies Based on a Combination of Clinical Risk Factors in High-Risk Women

Objective. To develop clinical risk tools for preeclampsia and small for gestational age (SGA) in high-risk women. Methods. Individual risk scores based on clinical risk factors were calculated using logistic regression and validated in 1687 women with obesity in first pregnancy, chronic hypertension, or previous preeclampsia. Results. The risk of preeclampsia varied from 7% in obese primiparae without hypertension to 30% when previous preeclampsia and chronic hypertension occurred together. A prediction model incorporating these risk factors had a sensitivity of 48 and 89% for preeclampsia delivered <34 weeks' gestation. Conclusion. Multiple clinical risk factors increase the risk of preeclampsia and SGA.     

子(癎)前期患者蛋白尿程度与围生儿结局的研究

目的:探讨子癎前期患者蛋白尿程度对其围生儿结局的影响。方法:对287例住院分娩的子癎前期患者根据蛋白尿程度进行分组,分别回顾性研究其围生儿结局,比较不同程度蛋白尿患者围生儿结局的差异。结果:随患者蛋白尿的加重,分娩孕周提前,新生儿出生体重明显下降;剖宫产分娩和治疗性引产数升高,而自然分娩数减少;低体重儿发生率、围生儿死亡率、医源性早产率、收住NICU率均明显升高,但新生儿窒息发生率差异无显著性。将所有病例根据分娩孕周分为两组,≥32周分娩者其围生儿结局在不同程度蛋白尿患者各组之间差异显著,而32周之前分娩者其围生儿结局在不同程度蛋白尿之间差异无显著性。结论:随蛋白尿加重,围生儿结局恶化,但较早的早产儿中,孕龄过小是造成围生儿不良结局的另一不利因素,因而终止妊娠应适时。     

Angiopoietin-2: A Promising Indicator for the Occurrence of Severe Preeclampsia

Background. The known connection between placental hypoxia and the development of preeclampsia suggests that angiogenic factors in the placenta would be changed and affect the maternal and/or umbilical cord plasma levels in patients with preeclampsia. Objective. The aim of this study was to determine the difference and correlation of placental mRNA expression and maternal/umbilical cord plasma concentrations of vascular endothelial growth factor A (VEGF-A), angiopoietin-1, and angiopoietin-2 between women with severe preeclampsia and normal pregnancies. Methods. Sixteen patients with severe preeclampsia and 29 normotensive pregnant women were studied. The placental mRNA expression was assessed using real-time quantitative RT-PCR analysis. Maternal/umbilical cord plasma levels were measured using an enzyme-linked immunoassay. Nonparametric methods were applied for statistical analysis. Results. Placental mRNA expression of angiopoietin-2 was significantly increased in patients with severe preeclampsia (p < 0.001). The maternal plasma angiopoietin-2 protein level was also significantly increased in women with severe preeclampsia (p < 0.05) and showed a positive correlation with the placental mRNA expression of angiopoietin-2 (r = 0.54, p < 0.005). For VEGF-A and angiopoietin-1, there were no significant differences between the two groups. A maternal plasma angiopoietin-2 concentration of 8.4 ng/mL had a sensitivity of 63% and a specificity of 83% for predicting severe preeclampsia. Conclusion. Placental angiopoietin-2 mRNA expression was increased and correlated with the maternal plasma angiopoietin-2 protein concentration in women with severe preeclampsia. This suggests that the plasma angiopoietin-2 protein level may be a candidate marker for severe preeclampsia.     

Locomotion of Human Neutrophils in Response to Plasma and Serum of Women with Preeclampsia

Objective: To examine whether the previously reported neutrophil activation which occurs in the maternal circulation of women with preeclampsia is due to a factor(s) in plasma/serum which increases neutrophil locomotion.

Methods: The locomotory responses of human neutrophils to plasma/serum of women with preeclampsia were compared with normal, pregnant women matched for maternal age and gestational age at blood sampling. Twelve patients from each group were studied. Preeclampsia was defined as persistent diastolic blood pressure > 90 mm Hg, with proteinuria > 0.3 g/24 h, in patients who were normotensive before 20 weeks gestation. A simple microcomputer-based system for real-time, analysis of neutrophil behavior in vitro was used to measure the dynamic parameters of locomotion. Locomotion of human neutrophils in response to plasma, serum (20%), and heat-inactivated serum from both groups of patients was measured. Serum was heat inactivated to destroy complement-derived chemotactic activity.

