Elevated Risk Of Preeclampsia Research Articles

Elevated Risk of Preeclampsia in Obese Pregnancies: The Interaction Between Metabolic Dysregulation and Placental Dysfunction

Preeclampsia, a hypertension condition during pregnancy, presents considerable dangers to both maternal and fetal well-being. Maternal obesity is becoming acknowledged as a significant modifiable risk factor for preeclampsia; however, the underlying mechanisms are intricate and varied. This paper explores how metabolic dysregulation in obese pregnancies can lead to issues with the placenta. Key problems include insulin resistance, chronic inflammation, oxidative stress, and the role of anti-angiogenic factors like soluble fms-like tyrosine kinase-1 (sFlt-1) based on existing literature and data. Elevated leptin and reduced adiponectin levels, common in obesity, further exacerbate endothelial dysfunction and contribute to systemic inflammation. Additionally, obesity-related dyslipidemia worsens the oxidative and inflammatory processes that drive placental ischemia and vascular complications in preeclampsia. Through a synthesis of current research, this study highlights the intricate relationship between maternal obesity and the heightened risk of preeclampsia, emphasizing the need for targeted interventions in weight management to improve pregnancy outcomes

Predictive Value of Thrombin Time in Early Preeclampsia

Background: Preeclampsia is a pregnancy-specific disease, which is easy to cause adverse outcomes in mother and child. Effective prediction of preeclampsia have important clinic al significance. This retrospective study aimed to investigate the utility of thrombin time during the first trimester as a predictive marker for preeclampsia. Methods: We meticulously examined the clinical characteristics of a cohort comprising 222 pregnant individuals with mild preeclampsia, 315 with severe preeclampsia, and 396 healthy pregnant women. Subsequently, we conducted both univariate and multiple regression analyses to discern variations in quantitative variables across these groups and to ascertain any discernible associations between thrombin time and the incidence of preeclampsia. Furthermore, we assessed the predictive performance of thrombin time by utilizing the receiver-operating characteristic (ROC) area under the curve (AUC). Results: Thrombin time exhibited a statistically significant prolongation in the preeclampsia cohort compared to the healthy pregnancy cohort (p < 0.05). This significance was maintained after adjusting for maternal age and gestation at testing in the logistic regression model. The AUC for thrombin time was found to be 0.953, with a commendable specificity of 97.28% and sensitivity of 92.48% in predicting preeclampsia. Conclusions: Our findings provide compelling evidence of a noteworthy association between prolonged thrombin time in the first trimester and an elevated risk of preeclampsia. The robust positive correlation underscores the potential of prolonged thrombin time as a predictive marker for the development of preeclampsia. Nevertheless, it is crucial to emphasize that further experimental studies are imperative to elucidate the underlying pathogenesis of thrombin time in the progression of preeclampsia.

Leveraging quality improvement to promote health equity: standardization of prenatal aspirin recommendations

ObjectiveAspirin (ASA) is recommended for patients at elevated risk of preeclampsia. Limited data exists on adherence to guidelines for ASA prescription. This project evaluates the implementation of a standardized approach to ASA prescription in an academic OB/Gyn practice.MethodsWe implemented a quality improvement project to evaluate compliance with the United States Preventative Services Task Force (USPSTF) recommendations for ASA to prevent preeclampsia. Pre-intervention, we analyzed prescription adherence at 201 New Obstetric (NOB) visits. A multi-step intervention was then implemented at 199 NOB visits. Nurses utilized a checklist created from USPSTF guidelines to identify high-risk patients, defined as having ≥1 high-risk factor or ≥2 moderate-risk factors. ASA orders were placed by physicians. A Plan-Do-Study-Act (PDSA) cycle was performed, and changes implemented. Primary outcome was percent of patients screened at RN intake visit (goal = 90%). Secondary outcomes were percent of patients who screened positive that received the ASA recommendation (goal = 80%) and percent screened and recommended by race.ResultsPre-intervention, 47% of patients met criteria for ASA and 28% received a documented recommendation. Post-intervention, 99% were screened. Half (48%) met criteria for an ASA recommendation and 79% received a recommendation (p = < 0.001). Rates of appropriate recommendation did not differ by Black (80%) vs. non-Black (79%) status (p = 0.25). Subsequent PDSA cycles for 12 months neared 100% RN screening rates. Physicians correctly recommended ASA 80–100% of the time.ConclusionIt is feasible, sustainable and equitable to standardize screening and implementation of ASA to patients at high risk for preeclampsia. Providers can easily reproduce our processes to improve delivery of equitable and reliable preventative obstetric care.

