Interleukin-18 concentrations in pregnancies complicated by preeclampsia with and without IUGR: A comparison with normotensive pregnant women with isolated IUGR and healthy pregnant women

ObjectiveThe aim of present study was to assess the maternal serum levels and clinical significance of interleukin-18 (IL-18) in pregnancies complicated by preeclampsia and/or intrauterine growth restriction (IUGR).Patients and methodsThe study was carried out on 30 patients with pregnancy complicated by severe preeclampsia (15 patients with IUGR and 15 with appropriate-for-gestational-age weight fetuses), 11 normotensive pregnant patients with pregnancy complicated by isolated IUGR and 32 healthy normotensive women with uncomplicated pregnancies. The interleukin-18 levels were determined using an ELISA assay.ResultsDecreased levels of maternal serum IL-18 in preeclamptic patients with and without IUGR were observed. Contrary to the preeclamptic women, no difference was found in the maternal serum levels of IL-18 in normotensive patients with pregnancies complicated by isolated fetal growth restriction. These levels were the same as observed in the healthy controls. The mean values of maternal serum IL-18 were 219.118 ± 180.079 pg/mL in the PRE group, 438.170 ± 229.657 pg/mL in the group of women with isolated IUGR, and 457.053 ± 528.142 pg/mL in the control group. The levels of maternal serum IL-18 were similar in both study preeclamptic subgroups. The mean values of IL-18 were 204.823 ± 188.171 pg/mL in the group PI and 233.414 ± 176.995 pg/mL in the P group.ConclusionsOur findings suggest that decreased levels of IL-18 in maternal serum play a significant role in etiology and pathogenesis of preeclampsia. But normotensive pregnancies complicated by isolated IUGR are not associated with the altered interleukin 18 levels in maternal serum.     

Maternal soluble human leukocyte antigen-G levels in pregnancies complicated by foetal intrauterine growth restriction with and without preeclampsia

ObjectiveThe aim of this study was to investigate the maternal serum of soluble human leukocyte antigen-G (sHLA-G) levels in pregnant women with an isolated intrauterine growth restricted foetus (IUGR) and in preeclamptic pregnancies with and without IUGR.Patients and methodsThe study was conducted on 31 normotensive patients with pregnancy complicated by IUGR, 17 preeclamptic patients with appropriate-for-gestational-age foetal intrauterine growth, 21 with preeclampsia complicated by IUGR, and 32 healthy pregnant controls. Maternal serum sHLA-G levels were calculated using the enzyme-linked immunosorbent assay.ResultsMaternal serum sHLA-G levels tended to be higher in both groups of preeclamptic patients, and were highest in patients with IUGR in the course of severe preeclampsia. Lower serum levels of sHLA-G were observed in the group of normotensive pregnant women with an intrauterine growth restricted foetus, but these differences were not statistically significant. The mean values were 22.759 ± 14.151 units/mL in the IUGR group, 25.948 ± 18.888 units/mL in preeclamptic patients with normal intrauterine foetal growth, 31.646 ± 27.576 units/mL in preeclamptic pregnant women with IUGR, and 24.178 ± 24.828 units/mL in the healthy controls.ConclusionsOur findings suggest that the increased levels of sHLA-G in the maternal serum may play a significant role in the pathogenesis of preeclampsia, especially in preeclampsia complicated by intrauterine foetal growth restriction. These associations may offer a better insight into the etiology and pathogenesis of preeclampsia with and without IUGR. It seems that sHLA-G does not play a clinically significant role in the pathogenesis of isolated intrauterine foetal growth restriction in normotensive pregnancies.     

