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Pathogenesis and genetics of pre-eclampsia
Abstract
After more than a century of intensive research, pre-eclampsia and eclampsia remain an enigmatic set of conditions. Aberration of the interaction between placental and maternal tissue is probably the primary cause, but the exact nature of the differences from normal pregnancy remain elusive. In this review attempts to understand the sequence of physiological changes have concentrated on vascular endothelium and oxidative stress issues. There are genetic components to susceptibility, but the relative contributions of maternal and fetal genotypes are still unclear. Whole-genome mapping could ultimately define the causative genes.
... However, it has been noted that not all women with reduced placental perfusion, develop preeclampsia. This paradox has led to the theory that preeclampsia is a two stage disorder with maternal-foetal interactions necessary to link the two stages 23 . ...
... Reduced placental perfusion is thought of as the first stage, while the second stage, the maternal syndrome, develops in a subgroup of women with certain genetic, environmental and behavioural characteristics as a response to factors produced by the poorly perfused placenta 23 . In a suitable maternal environment, oxidative stress and subsequent endothelial activation and injury result, initiating the coagulation cascade and ensuing multisystem sequelae 24 . ...
Background: Hypertensive disease in pregnancy accounts for about 10-15% of maternal deaths in sub-Saharan Africa and Asia. The relationship between maternal BMI and Hypertensive disease in pregnancy has received limited attention especially in these lowandmiddle-income settings. This study aimed to quantitatively describe the relationship between maternal BMI in the first half of pregnancy and the risk of developing hypertensive disease later in pregnancy.Methodology: A prospective cohort of pregnant women attending antenatal clinic at 37 Military Hospital, Accra between 15 June 2015 and 22nd March 2016 was conducted. A total of 196 consenting expectant mothers in the first half of pregnancy who met the inclusioncriteria were recruited based on their BMI classification as normal or abnormal. They were followed up at regular antenatal visits till delivery. At these visits, repeated measurements of weight and blood pressure were taken. Univariate and multivariate statistical analysis taking into account the other risk factors for hypertensive disease in pregnancy was performed. Level of significance was set at p<0.05.Results: Maternal BMI in the first half of pregnancy was significantly associated with developing hypertensive disease in pregnancy in second half of pregnancy. About 10 % of normal BMI mothers and 14% of abnormal BMI mothers developed hypertensive disease respectively. An increase in BMI within each BMI category was associated with an increased risk of developing Hypertensive disease in pregnancy.Conclusion: Promoting a healthy maternal BMI in the first half of pregnancy may help reduce the risk of hypertensive disease later in pregnancy.
... Pre-eclampsia (PE) is a multi-organ condition that arises after 20 weeks' gestation and is characterized by high blood pressure (BP >140/90 mmHg) and proteinuria. It is amongst the most prevalent pregnancy problems, involving 3-5% of all expectant mothers and common cause of maternal and perinatal mortality [1,2]. PE accounts for 12% of all maternal deaths worldwide, 1 but its contribution to feto-maternal morbidity and mortality is worsened in developing countries, with 10% rate of complication compared to the global complication rate of 2-8% [3,4]. ...
... It is amongst the most prevalent pregnancy problems, involving 3-5% of all expectant mothers and common cause of maternal and perinatal mortality [1,2]. PE accounts for 12% of all maternal deaths worldwide, 1 but its contribution to feto-maternal morbidity and mortality is worsened in developing countries, with 10% rate of complication compared to the global complication rate of 2-8% [3,4]. The prevalence of PE differs greatly globally, with its occurrence estimated to be seven times higher in developing countries, constituting 2.8% of live births as compared to 0.4% in developed countries [5]. ...
Aim: To assess the predictive values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV) for pre-eclampsia in pregnancy. Study Design: Retrospective cross-sectional study. Place and Duration of Study: Obstetrics and Gynecology unit of Tamale Teaching Hospital, Tamale, Ghana from 1 st January, 2021 to 31 st December, 2021. Methodology: The study recruited 161 pregnant women (79 pre-eclamptic pregnant women and 82 apparently healthy pregnant women as controls). Full blood count parameters were assessed using fully automated haematology analyzer. Neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio were calculated. Data analysis was done with SPSS version 22.0 and P<0.05 was considered statistically significant. Results: Pregnant women with PE had lower parity (P< .001) and gestational ages (P< .001) than their counterparts without PE. Haemoglobin (P= .007), red blood cells (P= .003), haematocrit (P= .01), absolute monocyte (P= .001) and MPV (P= .02) were significantly higher in the PE group compared to the controls. Also, pregnant women with PE had relatively higher MPV compared with the apparently healthy pregnant women without pre-eclampsia (P= .02), but NLR and PLR were not different between the two groups. Again, MPV significantly predicted PE (AUC: 0.609, P< .02) in pregnancy than NLR and PLR. Conclusion: Lower parity and gestational ages are significantly associated with pre-eclampsia. Hb, RBC, HCT, absolute monocyte count and MPV were higher in pre-eclamptic pregnant women. MPV is a better marker for predicting asymptomatic PE in pregnancy. NLR and PLR did not significantly predict PE in pregnancy.
... 3 A incidência de PE varia de 2% a 10% das gestações em todo o mundo; no Brasil representa a maior causa de mortalidade materna, com cerca de 37% das causas diretas. 4 Entre os diversos fatores de risco (FR) para desenvolver pré-eclâmpsia destacam-se: obesidade, diabetes mellitus, gestações múltiplas, trombofilias, lúpus, hipertenção arterial crônica, história de PE prévia ou familiar, primipaternidade, primiparidade e idade acima de 40 anos. 5 Segundo o Colégio Americano de Ginecologia e Obstetrícia, as síndromes hipertensivas durante a gravidez apresentam as seguintes modalidades: ...
Objetivos: Avaliar o conhecimento em relação à pré-eclâmpsia e sua prevenção entre médicos obstetras e residentes de obstetrícia e ginecologia. Materiais e métodos: O estudo será realizado por meio da aplicação de um questionário que abordará temas relacionados à prevenção da PE. Este questionário será entregue para médicos residentes de ginecologia e obstetrícia e para médicos obstetras que assistem pacientes com risco para PE. Resultados: nenhum dos participantes (0%) citou todos os fatores de alto risco para pré-eclampsia e apenas 5,41% dos participantes citou todos os critérios clínicos para suspeita de pré-eclâmpsia. Ainda, apenas 5,41% dos participantes reconheceu todos os critérios laboratoriais para pré-eclâmpsia. Apesar disso, a grande maioria (85,13%) citou AAS e cálcio ou apenas um deles como medida profilática para pré-eclampsia. Conclusão: A despeito dos avanços nos diagnósticos, nas medidas preventivas e nas condutas bem estabelecidas, a morbimortalidade relacionada às síndromes hipertensivas durante o ciclo gravídico puerperal mantém-se elevada. Em congruência com os resultados obtidos, acreditamos que seja devida à falta de identificação de grupos de risco, carência de prevenção adequada, dificuldade de manter um seguimento pré-natal diferenciado, demora realizar o diagnóstico, redução do uso do sulfato de magnésio, demora na conduta de interrupção da gestação e carência no seguimento puerperal destas doentes de risco.
... During the first trimester of pregnancy, 50-80% of the lymphocytes present in the decidua (the maternal uterine mucosa located directly at the maternal-fetal interface) are dNK cells characterized by being CD56 bright , CD16 neg [14]. The dNK cells display a distinctly different behavior compared with the blood circulating NK cells which only contain 5-10% of this specific CD56 bright CD16 neg subset [15]. The dNK cells are less cytotoxic and instead are able to regulate and support implantation and early pregnancy [16]. ...
Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in better placentation and fetus-growth, hence termed pregnancy trained dNKs (PTdNKs). Here we show that PTdNKs provide increased protection of the fetus from Fusobacterium nucleatum ( FN ) infection. We demonstrate that PTdNKs secrete elevated amounts of the bacteriocidal protein granulysin (GNLY) upon incubation with FN compared to dNKs derived from first pregnancies, which leads to increased killing of FN . Furthermore, we showed mechanistically that the GNLY secretion is mediated through the interaction of the FN ’s Fap2 protein with Gal-GalNAc present on PTdNKs. Finally, we show in vivo, using GNLY-tg mice that enhanced protection of the fetuses from FN infection is observed, as compared to wild type and that this enhance protection is NK cell dependent. Altogether, we show a new function for PTdNKs as protectors of the fetus from bacterial infection.
... According to a study involving 350 PE patients and 450 normal pregnant women, maternal levels of vitamin B12, folate, and homocysteine were higher in PE patients [33]. Folate might influence homocysteine levels, and hyperhomocysteinemia is believed to damage the vascular endothelium of the developing placenta, leading to endothelia injury [34]. However, a large-scale randomized controlled trail found no evidence that high-dose folate supplementation later in early pregnancy had any effort on preventing preeclampsia [35]. ...
Purpose
Epidemiological studies examining the association between circulating micronutrients and the risk of hypertensive disorders during pregnancy (HDP) have produced inconsistent results. Therefore, we conducted a Mendelian randomization (MR) analysis to evaluate the potential causal relationship between micronutrients and HDP.