A systematic review of association between vitamin D levels and pre-eclampsia in pregnant womens - An old problem revisited

The beneficial effects of sunlight in preventing bone-related disorders have been well-known for centuries. Vitamin D is a modified steroid, synthesised under the influence of sunlight in the skin. Low Vitamin D status has associated with a higher risk of pre-eclampsia in pregnant womens. The aim of this study was to undertake a systematic review of different studies investigating the association between Vitamin D levels and pre-eclampsia in pregnant womens. A systematic review was undertaken. MEDLINE, PUBMED, EMBASE, Google Scholar were searched. The review protocol was designed to answer the question. Search terms (Preeclampsia and Vitamin D or 1,25 dihydroxy vitamin D). The search was confined to peer-reviewed articles that were published in English and contained an abstract. Reference list of journal articles were also screened for additional citations fitting our search criteria. Twenty-Seven studies were included in the systematic review that investigates the association between Vitamin D and pre-eclampsia. The present systematic review concludes that maternal vitamin D deficiency in pregnancy is significantly associated with an elevated risk of preeclampsia. Pregnant womens should take vitamin D supplementation, expose themselves into the sunlight, and they should be physically active. Further taking Vitamin D supplementation in early pregnancy may be a simple way to reduce the risk of these adverse pregnancy outcomes.

Effects of early aspirin therapy on utero-placental hemodynamics in patients at risk of preeclampsia

Objectives To evaluate the effects of early aspirin therapy on the mean pulsatility index of both uterine arteries (utA PI) at 1st and 2nd trimester in women at risk of preeclampsia (PE). Methods Uterine artery (utA) blood flow characteristics were obtained in 315 women, 73 women at risk for PE and early aspirin treatment (group 1), 124 without specific risk factors and no aspirin treatment (group 2) and 118 women with manifest PE (group 3). Mean utA PI of group 1 and group 2 were compared within and between the groups at the 1st and 2nd trimester time points. Furthermore, values at 2nd trimester were compared with those of group 3. Observed to expected mean utA PI ratio (O/E ratio) were calculated for comparison between the groups. Results Mean utA PI of group 1 was significantly higher in the 1st trimester compared to group 2 (1.74 vs. 1.47, p = .0117). In the 2nd trimester mean PI decreased significantly in both groups from 1.74 to 1.16 in group 1 and from 1.47 to 0.90 in group 2 (p < .0001). Nevertheless, the difference between the groups was significantly higher in the 2nd trimester than in the 1st trimester (0.29 vs. 0.27, p < .001). Correction for gestational age by analyzing mean utA O/E ratios showed a comparable pattern with a significantly decrease in both groups (1.40 to 1.10 in group 1 and 1.18 to 0.78 in group 2, p < .0001), but a significant higher decrease in the 2nd trimester in group 2 (0.31 vs.0.22, p < 0001). The prevalence of PE was 15.1% (11/73) in group 1 (4 early/7 late onset PE) and 4.7% (6/124) in group 2 (1 early/5 late onset). Mean utA PI and O/E ratio obtained in the 2nd trimester were higher in all PE cases with no significant difference between early and late onset PE (1.49/1.57 and 1.25/1.36 in group 1 and 0.80/0.97 and 0.77/0.99 in group 2). However, mean utA PI and O/E ratio decreased in all cases without PE in both groups, whereas mean utA PI was 1,37 and O/E-ratio was 1,29 in patients with manifest PE at admission, with significantly higher values in early onset than in late onset PE (1.45/1.31 vs. 1.07/1.02, p < .0001). Conclusions Our results show that early aspirin treatment leads to a decrease of elevated mean utA PI between 1st and 2nd trimester in patients at elevated risk for PE which is inferior to the decrease observed in women at standard risk for PE. While aspirin improves trophoblast invasion during early second trimester, vascular resistance remains well above average levels. Limited vascular remodeling capacity in the utero-placental perfusion area seems to be the explanation why aspirin does not abrogate PE in all women and has little effect on birth weight. Another explanation might be that a dose of 100 mg aspirin was used as compared to the 150 mg which is recommended today. Our findings underscore the need to study the effects of intervention already during the early stages of trophoblast invasion in the first trimester.

