Risk Of Developing Preeclampsia Research Articles

Особливості стану плода і новонародженого в жінок високого ризику розвитку прееклампсії

Особливості стану плода і новонародженого в жінок високого ризику розвитку прееклампсії

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Objectives Vitamin D insufficiency is associated with a 5-fold increased risk for development of preeclampsia. We hypothesize that vitamin D plays an important role in the health of endothelial progenitor cells that participate in maternal and placental vasculogenesis and vascular endothelial repair. We asked if vitamin D antagonizes the negative effects of preeclampsia, or a preeclampsia-like environment, on fetal endothelial progenitor cell function. Methods Umbilical cord blood was obtained from preeclamptic and uncomplicated pregnancies. The mononuclear cells were isolated and seeded onto culture plates for outgrowth of endothelial colony forming progenitor cells (ECFCs). Placental explants from uncomplicated term pregnancies were incubated for 48 h under 2%, 8% or 21% O2. Explant conditioned media (CM) was collected and pooled according to oxygen level. Migration, proliferation, and tubule formation of ECFCs was determined in the presence/absence of CM or maternal serum, and 1,25(OH)2 vitamin D3. We inhibited the VEGF signaling pathway with Su5416 and blocked the VDR with VDR antagonist pyridoxal-5-phosphate or antiVDR siRNA. Results The number of cord blood-derived ECFC colonies was decreased in PE compared with controls (P = 0.04). Preeclampsia ECFCs showed reduced proliferation (P Conclusions Physiological concentrations of vitamin D3 promote the migration and capillary-like tubule formation of ECFCs in culture, minimizing negative effects of preeclampsia or preeclampsia-related factors. Such positive effects of vitamin D on progenitor cell function might improve placental and endothelial function and pregnancy outcome. Disclosures L. Brodowski: None. J. Burlakov: None. C.A. Hubel: None. F. von Versen-Hoynck: None.

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Objectives To study myeloperoxidase (–463 MPO promoter) and endothelial nitric oxide synthase (4a/b eNOS) genetic polymorphisms as susceptibility factors associated to NO bioavailability for the development of preeclampsia (PE) (study 1), as well as, to study in a follow up group, its influence on some biomarkers of cardiovascular disease at long term (study 2). Methods We evaluated 222 women, aged 35.11 ± 5.51 years, 124 (55.9%) with normal blood pressure in pregnancy (NBPP) and 98 (44.1%) with preeclampsia (PE). In a sub-sample of these, we also performed a prospective study, which 88 (62.9%) had previous PE, 2–16 years ago (study 2). We studied demographic, anthropometric, hemodynamic and biomarkers parameters, determined by conventional methods, such as: C-reactive protein (CRP), MPO and nitric oxide metabolites (total and nitrites), and others associated with liver function (AST and ALT) and lipid profile (cholesterol total, non-HDL, LDL, HDL, Apo A and B). The MPO and eNOS polymorphisms were evaluated by PCR-RFLP and PCR, respectively. Results Study 1 – the GG genotype of MPO was associated with the risk for development of PE (OR = 2.554; 95%CI 1.354–4.815, p = 0.006). However, eNOS 4a/b polymorphism was not associated with PE. Study 2 – only in GG genotype of MPO, the levels of MPO and nitrites were significant higher in PE comparing with NBPP ( p = 0.024 and p = 0.002, respectively). This pattern remained in the previously PE women who become hypertensive or normotensive after pregnancy ( p Conclusions The risk genotype of MPO (GG) was more associated with PE. This one and eNOS BB genotypes were more associated with higher levels of cardiovascular risk biomarkers, at long term. Disclosures A. Matos: None. A. Pereira da Silva: None. Â. Gil: None. C. Beatriz: None. A. Portelinha: None. I. Rebelo: None. M. Jose Areias: None. M. Bicho: None.

Polycystic ovary syndrome - a risk factor of pre-eclampsia after in vitro fertilisation.