Main Outcome Measures: Speed, persistence, and diffusion coefficient to describe the behavior of randomly moving cells.

Results: A significant stimulation of neutrophil locomotion in response to plasma, serum (20%), and heat-inactivated serum occurred in both groups compared with control cells incubated with phosphate-buffered saline; however, no significant differences were found in response to these three stimuli between the two groups of patients.

Conclusions: These studies found no evidence of a humoral factor in the plasma/serum of women with preeclampsia which alters the locomotion of human neutrophils. The existence of such a potential factor may be revealed, however, upon examination of subsequent stages of neutrophil activation, namely adhesion to endothelial cells and/or neutrophil metabolic activation.     

Placental Growth Factor: As an Early Second Trimester Predictive Marker for Preeclampsia in Normal and High-Risk Pregnancies in a Turkish Population

Objective

Placental growth factor (PlGF) is an angiogenetic factor and inducts the development of preeclampsia in a hypoxic environment. In this study, we examined maternal blood PlGF levels in a pregnant population between 16 and 19 weeks of gestation for determining the prospective value for early diagnosis of preeclampsia as a screening test.

Materials and Methods

In this prospective cross-sectional study, 114 nulliparous normotensive pregnant women were selected for the control group and 34 patients who have chronic hypertension or had a medical history of hypertensive disorders in previous pregnancies were selected for the study group.

Results

In the study group, the risk of preeclampsia increased 3.2 times when compared with the control with a confidence interval of 95 %. The cut-off value for PlGF for discriminating preeclamptic and non-preeclamptic patients was found to be 62.5 pg/ml.

Conclusion

Patients with a medical history of hypertensive disorders and low PIGF levels in early second trimester have an increased risk for preeclampsia.     

Severe Preeclampsia is Associated with a Positive Family History of Hypertension and Hypercholesterolemia

Objective. To investigate an association between a family history of cardiovascular disease and severe preeclampsia and/or HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets). Methods. One hundred twenty-eight women with a history of severe preeclampsia and/or HELLP syndrome and 123 women with previous uncomplicated pregnancies only were included in the study. All participants completed questionnaires about diagnoses of cardiovascular diseases, hypertension, and hypercholesterolemia among their first-degree relatives, which were subsequently confirmed by the relatives' general practitioners. The main outcome measures were the prevalence of cardiovascular diseases, hypertension, and hypercholesterolemia among first-degree relatives of both groups. Statistical analysis was done using χ²-analysis. Results. The prevalence of familial cardiovascular disease among women with a history of severe preeclampsia and/or HELLP syndrome (23%) compared to controls (19%) was not significantly different (OR 1.3, 95%CI 0.7–2.5). However, women with a history of severe preeclampsia and/or HELLP syndrome more often had one or more first-degree relatives with hypertension and/or hypercholesterolemia before the age of 60 years compared to controls (54% vs. 32%, respectively; OR 2.6, 95%CI 1.5–4.3). The prevalence of hypertension and hypercholesterolemia among first-degree relatives, irrespective of age, also was significantly higher among women with a history of severe preeclampsia and/or HELLP syndrome as compared to controls (60% vs. 42%, respectively; OR 2.0, 95%CI 1.2–3.4). Conclusion. Severe preeclampsia is associated with a positive family history of hypertension and/or hypercholesterolemia.     

Urinary Inositol Phosphoglycan P-Type as A Marker for Prediction of Preeclampsia and Novel Implications for the Pathophysiology of This Disorder