Lipid concentration in small for gestational age (SGA)pregnancies and hypertensive disorders

ObjectiveLow maternal serum lipid and high maternal serum lipid have both been associated with some complications in pregnancy. The lipid profiles in pregnancies complicated by small for gestational age (SGA) or hypertension disorders have been compared with those of normal pregnancies.MethodIn a prospective study, 900 pregnant women between 13 and 23 weeks of pregnancy were studied. Primarily, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, were measured. Ultimately, the serum lipid levels at 13–23 weeks of pregnancies were compared between the women who later suffered from hypertension disorders or SGA and the matched women with normal pregnancies.ResultsAt 13–23 weeks of pregnancy, the mean triglyceride levels were significantly higher in the women who later experienced preeclampsia when compared with normal, matched pregnancies with an appropriate weight for gestational age and women who had gestational hypertension (p = 0.001 and p = 0.014, respectively). Also, triglyceride levels were significantly higher in women with neonates with large for gestational age (LGA) in comparison with those who gave birth to neonates with SGA (p = 0.012) and with uncomplicated matched pregnant women who gave birth to neonates with weight >10th and <90th percentile for their gestational age (p = 0.007).ConclusionOnly the levels of TG and not any other lipids evaluated were found to be different in pregnancies complicated by preeclampsia when compared to pregnancies complicated by SGA.     

Plasma antithrombin levels correlate with albumin and total protein in gestational hypertension and preeclampsia

ObjectiveTo analyze the antithrombin-III (AT-III) activity in the plasma in relation to the serum albumin and total protein in preeclampsia and gestational hypertension.Study designThe medical records of 139 patients who were diagnosed with gestational hypertension (n = 33) and preeclampsia (n = 106) were reviewed, and the relationships between the activity of AT-III and serum albumin or total protein were evaluated.Main outcome measuresThe plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels.ResultsThere were significant correlations between AT-III activity and albumin in gestational hypertension (r = 0.504, p = 0.003) and preeclampsia (r = 0.343, p = 0.003). There were also significant correlations between AT-III activity and TP in gestational hypertension (r = 0.619, p = 0.001) and preeclampsia (r = 0.366, p = 0.001). Regression coefficients between AT-III and albumin and between AT-III and TP in gestational hypertension (23.7 and 14.0, respectively) were significantly steeper than those in preeclampsia (14.6 and 9.6, respectively).ConclusionsThe plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. This suggests that AT-III activity is more likely to decrease in gestational hypertension than in preeclampsia.     

Different levels of IL-1α, IL-6, TNF-α, NF-κB and PPAR-γ in monocyte cultures exposed by plasma preeclampsia and normotensive pregnancy

ObjectiveTo determine different levels of proinflammatory cytokines IL-1α, IL-6, TNF-α, nuclear NF-κB p50 and PPAR-γ in monocyte cultures exposed to normotensive pregnancy plasma compared with those exposed to preeclamptic plasma.Study designThe study involved primigravidae with preeclampsia (12) and normotensive pregnancy (12) in which their blood plasma was given to monocyte cultures from isolated PBMC of healthy and non-pregnant women. They were divided into 2 groups, the first group was incubated for 24 h and the second one was incubated for 48 h (step 1). The levels of IL-1α, IL-6, TNF-α, and nuclear NF-κB p50 as well as PPAR-γ of both groups were subsequently measured and compared (step 2). Data were analyzed to determine the differences and interaction between both treatment groups using one-way ANOVA.ResultsThere was a significantly different level (p-value <0.05) of IL-1α in monocyte cultures incubated for 24 h compared with those incubated for 48 h, as shown in step 1 of the study. Meanwhile, step 2 of the study found significantly different levels of IL-1α, IL-6, TNF-α, and NF-κB p50 in monocyte cultures exposed to preeclamptic plasma compared with those exposed to normotensive pregnancy, in which the latter showed higher levels. Both groups also showed decreased levels of PPARγ, in which monocyte culture exposed to severe preeclamptic plasma (p value <0.05).ConclusionPreeclamptic plasma significantly increased levels of proinflammatory cytokines IL-1a, IL-6, and TNF-a in monocyte cultures. This condition was consistent with the increasing of NF-κB p50 and decreasing of PPARγ.     