Taking into account an increasing number of pregnancies after the assisted reproduction, we tried to evaluate the risk of pre-eclampsia for mono-foetal pregnancy after IVF and to determine the degree of risk factors. The study included 16,400 patients, while 15,874 of them were after spontaneous conception and 526 after conception using assisted reproductive technologies. For the basic statistical analysis, we used frequency tables and basic statistical characteristics for numeric and ordinary variables. To verify the statistical dependence, we used contingency tables, Fisher exact test and the odds ratio. In the group of women after in vitro fertilisation, a higher incidence of pre-eclampsia was recorded than in the group of women after spontaneous conception. Conception via in vitro fertilisation represents the 3.4-fold risk of pre-eclampsia development (OR 3.404 95% CI 2.407-4.8). The major causes of a higher incidence of pre-eclampsia in case of assisted reproduction include: polycystic ovary syndrome, insulin resistance, subfertility, age and obesity of patients. Assisted reproductive technologies are not the cause of a higher incidence of pre-eclampsia in case of the assisted reproduction (Tab. 4, Fig. 2, Ref. 22).

The association of lectin-like oxidized LDL receptor 1 (LOX-1) K167N and 3'UTR188CT polymorphisms with maternal plasma soluble LOX-1 levels and preeclampsia risk in Turkish population.

To investigate the main effect of polymorphisms in genes involved in endothelial pathophysiological mechanisms, LOX-1 K167N and 3'UTR188CT single nucleotide polymorphisms (SNPs) in relation to preeclampsia (PE) risk and possible interactions between the gene polymorphisms and plasma oxLDL and soluble LOX-1 (sLOX-1) levels on PE in Turkish population. LOX-1 K167N and 3'UTR188CT polymorphisms were studied in 113 pregnant women with preeclampsia and 96 healthy pregnant women by the PCR-RFLP techniques. sLOX-1 and oxLDL levels were determined by enzyme-linked immunosorbent assay (ELISA) in all study subjects. Patients having LOX-1 3'UTR188CT (OR 3.55, 95% CI 1.89-6.67, P = 0.001) or 3'UTR188CC (OR 3.04, 95% CI 1.25-7.38, P = 0.012) genotype had a significantly higher risk of PE than those with 3'UTR188TT genotype. Also, patients having K167N KK (OR 2.73, 95% CI 1.33-5.61, P = 0.005) genotype had a significantly higher risk of PE than those with K167N NN genotype. LOX-1 3'UTR188TT and LOX-1 K167N NN genotype carriers were associated with significantly increased serum sLOX-1 level (P = 0.001). We further investigated the potential combined effect of these polymorphic variants on risk of PE development. According to the combined genotype analysis of LOX-1 3'UTR188TT and K167N NN polymorphisms, sLOX-1 and oxLDL levels also showed significant differences between PE patients and controls with or without combined TT/NN genotype carriers. Our findings indicate that higher plasma sLOX-1 and oxLDL concentrations, and the LOX-1 3'UTR188C>T and LOX-1 K167N gene polymorphisms were significantly associated with risk of developing preeclampsia. Plasma sLOX-1 may be a potential therapeutic target in the treatment of preeclampsia.

Maternal BMI and HDL as predictors of pregnancy outcome in women with type 1 diabetes

Objective: Diabetes in pregnancy is associated with increased risks of maternal as well as foetal complications.Methods: Retrospective data on 96 women and their 96 newborns were anonymously statistically analysed to assess pregnancies of type 1 diabetes (T1D) women managed in our hospital in past nine years. The outcomes of the neonates were divided into three categories according to the clinical status, presence of congenital abnormalities and infant’s treatment.Results: We found out that the outcome of newborn infants associated with maternal HbA1c before gestation as well as during the whole course of pregnancy (p < 0.02 for all). Surprisingly, neonatal outcome was strongly associated with the maternal BMI (p < 0.05). In our model, a lowering of BMI by one grade led to an 18% increase in the chance that the newborn will have no health problems. We did not observe an important worsening of chronic diabetic complications in mothers; however, regarding maternal clinical status, we found that preeclampsia occurrence was strongly and independently connected to HDL level (p < 0.01).Conclusion: Our data demonstrate that lower pregestational BMI could substantially improve T1D mothers' pregnancy outcome. Lower HDL levels in T1D mothers during pregnancy correlate with higher risk of preeclampsia development.

Prediction of early and late preeclampsia by flow-mediated dilation of the brachial artery.