Objective.Hypertensive disorders represent the most common complications of human pregnancy with substantial impact on fetal and maternal outcomes. Inositol phosphoglycan P-type has recently been identified as a novel marker of preeclampsia, the most severe form of hypertension during pregnancy, with a significant increase in urinary excretion preceding the clinical diagnosis. Methods.A prospective, longitudinal study was carried out to assess the potential of urinary levels of inositol phosphoglycan P-type as a screening test for preeclampsia. A specific ELISA-based test was used to assess urinary levels of P-IPG. Results.Nine patients out of 93 women recruited (496 urinary samples were collected) went on to develop preeclampsia in a cohort of women with high-risk pregnancies. A cut-off value of urinary inositol phosphoglycan P-type was identified by ROC analysis providing a sensitivity and specificity for the current protocol of 88.9% and 62.7%, respectively. Twenty-three women with healthy pregnancies had sporadic episodes of increased excretion of inositol phosphoglycan P-type during pregnancy that consistently resolved back to normal baseline without development of preeclampsia. There was no correlation of urine levels of inositol phosphoglycan P-type and urine protein and patients with gestational hypertension had normal levels of urine inositol phosphoglycan P-type. Conclusions.These findings suggest that, given the rapid raise of P-IPG before the onset of the disease, multiple assessments may help at identifying women at risk of developing preeclampsia.     

High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks’ gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels.     

Ischemia-Modified Albumin (IMA): A Novel Marker for Preeclampsia Independent of Uterine Artery Notching Identified by Doppler Ultrasound

Objective: To determine the predictive value of second trimester serum ischemia-modified albumin (IMA) levels for preeclampsia (PE), small for gestational age (SGA) and gestational diabetes mellitus (GDM). Methods: The study was conducted at a tertiary care hospital between May and August 2014. Healthy pregnant women (n?=?88) who were screened for fetal anomalies with ultrasound at 20–24 weeks of gestation were included in the study. Doppler measurements of the bilateral uterine arteries were performed in all the patients. Serum samples were obtained for an IMA assay. The maternal serum IMA levels were compared in pregnant women who had normal and abnormal uterine artery Doppler findings, including notching, and also in pregnant women who subsequently developed PE, SGA, and GDM during the follow-up period. Results: Uterine artery notching was not significantly predictive for PE, GDM or SGA (p?>?0.05). There was no significant difference between notching of the uterine arteries and serum IMA levels (p?>?0.05). Eight pregnant women (9.1%) subsequently developed PE. Serum IMA levels were significantly elevated in patients with PE compared with patients who did not subsequently develop PE (p?=?0.002). However, serum IMA levels were not significantly different in patients who subsequently developed SGA and GDM compared with women who did not (p?>?0.05). There was no correlation between serum IMA levels and maternal characteristics and laboratory findings. Conclusion: Maternal serum IMA levels at 20–24 weeks’ gestation might be a predictive biomarker for PE, independent of notching of the uterine arteries, maternal characteristics and laboratory findings.     

Complement Factor H Variant Y402H is Not a Risk Factor for Preeclampsia in the Finnish Population

Objective: Variations in complement factor H, which down-regulates the activity of the alternative complement pathway, have been associated with different vascular disorders. Here we examine whether factor H variation is involved in the etiology of preeclampsia. Methods: We studied 110 women with preeclampsia and 99 controls for complement factor H variations by sequencing. Results: No significant differences in the genotype or allele frequencies of the Y402H variant were detected between the two groups. No sequence variations were detected in the short consensus repeat domain 20 of the gene. Conclusions: Neither the Y402H variant, nor mutations in the short consensus repeat domain 20 of the gene is associated with preeclampsia. For examination of possible links to other polymorphisms or detection of small genotypic effects, studies in larger sample sets are warranted.     

Soluble Endoglin for the Prediction of Preeclampsia in a High Risk Cohort

Objectives. To evaluate soluble endoglin (sEng) and the soluble fms-like tyrosine kinase 1 (sFlt1) to placental growth factor (PlGF) ratio for the prediction of preeclampsia in high-risk women, and to evaluate differences in sEng between women with high-risk singleton and multiple gestation pregnancies. Study Design. We collected serial serum specimens from 119 women at high preeclampsia risk. sEng, sFlt1 and PlGF were measured by ELISA. Results. Among subjects who did not develop preeclampsia, mean serum sEng was significantly higher in those with multiple gestation pregnancies vs. high-risk singletons. Among women with singleton gestations, mean serum sEng was higher in subjects who developed early-onset (<34 weeks) and late-onset (≥ 34 weeks) preeclampsia, as compared with subjects without preeclampsia, from 22 weeks and 28 weeks gestation onward, respectively. The within-woman rate of change of sEng was also higher in women who later developed preeclampsia. Conclusions. sEng is higher in women with multiple gestations vs. high-risk singleton pregnancies. In high-risk women, serum sEng is increased prior to preeclampsia onset.     