Methods
Nine micronutrients (beta-carotene, vitamin B6, vitamin B12, calcium, zinc, selenium, copper, folate, and phosphorus) were selected as the exposure factors. Summary data for gestational hypertension (14,727 cases and 196,143 controls) and preeclampsia/eclampsia (7212 cases and 174,266 controls) were extracted from the FinnGen consortium. The MR analysis employed the inverse variance weighted method and conducted a range of sensitivity analyses.
Results
The inverse variance weighted method indicated no significant causal relationship between nine genetically predicted micronutrient concentrations and gestational hypertension, as well as preeclampsia/eclampsia. Sensitivity analyses suggested the absence of pleiotropy.
Conclusion
There is no strong evidence to support the causation between circulating micronutrients and hypertensive disorder during pregnancy.
... Зокрема, вона може зумовлювати звуження судин, відтак підвищення периферійного судинного опору, що швидко призводить до судинного ремоделювання, тобто структурних, механічних і функціональних змін резистивних артерій, що пов'язано з розвитком та ускладненнями гіпертензії [21,22]. ...
The objective: to determine the impact of COVID-19, which occurred before or during pregnancy, on the frequency of development and features of the course of gestational hypertension and preeclampsia.Materials and methods. An observational retrospective study with parallel control one was conducted. The pregnancy course and its outcomes in 178 women during the period of the COVID-19 pandemic – from March 2020 to January 2022 – who were observed in the women’s consultation of a private medical center, were analyzed. It is important to note that the medical documentation was taken one after the other, without being specially selected according to any principle, that is, the analysis carried out had the character of continuous screening.Out of 178 pregnant women, 125 (70.2%) persons were sick with COVID-19, they were included in the main group; 53 (29.8%) women who were part of the comparison group did not get sick. The groups are comparable by age and body mass index. The age of the women was 19–51 years; in the main group – 30.5±4.9 years, in the comparison group – 30.9±5.6 years. Body mass index (kg/m2) at the beginning of pregnancy in women of the main group was 21.6±4.3; comparison group – 22.9±4.8. There were 104 (58.4%) primigravida, 74 (41.6%) – multigravida. 117 (65.7%) women were primipara, 61 (34.3%) – multipara.All pregnant women were performed with a standard examination in accordance with the Order No. 417 of the Ministry of Health of Ukraine dated 15.07.2011. Clinical and anamnestic risk factors for the development of preeclampsia were assessed in all women without exception, on the basis of which 3 women were assigned to the risk group. In addition, 158 (88.8%) pregnant women as part of the first combined screening had an additional examination to determine the risk of developing preeclampsia, as a result of which additional 23 women were included in the risk group. As a result, 26 (14.6%) pregnant women from 12 weeks of gestation were prescribed prophylaxis using acetylsalicylic acid.Results. In women who have had COVID-19, hypertensive disorders of pregnancy develop statistically significantly less often than in those who have not had the disease. After mildly symptomatic COVID-19 the risks of hypertensive disorders in pregnant women are statistically significantly reduced: gestational hypertension – RR=1.15, 95% CI: 1.0–1.3; preeclampsia – RR=1.1, 95% CI: 1.0–1.2, all hypertensive disorders – BP=1.3, 95% CI: 1.1–1.6.The groups did not differ among themselves in the prevalence of generally accepted risk factors. The frequency of hypertensive disorders depending on the vaccination was analyzed. The risk of gestational hypertension in vaccinees who did not suffer from COVID-19 is reduced by 1.4 times (RR=1.4, 95% CI: 1.0–1.9), the risk of all hypertensive disorders in pregnant women in this same group is reduced 2 times (RR=2.0, 95% CI: 1.2–3.5).The development of preeclampsia also probably depends on the vaccination status (χ2=4.0; p=0.04; φ=-0.17). In non-vaccinated persons it increases by 1.1 times (RR=1.1, 95%CI: 1.2–1.8). The risk of all hypertensive disorders is also higher in the group with a negative vaccine status (RR=1.3, 95%CI: 1.0–1.7) only at the level of significance p=0.06, that is, it appears as a certain tendency.Conclusions. Hypertensive disorders associated with pregnancy are less likely to develop in women who have experienced COVID-19 in the preconception period or during pregnancy. Vaccination against COVID-19 reduces the frequency of hypertensive disorders in pregnant women, regardless of the disease presence.Since immune mechanisms, along with placental-vascular mechanisms play a significant role in the pathogenesis of preeclampsia, let’s assume that the experienced coronavirus infection or vaccination against it disrupts certain links of immunity, which results in a decrease in the frequency of hypertensive disorders in pregnant women.
... 4,5 In many cases of pregnancies with adverse outcomes, failure of trophoblast invasion of spiral arteries has been observed, resulting in high-resistance vasculature with persistent smooth muscle histology of the maternal blood vessels. 6,7 Current evidence suggests that the placental pathology associated with deficient spiral artery remodeling is principally the consequence of oxidative stress and mechanical injury resulting from turbulent intermittent blood flow rather than chronic hypoxia. 8 . ...
The aim of the study is to study women at risk of PIH (Primi & Multi) by Colour Doppler velocimetry of uterine arteries. Pregnant women attending the antenatal clinics, screened for possible participation in the present study after explaining the nature of the study. A patient was diagnosed to have PIH if there was a rise in systolic pressure of at least 30 mmHg or a diastolic of at least 15 mmHg over the previously known blood pressure or an absolute rise in the blood pressure of at least 140/90 mmHg was taken to diagnose women as a case of PIH.
Out of the 100 cases, maximum 35 cases (35%) were low risk primigravidae, followed by cases with history of PIH (15%), obesity (14%), Anemia (10%),Essential hypertension (7%), IUGR (7%),Which constitute 53%. Rest of the cases was family history of hypertension (6%), oligohydromnios (5%) and Twin (1%).Maximum cases i.e. 40% were illiterate, 28% cases were educated up to primary school and only 20% were educated up to middle school and above. Total 60% cases were literate. 77.2% babies were alive, Abortion were 5.3% and 16.76% cases were with poor perinatal outcome. Study shows that 22% cases showed abnormal waveform in colour Doppler, out of which 90.90% developed PIH, while 78% cases were with normal waveform out of which only 10.25% developed PIH later. For prediction of IUGR out of 22% of abnormal waveform 86.36 developed IUGR and out of 78% of normal waveform 20.51% developed IUGR.
We conclude that a women with high risk factor (nulliparity and others) having abnormal uterine artery waveforms between 16-28 weeks of gestation (presence of diastolic notch with/without high resistance) are at higher risk of development of PIH (90.90%) and IUGR (95%). An important aspect is the high negative predictive value for PIH (89.74%) and IUGR (78.66%) which helps to detect those patient who will not develop PIH and IUGR early positive prediction enables, one to take preventive measures early thus improving both maternal and perinatal prognosis.
... theories suggest abnormal placental implantation and abnormal trophoblastic invasion as possible causes 6 . The molecular basis of this condition is unresolved in study 7 . It has been postulated that fluctuations in maternal serum ions may be the precipitating cause of elevated blood pressures in preeclampsia 8,9 . ...
Introduction: There are many Hypertensive disorders in pregnancy like preeclampsia, eclampsia etc. Pre-eclampsia is the most common medical complication of pregnancy associated with increased maternal and infant mortality and morbidity. Some studies have implicated that low serum calcium levels may have a role in pre-eclampsia but other studies failed to find relation between low levels of these trace elements and pre-eclampsia. Objectives: To evaluate serum calcium in pre-eclampsia & non pregnant women. Materials and Methods: This cross sectional study was carried out in among 31 pre-eclampsia patients, aged 20 to 40 years, and gestational age ranges from 20 to40 weeks and 31 age matched normotensive non-pregnant women having no proteinuria. Serum calcium was measured by Colorimetric method. Results:The mean serum calcium level was 5.91 (±2.12) mg/dl in pre–eclampsia and was 5.72 (±2.46) mg/dl in normal women. Conclusion The mean serum calcium level did not differ significantly between the subjects of pre–eclampsia and normal women (t=0; p<.05). The means of both data sets are equal so we can conclude that there is no significant difference between them. Medicine Today 2023 Vol.35(2): 121-123
... 8 Although the exact etiology is unknown, the pathophysiological mechanism is characterized by the failure of the trophoblastic invasion of the spiral arteries, leading to maladaptation of maternal spiral arterioles, which may be associated with increased vascular resistance of the uterine artery and a decreased perfusion of the placenta. 9,10 The implicated vascular resistance and under-perfusion of the placenta, may lead to the release of antiangiogenic factors into the maternal circulation and alter maternal systemic endothelial function to cause hypertension and other manifestations of the disease. Other contributory factors include obesity, diabetes, calcium deficiency, maternal age, and job stress. ...
