Severe Hypertensive Disorders Of Pregnancy Research Articles

Association of maternal Toll-like receptor-4 alleles with susceptibility to early-onset preeclampsia in central Greece.

Altered maternal inflammatory responses may play a role in the development of hypertensive disorders of pregnancy like preeclampsia, its more severe early-onset form and intrauterine growth restriction. We evaluated the relation of common allelic variants of Toll-like receptor 4 (TLR4), known to impair the inflammatory response, with the susceptibility to early-onset preeclampsia in Central Greece. We compared the occurrence of TLR4 (Asp299Gly and Thr399Ile) alleles in heterozygous (A/G, C/T) and homozygous (G/G, T/T) states in 84 women with a history of early-onset preeclampsia and 94 age matched controls with a history of only uneventful pregnancies, by direct sequencing. Heterozygous TLR4 allelic variants were more common in women with a history of early-onset preeclampsia than in controls (GA for Asp299Gly: 14.3% vs 6.4% (AA), p = 0.053 & CT for Thr399Ile: 16.7% vs. 6.4% (CC), p = 0.019) and a stronger association was obtained when homozygous allelic carriers were also included (GA/GG for Asp299Gly: 16.7% vs. 6.4% (AA), p = 0.03 & TC/TT for Thr399Ile: 19.0% vs. 6.4% (CC), p = 0.01). We recorded association between common TLR4 gene variants and early-onset preeclampsia. Our findings support the involvement of maternal innate immune system in severe hypertensive disorders of pregnancy and point to the potential value of maternal TLR4 polymorphisms as predictors-risk factors of susceptibility to early-onset preeclampsia in Central Greece.

Maternal Serum Uric Acid as a Predictor of Severity of Hypertensive Disorders of Pregnancy: A Prospective Cohort Study.

Objective: To assess the relationship between maternal serum uric acid and severity of Hypertensive disorders of pregnancy in a rural tertiary care centre.Materials and Methods: Present study was conducted in Obstetrics and Gynaecology department of rural tertiary care cen-tre of Northern India over seven months (October 2016-May 2017) on 110 women admitted with a Hypertensive disorder of pregnancy (Gestational hypertension, Pre-eclampsia, Eclampsia) at ≥34 weeks gestation. Maternal serum uric acid levels were compared in three groups in relation to disease severity, mode of delivery, maternal outcome.Results: Of total 110 women with a Hypertensive disorder of pregnancy; 35 (31.81%) had Gestational Hypertension, 49 (44.54%) preeclampsia and 26 (23.63%) had eclampsia. Mean±SD values for serum uric acid were 5.47±1.93 mg/dl in women with Gestational Hypertension; 6.72±2.15 mg/dl in Pre-eclampsia and 8.71±2.97 mg/dl in the eclamptic group. Of 110 women 34(97.14%) with gestational hypertension, 27(55.10%) with pre-eclampsia and one (3.85%) with eclampsia re-mained stable in post-partum period, 17 (34.69%) women with severe pre-eclampsia and 15 (57.69%) with eclampsia re-quired intensive care in postpartum period and one (2.86%) women with gestational hypertension, five (10.20%) with pre-eclmapsia and ten (38.46%) with eclampsia required ventilator support and high dependency unit care. Of these 16 women with the severe disease, ten succumbed to death. Also, in women with serum uric acid,>6mg/dl, most common mode of de-livery was a lower segment cesarean section (50.90%).Conclusion: Significant correlation was observed between maternal serum uric acid, disease severity and maternal outcome.

Placental Exposure to Hypoxia and Oxidative Stress Causes Mitochondrial DNA Release into the Extracellular Space