ObjectiveTo assess the accuracy in the prediction of both early and late preeclampsia by flow-mediated dilation of the brachial artery (FMD), a biophysical marker for endothelial dysfunction.Materials and MethodsA total of 91 patients, considered at high risk for development of preeclampsia were submitted to brachial artery FMD between 24 and 28 weeks of gestation.ResultsNineteen out of the selected patients developed preeclampsia, 8 in its early form and 11 in the late form. With a cut-off value of 6.5%, the FMD sensitivity for early preeclampsia prediction was 75.0%, with specificity of 73.3%, positive predictive value (PPV) of 32.4% and negative predictive value (NPV) of 91.9%. For the prediction of late preeclampsia, sensitivity = 83.3%, specificity = 73.2%, PPV = 34.4% and NPV = 96.2% were observed. And for the prediction of all associated forms of preeclampsia, sensitivity = 84.2%, specificity = 73.6%, PPV = 45.7% and NPV = 94.6% were observed.ConclusionFMD of the brachial artery is a test with good accuracy in the prediction of both early and late preeclampsia, which may represent a positive impact on the follow-up of pregnant women at high risk for developing this syndrome.

Maternal and Perinatal Outcomes of Exercise in Pregnant Women with Chronic Hypertension and/or Previous Preeclampsia: A Randomized Controlled Trial.

Objectives. To evaluate the association between physical exercise supervised in pregnant women with chronic hypertension and/or previous preeclampsia and maternal and neonatal outcomes. Method. Randomized controlled trial, which included 116 pregnant women with chronic hypertension and/or previous preeclampsia, considered risk of preeclampsia development. They were divided into two groups: study group that performed physical exercise with a stationary bicycle once a week, for 30 minutes; the intensity was controlled (heart rate 20% above resting values), under professional supervision and a control group that was not engaged in any physical exercise. The data was retrieved from medical charts. Significance level assumed was 5%. Results. Women from study group performed 9.24 ± 7.03 of physical exercise sessions. There were no differences between groups comparing type of delivery and maternal outcomes, including maternal morbidity and hospitalization in intensive unit care, and neonatal outcomes, including birth weight, adequacy of weight to gestational age, prematurity, Apgar scale at first and fifth minutes, hospitalization in intensive unit care, and neonatal morbidity. Conclusions. Physical exercise using a stationary bicycle in pregnant women with chronic hypertension and/or previous preeclampsia, once a week, under professional supervision, did not interfere in the delivery method and did not produce maternal and neonatal risks of the occurrence of morbidity. This trial is registered with ClinicalTrials.gov NCT01395342.

P08.21: Screening for pre‐eclampsia by second trimester uterine artery Doppler evaluation

Second trimester uterine artery/UA/Doppler screening for pre-eclampsia (PE) has been well established. We present the results from a prospective study of high-risk singleton pregnancies undergoing such a screening between 2002 and 2009 in Bulgaria. Bilateral UA Doppler analysis was performed between 18 and 24 w.g. Mean RI and PI indices were calculated. Presence of notching was also recorded. Logistic regression analysis was performed. 169 pregnant women were enrolled in the study. 37 patients developed PE and 11 of those delivered < 34 w.g. There was no difference in the mean maternal age, parity and gestational age between the groups at inclusion. The 90th centile RI had a better sensitivity for PE than the 95th centile with a FPR < 10%. The high mean PI raised the relative risk /RR/ for development of PE 4.8 times (71% sensitivity and 5.3% FPR, P = 0.034). The mean RI > 90th centile was associated with a significant increase of the RR for development of PE and early PE—3.8 and 8.5 times, respectively (95% CI 1.34–10.9). The best predictor for development of PE and PE < 34 w.g. was the combination of RI > 90th centile and the presence of bilateral notching—65 times increased RR for development of early PE, with 81% sensitivity and 1.2% FPR (95% CI 6–699). UA Doppler analysis is a non-invasive screening modality for assessment of patients at risk for development of PE, in particular those requiring delivery < 34 w.g. RI and PI evaluation, combined with presence of notching, is the best predictor in identifying high-risk pregnancies.

Assessment of physical exercise using stationary bicycle for pregnant women with risk for preeclampsia development

Assessment of physical exercise using stationary bicycle for pregnant women with risk for preeclampsia development