Background: Studies have linked calcium to the aetiopathogenesis and prevention of preeclampsia, however, the precise mechanism involved is unclear therefore this study aimed to determine the relation between serum calcium and preeclampsia among normotensive pregnant women. Methods: The study was a cross-section descriptive design that included 88 pregnant women with singleton fetuses all at gestational ages above 20 weeks. Socio-demographic and obstetric data were obtained using a structured self-administered questionnaire. Urinary protein estimation was detected using the dipstick measurement of clean catch midstream urine specimens and blood samples were collected for serum calcium. Statistical analysis was done using SPSS version 21. Results: The majority of the participants 20 (45.5%) age range was between 15-44 years and the majority were also primigravida 31 (70.5%). Serum calcium level was significantly low among the study group 1.97±0.49 compared to the control 2.22±0.12. There was a significantly high systolic BP (162.11±18.01) and diastolic (104.88±16.69) among the study group with significant proteinuria. Conclusions: This finding suggested that serum calcium could be used as a marker for preeclampsia and based on the findings of this study, serial measurements of serum calcium among women who are at risk for pre-eclampsia may be used to predict the onset and severity of preeclampsia.
... Additionally, infants born to preeclamptic mothers face increased risks of prematurity, growth restriction, thrombocytopenia, and other adverse outcomes. 7 Various biological markers have been implicated in predicting the development of preeclampsia, including AFP, inhibin A, serum uric acid, microalbuminuria, urinary calcium, platelet count, fibronectin, human chorionic gonadotropin (hCG), VEGF, prostacyclin, CRP, and serum 25-hydroxy vitamin D. 8 The exact etiology and pathogenesis of hypertensive disorders of pregnancy are not fully understood. Abnormal placentation is considered one of the initial events in the disease process. ...
Background: Hypertensive disorders of pregnancy pose significant risks to maternal and fetal health, contributing to global morbidity and mortality. Despite extensive research, these disorders remain a public health concern, necessitating the identification and prediction of associated risks for effective prevention and management. Methods: A prospective observational study was conducted in a hospital setting, involving 200 antenatal women visiting the Department of Obstetrics and Gynecology for routine checkups over a six-month period. Sample size calculation was based on expected sensitivity and prevalence rates. Inclusion criteria were defined, and clinical examinations were performed on the participants. Results: Higher serum β-HCG levels were significantly associated with hypertensive disorders of pregnancy. Low levels correlated with 12 out of 122 cases, while high levels correlated with 59 out of 78 cases. Two deaths were linked to hypertensive disorders. Age did not show a significant association, but variations were observed among religious groups. Conclusions: This study concludes that higher serum β-HCG levels are significantly associated with the development of hypertensive disorders of pregnancy. Age did not show a significant association with these disorders, suggesting the involvement of other contributing factors. The findings provide valuable insights for clinical management and further research in this field, contributing to a better understanding of the etiology and predictors of hypertensive disorders of pregnancy.
... EOPE is a complex pregnancy complication that poses significant risks to the health of both mothers and fetuses, often leading to preterm birth, fetal growth restriction, and other complications with far-reaching consequences (Roberts and Cooper 2001). Aberrant gene expression has been implicated in the pathology of EOPE, with immune cell infiltration being a crucial factor. ...
Early-onset preeclampsia (EOPE) is a complex pregnancy complication that poses significant risks to the health of both mothers and fetuses, and research on its pathogenesis and pathophysiology remains insuffcient. This study aims to explore the role of candidate genes and their potential interaction mechanisms in EOPE through bioinformatics analysis techniques. Two gene expression datasets, GSE44711 and GSE74341, were obtained from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) between EOPE and gestational age-matched preterm control samples. Functional enrichment analysis was performed utilizing the kyoto encyclopedia of genes and genomes (KEGG), gene ontology (GO), and gene set enrichment analysis (GSEA). A protein–protein interaction (PPI) network was constructed using the STRING database, and hub DEGs were identified through Cytoscape software and comparative toxicogenomics database (CTD) analysis. Furthermore, a diagnostic logistic model was established using these hub genes, which were confirmed through reverse transcription polymerase chain reaction (RT-PCR). Finally, immune cell infiltration was analyzed using CIBERSORT. In total, 807 DEGs were identified in the GSE44711 dataset (451 upregulated genes and 356 downregulated genes), and 787 DEGs were identified in the GSE74341 dataset (446 upregulated genes and 341 downregulated genes). These DEGs were significantly enriched in various molecular functions such as extracellular matrix structural constituent, receptor-ligand activity binding, cytokine activity, and platelet-derived growth factor. KEGG and GSEA annotation revealed significant enrichment in pathways related to ECM-receptor interaction, PI3K-AKT signaling, and focal adhesion. Ten hub genes were identified through the CytoHubba plugin in Cytoscape. Among these hub genes, three key DEGs (COL1A1, SPP1, and THY1) were selected using CTD analysis and various topological methods in Cytoscape. The diagnostic logistic model based on these three genes exhibited high efficiency in predicting EOPE (AUC = 0.922). RT-PCR analysis confirmed the downregulation of these genes in EOPE, and immune cell infiltration analysis suggested the significant role of M1 and M2 macrophages in EOPE. In conclusion, this study highlights the association of three key genes (COL1A1, SPP1, and THY1) with EOPE and their contribution to high diagnostic efficiency in the logistic model. Additionally, it provides new insights for future research on EOPE and emphasizes the diagnostic value of these identified genes. More research is needed to explore their functional and diagnostic significance in EOPE.
... It takes place only in the presence of placenta even without fetus (hydatidiform mole), and typically improves postpartum. 3,4 Hypoperfusion and ischemic conditions evidently show the abnormal placenta. PE is known to be originated from disordered vascular development of the placenta which further widely spreads anti-angiogenic factors into the maternal circulation and causes a systemic endothelial cell dysfunction and microangiopathy. ...
Background: Eclampsia is an unpredictable multi-organ disease unique to pregnancy and is largely a preventable condition, responsible for high maternal and perinatal mortality. Methods: The present study was conducted in the Department of Obstetrics and Gynaecology in Maharani Laxmi Bai Medical College, Jhansi. It was a retrospective study conducted over a period of 12 months on all eclamptic cases attending our hospital and feto-maternal outcome data was analysed. Results: The incidence of eclampsia in our hospital was 2.22%. Most of the eclamptic cases were antepartum eclampsia constituting 81.48%. During the study period there were a total of 2430 obstetric admissions out of which 54 were eclamptic cases. There were 89 near miss cases and 21 maternal deaths. 16 (17.97%) near miss cases and 7(33.33%) maternal deaths were due to eclampsia. 37.03% patients had complications. Pulmonary edema/ARDS was the most common complication seen in our study. Early neonatal mortality in our study was 11.11%, 11 new-borns needed NICU care. Prematurity was the most common cause. Conclusions: Adequate screening, monitoring and routine check-up during and after pregnancy may prevent worsening the maternal and foetal outcome. Lack of antenatal care is a common risk factor for eclampsia is and this needs to be addressed to prevent this serious complication of pregnancy.
... A study confirmed the involvement of large-conductance K+ (BKca) in coronary endothelium-dependent relaxation mediated by TRPV1 (4); however, to the best of our knowledge, there are no reports on the role of TRPV1 and the KATP subtype SUR2B/Kir6.1 in severe preeclampsia. Since the placenta is a vital tissue that connects the fetus to the mother, and once the placenta has been delivered, this illness may be rapidly treated; there is no doubt that the placenta has an essential role in the development of this disease (12). As one of the vasoactive substances regulating blood flow homeostasis in the body, NO must also be one of the crucial factors regulating blood flow perfusion in the placental artery (13). ...
Severe preeclampsia is one of the most serious obstetric diseases. However, the pathogenesis of the disease is not fully understood. In the present study, placental artery and blood serum was collected from patients with severe preeclampsia, as well as from normal pregnant women. The results of reverse transcription-quantitative (q)PCR, western blotting, and immunohistochemical staining revealed markedly decreased transient receptor potential cation channel subfamily V member 1 (TRPV1), ATP-sensitive potassium channel (KATP) subtype Kir6.1/SUR2B and endothelial nitric oxide synthase (eNOS) expression in severe preeclampsia tissue specimens compared with those in samples from normal pregnant women. The nitrate reduction method indicated lower NO levels in the tissue specimens and serum of patients with severe preeclampsia. Moreover, hematoxylin-eosin staining showed that the endothelial cell layer in the placental artery of patients with severe preeclampsia was notably damaged. To investigate the potential role of TRPV1-KATP channels in severe preeclampsia, HUVECs were used for in vitro experiments. The samples were divided into a control group, a TRPV1 agonist group (capsaicin) and a TRPV1 inhibitor group (capsazepine). qPCR and western blotting revealed that the relative gene and protein expression levels of TRPV1, Kir6.1, SUR2B and eNOS in the control group were significantly lower than those in the capsaicin group and considerably higher than those in the capsazepine group. Based on previous studies and the results of the present study, we hypothesized that impairment of the endothelial TRPV1-KATP channels results in decreased eNOS/NO pathway activity, which may be one of the mechanisms involved in severe preeclampsia. The increase in NO generation mediated by TRPV1-KATP may be a suitable target for the management of severe preeclampsia.