Increased Risk of Pre-eclampsia After Frozen-Thawed Embryo Transfer in Programming Cycles.

Objective: This study aims to investigate whether obstetric complications and perinatal outcomes after frozen embryo transfer (FET) in the programming cycles differ from that in the natural cycles.Methods: We conducted a retrospective cohort study collecting a total of 14,373 singletons born after frozen embryo transfer at the Center for Reproductive Medicine Affiliated to Shandong University from September 2013 to September 2018. The women were divided into two groups according to the regimens for endometrium preparation: either natural cycles (n = 10,211) or programming cycles (n = 4,162). The primary outcomes were the incidence of obstetric complications consisting of pre-eclampsia, gestational diabetes mellitus, placenta previa, placental abruption, and postpartum hemorrhage. The perinatal outcomes included average birthweight, low birthweight (LBW), very LBW, macrosomia, large for gestational age, and small for gestational age. Multivariable logistic regression analysis was performed to adjust for potential confounders.Results: The incidences of pre-eclampsia (8.6 vs. 3.8%) and postpartum hemorrhage (0.7 vs. 0.2%) in the programming FET cycles were significantly higher than those in the natural FET cycles. The logistic regression analysis showed that, compared to the natural FET cycles, the programming FET cycles were associated with an elevated risk of pre-eclampsia (aOR, 2.55; 95% CI, 2.06–3.16) and postpartum hemorrhage (aOR, 2.94; 95% CI, 1.44–5.99).Conclusion: The women with singleton delivery after frozen-thawed embryo transfer in the programming cycles had an elevated risk of pre-eclampsia and postpartum hemorrhage, which was speculated to be associated with the absence of the corpus luteum.

Prediction of pre-eclampsia in nulliparous women using routinely collected maternal characteristics: a model development and validation study

BackgroundGuidelines recommend identifying in early pregnancy women at elevated risk of pre-eclampsia. The aim of this study was to develop and validate a pre-eclampsia risk prediction model for nulliparous women attending routine antenatal care “the Western Sydney (WS) model”; and to compare its performance with the National Institute of Health and Care Excellence (NICE) risk factor-list approach for classifying women as high-risk.MethodsThis retrospective cohort study included all nulliparous women who gave birth in three public hospitals in the Western-Sydney-Local-Health-District, Australia 2011–2014. Using births from 2011 to 2012, multivariable logistic regression incorporated established maternal risk factors to develop and internally validate the WS model. The WS model was then externally validated using births from 2013 to 2014, assessing its discrimination and calibration. We fitted the final WS model for all births from 2011 to 2014, and compared its accuracy in predicting pre-eclampsia with the NICE approach.ResultsAmong 12,395 births to nulliparous women in 2011–2014, there were 293 (2.4%) pre-eclampsia events. The WS model included: maternal age, body mass index, ethnicity, multiple pregnancy, family history of pre-eclampsia, autoimmune disease, chronic hypertension and chronic renal disease. In the validation sample (6201 births), the model c-statistic was 0.70 (95% confidence interval 0.65–0.75). The observed:expected ratio for pre-eclampsia was 0.91, with a Hosmer-Lemeshow goodness-of-fit test p-value of 0.20. In the entire study sample of 12,395 births, 374 (3.0%) women had a WS model-estimated pre-eclampsia risk ≥8%, the pre-specified risk-threshold for considering aspirin prophylaxis. Of these, 54 (14.4%) developed pre-eclampsia (sensitivity 18% (14–23), specificity 97% (97–98)). Using the NICE approach, 1173 (9.5%) women were classified as high-risk, of which 107 (9.1%) developed pre-eclampsia (sensitivity 37% (31–42), specificity 91% (91–92)). The final model showed similar accuracy to the NICE approach when using lower risk-threshold of ≥4% to classify women as high-risk for pre-eclampsia.ConclusionThe WS risk model that combines readily-available maternal characteristics achieved modest performance for prediction of pre-eclampsia in nulliparous women. The model did not outperform the NICE approach, but has the advantage of providing individualised absolute risk estimates, to assist with counselling, inform decisions for further testing, and consideration of aspirin prophylaxis.