Estimating risk factors for development of preeclampsia in teen mothers

Our objective was to identify potentially modifiable risk factors for preeclampsia in a contemporary American teen population. We conducted a retrospective cohort analysis of all teenage deliveries (≤18 years old) at one institution over a 4-year-period. All cases of preeclampsia were identified using the National Working Group for Hypertension in Pregnancy diagnostic criteria and compared to normotensive teenage mothers. Of the 730 included teen deliveries, 65 (8.9 %) women developed preeclampsia and demonstrated a higher prepregnancy body mass index when compared with controls (32.9 ± 8.4 vs. 30.3 ± 6.1 kg/m(2), p = 0.002). Maternal obesity (body mass index ≥30 kg/m(2), RR 1.6, 95 % CI 1.0-2.8) and gestational weight gain above the Institute of Medicine recommended levels (RR 2.6, 95 % CI 1.5-4.4) were associated with higher risk for development of preeclampsia. When evaluating by severity or onset of disease, excessive weight gain in pregnancy was the strongest risk factor for mild (n = 58) or late onset (n = 54) preeclampsia (RR 2.5, 95 % CI 1.4-3.4). Maternal obesity and excessive gestational weight gain place the gravid teen at increased risk for preeclampsia. The modifiable nature of these risk factors permits the possibility of intervention and prevention.

PP046. Adherence to exercise with bicycle during pregnancy in women with risk of preeclampsia

Physical activity (PA) has been proposed as an important part of hypertension's treatment and has been studied as a possibility for the prevention of preeclampsia (PE) and its complications. PA is recommended during pregnancy because it may be beneficial to maternal health. However, some studies relate the difficulty in adherence to exercise during pregnancy. The objective of this study was to evaluate the adherence to exercise with bicycle in pregnant women with risk of preeclampsia development and characterize these pregnants. This is a secondary analysis of a randomized clinical trial at the Women's Hospital Dr. José Aristodemo Pinotti - CAISM/Unicamp, Brazil. We enrolled 116 pregnant women presenting with chronic hypertension (CH), previous PE or both factors associated (risk of PE development). Women from 12 to 20 gestational weeks were selected from the prenatal outpatient clinic and randomly allocated to the study (SG) or non-interventional group (NIG). Women at the SG performed exercise using stationary bicycle (horizontal bench model) during 30min, once a week, under a physical therapist supervision. The HR was maintained at 20% above resting heart rate and up to 140 beats per minute, and the BP was evaluated before and after exercise. The NIG followed regular prenatal routine with weekly returns for HR and BP measurements. We analyzed the adherence of the SG to exercise with bicycle and their sociodemographic and clinical characteristics. We invited 152 pregnants to participate and 33 (21.7%) refused. 116 pregnants were randomized and 58 were allocated to the SG. The mean age was 31.7±6.2 and mean of Body Mass Index (BMI) was 34.9±7.9kg/m(2). Previous PE were prevalent in 16 (27.6%) pregnant, CH in 51 (87.9%) pregnant and 9 (15.5(10.5%) pregnants relate to exercise before pregnancy. The average sessions performed by the SG using stationary bicycle were 9.24±7.03. That those who realized less than the mean session of the SG 14 had discontinued, 3 changed the prenatal city, 4 had TPP, 3 had difficulty in controlling blood pressure, 1 had autoimmune hepatitis diagnosis and 1 had fetal malformation. Considering the sociodemographic and clinical characteristics of these 27 the majority were obese and had had CH, they were not used to practice any type of exercise before pregnancy. Most of them were not primiparous, also had more children at home and found difficul to find time for exercise. The majority did not live next to our center. The majority of our population were obese, sedentary before pregnancy and with CH. In this study exercise, performed once a week, using stationary bicycle in pregnant women of high risk PE, seems to be difficult.

741: Estimating risk factors for development of preeclampsia in gravid teens

Some population-based studies have implicated young maternal age as an independent risk factor for preeclampsia; however, data are lacking with respect to the specific maternal characteristics rendering this group as high risk. Our objective was to estimate risk factors for development of preeclampsia in pregnant teens. In a cohort study of all nulliparous teen (≤18 years old) deliveries over a 4-year period at one institution, we identified all cases of preeclampsia using the National Working Group for Hypertension in Pregnancy diagnostic criteria. Group comparisons and analysis was performed using Fishers exact, Student's t-test, and logistic regression modeling. Of the 730 included teen deliveries, 65 (9%) women developed preeclampsia, and demonstrated a higher pre-pregnancy body mass index (BMI) when compared with controls (32.9 vs. 30.3 kg/m2, p=0.002). Maternal obesity (BMI ≥ 30 kg/m2, RR: 1.6, 95% CI: 1.0-2.8) and gestational weight gain above the Institute of Medicine (IOM) recommended levels (RR: 2.6, 95% CI: 1.5-4.4) were associated with higher risk for development of preeclampsia. When evaluating by severity or onset of disease, weight gain above IOM recommended levels appeared as the single strongest factor associated with the development of mild (n=58) or late onset (n=54) disease (RR: 2.5, 95% CI: 1.4-3.4). Maternal obesity and higher than IOM recommended gestational weight gain place the gravid teen at increased risk for preeclampsia. The modifiable nature of these risk factors permit the possibility of intervention and prevention. The absence of obesity's impact on early onset or severe disease in our cohort further supports a role for an underlying genetic predisposition in these women.