BackgroundIn preeclampsia, a severe hypertensive disorder of pregnancy, placentae experience reduced perfusion, increased cell death, and oxidative stress, with an increase in circulating cell‐free mitochondrial DNA (mtDNA). Our lab has shown that a synthetic mimetic of mtDNA during rodent pregnancy increases maternal blood pressure and vascular reactivity, features of human preeclampsia. The main objective of this study was to determine the role of hypoxia and oxidative stress in mtDNA release from placental cells, and to examine the effects of soluble factors from hypoxia‐exposed placentae on vascular reactivity.Hypotheses Exposure to hypoxia and oxidative stress will result in mtDNA release via cell‐death dependent mechanisms in human trophoblast cells. Soluble factors from hypoxia‐exposed placentae will result in reduced vasodilation in rat maternal arteries. MethodsTo examine the effects of preeclampsia‐related placental stressors on mtDNA release, we treated human trophoblast cells (BeWo cell line) with: 1) hypoxia (1% O2) vs. normoxia (21% O2) for 15 h, or 2) a mitochondrial complex I inhibitor (Rotenone, 10 μM) vs. vehicle for 4 h. mtDNA in cell culture supernatant was measured using absolute qPCR and cell death was quantified using flow cytometry. To test the effects of hypoxic placenta‐derived factors on maternal vascular function, we used mesenteric arteries and placenta‐conditioned media (PLmedia) from pregnant rats. Placentae were incubated in physiological salt solution (37°C) for 3 h in either 1% or 21% O2, while arteries were mounted on a wire myograph and underwent a baseline [(−) PLmedia] concentration‐response curve (CRC) to acetylcholine (ACh, 10−9 – 3×10−5 M) followed by 30‐min incubation with PLmedia, after which the CRC was repeated.ResultsExposure of trophoblast cells to rotenone resulted in cell death (Vehicle: 28.17 ± 2.67% vs. Rotenone: 48.43 ± 1.22%, n = 3, P = 0.002) and mtDNA release (Vehicle: 1.69 ± 0.12 ng/uL vs. Rotenone: 2.39 ± 0.10 ng/uL, n = 5, P = 0.002). Hypoxia did not induce trophoblast cell death (Normoxia: 24.7 ± 0.50% vs. Hypoxia: 24.25 ± 0.45%, n = 2, P = 0.6), but increased release of mtDNA (Normoxia: 14.22 ± 1.20 pg/uL vs. Hypoxia: 20.64 ± 0.39 pg/uL, n = 3, P = 0.007). PLmedia from normoxic and hypoxic placentae reduced sensitivity to ACh (−logEC50, Normoxia: −)PLmedia: 7.48 ± 0.03 vs. (+)PLmedia: 6.96 ± 0.10, n = 4, P = 0.02; Hypoxia: (−)PLmedia: 7.35 ± 0.35 vs. (+)PLmedia: 6.70 ± 0.29, n = 3, P = 0.08).ConclusionsA placental cell model of mitochondrial stress results in cell death and release of mtDNA, while a hypoxic model of stress results in release of mtDNA without cell death. Placental factors decrease resistance artery sensitivity to vasodilators in both normoxic and hypoxic conditions, indicating that the placenta contributes to maternal vascular tone in healthy pregnancies and in pregnancies complicated with reduced perfusion. Ongoing studies investigate the vasoactive potential of placenta‐derived cell‐free mtDNA.Support or Funding InformationAmerican Heart Association (13SDG17050056, 18PRE33960162)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Maternal psychological distress after severe pregnancy hypertension was associated with increased child behavioural problems at the age of 12.

We examined the association between early maternal psychological distress after severe hypertensive disorders of pregnancy (HDP) and behavioural issues in their 12-year-old offspring. This secondary analyses of a prospective mother-child birth cohort focused on 95 women with severe HDP and their singleton offspring. The mothers were recruited during pregnancy from 2000 to 2003 in Amsterdam, the Netherlands. Maternal distress at child term age and three months post-term was measured using the Symptom Checklist-90. The Child Behaviour Checklist for six years to 18years was used to quantify social and attention problems in their offspring at 12years of age. Perinatal and neonatal risk factors were also analysed. The children were born at a mean age of just under 32weeks and 90% weighed below the 10th percentile. High psychological distress (score ≥133) affected 45% of the mothers at term age and 44% three months post-term. Child social problems were significantly associated with maternal distress at three months and were highest in cases of high maternal distress in combination with major neonatal morbidity. Child attention problems were associated with maternal anxiety at three months post-term. Early maternal psychological distress after severe maternal HDP was associated with childhood behavioural issues at the age of 12.