118. Significant increase of soluble B7-H4 in women at high-risk for preeclampsia in the first trimester: A potential immunological biomarker for immunologically-mediated pregnancy complications?

Introduction The successful outcome of pregnancy requires adequate immune tolerance. A lack of appropriate tolerance might cause placental dysfunction and pregnancy complications such as preeclampsia (PE). Members of the B7 family play an essential role in maintaining immune tolerance in pregnancy by effecting T cells. Objectives B7-H4 is responsible for the negative regulation of T-cell-mediated immune response and might play an important role in PE. We currently revealed that sB7-H4 is involved in the spontaneous onset of labor and is elevated in early pregnancy in women with a preterm premature rupture of the amniotic membranes (pPROM). Thus, here we investigated the association between PE and sB7-H4 levels. Material and methods Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in first trimester with elevated risk for PE Results In women at elevated risk for PE in first trimester significantly higher levels of sB7-H4 were detected compared to controls (p Conclusion sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE.

Soluble B7‐H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia

B7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta. Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13weeks' gestation with elevated risk for PE (n=48) and women without elevated risk for PE (n=47). In the third trimester, sB7-H4 serum levels (n=166) and B7-H4 mRNA expression in the placenta (n=54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls. In the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P<.0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P=.01 and P=.006, respectively) and late-onset PE (P=.03 and P=.004, respectively) compared to healthy controls, but not compared to FGR. sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE.

P 40 Infant but not maternal APOL1 variant genotypes are associated with increased risk for preeclampsia in African Americans

Introduction APOL1 genetic variants are common among African Americans (AA), and account for much of the increased risk of chronic kidney disease among AA. APOL1 is abundantly transcribed in the placenta, shows abnormal expression in preeclampsia and APOL1 transgenic mice manifest preeclampsia. As AAs are at elevated risk for preeclampsia, prematurity and low birth weight, we studied the relationship between these conditions and APOL1 status. Methods CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood), is a study of 1503 mothers and infants, including 990 AA women. Gestational age was determined by ultrasound or reported last menstrual cycle. Birthweight and pregnancy complications were abstracted from mother’s medical record. APOL1 genotyping was performed with TaqMan assay and validated by Sanger sequencing. Mothers and children were categorized as having 0, 1 or 2 risk alleles (RA) (with 2 RA denoting risk variant homozygotes or compound heterozygotes). Multivariate analyses for a recessive model were performed, adjusted for maternal age, income, and gender. Population attributable risk was calculated using standard approaches. Results Among 990 AA CANDLE mothers, the mean delivery age was 24.7 y and mean gestational age was 38.7 w. Of 921 genotyped mothers, 100 (10.9%) had 2 risk alleles (RA); of 747 genotyped children, 103 (13.8%) had 2 RAs. There was no association between maternal or child APOL1 status and gestational age or birth weight among all pregnancies or when the analysis excluded mothers with electively induced labor or C-sections. An increased risk for preeclampsia was seen with the child’s APOL1 2 RA status. Among all pregnancies, mothers of children with 2 RA status had a 1.9-fold increase in risk for preeclampsia (OR 1.9; 95% CI 1.1,3.5). When electively induced labor and C-sections were excluded, the risk for preeclampsia among mothers of children with 2 RA was further increased (OR 2.1; 95% CI 1.1,4.0). Discussion Mothers of children with APOL1 2RA status are at an increased risk for preeclampsia. Our results suggest that approximately 10% of preeclampsia among AA is related to APOL1.