... Preeclampsia is associated with reduced placental surface area. One apparent cause of abnormal placentation is impaired invasion of the maternal spiral arteries by the trophoblast at implantation [106]. In the Helsinki Birth Cohort, placentas from pregnancies complicated by preeclampsia had a more oval surface than those from normotensive pregnancies because of a disproportionate reduction in the width [107], leading to a more oval shape. ...
There is a pandemic of chronic disease that is widespread across the globe. Low birthweight, as a result of slow fetal growth, is associated with increased rates of chronic disease including coronary heart disease and related disorders, stroke, hypertension, obesity, and type 2 diabetes. These associations extend across the entire range of birthweight. People who were small at birth have elevated risks for later disease because they have reduced functional capacity in specific organs, altered settings of hormones and metabolism, or harmful responses to adverse influences in the postnatal environment. People born at the high end of the birthweight scale who put on weight rapidly during infancy and early childhood also have elevated risks for chronic disease. The most common chronic diseases are the consequences of developmental plasticity, the biological process by which one genotype can give rise to a range of different physiological or morphological phenotypes in response to environmental stressors during development. This is often referred to as programming.Slow growth in infancy and rapid weight gain after the age of one year further increase the risk of later disease. Slow fetal growth is the product of the mother’s body composition and diet before and during pregnancy, together with her metabolism. The placenta is complicit in the growth of the fetus and hence in the programing of disease. The vulnerability for adult-onset chronic disease can be firmly entrenched during prenatal stages but can also arise independently during childhood when individuals remain plastic, providing the underpinnings for harm from adverse childhood experiences that progress to chronic conditions and mental disorders.KeywordsBirthweightFetal programmingFetal growthPlacentaChronic diseaseCardiovascular disease
... These changes in lipid metabolism during pregnancy promote the accumulation of maternal fat stores in the first twothirds of gestation in order to serve as a source of calories for the mother and fetus in late pregnancy and during lactation. Cholesterol is also necessary for placental steroid synthesis, and triglycerides are used for placental oxidation and membrane formation (11, 12) Reversal of the hyperlipidemia of pregnancy begins within hours of delivery and is essentially complete by 6-10 weeks postpartum (13)." ...
Background: Although, different protocols of chemotherapy are recommended for the treatment of metastatic breast cancer, still response rates are variable.Objectives: The aim of this study is to investigate the effects and correlation of different chemotherapy administered to metastatic breast cancer patients on serum levels of some biomarkers.Patients and methods: Thirty metastatic breast cancer patients were enrolled in the study. The patients received different protocols of chemotherapy. Blood samples were taken from the patients before and after the last cycle of each protocol and from 20 healthy control and serum levels of biomarkers IL-6, leptin, CA 15-3 and p53 were estimated by Elisa.Results: The mean serum levels of IL-6, leptin, CA 15-3 and p53 were significantly (P ≤ 0.01) higher in patients before and after chemotherapy compared to controls. A significant (P≤0.01) higher mean levels of IL-6, leptin and p53 was found in the patients after chemotherapy compared to before chemotherapy with the exception of mean serum levels of CA 15-3 that did not differed significantly (P≥0.174) after chemotherapy compared to before chemotherapy. A significant correlation was found between hormone status and the mean serum level of leptin and between the mean serum levels of CA15-3 and IL-6.Conclusion: The results highlights that the biomarkers IL-6, leptin, CA 15-3, p53 play a role in breast cancer progression and metastasis and could be helpful in predicting and monitoring chemosensitivity to these chemotherapeutic drugs.
... These changes in lipid metabolism during pregnancy promote the accumulation of maternal fat stores in the first twothirds of gestation in order to serve as a source of calories for the mother and fetus in late pregnancy and during lactation. Cholesterol is also necessary for placental steroid synthesis, and triglycerides are used for placental oxidation and membrane formation (11, 12) Reversal of the hyperlipidemia of pregnancy begins within hours of delivery and is essentially complete by 6-10 weeks postpartum (13)." ...
Background: “According to the current knowledge, changes in lipid profile in pregnancy is a major contributor in the pathogenesis of preeclampsia. The present study was designed to compare the changes in lipid profile in normal pregnancy and in patients with history of recurrent pre-eclampsia (PE).”Objective: Assessment the relationship between lipid profiles changes in women with history of recurrent preeclampsia in comparison to normal pregnancy in early pregnancy.Patients and Methods: Measurement of lipid profile changes in women with history of recurrent preeclampsia (more than two preeclampsia in previous pregnancies) at 12 to 16 weeks of pregnancy and compared to normal pregnancy as a control group who does not have history of preeclampsia also early in pregnancyResults: The patients with history of recurrent Preeclampsia had significantly higher mean total cholesterol level compared to controls (216.1 ± 25.5 mg/dl) and (195.6 ± 23.2 mg/dl), respectively, (P<0.05).The mean HDL cholesterol (HDL-C) level was significantly lower in PE group (49.3 ± 9.2 mg/dl) than controls (52.2 ± 8.4 mg/dl), (P<0.05). The mean level of LDL cholesterol was (122.3 ± 28.7) mg/dl in PE group and it was significantly higher than the (108.6 ± 26.8 mg/dl) of controls, (P<0.05). Similarly, the mean VLDL cholesterol was also higher in women with history of recurrent preeclampsia than control group, (44.8 ± 12.6) vs. (34.8 ± 7.3) mg/dl, respectively, (P<0.05). The Triglycerides (TG) was also elevated in women with history of recurrent preeclampsia where the mean TG level was (224.2 ± 63.1 mg/dl) compared to (174.6 ± 36.3mg/dl) in controls, (P<0.05).Conclusion: “This study showed that the women who have history of recurrent preeclampsia had disturbed lipid profile (increased levels of total TC, TG, VLDL-C and LDL-C concentration) in addition to decrease the high density lipoprotein cholesterol (HDL-C) level in subsequent pregnancy compared to normal pregnancy.”
... The risk of such complications is considerably higher when PE is severe and/or earlyonset, leading to preterm birth at less than 37 weeks' gestation [18][19][20][21]. PE is associated with vascular endothelium dysfunction, insulin resistance, hyperlipidaemia, hypercoagulability and inflammation [22][23][24]. Thus, PE shares many aetiologies with CVD. ...
Objectives
The objective of this study was to investigate whether oscillometric AS measurements are different in pregnant women with and without preeclampsia (PE).
Study design
This was a prospective case–control study in singleton pregnancies that had been diagnosed with PE (n = 46) versus normotensive controls (n = 46) between 2014 and 2019. In the case group, pregnancies complicated by PE were classified as either early-onset (<34 weeks of gestation) or late-onset (≥34 weeks of gestation) PE and subgroup analysis was performed.
Main outcome measures
Pulse wave velocity (PWV), augmentation index (Alx), and Alx at a heart rate of 75 beats per minute (Alx-75) were measured using a brachial cuff-based automatic oscillometric device (Mobil-O-Graph 24 h PWA).
Results
In pregnancies complicated by PE, in comparison with normotensive pregnancies, there were significant differences in PWV (p ˂ .001), and Alx-75 (p ˂ .001). In pregnancies complicated by early-onset PE, in comparison with pregnancies complicated by late-onset PE, there were significant differences in PWV (p = .006), and Alx-75 (p = .009). There was no significant difference in Alx in either of the analyses.
Conclusions
PWV and Alx-75 are higher in pregnancies complicated by PE, in comparison with normotensive pregnancies, as well as in early-onset PE, in comparison with late-onset PE.
Key messages
Pulse wave velocity is higher in pregnancies complicated by preeclampsia.
Augmentation index at a heart rate of 75 beats per minute is higher in pregnancies complicated by preeclampsia.
Arterial stiffness assessment is a promising risk-stratification tool for future cardiovascular complications but further studies are required.
... sFlt1 expression is essential in the maintenance of corneal avascularity suggesting that sFlt-1 may work in synergy to inhibit angiogenesis in various avascular areas of the body [17]. sFlt1 overexpression is also a canonical marker in the pregnancy disorder pre-eclampsia, where it inhibits pro-angiogenic factors and prevent proper blood vessel formation in the placenta [21,[45][46][47]. Although this is the first time sFlt1 has been suggested to be important in the progression of angiogenesis during AVS, previous literature has pointed to several other factors involved in the same process. ...
Aortic valve stenosis is the most common valve disease in the western world. Central to the pathogenesis of this disease is the growth of new blood vessels (angiogenesis) within the aortic valve allowing infiltration of immune cells and development of intra-valve inflammation. Identifying the cellular mediators involved in this angiogenesis is important as this may reveal new therapeutic targets which could ultimately prevent the progression of aortic valve stenosis. Aortic valves from patients undergoing surgery for aortic valve replacement or dilation of the aortic arch were examined both ex vivo and in vitro. We now demonstrate that the anti-angiogenic protein, soluble fms-like tyrosine kinase 1 (sFlt1), a non-signalling soluble receptor for vascular endothelial growth factor, is constitutively expressed in non-diseased valves. sFlt-1 expression was, however, significantly reduced in aortic valve tissue from patients with aortic valve stenosis while protein markers of hypoxia were simultaneously increased. Exposure of primary-cultured valve interstitial cells to hypoxia resulted in a decrease in the expression of sFLt-1. We further reveal using a bioassay that siRNA knock-down of sFlt1 in valve interstitial cells directly results in a pro-angiogenic environment. Finally, incubation of aortic valves with sphingosine 1-phosphate, a bioactive lipid-mediator, increased sFlt-1 expression and inhibited angiogenesis within valve tissue. In conclusion, this study demonstrates that sFlt1 expression is directly correlated with angiogenesis in aortic valves and the observed decrease in sFlt-1 expression in aortic valve stenosis could increase valve inflammation, promoting disease progression. This could be a viable therapeutic target in treating this disease.
