A pilot study of the association of <i>FLT1</i> gene polymorphism with the risk of developing preeclampsia

Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies

In this issue of Hypertension , Rasmussen and Irgens provide strong support for the relationship of preeclampsia and intrauterine growth restriction (IUGR). They also provide data that support but also some that argue against the concept that the pregnancy complication, preeclampsia, may be more than one disease.1 In previous studies these authors demonstrated that women who have had a growth-restricted infant without preeclampsia are more likely to have preeclampsia in a subsequent pregnancy.2 Those data and similar findings in the current study support pathological findings indicating the similarity of IUGR and preeclampsia.3 In preeclampsia, IUGR and interestingly also in about one third of cases of preterm birth,4 the maternal myometrial and decidual vessels perfusing the placental site do not undergo the normal remodeling of pregnancy. In normal pregnancy trophoblastic invasion is associated with a greatly increased diameter and removal of vascular smooth muscle from the wall of these vessels. This results in large diameter, flaccid, unresponsive tubes that greatly increase placental perfusion. These changes are not present in pregnancies complicated by IUGR, preeclampsia, and some with preterm births. Implicit in the current study is the concept that preterm birth as well as IUGR is related to subsequent preeclampsia. Although preterm birth is not assessed directly, the effect of low birth weight (IUGR and preterm birth) was greater than the effect of IUGR alone. In a far smaller study our group was able to more directly support the relationship of preterm birth and preeclampsia, as women with early onset preeclampsia were more likely to have preterm birth in a subsequent nonpreeclamptic pregnancy.5 The current study extends the prior observation of the relationship of IUGR and preeclampsia but also raises other interesting points. In this larger study the authors were …

Preeclampsia (PE) is associated with persistent cardiac abnormalities and a high cardiovascular risk during the woman life. Early onset PE presenting before the 34 th gestational week is a more severe form of disease, but its relevance on cardiac abnormalities is unknown. The aim of this study was to assess cardiac structure and function in women with PE without preexistent hypertension. One month after delivery, the clinical and echocardiographic variables of 65 preeclamptic women (age 36±6 y), 37% of which with early PE, was compared with a group of 30 normotensive (age 37±6 y), 16 hypertensive (age 40±5 y) nonpregnant women, and 6 women with normal pregnancy (age 36±5 y) who were matched for age and height. Despite comparable antihypertensive treatment, women with early PE had lower 24-hour average systolic and diastolic blood pressure than those with late PE (125±11 Vs 136±15). Left ventricle (LV) relative wall thickness was significantly greater in women with early PE (0.36±0.06) than in those with late PE (0.31±0.07; p<0.05) and normotensive (0.30±0.06; p<0.05) women, but not hypertensive women (figure). Women with early and late PE had comparably greater LV mass and worse diastolic function as assessed by the E/A ratio (PE 1.6±0.4 Vs 1.8±0.4 P<0.01) and isovolumic relaxation time (PE 96±28 Vs 73±12 msec, P<0.001) than normotensive women. In conclusion, women with early onset PE have more pronounced LV concentric remodeling than women with late onset PE. This observation could account for the greater cardiovascular risk of these patients and might prompt the use of antihypertensive drugs specifically acting on LV remodeling.

Excessive inflammation is involved in preeclampsia (PE) pathogenesis. Lipoxin A4 (LXA4) is an eicosanoid that counter-regulates inflammation. The main objective of this study was to determine LXA4 plasma levels in PE women. The correlations among LXA4 levels, ultrasensitive C-reactive protein (us-CRP) levels, and clinical/laboratory parameters of the studied participants were also investigated. LXA4 plasma levels were determined by ELISA in 23 nonpregnant, 26 normotensive pregnant, and 27 PE women (early PE (N = 10) and late PE (N = 17)), according to gestational age (GA) at clinical symptoms onset). The clinical/laboratory parameters included in Spearman's correlation analysis were: systolic and diastolic blood pressure (SBP and DBP, respectively), lactate dehydrogenase (LDH) activity, platelet count, proteinuria, and white blood cell count (WBC). LXA4 levels were higher in PE women than in nonpregnant and normotensive pregnant women, and similar between nonpregnant and normotensive pregnant women. LXA4 plasma levels were higher in early PE vs. normotensive pregnancy (GA < 34 weeks) and in late PE vs. normotensive pregnancy (GA ≥ 34 weeks). No significant differences were detected between early and late PE. LXA4 levels were positively correlated with us-CRP levels, SBP, DBP, and WBC. No significant correlation was detected between LXA4 levels and the other laboratory parameters. Chronic inflammation in PE, in spite of increased levels of LXA4, points to a possible failure in this regulatory pathway. Further studies are necessary to clarify this issue and to evaluate the role of LXA4 and other proresolving mediators of inflammation in the pathogenesis of PE.