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study

ObjectiveTo determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction.MethodsThis is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5 months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45 years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration.ResultsSixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p < 0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR = 6.18, 95% CI 1.59, 24.02; p = 0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction.ConclusionsOur study supports previous findings that preeclampsia is associated with diastolic dysfunction.     

Placental Release of Distinct DNA-associated Micro-particles into Maternal Circulation: Reflective of Gestation Time and Preeclampsia

BackgroundThe aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia.MethodsDNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis.ResultsDNA-associated HLA-G⁺ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in the first and second trimesters. DNA-associated PLAP⁺ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in the second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G⁺ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G⁺ MPs from the plasma of normal pregnant women (p < 0.03).ConclusionsHLA-G⁺ and PLAP⁺ MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G⁺ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts.     

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia

ObjectiveTo explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease.Study designEDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n = 71, preeclampsia n = 105, type 2 diabetes n = 17, gestational diabetes n = 61, diabetes with preeclampsia n = 8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients.ResultsIn contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only.ConclusionWomen with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.     

Intérêt du dosage des d-dimères comme marqueurs de sévérité en cas de prééclampsie

ObjectivesAlterations in blood coagulation and fibrinolysis play a major role in the pathogenesis of preeclampsia. HELLP syndrome is associated with hypercoagulability and leads to maternal and perinatal complications. Our purpose was to evaluate d-dimer as a marker for severity in pregnancies with preeclampsia.Patients and methodsPlasma d-dimer levels were measured using an enzyme-linked immunosorbent assay (ELISA) technique. We studied the association between d-dimer levels and clinical and biological characteristics of pregnancies complicated by preeclampsia.Resultsd-dimer values increased with increasing gestational age. Patients with HELLP syndrome had mean d-dimer values significantly greater than patients with preeclampsia alone (3848 ± 2551 versus 1578 ± 1077, P < 0.001). However, the level of d-dimer at the time of admission was poorly predictive of occurrence of HELLP syndrome. Area under of the ROC curve was 0.69 (CI 95%: 0,59–0,79). The best threshold was 2170 ng/mL with a sensitivity of 0.91 and a specificity of 0.40. Other severity criteria of preeclampsia were not associated with higher levels of d-dimer.Discussion and conclusionIn preeclamptic patients, d-dimer levels were related with gestational age and HELLP syndrome. However, accuracy of this test to predict occurrence of HELLP syndrome or severe preeclampsia was too low to recommend its use routinely.     

Transfer function analysis of dynamic cerebral autoregulation in preeclampsia

ObjectiveThe cerebral circulatory effects of preeclampsia on the latency (phase) and the efficiency (gain) of the cerebral autoregulatory response is unknown. Preeclampsia causes a progressive impairment of the cerebral autoregulatory response. We sought to identify these dynamic cerebral autoregulation changes in preeclampsia.Study designWe simultaneously measured continuously beat to beat outputs of mean arterial pressure (MAP) (Pilot 9200) and beat to beat, systolic, diastolic, and mean cerebral blood flow (MCBFV) (Nicolet Vascular TCD) for 2 min with the patient during supine rest. Five preeclamptic and 5 matched normotensive controls were studied. R–R intervals, MAP, and MCBFV were analyzed in the frequency domain. Data sets were fast Fourier transformed and power spectral densities were calculated. We calculated the phase angle (which represents the temporal relationship between the MAP and mean MCBFV) and the transfer function (amplitude or gain between changes in the MCBFV signal and the MAP signal). All continuous data was compared between the two groups using T tests.ResultsWe identified a significant difference between (1) the gain between the normotensive and preeclamptic groups (.29 ± .07 vs .10 ± .04) (p < .01, and (2) the phase angle (59 ± 12 vs 129 ± 31), p < .01. The preeclamptic group showed significant decrease in gain but an increase in phase angle).ConclusionPreeclampsia paradoxically results in a significant improvement in dynamic cerebral autoregulation as demonstrated by an increase in phase and a decrease in gain. Clinical studies that can systematically assess the progression of these dynamic autoregulation changes are needed.     