... Pre-eclampsia is believed to be one of the leading causes of maternal and fetal mortality and morbidity worldwide [2][3][4]. Severe pre-eclampsia is associated with different degrees of fetal injury. The main impact on the fetus is undernutrition as a result of uteroplacental vascular insufficiency, which leads to growth retardation [5,6]. ...
... Preeclampsia is a multifactorial syndrome marked by a slew of signs and symptoms, including the advent of new-onset hypertension and proteinuria during the third trimester of pregnancy, which is generally accompanied by edema and hyperuricemia. or high blood pressure [1,2,3], or high blood pressure is linked to considerable organic dysfunction after 20 weeks of pregnancy, as well as a high maternal mortality rate due to complications like eclampsia, HELLP syndrome, and edema [4][5][6][7]. It causes complications in 2% to 8% of pregnancies, and it is responsible for up to 14% of maternal deaths. ...
Preeclampsia is a multifactorial condition characterized by a constellation of signs and symptoms, including the new onset of hypertension and proteinuria during the last trimester of pregnancy. Women with preeclampsia diagnoses have an increased risk of developing renal diseases later in life. This study was aimed at evaluating serum uric acid, serum creatinine and serum urea in preeclamptic women and comparing values to normal pregnancy women. A total of 100 pregnant women were enrolled in this study. Out of 40 normal pregnant women, 60 suffered from preeclampsia. Blood samples were collected in a plane test tube for the assay of urea, creatinine and uric acid levels. Levels of serum urea and uric acid were increased significantly in the preeclampsia group (29.6 ± 13.8 & 5.80 ± 1.13) compared to the control group (20.50 ± 2.70& 2.982 ± 0.672) respectively. Meanwhile, the level of serum creatinine was increased without any significant differences between the preeclampsia group (0.842 ± 0.346) and the control group (0.798 ± 0.312). Results found a positive association (p<0.000) between serum creatinine and serum urea. We conclude from this study that preeclampsia has deleterious effects on renal function as shown by alteration of (serum urea and serum uric acid). These parameters can be taken as predictors of the disease. Therefore, assessment of these parameters helps in monitoring the function of the kidney in preeclampsia.
... Working group of the National High Blood Pressure Education Program (2000) describes four types of hypertensive disorders: 1) Gestational hypertension (formerly Pregnancy Induced Hypertension), 2) Preeclampsia and Eclampsia syndrome, 3) Preeclampsia syndrome superimposed on chronic hypertension and 4) Chronic hypertension 1. According to the norms of American college of obstetrics and Gynecologists, the diagnostic criteria for gestational hypertension [Pregnancy Induced Hypertension (PIH)] is 1) Systolic Blood pressure ≥140 mm/Hg 2) Diastolic Blood pressure ≥90 mm/Hg Or 3) increase of ≥30 mm/Hg in Systolic pressure Or 4) increase of ≥15 mm/Hg in Diastolic pressure, in a previously normotensive woman [4].It has been reported that renal abnormalities occur in a considerable number of pregnancies complicated by preeclampsia [5,6], resulting in very poor prognosis to maternal and fetal outcomes [7,8] . Pre-eclampsia, the most common medical complication of the second half of pregnancy is a complex multi-organ disorder that is characterized by hypertension, edema and proteinuria, most frequently observed in the primigravida, contributing significantly to maternal and neonatal mortality and morbidity. ...
OBJECTIVE: To compare the observed and expected prevalence rate of gestational hypertension in north India. DESIGN: observational cross-sectional study. SUBJECTS: The total sample size was taken 200, out of which 31 were gestational hypertensive and 169 the gestational normotensive based upon set of inclusion criteria and exclusion criteria. MAIN OUTCOME MEASURES: The prevalence rate of gestational hypertension among pregnant women in north India, I, e,13-15% showed the same as of national range which in this study proved by the p value being lesser than 0.05. The p value probability is 0.016244 which is lesser than 0.05.(0.05>0.016244). CONCLUSION: Gestational hypertension is both the cumbersome and burdensome health hazard upon both among population and government authorities. Since the national prevalence rate range from 12% to 13%, this rate actually varies in different regions, which in here according to present study the prevalence rate shows higher than the national range.
... Gestational hypertension and preeclampsia are characterized by lower levels of estrogen [40][41][42][43][44][45] and insulin-like growth factor [46] and elevated concentrations of antiangiogenic factors [47,48] and androgens [41,45] which could contribute to decreased breast cancer risk. Conversely, the release of proinflammatory factors into maternal circulation in HDOP could potentially increase breast cancer risk [14,17,20,[41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. ...
Purpose
Compared to white women, Black women have increased risk of developing hypertensive diseases of pregnancy (HDOP) and have a higher incidence of aggressive breast cancer subtypes. Few studies of HDOP and breast cancer risk have included large numbers of Black women. This study examined the relation of HDOP to incidence of breast cancer overall and by estrogen receptor (ER) status in Black women.
Methods
We followed 42,982 parous women in the Black Women’s Health Study, a nationwide prospective study of Black women. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess associations of self-reported HDOP, including preeclampsia and gestational hypertension, with breast cancer incidence overall and by ER subtype, adjusted for age and established breast cancer risk factors.
Results
Over 20 years of follow-up, we identified 2376 incident breast cancer cases. History of HDOP (11.7%) was not associated with breast cancer risk overall (HR 0.98; 95% CI 0.87, 1.11). HRs for invasive ER+ and ER– breast cancer were 1.11 (95% CI 0.93, 1.34) and 0.81 (95% CI 0.61, 1.07), respectively.
Conclusions
HDOP was not associated with risk of overall breast cancer in Black women. A suggestive inverse association with ER– breast cancer may reflect an anti-tumorigenic hormone profile in HDOP, but those results require confirmation in other studies.
... Preeclampsia is a pregnancy disorder clinically recognized by increased systolic blood pressure and symptoms of liver and kidney damages. Preeclampsia often appears on the 20 th weeks of pregnant women whose blood pressure had been normal (Roberts and Cooper, 2001). Several research groups unraveled the essential diagnostic roles of the EVs as well as the mediation of preeclampsia pathogenesis and other placental disorders (van der Post et al., 2011;Mitchell et al., 2015;Tsochandaridis et al., 2015;Gilani et al., 2016;Cuffe et al., 2017;Ermini et al., 2017;Pillay et al., 2017;Salomon and Rice, 2017;Tannetta et al., 2017a;Tannetta et al., 2017b;Jin and Menon, 2018;Morgan, 2018;Salomon et al., 2018). ...
Extracellular vesicles (EVs) are nanovesicles that carry bioactive cargoes
of proteins, lipids, mRNAs, and miRNAs between living cells. Their role in cellular
communication has gained the attention of several research reports globally in the last
decade. EVs are critically involved in sperm functions, oocyte functions, fertilization,
embryonic development, and pregnancy. The review summarizes the state-of-the-art of EVs research in the diagnostic and therapeutic (theranostic) potentials of the
EVs during the pregnancy that might provide a solution for gestational disturbances
such as implantation failure, maternal health problems, gestational diabetes, and
preeclampsia. EVs can be found in all biological fluids of the fetus and the mother and
would provide a non-invasive and excellent tool for diagnostic purposes. Moreover, we
provide the current efforts in manufacturing and designing targeted therapeutics using
synthetic and semi-synthetic nanovesicles mimicking the natural EVs for efficient drug
delivery during pregnancy.
... Early onset of preeclampsia is associated with elevation levels of protein, carbonyl, lipid peroxides, nitrotyrosine residues and DNA oxidation, which are all indicators of placental oxidative stress (Burton et al., 2009). The oxidative stress of preeclampsia is thought to originate from insufficient spiral artery conversion (Roberts and Cooper, 2001), which leads to discontinuous placental perfusion and a low level ischemia reperfusion (Burton and Young, 2011). ...