Pre-eclampsia Protectors and Promoters

A new study identifies genes linked to the risk for preeclampsia in a population from sub-Saharan Africa. These genes encode for human leukocyte antigen (HLA) ligands on trophoblasts and receptors that recognize these ligands, which are present on maternal Natural Killer (NK) cells [1]. Trophoblast invasion of the uterine tissue leads to the remodeling of uterine arteries into large vessels, thereby tapping the mother’s blood supply. This is a carefully equilibrated event. Too aggressive of an invasion can result in outsized babies, exposure to excess nutrients and oxygen in utero, and placental overgrowth conditions that can lead to hemorrhage. Poor invasion can result in such conditions as fetal growth restriction and pre-eclampsia. Maternal NK cells modulate the activity of trophoblasts, determining the extent of invasion in humans. This modulation occurs via HLA-C ligands on trophoblast cells, which recognize a key family of receptors on NK cells: killer-cell immunoglobulin-like receptors (KIRs). In previous studies, Ashley Moffett and colleagues found that genetic risk for pre-eclampsia, and some related conditions such as fetal growth restriction, is linked to various genetic variants at the KIR and HLA-C loci. But their studies, conducted primarily in European populations, limit their analysis. In the new study, the researchers turned to women of sub-Saharan African ancestry, who have elevated rates of pre-eclampsia and also a high diversity of KIR genotypes, and found some parallels and some differences with European women. Moffett and colleagues studied pregnant women at a hospital in Kampala, Uganda: 251 with pre-eclampsia and 483 without the condition. As with Europeans, they found elevated risk for pre-eclampsia in women homozygous for one of two major haplotypes, the KIR A haplotype. This risk was even higher if the fetus also had particular HLA-C alleles, which encode C2 epitopes (all HLA-C alleles encode either a C1 or C2 epitope). The researchers also identified three KIR genes that seemed to protect against pre-eclampsia in the women in Kampala—alleles that are rare in Europeans. A KIR gene known to be protective in Europeans was found at only low frequency in the women from Kampala. The study highlights the need for global genetic studies to assess pre-eclampsia risk—curiously, distinct human populations seem to have evolved to have distinct mixes of favorable KIR-HLA-C combinations. Future research should flesh out the biological mechanisms. One study, for instance, showed that favorable KIR-HLA-C combinations result in increased production of soluble factors that promote trophoblast invasion.

Current insights into thrombotic microangiopathies: Thrombotic thrombocytopenic purpura and pregnancy

The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with ThromboSpondin type 1 domains, no. 13). In several affected women disease onset during their first pregnancy leads to the diagnosis of hereditary TTP. Without plasma treatment mother and especially fetus are at high risk of dying. The relapse risk during a next pregnancy is almost 100% but regular plasma transfusion starting in early pregnancy will prevent acute TTP flare-up and may result in successful pregnancy outcome. Pregnancy may also constitute a mild risk factor for the onset of acute acquired TTP caused by autoantibody-mediated severe ADAMTS13 deficiency. Women having survived acute acquired TTP may not be at very high risk of TTP relapse during an ensuing next pregnancy but seem to have an elevated risk of preeclampsia. Monitoring of ADAMTS13 activity and inhibitor titre during pregnancy may help to guide management and to avoid disease recurrence. Finally, TTP needs to be distinguished from the much more frequent hypertensive pregnancy complications, preeclampsia and especially HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count) syndrome.

Significance of maternal periodontal health in preeclampsia.

Objective:The aim of the present case–control study was to evaluate the association between maternal periodontitis and preeclampsia. Association studies between maternal periodontitis and elevated risk for preeclampsia have shown conflicting results. Periodontal maintenance is necessary to reduce the risk of adverse pregnancy outcomes like preeclampsia.Materials and Methods:Periodontal parameters [bleeding on probing, probing depth (PD), and clinical attachment level (CAL)] of 1320 women were assessed, followed by retrieval of their demographic and medical data from the medical records. Based on the medical records, 80 women were excluded from the study, leaving 1240 females as the eligible sample for the study. The women were divided into control group (1120 non-preeclamptic women who gave birth to infants with adequate gestational age) and case group (120 preeclamptic women). Logistic regression analysis revealed that primiparity and maternal periodontitis were the two significant variables causing preeclampsia. Further analysis was carried out by matching the two groups for primiparity to find the significance of maternal periodontitis. Maternal periodontitis was defined as PD ≥4 mm and CAL ≥3 mm at the same site in at least four teeth.Results:The results showed that maternal periodontitis (odds ratio 19.8) was associated with preeclampsia. Maternal periodontitis also remained associated with preeclampsia after matching for primiparity, which was another significant confounding factor in the study (odds ratio 9.33).Conclusion:Maternal periodontitis is a risk factor associated with preeclampsia, emphasizing the importance of periodontal care in prenatal programs.