Objective: Preeclampsia (PE) is a maternal complication characterized by hypertension and proteinuria that usually occurs after the 20th gestational week and resolves after delivery. PE is associated with persistent cardiac abnormalities and a high cardiovascular risk during the woman life. Early onset PE presenting before the 34th gestational week is a more severe form of disease, but its relevance on cardiac abnormalities in comparison to the forms with later onset is not clear. The aim of this study was to assess cardiac structure and function in women with PE without preexistent hypertension. Design and method: One month after delivery, the clinical and echocardiographic variables of 54 preeclamptic women (age 36 ± 6 y), 39% of which with early PE, was compared with a group of 54 normotensive (age 37 ± 6 y) and 15 hypertensive (age 41 ± 5 y) nonpregnant women who were matched for age and height. Results: Despite comparable antihypertensive treatment, women with early PE had lower 24-hour average systolic and diastolic blood pressure than those with late PE. Left ventricle (LV) relative wall thickness was significantly greater in women with early PE (0.39 ± 0.10) than in those with late PE (0.31 ± 0.07; p < 0.001) and normotensive (0.29 ± 0.05; p < 0.001) women, but not hypertensive women (figure). Women with early and late PE had comparably greater LV mass and worse diastolic function as assessed by the E/A ratio, isovolumic relaxation time, and tissue Doppler imaging, than normotensive woman. No differences in LV systolic function were observed between preeclamptic and normotensive woman. Conclusions: Women with early onset PE have more pronounced LV concentric remodeling than women with late onset PE. This observation could account for the greater cardiovascular risk of these patients and might prompt the use of antihypertensive drugs specifically acting on LV remodeling.

OP003. Placental perfusion in normal pregnancy and in early and late preeclampsia: A magnetic resonance imaging study

Annotation. Preeclampsia is one of the leading causes of maternal and perinatal death, and it complicates from 5 to 8% of all pregnancies. The aim of the research was to show the differences in anamnesis, diagnostics and prognosis, in groups of pregnant with hypertensive disorders. Retrospective investigation included 138 delivery histories and perinatal record cards from Vinnitsya Municipal Clinical Maternity hospital №1, in a period from 2016 till 2018. Women were divided into two investigated groups: I – 36 women with early preeclampsia, and II group – 52 women with late preeclampsia, and a control group of 50 women. The structure of somatic and gynecological diseases of pregnant women was studied, the severity of preeclampsia and the condition of the newborn were assessed according to the Apgar scale. Statistical processing of the obtained results was performed by odds ratio, its standard error and 95% confidence interval were calculated according to D. G. Altman (1991). It is established that in women with obesity or excessive body weight (every second women in groups), and those who had cardiovascular disorders (twice more often with late preeclampsia) developed preeclampsia more often, comparing to control group. All cases of antenatal and early neonatal death of newborn were registered in a group with early preeclampsia, which points out on heavier flow of the disease and different pathogenesis. Cases of early pregnancy toxemia and edema of pregnant occurred twice more often, in group with early preeclampsia, and ran more heavy (up to the development of ascites), comparing to the second group. Debut of symptoms was earlier, that requires earlier prophylaxis (since week 12). Fetal intrauterine growth retardation, reversible and high resistant blood stream during ultrasound were marked only in group with EP. In future, this research together with pathohistological investigation of placentas and immunohistochemical research of those tissues, can underlie predictive and preventive personalized system for early and late preeclampsia.