During pregnancy elevation of metabolic activities takes place which requires oxygen, thereby leading to an increase in oxidative stress. The present study evaluated the impact of age on the oxidative stress and antioxidant status of pregnant and lactating mothers in Owerri and Orlu area of Imo State, Nigeria. Malondialdehyde (MDA), a product of lipid peroxidation, represents oxidative stress. Glutathione peroxidase (GPx) and superoxide dismutase were measured for enzymatic antioxidants, while vitamins C and E represented the dietary antioxidants. Two hundred pregnant and lactating mothers participated in the survey. Towards the end of each trimester, blood samples were collected from the volunteers and analyzed for some marker of oxidative stress and antioxidants. Results showed that oxidative stress increased as the age of the pregnant women increased. This increase were not significant (p<0.05). The oxidative stress increased also as the gestation period increased. Malondialdehyde level was highest among 40-45 years age group (6.81±0.10Mol/ml) in the third trimester. Antioxidant levels were highest in age group 24-29 and decreased. Although the decrease was not statistically significant (p<0.05). Women in the lactating group have decreased MDA level compared to their counterparts in the third trimester. The antioxidant level of the lactating mothers also increased. From the study, older pregnant women requires more dietary antioxidant to supplement their endogenous antioxidants.
Endometrial decidualization resistance (DR) is implicated in various gynaecological and obstetric conditions. Employing a multi-omic strategy, we unraveled the cellular and molecular characteristics of DR in patients that have suffered severe preeclampsia (sPE). Morphological analysis unveiled significant glandular anatomical abnormalities, confirmed histologically. Single-cell RNA sequencing (scRNA-seq) of endometrial samples from sPE cases (n=11) and controls (n=12) revealed sPE-associated shifts in cell composition, manifesting as a stromal mosaic state characterized by proliferative stromal cells (MMP11, SFRP1+) alongside IGFBP1+ decidualized cells, with concurrent epithelial mosaicism and a dearth of epithelial-stromal transition associated with decidualization. Cell-cell communication network mapping underscored aberrant crosstalk among specific cell types, implicating crucial pathways such as endoglin and WNT. Spatial transcriptomics in a replication cohort validated DR-associated features. Laser capture microdissection/mass spectrometry in a second replication cohort corroborated several scRNA-seq findings, notably the absence of stromal to epithelial transition at a pathway level, indicating disrupted response to steroid hormones, particularly estrogens. These insights shed light on potential molecular mechanisms underpinning DR pathogenesis in the context of sPE.
Background: Hypertensive disorders of pregnancy are among the major complications of pregnancy and are important causes of maternal and perinatal morbidity and mortality. Evidences have indicated that higher energy intake during pregnancy are the modifiable risk factors of developing hypertension in pregnancy. Aim and Objective: To identify the dietary factors and its association with hypertensive disorders of pregnancy. Material and Methods: The cross sectional study was conducted in a rural area of Kashmir Valley. The data so collected was compiled and subjected to analysis using SPSS version 20.00. Results: The mean daily intake of calories (kcal) in women with hypertension was found to be significantly higher (2203±375) as compared to normotensive women (1995.80±505.296). Conclusion: Unbalanced diet may be the possible associated factor for hypertension in pregnancy. Introduction Hypertensive disorders of pregnancy are among the major complications of pregnancy and are important causes of maternal and perinatal morbidity and mortality [1] .Several studies have analyzed the risk factors for hypertensive disorders in pregnancy and the identified risk factors include obesity, a family history of hypertension, alcohol intake, heart failure, stroke and left ventricular hypertrophy and smoking [2]. Although there is little data regarding dietary intake and HDP, few evidences have indicated that higher energy intake during pregnancy to be the modifiable risk factors of developing gestational hypertension [3] .
Headache during pregnancy can be due to primary causes such as migraine but can also be a presenting symptom of secondary causes including life threatening conditions. This is a minireview of secondary causes of headache during pregnancy and the puerperium. Unique alterations in physiological and vascular functions as well as in the coagulation pathway which occur during pregnancy increase the risk of most of these secondary conditions which include preeclampsia, eclampsia, hemorrhagic stroke, cerebral venous, sinus thrombosis, reversible cerebral vascular syndrome, and posterior reversible encephalopathy. Marked increase in progesterone level in pregnancy is also associated with the growth of tumors such as meningiomas, as 70% of these tumors are positive for progesterone receptors and increase in size can lead to headache along with other neurological symptoms. Hemodynamic changes can lead to the growth of meningiomas as well. Although hormone producing pituitary tumors are usually not conducing to pregnancy, women with known pituitary tumors who do get pregnant may become symptomatic during pregnancy and develop secondary headache. Another rare cause of secondary headache during pregnancy is pituitary apoplexy. Although its occurrence is uncommon, it needs to be properly recognized and treated to avoid endocrine and visual complications. Other rare entities with increased incidence during the puerperium such postdural puncture headache will be also discussed. In summary, new onset headache during pregnancy deserves special attention because in the absence of proper recognition and treatment, secondary headache disorders can endanger the life of the mother and the fetus.
Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development.
Racial disparities exist in the prevalence of preeclampsia (PE), with women of African ancestry suffering the highest rates of morbidity and mortality. Genetic changes may play a role in the preponderance of PE among women of African ancestry. This review discusses 30 genes with variants that have been studied in PE in women of African ancestry. These studies found that a single gene is not responsible for PE susceptibility as 13 genes have been implicated. These genes subserve endothelial, immune, hemodynamic, homeostatic, thrombophilic, oxidative stress, and lipid metabolic pathways. Notably, maternal-fetal gene interactions also contribute to the susceptibility of the disease. For instance, the maternal KIR AA genotype and paternally inherited fetal HLA-C2 genotype confer risk for developing PE. Additionally, genetic changes such as epigenetic modulation of expression of the MTHFR gene through DNA methylation is also associated with the occurrence of PE. In contrast, some genes such as the KIR B centromeric region protect against development of PE in some women. The soluble fms-like tyrosine kinase 1 (sFlt-1) contributes to the development of PE and is a potential novel therapeutic option for targeted gene silencing of anti-angiogenic sFLT-1 gene. Additionally, NOS3 gene is an important target for pharmacogenomics because it is responsible for the production of endothelial nitric oxide. In conclusion, maternal genetic and epigenetic variants confer susceptibility to PE, indicating the need for further studies to develop a screening tool incorporating maternal genetic variants to identify women at high risk for PE and offer them a preventive therapy.
The Siglecs family is a group of type I sialic acid-binding immunoglobulin-like receptors that regulate cellular signaling by recognizing sialic acid epitopes. Siglecs are predominantly expressed on the surface of leukocytes, where they play a crucial role in regulating immune activity. Pathogens can exploit inhibitory Siglecs by utilizing their sialic acid components to promote invasion or suppress immune functions, facilitating immune evasion. The establishing of an immune-balanced maternal-fetal interface microenvironment is essential for a successful pregnancy. Dysfunctional immune cells may lead to adverse pregnancy outcomes. Siglecs are important for inducing a phenotypic switch in leukocytes at the maternal-fetal interface toward a less toxic and more tolerant phenotype. Recent discoveries regarding Siglecs in the reproductive system have drawn further attention to their potential roles in reproduction. In this review, we primarily discuss the latest advances in understanding the impact of Siglecs as immune regulators on infections and pregnancy.
Preeclampsia is a complication of pregnancy that is the leading cause of maternal morbidity and mortality worldwide. It is associated with significant cardiovascular risk for mothers and their offspring, which is especially important as cardiovascular disease (CVD) is the leading cause of mortality for women in the United States and worldwide. This chapter summarizes the evidence demonstrating the impact of preeclampsia on short-term and long-term cardiovascular health as well as on offspring cardiovascular health. Preeclampsia has been shown to result in persisting cardiac dysfunction, an increased risk of stroke and myocardial infarction, increased likelihood of developing cardiovascular risk factors, and increased risk of coronary artery disease and heart failure. Current interventions for women with a history of preeclampsia are not sufficient and improved multidisciplinary guidelines for follow-up and education of these women are necessary to decrease their cardiovascular risk. Future studies examining the interaction between adverse cardiovascular risk factors and the development of preeclampsia and CVD as well as the pathophysiology of preeclampsia itself are necessary to continue developing the field of cardio-obstetrics.KeywordsPreeclampsiaMaternal cardiovascular healthOffspring cardiovascular health
DNA methylation is the most commonly studied epigenetic mark in humans, as it is well recognised as a stable, heritable mark that can affect genome function and influence gene expression. Somatic DNA methylation patterns that can persist throughout life are established shortly after fertilisation when the majority of epigenetic marks, including DNA methylation, are erased from the pre-implantation embryo. Therefore, the period around conception is potentially critical for influencing DNA methylation, including methylation at imprinted alleles and metastable epialleles (MEs), loci where methylation varies between individuals but is correlated across tissues. Exposures before and during conception can affect pregnancy outcomes and health throughout life. Retrospective studies of the survivors of famines, such as those exposed to the Dutch Hunger Winter of 1944-45, have linked exposures around conception to later disease outcomes, some of which correlate with DNA methylation changes at certain genes. Animal models have shown more directly that DNA methylation can be affected by dietary supplements that act as cofactors in one-carbon metabolism, and in humans, methylation at birth has been associated with peri-conceptional micronutrient supplementation. However, directly showing a role of micronutrients in shaping the epigenome has proven difficult. Recently, the placenta, a tissue with a unique hypomethylated methylome, has been shown to possess great inter-individual variability, which we highlight as a promising target tissue for studying MEs and mixed environmental exposures. The placenta has a critical role shaping the health of the fetus. Placenta-associated pregnancy complications, such as preeclampsia and intrauterine growth restriction, are all associated with aberrant patterns of DNA methylation and expression which are only now being linked to disease risk later in life.