737: First-trimester metabolomic signature markers and preeclampsia: effect of maternal smoking

and preeclampsia: effect of maternal smoking Anthony Odibo, Alison Cahill, Katherine Goetzinger, Linda Odibo, Methodius Tuuli, Dennis Dietzen Washington University in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO, Washington University in St Louis, Department of Pathology, St Louis, MO OBJECTIVE: Recent studies suggest that early assessment of metabolomic markers in maternal serum can predict pregnancies at risk for later development of preeclampsia. We sought to test the hypothesis that the profile of first-trimester metabolic biomarkers is differentially altered by maternal smoking status in women who later develop preeclampsia (PE) compared with non-preeclamptic controls. STUDY DESIGN: We conducted a nested-case control study within a prospective cohort of pregnant women followed from first-trimester to delivery. Cases that developed PE at any gestational age (GA) were compared to controls without PE, matched for GA within three days. Maternal blood obtained at 11-14 weeks gestation was analyzed for 40 acylcarnitine species (C2-C18 saturated, unsaturated, and hydroxylated) and 32 amino acids by LC tandem mass spectrometry. The metabolite levels for the cases and control were compared using Students t test, Mann-Whitney test, Chi-squared or Fischer exact test, stratified by maternal smoking status. RESULTS: We compared 41 cases with PE (including 8 smokers) with 41 controls (including 5 smokers). We found four metabolites [Hydroxyhexanoylcarnitine (C6OH), alanine, phenylalanine, and glutamate], that were significantly higher in the cases with PE compared with the control group. When stratified by smoking status, significant differences were noted in metabolic profiles with PE and the control groups across strata (6 metabolites reduced in smoking PE and 4 in smoking controls). For example, C6OH is elevated in PE compared with controls but reduced in both smoking controls and PE (see box plot). CONCLUSION: While metabolic signatures are promising tools in screening for PE in the first-trimester, our findings suggest that maternal smoking status should be adjusted for in future studies. 738 Angiotensinogen overexpression alters uteroplacental blood flow and leads to pregnancy induced hypertension and fetal growth restriction Antonio Frias, Jessica Hebert, Amy Schilling, Jonathan Lindner, Terry Morgan Oregon Health and Science University, Department of Obstetrics and Gynecology, Portland, OR, Oregon Health & Science University, Pathology, Portland, OR, Oregon Health & Science University, Cardiology, Portland, OR OBJECTIVE: Preeclampsia and intrauterine growth restriction often occur together and have similar placental pathology. A common human angiotensinogen (AGT) promoter variant [A( 6)] is linked with an increased risk of preeclampsia, IUGR and aberrant spiral artery remodeling. We hypothesized that increased maternal AGT causes abnormal uteroplacental blood flow with increased sflt-1 expression leading to pregnancy induced hypertension and IUGR. STUDY DESIGN: We used a transgenic mouse model constructed to mimic the A( 6) haplotype. Maternal mean arterial pressure was measured by radio-telemetry in transgenic and control mice before and during pregnancy. Placental and maternal serum plasma sflt-1 levels were measured by real-time PCR and ELISA. Umbilical artery S/D ratio was measured using VisualsonicVevo 660 at gestational day 15.5 (E15.5) and E18. Uteroplacental blood flow and flux rates were measured at day E15.5 in vivo using at least three pups per litter by microbubble-enhanced ultrasound. RESULTS: Transgenic mice develop pregnancy induced hypertension and have growth restricted progeny (p 0.05). Doppler ultrasound demonstrated absent end diastolic flow at E15.5 and E18 in transgenic dams but normal diastolic flow in controls. Placental blood flow flux rates were significantly different between genotypes (P 0.01). Controls had a distinct spiral artery and showed slow filling of the placental labyrinth with a five second delay compared with the uterine wall (Figure 1). In contrast, transgenic dams had no distinct spiral artery and showed nearly instantaneous filling of the labyrinth (Figure 1). Transgenic maternal serum and placentas overexpressed sflt-1 compared with controls (p 0.0001). CONCLUSION: Our murine model that overexpresses AGT at levels similar to the human haplotype results in pregnancy induced hypertension, fetal growth restriction, and elevated sflt-1 levels. Our novel real-time in vivo measurements reveal these findings may be a consequence of abnormal spiral artery remodeling and faster uteroplacental blood flow resulting in increased placental sflt-1 secretion into maternal blood. www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease Poster Session V