302-POS

Objectives Assessing risk of developing a hypertensive disorder of pregnancy (HDP) in nulliparous women is imprecise. Previous evidence suggests that self-reported family history of cardiovascular disease and risk (in particular risk in the woman’s father) may improve identification of preeclampsia (Parker, ISOM 2012). The aim of this study was to evaluate maternal report of paternal family history of cardiovascular disease (CVD) or risk (CVR) as a risk factor for HDP including preeclampsia. Methods Women were recruited prospectively and reported on cardiovascular health in themselves, their partners and first degree relatives (n = 997). HDP diagnoses were assigned using SOMANZ (2008) criteria. Results Preeclampsia was diagnosed in 12.6% of women, gestational hypertension in 6.2%. CVD/CVR was reported by 22.3% of mothers (1.7% CVD alone) and 9.3% of partners (1.7% CVD alone). Median age of the women was 27 years (range 16–45), median age of the partners was 30 years (range 26–34). All partners with CVD were under 45 years old (median 32, range 24–39). The median age of men with risk alone was 33 years (range 29–38). Partners’ CVD increased risk of preeclampsia (5.6% vs. 1.7%; OR = 5.07, 95% CI 1.72–14.94, p = .003) adjusted for maternal age, BMI, smoking and maternal CVD/CVR. No increase in risk of gestational hypertension was evident. Partners’ CVR did not appear to increase risk of HDP. Conclusions History of CVD in the woman’s partner may indicate elevated risk of preeclampsia however, the low frequency of CVD in partners at this young age impacts on the sample size and should be examined in future research. Disclosures C.E. Parker: None. D.A. Doherty: None. B.N. Walters: None.

Placental Protein 13 (PP13) - A Placental Immunoregulatory Galectin Protecting Pregnancy.

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a “jelly-roll” fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure due to vasodilatation in pregnant animals suggest its therapeutic potential in preeclampsia.

Ethnic Differences in Blood Pressure and Hypertensive Complications During Pregnancy

The aim was to investigate ethnic differences in blood pressure levels in each trimester of pregnancy and the risk of gestational hypertensive disorders and the degree to which such differences can be explained by education and lifestyle-related factors. The study included 6215 women participating in a population-based prospective cohort study from early pregnancy onward in Rotterdam. Ethnicity was assessed at enrollment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical charts. Lifestyle factors included smoking, alcohol, caffeine intake, folic acid supplementation, sodium and energy intake, body mass index, and maternal stress. Associations and explanatory pathways were investigated using linear and logistic regression analysis. Dutch pregnant women had higher systolic blood pressure levels as compared with women in other ethnic groups in each trimester of pregnancy. Compared with Dutch women, Turkish and Moroccan women had lower diastolic blood pressure levels in each trimester. These differences remained after adjusting for education and lifestyle factors. Turkish and Moroccan women had a lower risk of gestational hypertension as compared with Dutch women (odds ratio, 0.32 [95% CI, 0.18–0.58] and odds ratio, 0.28 [95% CI, 0.14–0.58]), and Cape Verdean women had an elevated risk of preeclampsia (odds ratio, 2.22 [95% CI, 1.22–4.07]). Differences could not be explained by education or lifestyle. Substantial ethnic differences were observed in blood pressure levels and risk of gestational hypertensive disorders in each trimester of pregnancy, and a wide range of variables could not explain these differences.