Because early and late preeclampsia (PE) are thought to be different disease entities, we compared maternal cardiac function at 24 weeks gestation in a group of normotensive asymptomatic patients with subsequent development of early (<34 weeks gestation) and late (>or=34 weeks gestation) PE (blood pressure >140/90+proteinuria >300 mg/dL) to detect possible early differences in the hemodynamic state. A group of 1345 nulliparous normotensive asymptomatic women underwent at 24 weeks gestation uterine artery Doppler evaluation and maternal echocardiography calculating total vascular resistance. In the subsequent follow-up 107 patients showed PE: 32 patients had late and 75 had early PE. Five of 32 patients with late PE and 45 of 75 patients with early PE had bilateral notching of the uterine artery at 24 weeks (15.6% versus 60.0%; P<0.05). Total vascular resistance was 1605+/-248 versus 739+/-244 dyn . s . cm(-5), and cardiac output was 4.49+/-1.09 versus 8.96+/-1.83 L in early versus late PE (P<0.001). Prepregnancy body mass index was higher in late versus early PE (28+/-6 versus 24+/-2 kg/m(2); P<0.001). Early and late PE appear to develop from different hemodynamic states. Late PE appears to be more frequent in patients with high body mass index and low total vascular resistance; earlier forms of PE appear to be more frequent in patients with lower BMI and with bilateral notching of the uterine artery. These findings support the hypothesis of different hemodynamics and origins for early PE (placental mediated, linked to defective trophoblast invasion with high percentage of altered uterine artery Doppler) and late PE (linked to constitutional factors such as high body mass index).

Objective: The aim of the present study is to investigate whether alterations in the serum levels of apelin and YKL-40 differ between early and late onset pre-eclampsia and whether there is a correlation between apelin and YKL-40 in women who subsequently develop early and late pre-eclampsia. Materials and methods: A total number of 80 pregnant women, 40 with normal pregnancy and 40 with pre-eclampsia, were included in the present study. Both the normal pregnant and pre-eclamptic subjects were subdivided into two groups. Serum YKL-40 and apelin concentrations were measured. Results: Mean maternal serum YKL-40 levels were both lower in women who subsequently developed early (87.45 ± 3.07 versus 103.40 ± 4.29) or late (96.43 ± 4.06 versus 99.87 ± 3.63) pre-eclampsia than those who remained normotensive. The difference was significant in early-onset preeclamptic women (p < 0.05) rather than late-onset pre-eclamptic ones (p > 0.05). Mean maternal serum apelin levels were both higher in women who subsequently developed early (8.6 ± 3.6 versus 5.7 ± 1.2) or late (9.6 ± 2.5 versus 8.1 ± 1.8) pre-eclampsia than those who remained normotensive. The difference was significant in early-onset preeclamptic women (p < 0.05) rather than late-onset pre-eclamptic ones (p > 0.05). There was a significant negative correlation between serum apelin and YKL-40 levels (r = −0.48, p = 0.001). Conclusion: Circulating levels of apelin are significantly increased in early-onset pre-eclampsia, indicating the role of apelin in the discrimination of the early-onset of pre-eclampsia. On the other hand, maternal serum YKL-40 levels are not elavated significantly, indicating that adipose-derived apelin is primarily involved in the vascular pathogenesis of early-onset pre-eclampsia than macrophage-derived YKL-40.

BackgroundPreeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties that has been much studied in various animal models of inflammation but poorly studied in the context of human inflammatory diseases. The main objective of this study was to measure AnxA1 levels in PE women and to compare those levels in normotensive pregnant and non-pregnant women. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants.MethodsThis study included 40 non-pregnant, 38 normotensive pregnant and 51 PE women. PE women were stratified in early (N = 23) and late (N = 28) subgroups, according to gestational age (GA) at onset of clinical symptoms. Protein AnxA1 and us-CRP plasma levels were determined by ELISA and immunoturbidimetric assays, respectively. Transcript levels of AnxA1 in peripheral blood mononuclear cells (PBMC) were measured by real time RT-PCR.ResultsIncreased levels of AnxA1 coincided with higher us-CRP levels in the plasma of PE women. Pregnant women with early PE had higher levels of AnxA1 and us-CRP than normotensive pregnant women with GA <34 weeks. No significant difference was found for AnxA1 and us-CRP, comparing late PE and normotensive pregnant women with GA ≥34 weeks. AnxA1 mRNA levels in PBMC were similar among the studied groups. AnxA1 was positively correlated with sTNF-R1, but not with us-CRP.ConclusionsOur data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis. However, more studies are needed to clarify the role of AnxA1 and other proresolving molecules in the context of the systemic inflammatory response in this intriguing disease.