Adverse pregnancy and perinatal outcome in patients with recurrent pregnancy loss: Multiple imputation analyses with propensity score adjustment applied to a large-scale birth cohort of the Japan Environment and Children's Study.

ProblemSeveral studies have reported the increased risk of preterm birth, premature rupture of membranes, and low birth weight in patients with recurrent pregnancy loss (RPL). There have been a limited number of large population‐based studies examining adverse pregnancy and perinatal outcome after RPL. Multiple‐imputed analyses (MIA) adjusting for biases due to missing data is also lacking.Method of studyA nationwide birth cohort study known as the “Japan Environment and Children’s Study (JECS)” was conducted by the Ministry of the Environment. The subjects consisted of 104 102 registered children (including fetuses or embryos).ResultsNo increased risk of a congenital anomaly, aneuploidy, neonatal asphyxia, or a small for date infant was observed among the children from women with a history of RPL. A novel increased risk of placental adhesion and uterine infection was found. The adjusted ORs using MIA in women with three or more PL were 1.76 (95% CI, 1.04‐2.96) for a stillbirth, 1.68 (1.12‐2.52) for a pregnancy loss, 2.53 (1.17‐5.47) for placental adhesion, 1.87 (1.37‐2.55) and 1.60 (.99‐2.57) for mild and severe hypertensive disorders of pregnancy, respectively, 1.94 (1.06‐3.55) for uterine infection, 1.28 (1.11‐1.47) for caesarean section and .86 (.76‐.98) for a male infant.ConclusionMIA better quantified the risk, which could encourage women who might hesitate to attempt a subsequent pregnancy.

Associations between postpartum depression and hypertensive disorders of pregnancy.

To identify possible relationships between postpartum depression and hypertensive disorders of pregnancy (HDP), as well as the associated risk factors for developing postpartum depression. The present prospective descriptive cross-sectional study was conducted among postpartum women who attended a public maternity hospital in Brazil between January 15, 2015, and January 15, 2017. The diagnosis and severity of HDP were based on blood pressure measurements (systolic ≥140mm Hg or diastolic ≥90mmHg), proteinuria, clinical findings, and laboratory findings. A group of normotensive women was also included. The Edinburgh Postnatal Depression Scale was used to assess the risk of postpartum depression. Of 168 participants (42 with HDP and 126 normotensive), 40 (23.8%) women displayed depressive symptoms (25 normotensive and 15 with HDP). The probability of postpartum depression correlated with a diagnosis of HDP (Spearman correlation coefficient [rS ] 0.219; P=0.004); premonitory signs of eclampsia (rS 0.171; P=0.027); magnesium sulfate therapy (rS 0.199; P=0.010); diastolic blood pressure (rS 0.165; P=0.033); and use of milk formula during hospitalization (rS 0.152; P=0.048). Women diagnosed with HDP were more likely to have depressive symptoms than their normotensive counterparts.

Visual evoked potentials in women with and without preeclampsia during pregnancy and postpartum.

Preeclampsia is a severe hypertensive disorder of pregnancy which may lead to brain complications such as eclampsia. Visual symptoms are present in ∼25% of preeclamptic women suggesting the visual cortex to be altered during preeclampsia. Visual evoked potentials (VEPs) measure the functional neuronal integrity of the visual pathway from retina to the occipital cortex of the brain. The objective of this study was to compare neurophysiological changes in women with preeclampsia and other hypertensive disorders of pregnancy, using VEPs. We hypothesized that women with preeclampsia and other hypertensive disorders of pregnancy develop abnormal latency and amplitude of VEPs as compared with normotensive pregnant women. We performed a prospective observational study in 15 women with mild preeclampsia, 33 with severe preeclampsia (sPE), eight women with chronic hypertension, nine with pregnancy-induced hypertension, and 29 normotensive pregnant women. VEP measurements were made at four different time points of gestation (12-14 weeks, 26-28 weeks, 32-34 weeks, 36-40 weeks) and 6-8 weeks postpartum. We defined reference values for normotensive pregnant women. Normotensive pregnant women had a shorter latency during pregnancy compared to their postpartum value (P = 0.005). Women with sPE had a prolonged latency of VEPs compared with normotensive pregnant women (P = 0.006), a difference that disappeared postpartum. Our study showed neurophysiological adaptation to pregnancy of the visual cortex in normotensive pregnant women, that seemed to be absent in women with sPE. The study groups of women with chronic hypertension and pregnancy-induced hypertension were to small to draw any conslusions from.