High Uric Acid Level During the First 20 Weeks of Pregnancy is Associated with Higher Risk for Gestational Diabetes Mellitus and Mild Preeclampsia

Objective. To examine the association between uric acid (UA) level during the first 20 weeks of pregnancy and the development of gestational diabetes mellitus (GDM) and preeclampsia in the second half of pregnancy. Methods. The study population included registered births (n = 5507) between 2001 and 2007 in a tertiary medical center. The UA levels during the first 20 weeks of pregnancy were sorted by UA ≤ 2.4 mEq/L; UA = 2.5–4.0 mEq/L, UA = 4.1–5.5 mEq/L, and UA > 5.5 mEq/L. The linear-by-linear chi-square test and ROC curves were used to determine the association between UA level during the first 20 weeks and pregnancy complications. Multivariate analyses were performed to demonstrate whether UA level is an independent factor for the prevalence of preeclampsia and GDM. Results. Significant linear association was documented between UA level in the first 20 weeks and the prevalence of GDM and mild preeclampsia. The lowest and the highest prevalence of GDM were found in the UA ≤ 2.4 mEq/L group (6.3%) and in the UA > 5.5 mEq/L group (10.5%) (p < 0.001), respectively. Mild preeclampsia was diagnosed in 2.1% of the patients from the UA ≤ 2.4 mEq/L group, 3.3% from the UA = 2.5–4.0 mEq/L group, 5.3% from the UA = 4.1–5.5 mEq/L group, and 4.5% from the UA > 5.5 mEq/L group (p < 0.001). Three multiple logistic regression models controlling for maternal age showed that UA level is an independent risk factor for both GDM and mild preeclampsia. Conclusions. UA levels in the highest quartile of the normal range during the first 20 weeks of pregnancy are associated with higher risk for the development of GDM and mild preeclampsia.     

The Value of a Single Fetal Fibronectin Assay as a Screen for Preterm Labor and Delivery

It has been shown that serial fetal fibronectin sampling has close to a 70% sensitivity in detecting preterm labor or delivery in an asymptomatic population. The objective of this study was to access the usefulness of a single vaginal fetal-fibronectin assay in the mid-second trimester from asympto matic women in predicting preterm labor and delivery. Vaginal samples were obtained from 54 consenting women who received routine prenatal care in our inner-city general obstetrical clinc. A sensitive immunoassay was used for vaginal fetal fibronectin quantitative analysis. Both patients and clinicians were blinded to fetal fibronectin results. Correlation of fetal fibronectin status with outcome was determined. The spontaneous preterm delivery rate was 19% (10/54). The presence of vaginal fetal fibronectin (< 50 ng/ml) had a sensitivity in predicting preterm labor or delivery of 19% with positive and negative predictive values of 38% and 71%, respectively. The specificity was 86% in this study. For women with preterm labor or delivery prior to 34 weeks, fetal fibronectin had a sensitivity of 75%, a specificity of 90% and a negative predictive value of 98%. These results agree with other investigators who have demonstrated that positive fetal fibronectin correlates with preterm labor or delivery within a 3-4 week period of sampling. Although clinicians may find monthly fetal fibronectin sampling impractical, sampling twice in the second trimester (22-24 weeks and 26-28 weeks) may help in identifying those women destined to deliver preterm in the gestational period with the highest neonatal risk and cost (24-32 weeks).     

Preeclampsia: Diagnosis and management of the atypical presentation

Preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome remain as major obstetric problems that plague a large percentage of women resulting in an equally large percentage of maternal and perinatal morbidities. It is important that a clinician makes the most accurate diagnosis possible to prevent these adverse maternal and perinatal outcomes. In general, most women will have a classical presentation of preeclampsia (hypertension and proteinuria) at >20 weeks gestation and <48 hours postpartum. However, recent studies have suggested that some women will develop preeclampsia without the classical findings. The purpose of this review is to increase awareness of the non-classical and atypical features of preeclampsia, eclampsia, and HELLP syndrome and their respective management. Atypical cases are those that develop before 20 weeks, beyond 48 hours postpartum and those that present with some of the signs and symptoms of preeclampsia without the usual hypertension or proteinuria. By formulating a rational stepwise approach towards diagnosis, we may prevent the costly consequence of a missed diagnosis and its eventual possible fatalities.