Interferon-induced transmembrane proteins (IFITMs) are restriction factors that block many viruses from entering cells. High levels of type I interferon (IFN) are associated with adverse pregnancy outcomes, and IFITMs have been shown to impair the formation of syncytiotrophoblast. Here, we examine whether IFITMs affect another critical step of placental development, extravillous cytotrophoblast (EVCT) invasion. We conducted experiments using in vitro/ex vivo models of EVCT, mice treated in vivo with the IFN-inducer poly (I:C), and human pathological placental sections. Cells treated with IFN-β demonstrated upregulation of IFITMs and reduced invasive abilities. Transduction experiments confirmed that IFITM1 contributed to the decreased cell invasion. Similarly, migration of trophoblast giant cells, the mouse equivalent of human EVCTs, was significantly reduced in poly (I:C)-treated mice. Finally, analysis of CMV- and bacterial-infected human placentas revealed upregulated IFITM1 expression. These data demonstrate that high levels of IFITM1 impair trophoblast invasion and could explain the placental dysfunctions associated with IFN-mediated disorders.
Early pregnancy is a complex and well-orchestrated differentiation process that involves all the cellular elements of the fetal-maternal interface. Aberrant trophoblast-decidual interactions can lead to miscarriage and disorders that occur later in pregnancy, including preeclampsia, intrauterine fetal growth restriction, and preterm labor. A great deal of research on the regulation of implantation and placentation has been performed in a wide range of species. However, there is significant species variation regarding trophoblast differentiation as well as decidual-specific gene expression and regulation. Most of the relevant information has been obtained from studies using mouse models. A comprehensive understanding of the physiology and pathology of human implantation and placentation has only recently been obtained because of emerging advanced technologies. With the derivation of human trophoblast stem cells, 3D-organoid cultures, and single-cell analyses of differentiated cells, cell type-specific transcript profiles and functions were generated, and each exhibited a unique signature. Additionally, through integrative transcriptomic information, researchers can uncover the cellular dysfunction of embryonic and placental cells in peri-implantation embryos and the early pathological placenta. In fact, the clinical utility of fetal-maternal cellular trafficking has been applied for the noninvasive prenatal diagnosis of aneuploidies and the prediction of pregnancy complications. Furthermore, recent studies have proposed a viable path toward the development of therapeutic strategies targeting placenta-enriched molecules for placental dysfunction and diseases.
Hypertensive disorders of pregnancy (HDP), including gestational hypertension (GH) and preeclampsia (PE), cause significant morbidity and mortality among pregnant women. Several environmental toxins, particularly those that affect the normal function of the placenta and the endothelium, are emerging as potential risk factors for HDP. Among them, per- and polyfluoroalkyl substances (PFAS), widely used in a variety of commercial products, have been related to a variety of adverse health effects including HDP. This study was conducted by searching three databases for observational studies reporting associations between PFAS and HDP, all of which were published before December 2022. We used random-effects meta-analysis to calculate pooled risk estimates, and assessing each combination of exposure and outcome for quality and level of evidence. In total, 15 studies were included in the systematic review and meta-analysis. The results from meta-analyses showed that risk of PE was increased with exposure to PFOA (perfluorooctanoic acid) (RR = 1.39, 95% CI = 1.05, 1.85; N = 6 studies; exposure = 1 ln-unit increment; low certainty), PFOS (perfluorooctane sulfonate) (RR = 1.51, 95% CI = 1.23, 1.86; N = 6 studies; exposure = 1 ln-unit increment; moderate certainty), and PFHxS (perfluorohexane sulfonate) (RR = 1.39, 95% CI = 1.10, 1.76; N = 6 studies; exposure = 1 ln-unit increment; low certainty). PFOS was also associated with an increased risk of HDP (RR = 1.39, 95% CI = 1.10, 1.76; exposure = 1 ln-unit increment; low certainty). Exposure to legacy PFAS (PFOA, PFOS, PFHxS) is associated with an increased risk of PE, and PFOS is further associated with HDP. In view of the limitations of meta-analysis and quality of evidence, these findings should be interpreted with caution. Further research is required that assesses exposure to multiple PFAS in diverse and well-powered cohorts.
Background
This study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE).
Methods
All pregnant women that received the Quadruple test for Down syndrome at 15+ 0-20+ 6 weeks’ gestation were recruited. Maternal serum α-fetoprotein, β-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model’s predictive ability.
Results
Fifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60).
Conclusions
Our model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended.
Abstract
Introduction: Given the high prevalence of severe preeclampsia and its complications and the conflicting reports on the role of antiphospholipid antibodies, especially anti-cardiolipin, this study was performed aimed to compare the anti-cardiolipin antibody titer in pregnant women with preeclampsia and control group.
Methods: In this case-control study, 220 pregnant women in the third trimester of pregnancy who referred to Ali ibn-e Abitaleb Hospital in Zahedan in 2012 were evaluated in two groups of pregnant women with preeclampsia and control group. 4 cc of blood samples were taken from all the women under study and sent to the laboratory for tests under standard conditions. Anticardiolipin IgG and IgM levels were determined by ELISA method. Data were analyzed by SPSS (version 19) and Mann-Whitney test. P<0.05 was considered statistically significant.
Results: In the present study, the mean IgM antibody titers in pregnant women with severe preeclampsia were 1.0±856.842 mg/L and in the control group 2.1±215.610 mg/L which was not significantly different between the two groups (P=0.531). Mean IgG antibody titers were also 2.1±468.163 mg/L in pregnant women with severe preeclampsia and 2.139±0.545 mg/L in the control group which was not significantly different between the two groups (P=0.345).
Conclusion: In this study, no correlation was found between the levels of anti-cardiolipin antibody titers in pregnant women with preeclampsia compared with normal pregnant women.
Keywords
Anti-Cardiolipin antibody Preeclampsia Pregnancy
Preeclampsia (PE) presents with maternal de novo hypertension and significant proteinuria and is one of the leading causes of maternal and perinatal morbidity and mortality with unknown etiology. The disease is associated with inflammatory vascular response and severe red blood cell (RBC) morphology changes. This study examined the nanoscopic morphological changes of RBCs from PE women versus normotensive healthy pregnant controls (PCs) and non-pregnant controls (NPCs) applying atomic force microscopy (AFM) imaging. The results revealed that the membrane of fresh PE RBCs differed significantly from healthy ones by the presence of invaginations and protrusions and an increased roughness value (Rrms) (4.7 ± 0.8 nm for PE vs. 3.8 ± 0.5 nm and 2.9 ± 0.4 nm for PCs and NPCs, respectively). PE-cells aging resulted in more pronounced protrusions and concavities, with exponentially increasing Rrms values, in contrast to the controls, where the Rrms parameter decreased linearly with time. The Rrms, evaluated on a 2 × 2 µm2 scanned area, for senescent PE cells (13 ± 2.0 nm) was significantly higher (p < 0.01) than that of PCs (1.5 ± 0.2 nm) and NPCs (1.9 ± 0.2 nm). Furthermore, the RBCs from PE patients appeared fragile, and often only ghosts were observed instead of intact cells at 20–30 days of aging. Oxidative-stress simulation on healthy cells led to RBC membrane features similar to those observed for PE cells. The results demonstrate that the most pronounced effects on RBCs in PE patients are related to impaired membrane homogeneity and strongly altered roughness values, as well as to vesiculation and ghost formation in the course of cell aging.
Objective
To describe the rate of hypertensive disorder of pregnancy (HDP) among mothers of very preterm infants (VPIs) admitted to Chinese neonatal intensive care units (NICUs), and to investigate the relationship between HDP and the outcomes of VPIs.
Study design
Cohort study of all VPIs born at a gestational age of 24 ⁺⁰ –31 ⁺⁶ weeks and admitted to 57 tertiary NICUs of the Chinese Neonatal Network (CHNN) in 2019. Infants with severe congenital anomalies or missing maternal HDP information were excluded. Two multivariate logistic regression models were generated to assess the relationship between HDP and neonatal outcomes.
Results
Among 9,262 infants enrolled, 1,744 (18.8%) infants were born to mothers with HDP, with an increasing incidence with increasing gestational age. VPIs born to mothers with HDP had higher gestational age but lower birth weight and were more likely to be small for gestational age. Mothers with HDP were more likely to receive antenatal steroids, MgSO 4 and cesarean section. Infants in the HDP group showed higher observed rates of mortality or any morbidity than infants in the non-HDP group (50.2% vs. 47.2%, crude odds ratio (OR) 1.13, 95% CI 1.02–1.26). However, the associations between HDP and adverse outcomes were not significant after adjustment. In the HDP group, mothers of 1,324/1,688 (78.4%) infants were diagnosed with preeclampsia/eclampsia. Infants born to mothers with preeclampsia/eclampsia had significantly lower odds of early death and severe retinopathy of prematurity.