Transient gestational hypertension: Not always a benign event

ObjectivePregnancy outcome in women with transient gestational hypertension (TGH);defined as de novo blood pressure elevation after 20 weeks gestation that normalizes by subsequent evaluation in a Day Assessment Unit.Study designRetrospective cohort analysis of hypertensive pregnancies between 2003 and 2008.Main outcome measuresFinal hypertensive delivery diagnosis and composites of adverse maternal and fetal outcome.ResultsOverall 1417 women were referred; 890 met criteria; 41% (65% of study population) had TGH. Twenty percent with TGH developed gestational hypertension and 19% preeclampsia. Women with TGH who developed preeclampsia had similar composite adverse maternal outcomes to other preeclamptic women (51% vs. 63%; p = 0.24) but fewer adverse fetal outcomes (50% vs. 71%; p < 0.01) due to less prematurity (30% vs. 45%; p = 0.02) and small for gestational age babies (33% vs. 51%; p = 0.02). Within the TGH population;developing gestational hypertension or preeclampsia was associated with referral at gestation <33 weeks (RRR 2.8; p < 0.01);initial average systolic blood pressure 130–139 mmHg (RRR 2.1; p < 0.01) and initial average diastolic blood pressure 80–89 mmHg (RRR 3.2; p < 0.01).ConclusionTGH after 20 weeks is common in pregnancy. Although initial assessment implies low risk;the risk of progression to gestational hypertension or preeclampsia is substantial and warrants appropriate clinical surveillance.     

Use of first or second trimester serum markers,or both,to predict preeclampsia

ObjectivesPreeclampsia is a serious complication of pregnancy, threatening fetal and maternal health. The aim of our study is to examine the association between preeclampsia and biochemical markers, in matched first and second trimester maternal serum samples.Study designThis is a nested case/control study derived from the cohort of pregnancies delivering at Women & Infants Hospital. Cases were identified at a clinic or by hospital codes, and individually confirmed by record review. Stored samples were available from ‘integrated’ Down syndrome screening. Results were expressed as multiples of the median (MoM).Main outcome measuresPreeclampsia was classified as early/severe, late/severe, or mild based on professional guidelines. An additional adverse outcome group had only gestational hypertension.ResultsNinety-eight cases were each matched with five control pregnancies. Population distribution parameters and within and between trimester correlations were derived for cases and controls for six markers, as well as in case subgroups. The strongest associations were for early/severe preeclampsia with second trimester PAPP-A (rank sum test 2.30, p < 0.01); PlGF (2.60, p < 0.05) inhibin A (4.45, p < 0.05) and endoglin (4.25, p < 0.05). No strong associations were found for sVEGF-R and FLRG. Second trimester associations were stronger than those in the first (e.g., PAPP-A 2.45, p < 0.01). No between-trimester associations were found that would provide important improvements in prediction.ConclusionsThis matched analysis of the serum markers in early pregnancy allows for direct comparison of first and second trimester associations with preeclampsia. PAPP-A and PlGF are equally and highly predictive of early/severe preeclampsia.     