Preeclampsia (PE) is one of the most common complications of pregnancy, and it can be after 20 weeks of gestation. It ends only with a complete dissection of afterbirth. Traditionally, PE is subdivided into the early one, taking place through 34 weeks of pregnancy (EOPE) and the late one, which is after 34 weeks of gestation (LOPE). Clinical manifestations are similar in both cases however, risk factors and the severity of PE are different . It has been established that EOPE is determined by impaired trophoblast invasion and transformation of the spiral arteries of the uterus in early pregnancy, and late onset of PE is associated with oxidative stress of syncytiotrophoblast, which occurs secondarily, with limited gas exchange and insufficient intake of nutrients. Numerous studies have noted a significant contribution of immune responses to the pathogenesis of preeclampsia, however, the state of B-lymphocytes in EOPE and LOPE has not been studied. A comprehensive assessment of the condition of women with early (up to 34 weeks of pregnancy inclusive) and late (after 34 weeks) development of preeclampsia was carried out, taking into account clinical and anamnestic characteristics, the peculiarities of the formation of the structural components of the placenta, as well as determining the nature of differentiation and functional activity of B-lymphocytes. In peripheral venous blood, the content of CD19+, CD20+, CD19+CD27+IgD±, CD19+CD20- CD38+, CD20+CD5+-cells and serum levels of IL-5, IL-9, IL-13 were examined. Morphological examination included gross description, organometry, survey histology, and transmission electron microscopy. In the group of women with early preeclampsia in history, there were more often perinatal losses, premature births and medical abortions, and in the current pregnancy, intrauterine infection, oligohydramnios, placental insufficiency and fetal growth retardation. With late preeclampsia, metabolic syndrome, anemia, and a history of arterial hypertension were more often observed. In the peripheral blood of all women with preeclampsia, there was an increase in the content of CD20+CD5+-cells in comparison with those in uncomplicated pregnancy, more pronounced in the late onset of preeclampsia. Only in women with early preeclampsia blood levels of CD19+CD20- CD38+ and CD19+CD27+IgD±-cells, IL-5, IL-9 and IL-13 increased. Studies of the placenta in early preeclampsia indicated impaired implantation and pathological placentation with the development of primary placental insufficiency, which becomes chronic. In late preeclampsia, the development of placental insufficiency was determined by chronic disorders of maternal and fetal hemocirculation with increased deposition of fibrin and fibrinoid in the basal lamina and in the zones of villous epithelium necrosis. The study showed that the timing of the manifestation of preeclampsia is determined by the action of factors of the clinical history, structural rearrangements in the placenta and immune responses of B-lymphocytes are closely interrelated.

PP051. Prediction of preeclampsia with the sFlt-1/PLGF ratio: impact of the slope of repeated measurements

O124. Preeclampsia: Two different clinical phenotypes – Two different pregnancy outcomes

An analysis of the differences between early and late preeclampsia with severe hypertension.

Introduction. In preeclampsia (PE), the hemostasis system, including the platelet component, changes significantly. The purpose of the work was to identify the peculiarities of the morpho-functional characteristics of platelets in women with early and late PE. Material and methods. The main group consisted of 26 women with early PE and 46 women with late PE. The control group consisted of women with normal pregnancies without hypertensive disorders, of whom 17 were at a gestational age of 260–336 weeks and 42 were at a gestational age of 340–394 weeks. The ADVIA 2120i hematology analyzer was used to evaluate platelet concentration (PLT), platelet distribution width (PDW), mean platelet volume (MPV), concentration of large platelets (Large PLT), percentage of large platelets from the total number of platelets (%LP), mean platelet component concentration (MPC), mean dry platelet mass (MPM). Results. Women with early PE have increased PDW, MPV, LargePlt, %LP and MPM indices compared to women with normal pregnancies up to 34 weeks. Female patients with late PE had lower PLT and higher PDW, %LP, MPC, MPM compared to women with normal pregnancies after 34 weeks. In late PE, PLT is reduced and PDW, %LP and MPM are increased compared to early PE. Conclusion. The detected changes in platelet indices in women with PE, regardless of the period of its onset, indirectly indicate increased thrombopoiesis and high functional activity of young platelets. However, the mechanisms that increase platelet activation in early and late preeclampsia differ.