Maternal and Perinatal Outcome in Women with Systemic Lupus Erythematosus: A Retrospective Bicenter Cohort Study.

Objective To investigate disease activity around and during pregnancy and pregnancy outcome in women with systemic lupus erythematosus (SLE) considering antiphospholipid antibody status. Moreover, differences between first and consecutive pregnancies were examined. Methods Pregnancies > 16 weeks gestation of SLE patients receiving joint care from rheumatologists and gynecologists in two tertiary centers in the Netherlands between 2000 and 2015 were included. Disease activity, flare rate, and pregnancy outcomes and complications were assessed. Results Ninety-six women (84% Caucasian) with 144 pregnancies were included. The median SLE(P)DAI score was 2 before, during, and after pregnancy. Flare rates were 6.3%, 20.1%, and 15.3%, respectively. Severe hypertensive disorder of pregnancy, intrauterine fetal death, preterm birth, and small-for-gestational age infants occurred in 18.1%, 4.1%, 32.7%, and 14.8%, respectively. Complication rates were similar in the first and consecutive pregnancies. Half of the women did not experience any pregnancy complication whereas 42.7% developed a complication during all pregnancies. Mean number of pregnancies was 2.4 and live births 1.7. Conclusion In this SLE population with low disease activity, pregnancy complications were present irrespective of antiphospholipid antibody status. Furthermore, there were no differences in complication rates between the first and consecutive pregnancies as seen in healthy mothers. This information is useful for patient counseling.

Prediction of progression to severe disease in women with late preterm hypertensive disorders of pregnancy.

If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk. We developed a prediction model using data from the HYPITAT-II trail, which evaluated immediate delivery vs. expectant monitoring in women with non-severe hypertensive disorders of pregnancy between 34 and 37weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities. We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p=0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73-0.81, p<0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, <0.44 and >0.45, respectively). In women with non-severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice.

Maternal medical conditions during pregnancy and gross motor development up to age 24 months in the Upstate KIDS study.

We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months. We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children's motor milestone achievement at 4, 8, 12, 18, and 24 months of age. After adjustment for covariates (including pre-pregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support (hazard ratio [HR]=0.84, 95% confidence interval [CI] 0.75-0.93), walking with assistance (HR=0.88, 95% CI 0.77-0.98), and walking alone (HR=0.88, 95% CI 0.77-0.99) than children of females with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birthweight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors. Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity.

Goal-directed Fluid Therapy May Improve Hemodynamic Stability of Parturient with Hypertensive Disorders of Pregnancy Under Combined Spinal Epidural Anesthesia for Cesarean Delivery and the Well-being of Newborns.

Background:Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy (HDP) can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy (GDFT) with LiDCOrapid system can improve well-being of both HDP parturient and their babies.Methods:Fifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer's solution (LR), parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume (ΔSV) provided via LiDCOrapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events.Results:The severity of HDP was similar between two groups. The total LR infusion (P < 0.01) and urine output (P < 0.05) were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group (P < 0.01). There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased (P < 0.05), and the incidences of neonatal hypercapnia and hypoxemia were statistically increased (P < 0.05) than in the GDFT group.Conclusions:Dynamic responsiveness guided fluid therapy with the LiDCOrapid system may provide potential benefits to stable HDP parturient and their babies.

Outcome of Patients Admitted to Obstetric Intensive Care Unit With Severe Preeclampsia, Eclampsia or HELLP Syndrome

Objectives: Hypertensive disorders of pregnancy are associated with maternal mortality and morbidity. Patients with these diseases usually require intensive care. This study reviewed pregnant women with severe preeclampsia, eclampsia or HELLP syndrome who needed intensive care and were consequently admitted to intensive care unit (ICU). Materials and Methods: In this retrospective study, data of all preeclamptic and eclamptic women and patients with HELLP syndrome who delivered at Al-Zahra hospital over a 1-year period from March 2012 to March 2013 were reviewed. Results: Of 9812 women delivered in our center, 56 women with severe hypertensive disorders required ICU admission (0.6%). The most common therapeutic interventions included vasodilator agents and transfusion. No case of maternal mortality was reported; while 5 cases of fetal death (8.9%) due to intrauterine death were reported. Conclusion: Outcome of patients admitted in ICU for severe hypertensive disorders of pregnancy is generally good. Intensive care management should be considered in every referral obstetric center.