Maternal hypertensive diseases negatively affect offspring motor development

ObjectiveHypertension in pregnancy and preeclampsia have been linked to poor outcomes in cognitive, mental and psychomotor development; however, few longitudinal studies have researched their effect on offspring motor development, particularly in late childhood and adolescence. The purpose of this study was to determine if maternal hypertensive diseases during pregnancy are a risk factor for compromised motor development at 10, 14, and 17 years.Study designLongitudinal cohort study using data from the Western Australian Pregnancy Cohort Study (Raine).Main outcome measureOffspring (n = 2868) were classified by their maternal blood pressure profiles during pregnancy: normotension (n = 2133), hypertension (n = 626) and preeclampsia (n = 109). Offspring motor development, at 10, 14, and 17 years was measured by the Neuromuscular Developmental Index (NDI) of the McCarron Assessment of Motor Development (MAND).MethodsLinear mixed models were used to compare outcomes between pregnancy groups.ResultsOffspring from pregnancies complicated by preeclampsia had poorer motor outcomes at all ages than offspring from either normotensive mothers (p ⩽ 0.001) or those with hypertension (p = 0.002).ConclusionHypertensive diseases during pregnancy, in particular preeclampsia, have long term and possibly permanent consequences for motor development of offspring.     

The brain study: Cognition,quality of life and social functioning following preeclampsia; An observational study

ObjectivesPreviously preeclamptic women may express cognitive difficulties, which have largely been unappreciated or attributed to stresses of a complicated pregnancy. This study aimed to explore the scope of perceived neurocognitive and psychosocial problems as well as quality of life following preeclampsia.Study designObservational study. Through website promotion and e-mail, registrants of the USA-based Preeclampsia Foundation who experienced preeclampsia in the past 20 years were invited to complete a web-based survey. Participants were requested to ask an acquaintance that had a normotensive pregnancy to also complete the survey (controls).Main outcome measuresThe Cognitive Failures Questionnaire (CFQ), abbreviated WHO Quality Of Life questionnaire (WHOQOL-BREF), Social Functioning Questionnaire (SFQ) and Breslau Short Screening Scale for DSM-IV Posttraumatic Stress Disorder were used in the survey. Analysis was performed using Mann–Whitney U tests and linear regression.Results966 cases and 342 controls completed the survey (median age 34, median time since first pregnancy 4 vs. 5 years). Cases scored significantly worse on CFQ (median 35 vs. 27), WHOQOL-BREF domains physical health (15 vs. 17), psychological (13 vs. 15), social relationships (13 vs. 15) and environment (15 vs. 16), and SFQ (8 vs. 7). All p < 0.001. Multivariable analysis showed an independent significant effect of eclampsia on CFQ and of migraine on all questionnaires and the effect of preeclampsia was still present after adjustment for confounders. Posttraumatic stress symptoms accounted for part of the relationships.ConclusionsPreviously preeclamptic women appear to perceive more cognitive and social problems, and report poorer quality of life compared to a group of women with normotensive pregnancies. Research relating to the origin and management of these issues is needed.     

Endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism and expression in North Indian preeclamptic women

BackgroundPathophysiological processes in preeclampsia (PE) are influenced by genetic factors, nitric oxide synthases seem to play important roles, although their expression in and their role is still unclear. To better characterize the host genetic factors determining the susceptibility to PE, we evaluated the influence of polymorphisms (Glu298Asp) in the endothelial nitric oxide synthase (eNOS) gene on the risk of developing PE by checking the expression level.MethodsWe conducted a hospital-based case-control study including 300 women with preeclampsia and 200 healthy pregnant women. Their blood samples were analyzed for levels of nitric oxide, eNOS gene polymorphism and expression. eNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction with control β-Actin gene mRNA levels.ResultsThe mRNA expression of eNOS gene was found to be significantly lower in blood (P < 0.05) from women with PE compared to that from normal pregnancies. The total nitric oxide levels (P < 0.001) were decreased in study Group as compared to healthy pregnant patients. The intergenotypic variation of nitric oxide levels in preeclamptic women was found to be significant (P < 0.001).ConclusionsThese results indicate the relationship between reduced nitric oxide levels and eNOS gene polymorphism leading to its altered expression in preeclamptic women.     