Mid-trimester uterine artery Doppler ultrasound as a predictor of adverse obstetric outcome in high-risk pregnancy

Objective The aim of this study was to assess uterine artery Doppler ultrasonography efficiency in prediction of adverse pregnancy outcome in high-risk pregnancies. Materials and Methods We selected 70 pregnant women who were high risk for development of preeclampsia, abruption, low birth weight (LBW), and preterm delivery during their pregnancy, and Doppler ultrasonography was performed for them in 18–24 gestational weeks for evaluation of uterine artery notching. Absence of diastolic flow in uterine artery waves was defined as notching. The women were divided into two groups: with notching (Group A) and without notching (Group B), then they were compared for complications such as preeclampsia, abruption, LBW, and preterm delivery. Results In 70 high-risk pregnant women, 27 women (39.2%) were in Group A and the others were in Group B. The birth weight in Groups A and B was 2,897.5 ± 757.15 and 3,248.39 ± 374.27, respectively. In our study, 15 patients were delivered before 37 gestational weeks (preterm labor). Preeclampsia, abruption, and LBW were significantly higher in the group with positive notching, but preterm delivery did not show any statistical difference between the two groups. Conclusion According to the results, uterine artery Doppler ultrasonography had high negative predictive value for prediction of preeclampsia, abruption, and LBW. Therefore, absence of uterine artery notching in mid-trimester evaluation of high-risk pregnant women may predict better pregnancy outcome. We recommend Doppler ultrasonography for all high-risk pregnant women in second trimester for prediction of pregnancy outcome.

The HLA-G 14bp gene polymorphism and decidual HLA-G 14bp gene expression in pre-eclamptic and normal pregnancies

Trophoblast expression of the non-classical MHC, HLA-G, is considered essential for feto-maternal immune tolerance and successful placentation in pregnancy. The HLA-G 14 bp polymorphism in the 3′-untranslated region (UTR) of the HLA-G gene has been reported to be associated with development of pre-eclampsia (PE). In this study, maternal (peripheral blood, n = 54) and fetal (cord blood, n = 57) HLA-G 14 bp genotypes have been determined by PCR in pre-eclamptic and normal pregnancies. In addition, HLA-G 14 bp gene expression in decidua basalis ( n = 59) was analyzed by RT-PCR. The pre-eclamptic syndrome was neither associated with the HLA-G 14 bp genotype (maternal or fetal), nor with altered decidual HLA-G 14 bp gene expression. Furthermore, the HLA-G 14 bp mRNA expressed in decidua basalis was of fetal origin and all potential transcripts, as predicted from the fetal HLA-G 14 bp genotype, were expressed. In contrast to previous findings, we found no correlation between the HLA-G 14 bp polymorphism and fetal growth. In conclusion, the fetal HLA-G 14 bp genotype is reflected in the decidual HLA-G mRNA splice form profile, but does not appear to be associated with increased risk for development of PE.

Mean Arterial Pressure at 11 +0 to 13 +6 Weeks in the Prediction of Preeclampsia

This study aimed to determine the performance of screening for preeclampsia (PE) by maternal medical history and mean arterial pressure (MAP) at 11(+0) to 13(+6) weeks. In 5590 women with singleton pregnancies attending for routine care at 11(+0) to 13(+6) week's gestation we recorded maternal variables and measured the MAP. We excluded 397 because they had missing outcome data or the pregnancies resulted in miscarriage or termination. In 104 patients there was subsequent development of PE, 97 developed gestational hypertension, 574 delivered small-for-gestational-age newborns, and 4418 were unaffected by PE, gestational hypertension, or small for gestational age. A multivariate Gaussian model was fitted to the distribution of log multiple of the median MAP in the PE and unaffected groups. Likelihood ratios for log multiple of the median MAP were computed and used together with maternal variables to produce patient-specific risks for each case. Detection rates and false-positive rates were calculated by taking the proportions with risks above a given risk threshold. In the unaffected group, log MAP was influenced by maternal age, ethnic origin, smoking, family and personal history of PE, and fetal crown-rump length. In the prediction of PE, significant contributions were provided by log multiple of the median MAP, ethnic origin, body mass index, and personal history of PE. The detection rate of PE by log multiple of the median MAP and maternal variables was 62.5% for a false-positive rate of 10%. Maternal variables, together with MAP, at 11(+0) to 13(+6) weeks identify a group at high risk for development of PE.