OS036. Ethnic differences in blood pressure and hypertensivecomplications during pregnancy; the generation R Study

Blood pressure levels during pregnancy are important risk factors for gestational hypertensive disorders. Non-pregnant women from ethnic minority groups are found to have higher blood pressure levels compared to white women. Little is known about variation in blood pressure development during pregnancy across different ethnic groups. To investigate ethnic differences in blood pressure levels in each trimester of pregnancy and the risk of gestational hypertensive disorders and the degree to which such differences can be explained by education and lifestyle related factors. The study included 6215 women participating in a population-based prospective cohort study from early pregnancy onwards in Rotterdam, The Netherlands. Ethnicity was assessed at enrolment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical records. Lifestyle factors included smoking, alcohol, caffeine intake, folic acid supplementation, sodium and energy intake, body mass index and maternal stress. Associations and explanatory pathways were investigated using linear and logistic regression analysis. Dutch pregnant women had higher systolic blood pressure levels as compared to women in other ethnic groups in each trimester of pregnancy. Compared to Dutch women, Turkish and Moroccan women had lower diastolic blood pressure levels in each trimester. These differences remained after adjusting for education and lifestyle factors. Turkish and Moroccan women had a lower risk of gestational hypertension as compared to Dutch women (OR 0.32; 95% CI: 0.18, 0.58 and OR 0.28; 95% CI: 0.14, 0.58) and Cape Verdean women had an elevated risk of preeclampsia (OR 2.22; 95% CI: 1.22, 4.07). Differences could not be explained by education or lifestyle. Substantial ethnic differences were observed in blood pressure levels in each trimester of pregnancy and risk of gestational hypertensive disorders. A wide range of potential explanatory variables could not explain these differences.

AGT M235T polymorphism contributes to risk of preeclampsia: evidence from a meta-analysis

Preeclampsia a hypertensive disorder of pregnancy that mainly manifests as high blood pressure and proteinuria. Angiotensinogen (AGT) plays important roles in the regulation of blood pressure. The purpose of this study was to investigate the relationship between AGT M235T polymorphism and risk of preeclampsia using a meta-analysis. In this meta-analysis, 22 studies were selected by searching PubMed, EMBASE, ISI and CNKI databases up to October 2011. Crude odds ratios with corresponding 95% confidence intervals were used to evaluate the association between the AGT M235T polymorphism and risk of preeclampsia. Subgroup analyses were conducted by ethnicity and parity. The TT genotype of the AGT M235T polymorphism was associated with elevated risk of preeclampsia in the overall analysis. In subgroup analysis according to ethnicity, increased risks were also found in Caucasians. After stratification based on parity, the excess risk was found in multigravida. These results showed that the TT genotype may play critical roles in the development of preeclampsia.

Elevated Risk of Preeclampsia in Pregnant Women With Depression: Depression or Antidepressants?

A previous study suggested an increased risk of preeclampsia among women treated with selective serotonin reuptake inhibitors (SSRIs). Using population-based health-care utilization databases from British Columbia (1997-2006), the authors conducted a study of 69,448 pregnancies in women with depression. They compared risk of preeclampsia in women using SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) between gestational weeks 10 and 20 with risk in depressed women not using antidepressants. Among prepregnancy antidepressant users, the authors compared the risk in women who continued antidepressants between gestational weeks 10 and 24 with the risk in those who discontinued. Relative risks and 95% confidence intervals were estimated. The risk of preeclampsia in depressed women not treated with antidepressants (2.4%) was similar to that in women without depression (2.3%). Compared with women with untreated depression, women treated with SSRI, SNRI, and TCA monotherapy had adjusted relative risks of 1.22 (95% confidence interval (CI): 0.97, 1.54), 1.95 (95% CI: 1.25, 3.03), and 3.23 (95% CI: 1.87, 5.59), respectively. Within prepregnancy antidepressant users, the relative risk for preeclampsia among continuers compared with discontinuers was 1.32 (95% CI: 0.95, 1.84) for SSRI, 3.43 (95% CI: 1.77, 6.65) for SNRI, and 3.26 (95% CI: 1.04, 10.24) for TCA monotherapy. Study results suggest that women who use antidepressants during pregnancy, especially SNRIs and TCAs, have an elevated risk of preeclampsia. These associations may reflect drug effects or more severe depression.

Low-dose aspirin for prevention of pre-eclampsia and its complications: a cost-effectiveness analysis

ObjectiveThe authors investigated whether low-dose aspirin (ASA) is a cost-effective means of reducing the risk of pre-eclampsia.Study DesignA decision analytic model was designed comparing ASA prophylaxis vs no prophylaxis in...