Rare case of exudative retinal detachment in Normotensive HELLP syndrome: A Case Report

HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) is defined as a severe form of preeclampsia which leads to maternal, fetal morbidities and sometimes even death. HELLP syndrome usually occurs in severe preeclampsia; but sometimes it may present with atypical clinical features. Bilateral, serous, non-rhegmatogenous retinal detachment is a rare complication in severe hypertensive disorders of pregnancy, in most of the cases serous detachment is associated with development of hypertensive retinopathy. Here we report a rare case of 24-year-old female who presented at 36 weeks of pregnancy with headache, and diminution of vision in both eyes. Two days after admission a proteinuria of 440 mg/24 h was detected. She had platelet count of 70,000/ cc 3 and elevated liver enzymes. However the patient had normal blood pressure. Her serum was creatinine normal. The patient required a platelet transfusion. Fundus examination revealed exudative retinal detachment involving inferior quadrant. No signs of hypertensive retinopathy were noted. Prompt recovery with good visual acuity occurred after the pregnancy ended.

Impact of non-steroidal anti-inflammatory drugs on hypertensive disorders of pregnancy

Non-steroidal anti-inflammatory drug (NSAID) use has the potential to adversely affect blood pressure in women with hypertensive disorders of pregnancy. We sought to evaluate this association. Women affected with severe hypertensive disorders of pregnancy were identified by retrospective chart review. The medication administration record was then used to identify controls (no NSAID exposure) until a sufficient number of patients were obtained, after which the cases (NSAID exposed) were identified in a chronological manner during the same study period until a 2:1 ratio was achieved. The primary outcome was the change in mean of all postpartum mean arterial pressures (MAP) throughout the hospital stay. Power analysis showed that 146 exposed and 73 unexposed subjects were necessary to obtain 90% power to detect a MAP difference of 10mmHg between the groups. Secondary outcomes included: initiation of anti-hypertensive medication, need for increased doses of anti-hypertension medication, and adverse events related to hypertension. 223 women had severe hypertensive disorders of pregnancy, of whom 75 (34%) were not exposed to NSAIDs and 148 (66%) were exposed. NSAID exposure was not associated with a difference in the average MAP postpartum (p=0.70), nor any of the secondary outcomes evaluated. Exposure to NSAIDs was less likely as serum creatinine increased (p=0.012). In women with severe hypertensive disorders of pregnancy, NSAIDs did not appear to increase the average postpartum MAP, increase the requirement for anti-hypertensive medications, or increase the rate of adverse postpartum events.

Hydralazine vs labetalol for the treatment of severe hypertensive disorders of pregnancy. A randomized, controlled trial.

Hydralazine and labetalol for intravenous use are equally effective in the management of hypertensive crisis in pregnant patients (24weeks or more) with severe hypertensive disorders of pregnancy, showing a similar frequency of adverse effects in both groups.

Background Rates of Adverse Pregnancy Outcomes for Assessing the Safety of Maternal Vaccine Trials in Sub-Saharan Africa

BackgroundMaternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa.MethodsWe developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed.FindingsAccounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6–73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9–16.4) or premature (median 15.4%, IQR: 10.6–19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5–17.6), with the musculoskeletal system comprising 30%.InterpretationSome clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of adverse pregnancy outcomes will improve safety assessment of interventions during pregnancy.