Prenatal Influences and Endothelial Dysfunction

Hypertension during pregnancy when associated with new-onset proteinuria is termed “preeclampsia.”1,2 Preeclampsia is thought to initiate with improper remodeling of the uterine spiral arteries leading to reduced placental/fetal perfusion and subsequent extensive dysfunction of the maternal vascular endothelium.1,2 Reduced placental perfusion, however, may not always result in preeclampsia.1 Additionally, reduced placental perfusion may not necessarily reflect an imbalance between nutrient delivery and the metabolic needs of the fetus. Nonetheless, based on the fact that low placental perfusion is not always associated with preeclampsia, Roberts and Gammill1 proposed that the maternal response to reduced placental perfusion requires interaction with pre-existing maternal factors. Maternal factors that may contribute to increased maternal susceptibility to reduced placental perfusion and development of preeclampsia or hypertensive disorders of pregnancy include genetic, behavioral, and environmental factors.1 Numerous studies indicate that a genetic component may contribute to increased risk for preeclampsia and hypertensive disorders of pregnancy.1,3,4 Women and men born to a woman with preeclampsia are at greater risk for developing, or fathering, a preeclamptic pregnancy, suggesting transmission of a fetal gene for increased susceptibility to preeclampsia.3,4 However, this susceptibility is greater in women than in men, suggesting passage of maternal susceptibility …

Assessment of risk for the development of pre‐eclampsia by maternal characteristics and uterine artery Doppler

To develop a method for the estimation of patient-specific risk for the development of pre-eclampsia by combining maternal history and uterine artery Doppler. Prospective multicentre observational study. Antenatal clinics in seven hospitals in the UK and three overseas centres. Unselected women with singleton pregnancies attending for routine antenatal care. Doppler studies of the uterine arteries were performed using colour flow mapping and pulsed wave Doppler at 23 weeks of gestation. The mean pulsatility index (PI) of the two uterine arteries was calculated. Doppler and maternal history variables were combined to develop a model for risk assessment. The incidence of pre-eclampsia was used to derive the prior risk for this complication. The posterior risk was derived by multiplying the prior odds with likelihood ratios (LRs) derived from independent risk factors identified from the maternal history, and the LR estimated from the heights of the frequency distributions of mean PI in affected and unaffected pregnancies. Pre-eclampsia. There were 17,480 women recruited to the study, in which 17,319 (99.1%) of these Doppler examination of both uterine arteries were completed, and outcome data were available in 16,806 (97.0%). Pre-eclampsia occurred in 369 (2.20%) cases. Significant independent prediction of pre-eclampsia was provided by mean PI, ethnic origin, body mass index (BMI), parity, cigarette smoking, history of hypertension and family or personal history of pre-eclampsia. Models were derived allowing calculation of patient-specific risk for development of pre-eclampsia. For a false-positive rate of 25%, the detection rate of pre-eclampsia by screening using maternal history was 45.3%, with uterine artery Doppler it was 63.1% and with combined assessment it was 67.5%. Combining risk factors in the mother's history with Doppler of the uterine arteries allows calculation of patient-specific risk for the development of pre-eclampsia.

Glucose 6 phosphate dehydrogenase (G6PD) deficiency is a possible risk factor for the development of preeclampsia

Preeclampsia is partially attributed to lipid peroxidation of the syncytitrophoblast plasma membranes (SPMs). Peroxidation of the SPMs could be augmented when the capacity of the cells to produce antioxidant molecules is diminished. One of the most important antioxidant molecules that protects the SPMs is the reduced glutathione (GSH). The latter is produced in the pentose phosphate pathway that requires normal activity of glucose 6 phosphate dehydrogenase (G6PD). Therefore, it is hypothesized that pregnant women with G6PD deficiency are at higher risk for development of preeclampsia than those with normal G6PD activity. Deficiency of this enzyme leads to the deficiency of reduced GSH which is required to protect SPMs against lipid peroxidation and the consequent obstetric morbidity.