Circulating endothelial progenitor cells and placental abruption in women with preeclampsia

ObjectiveAbnormalities in circulating angiogenic factors and endothelial progenitor cells (EPCs) have been reported in patients with preeclampsia and placental abruption. The objective of this study was to determine whether the number of EPCs is altered in patients with placental abruption.DesignA case control study.SettingHiroshima University Hospital in Japan.SamplePregnant Japanese women with preeclampsia (n = 27) and those without any complications (n = 15).MethodThe EPC (CD45^lowCD34⁺CD133⁺ cells) counts were examined using flow cytometry in peripheral blood collected from 27 women with preeclampsia and 15 normal pregnant women. Among the 27 women with preeclampsia, five subsequently developed placental abruption. All subjects were divided into three groups: normal pregnancy (NP, n = 15), preeclampsia without placenta abruption (PE, n = 22) and preeclampsia with placental abruption (PA, n = 5).Main outcome measuresThe EPC counts were measured in pregnant women with preeclampsia who subsequently developed placental abruption.ResultsThe EPC count in the PE group significantly decreased in comparison to that observed in the NP group (620 cells/ml versus 1918 cells/ml, P < 0.01). In the PA group, the EPC count was found to markedly decrease in comparison to that observed in the PE group (221 cells/ml, P < 0.05).ConclusionsThe number of EPCs was found to significantly decrease in preeclamptic women who subsequently developed placental abruption.     

Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22

ObjectiveFour putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort.MethodsThe four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software.ResultsNominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033).ConclusionsOur collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).     

Baseline placental growth factor levels for the prediction of benefit from early aspirin prophylaxis for preeclampsia prevention

ObjectivePlacental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin.Study designSecondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60 mg/d (n = 102) or placebo (n = 72), with PlGF collected at 13 w 0 d–16 w 6 d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders.ResultsROC analysis indicated 87.71 pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p = 0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p = 0.445).ConclusionsUnlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated.CondensationHigh-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin.     

Higher plasma AOPP is associated with increased proteinuria excretion and decreased glomerular filtration rate in pre-eclamptic women

BackgroundAdvanced oxidation protein products (AOPP) as a novel biomarker of oxidative stress has been demonstrated in chronic kidney disease (CKD) patients. The research was to investigate the plasma AOPP level in pre-eclamptic pregnant women and its correlation with 24-h proteinuria collection, cystatin C(CC), uric acid(UA) and creatinine(Cr).MethodsFifty pre-eclamptic women, including 22 mild and 28 severe preeclampsia were enrolled. Twentyfive healthy singleton pregnant women were selected as control. Blood samples were obtained from all groups to measure the levels of AOPP, CC, UA, Cr and other biochemical parameters at admission. Total protein in the 24 h urine collection was measured. Pearson correlation was performed to evaluate the associations between plasma AOPP level and 24-h proteinuria collection, plasma cystatin C, uric acid and creatinine.ResultsThe means of AOPP levels were significantly different among severe, mild pre-eclampsia and normotensive pregnant women (88.6 ± 10.0 μmmol/L, 72.1 ± 11.1 μmmol/L and 48.7 ± 11.3 μmmol/L). The means of cystatin C levels were significantly different among severe, mild pre-eclampsia and normotensive pregnant women (1.8 ± 0.6 μmmol/L, 1.2 ± 0.3 μmmol/L and 1.0 ± 0.2 μmmol/L). Mild, severe pre-eclampsia and control groups did not differ significantly from each other with respect to uric acid and creatinine. Significant positive correlation between AOPP and 24-h proteinuria excretion in preeclamptic pregnant women was found in mild and severe preeclamptic pregnant women (r = 0.792). Significant positive correlation between AOPP and cystatin C was found in normal and preeclamptic pregnant women (r = 0.521).ConclusionPlasma AOPP level had a significant positive correlation with 24-h proteinuria excretion and cystatin C. Further research about the relevance between the level of AOPP and the onset of preeclampsia was needed in order to have a profound prospective in oxidative stress and preeclampsia.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation

Objectives.?The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies.

Patients and methods.?The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method.

Results.?There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood.

Conclusions.?It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.