Conclusions
Nearly one-fifth of VPIs were born to mothers with HDP in Chinese NICUs. No significant association was identified between HDP and adverse neonatal short-term outcomes of VPIs, while long-term follow-up of these infants is needed.
The purpose of this study is to investigate preeclampsia. It used the visualization tools of CiteSpace, VOSviewer, Gunnmap, Bibliometrix ® , and Carrot2 to analyze 3,754 preeclampsia studies from 1985 to 2020 in Obstetrics and Gynecology areas. Carrot2 was used to explain each cluster in extra detail. The results found that there is an increasing trend in many publications related to preeclampsia from 1985 to 2020. The number of studies on preeclampsia has increased significantly in the last century. Analysis of the keywords found a strong relationship with preeclampsia concepts and keywords classified into five categories. Co-citation analysis was also performed which was classified into six categories. Reading the article offers important to support not only to grind the context of preeclampsia challenges but also to design a new trend in this field. The number of studies on preeclampsia has substantially improved over the decades ago. The findings of documents published from 1985 to 2020 showed three stages in research on this subject: 1985 to 1997 (a seeding stage), 1997–2005 (rapid growth stage), and 2005 onwards (development stage).
Objective:
This study investigates the association of C1q gene (rs292001 and rs294183) polymorphisms in HIV infected and uninfected preeclamptic women of African ancestry.
Materials and methods:
The study population consisted of 325 pregnant women of African ancestry grouped into 145 normotensive pregnant women (72 HIV uninfected normotensive, 73 HIV infected normotensive) and 180 preeclamptic pregnant women (103 HIV uninfected preeclamptics, 77 HIV infected preeclamptics). Preeclamptic pregnant women were further sub-grouped into 79 early-onset preeclampsia (EOPE) (40 HIV uninfected EOPE, 39 HIV infected EOPE) and 101 late-onset preeclampsia (LOPE) (63 HIV uninfected LOPE, 38 HIV infected LOPE). Genotyping of complement C1q gene polymorphisms (rs292001 and rs294183) was detected using a TaqMan® SNP Genotyping assay from purified DNA.
Results:
No significant differences in allelic and genotype frequencies of rs292001 and rs294183 between preeclamptic and normotensive women were observed. Likewise, there were no significant differences in allelic and genotype frequencies between HIV infected normotensive vs HIV infected preeclampsia and HIV uninfected normotensive vs HIV uninfected preeclampsia for both SNPs. However, the odds ratio of preeclamptic women having the GA genotype was 1:2.
Conclusion:
We demonstrate that SNPs of the C1q gene (rs292001 and rs294183) are not associated with the pathogenesis of PE development in women of African ancestry. The role ofC1qrs292001 heterozygous GA is highlighted (with and without HIV infection) may affect susceptibility to PE development. Notably, this dysregulation may affect C1q translation and protein output thus influencing the downstream role of the complement system and functional immunology in HIV infection comorbid with PE.
The rationale and importance of folic acid supplementation during pregnancy for fetal congenital defect prevention are accepted worldwide. Moreover, a sufficient plasma concentration of folates can reduce the incidence of spontaneous abortions, and support the normal expansion of placental blood vessels, ensuring physiological placental blood flow, thus promoting appropriate fetal growth and development. Furthermore, there is emerging evidence that long-term supplementation with folic acid can effectively prevent preeclampsia. Preeclampsia is unique to the human species in complications during pregnancy, which contributes to maternal and perinatal mortality worldwide. In the pathogenesis of preeclampsia abnormal placental invasion, the excess of antiangiogenic factors and maternal–placental syndrome play a key role. Increased blood levels of homocysteine during pregnancy are associated with the risk of preeclampsia. Moreover, hyperhomocysteinemia has been proposed to be an independent risk factor for preeclampsia. Folate supplementation helps to decrease elevated levels of homocysteine; thus, the role of folic acid supplementation in pregnancy is even more important. Multiple reports suggest that folate administration decreases the level of serum homocysteine and, therefore, reduce the risk and severity of preeclampsia. However, the association between folic acid supplementation and the decreased risk of preeclampsia has been investigated with controversial conclusions. Currently, the optimal dose of folic acid that is effective for preeclampsia prevention remains uncertain. In this review, we aim to summarize the accumulated knowledge on the role of folic acid in the pathogenesis of preeclampsia, and the possible impact of folate supplementation on the decreased risk of preeclampsia.
Background: Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins.
Objective: To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins.
Search Strategy: Electronic databases were searched from inception to January 2022
Selection Criteria: Cohort studies and randomized controlled trials.
Data collection and analysis: Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable.
Main Results: The analysis included ten studies describing 1,391 women with uteroplacental insufficiency disorders: 703 treated with pravastatin and 688 not treated with statins. Women treated with pravastatin demonstrated significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01–0.87, p = 0.04, I ² = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23–0.75, p = 0.004, I ² = 25%). In subgroup analysis, prolongation of pregnancy from study entry to delivery was statistically significant in cohort studies (mean difference 8.93 weeks, 95%CI:4.22–13.95, p = 0.00) but not in randomized control studies. Trends were observed toward a decrease in preeclampsia diagnoses (OR = 0.54, 95%CI:0.27–1.09, p = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09–1.13, p = 0.08, I ² = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14–212, p = 0.08, I ² = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R ² = 1).
Conclusion: Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ identifier CRD42020165804 17/2/2020.
Background: Pre-eclampsia is a syndrome of immune system of pregnant females, which causes severe obstetrical complications. Low serum level of 25-hydroxyvitamin-D is common during pregnancy complicated with preeclampsia but local evidence is missing. Aim: To determine the association of pre-eclampsia with decreased vitamin- D levels during two phases of gestation (after 20 weeks) over a period of six months. Study design: Cohort study Place and duration of study: Department of Obstetrics and Gynaecology, Lady Willingdon Hospital, Lahore from 4th February 2019 to 3rd August 2019. Methodology: One hundred and seventy females were enrolled in study at 20 weeks gestational age. They were divided into two groups (85 patients in each group). Those with normal Vitamin D3 levels (>30 ng/ml) were grouped as Low risk group and those with relatively low (insufficient) serum vitamin D3 levels (between 21-29 ng/ml) were grouped as high-risk group with potential risk factor for pre-eclampsia. Both groups were followed from 24+1 weeks to 36 weeks of gestation with every two weeks’ interval, for assessment of development of pre-eclampsia or not. Both groups were followed up and outcome was noted. Results: The mean age of the patients was 26.44±4.08 years and mean gestational age was 35.47±2.34 weeks. One hundred and 42(83.53%) patients appeared with PIH while 28(16.47%) patients appeared with preeclampsia. Among high risk patients, preeclampsia was noted in 26(30.6%) patients while in low risk group patients, preeclampsia was noted in 2(2.4%) patients (p<0.001). Conclusion: A significant association observed between pre-eclampsia and decreased vitamin D level during phases of pregnancy. Keywords: Vitamin D level, Preeclampsia, Hypertension
Preeclampsia (PE) is a leading cause of maternal-fetal mortality worldwide, and obesity is an important risk factor. Genes associated with pathophysiological events common to preeclampsia and obesity, such as PLAC8 , remain to be studied; therefore, the aim of the present study was to evaluate this gene in the placentas of women affected with preeclampsia and healthy pregnant women. This case-controlled study included 71 healthy and 64 preeclampsia pregnancies. Gene expression was evaluated in primary human cytotrophoblasts (PHCT) from six normal and six preeclampsia pregnancies, and protein expression was verified in placentas from five healthy and six preeclampsia pregnancies. The whole coding and 5′ regions of the PLAC8 gene were sequenced from healthy ( n = 10) and preeclamptic ( n = 10) pregnancies. The presence of the observed nucleotide variations was analyzed by RT-PCR in the total population. Statistical analyses were performed accordingly. Obesity was associated with severe preeclampsia (SPE) (OR = 3.34; CI 95% 1.3–8.2, p < 0.01). Significantly higher mRNA and protein expression was observed in preeclamptic vs. healthy placentas ( p < 0.05). After sequencing, a single nucleotide variation was identified in 10 cases and one control ( p < 0.01), which was then evaluated in the total population showing no association with preeclampsia. This preliminary study confirms the association of SPE with obesity and suggests higher expression of PLAC8 mRNA and protein in placentas from preeclampsia. No differences in nucleotide variations between cases and controls of the whole population were observed. Further research is required to evaluate the implications of higher gene/protein expression in preeclampsia and the causes of such variation.
Pregnancy-induced hypertension (PIH) is a heterogeneous disorder which complicates 5-7% of all pregnancies and remains a leading cause of maternal, fetal and neonatal morbidity and mortality. Severe preeclampsia is the most distinctive and life-threatening form; a multi-system disorder more common in first pregnancies, it is characterized by high blood pressure and proteinuria. In a series of Caucasian women with pregnancy-induced hypertension, we have observed a significant association of preeclampsia with a molecular variant of angiotensinogen, T235, found previously to be associated with essential hypertension. This finding is corroborated in a sample ascertained in Japan. Together, these observations support a new pathophysiological interpretation of preeclampsia and of its relation to some forms of essential hypertension.