OS023. Postpartum cardiovascular disease risk factors in women with ahistory of early onset preeclampsia, late onset preeclampsia and pregnancy induced hypertension

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women. Epidemiological studies have shown an increased risk of a CVD event in women who have had a hypertensive disorder in one of their previous pregnancies. These data also suggest that these increased risks are associated with severity and time of onset of pre-eclampsia. Risk factors for CVD have not yet been compared between women who experienced early versus late and mild versus severe hypertensive disorders of pregnancy. In this study we compared classic CVD risk factors of postpartum women with previous early-onset preeclampsia (EOPE), late onset pre-eclampsia (LOPE) and pregnancy induced hypertension (PIH). A total of 81 women with previous EOPE (delivery required ⩽34weeks), 76 with LOPE (delivery ⩾36weeks) and 229 with PIH were included along with 79 healthy controls. Statistical analyses were performed using generalized linear models in PASW statistics 17.0, SPSS Inc. Adjusted means of blood pressure, fasting plasma glucose levels and LDL levels were significantly increased after all hypertensive disorders of pregnancy compared to controls. This increase of CVD risk factors was significantly correlated with severity and time of onset of the disease (Table 1). The prevalence of metabolic syndrome (BMI>30kg/m(2) and ⩾2 of the following; triglycerides ⩾150mg/dl, HDL cholesterol ⩾50mg/dl, systolic blood pressure ⩾130 or diastolic blood pressure ⩾85 and fasting plasma glucose levels ⩾100mg/dl) did not differ between the study groups; women who had PIH had the highest number of components of the metabolic syndrome (). These results further establish the predisposition to CVD in women with previous pre-eclampsia or PIH. EOPE is associated with a more pronounced CVD risk factor profile than LOPE or PIH, which may explain the previously described higher CVD event risk.

The Value of Post-Partum Intra-Venous Pyelography in Severe Hypertensive Disorders of Pregnancy and Eclampsia

Intra-venous pyelographic studies were carried out at various times after delivery in 315 cases of Severe Pre-Eclamptic Toxaemia/Eclampsia. Abnormal findings were recorded in 24 cases. — an incidence of 7.6 per cent. Impairment of renal function and dilatation of the renal system constituted the main abnormal findings (17 cases), while silent renal / ureteric stone was present in 4 cases. From this study it is. advocated that intra-venous pyelography should form an integrat part of the routine investigation of cases of severe hypertensive disorders of pregnancy and eclampsia.

554: Is chorionic villus sampling (CVS) associated with development of hypertensive disorders of pregnancy?

Late first trimester placenta disruption has been suggested to predispose to preeclampsia (PEC)/gestational hypertension (HTN). (Obstet Gynecol 2005;105:587). A recent study suggests an association between CVS and severe hypertensive disorders of pregnancy (AJOG 2007; 196:591e1-e7). Our objective is to evaluate if there is any association between CVS and hypertensive disorders of pregnancy.

Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome

BackgroundAltered maternal inflammatory responses play a role in the development of preeclampsia and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. We examined whether allelic variants of the innate immune receptors Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 2 (NOD2), that impair the inflammatory response to endotoxin, are related to preeclampsia and HELLP syndrome.Methods and FindingsWe determined five common mutations in TLR4 (D299G and T399I) and NOD2 (R702W, G908R and L1007fs) in 340 primiparous women with a history of early-onset preeclampsia, of whom 177 women developed HELLP syndrome and in 113 women with a history of only uneventful pregnancies as controls. In addition, we assessed plasma levels of pro-inflammatory biomarkers C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, fibrinogen and von Willebrand factor in a subset of 214 women included at least six months after delivery. After adjustment for maternal age and chronic hypertension, attenuating allelic variants of TLR4 were more common in women with a history of early-onset preeclampsia than in controls (OR 2.9 [95% CI 1.2–6.7]). Highest frequencies for TLR4 variants were observed in women who developed HELLP syndrome (adjusted OR 4.1 [95% CI 1.7–9.8]). In addition, high levels of interleukin-6 and fibrinogen were associated with a history of early-onset preeclampsia. Combined positivity for any of the TLR4 and NOD2 allelic variants and high levels of interleukin-6 was 6.9-fold more common in women with a history of early-onset preeclampsia (95% CI 2.1–23.2) compared to controls.ConclusionsWe observed an association of common TLR4 and NOD2 gene variants, and pro-inflammatory phenotype with a history of early-onset preeclampsia and HELLP syndrome. These findings suggest involvement of the maternal innate immune system in severe hypertensive disorders of pregnancy.