Preeclampsia Pregnancy Research Articles

P-751 Development of hypertensive complications in oocyte donation pregnancy: a systematic review and individual participant data meta-analysis (DONOR IPD)

Abstract Study question Is the risk for hypertensive complications, including pregnancy-induced hypertension and preeclampsia, increased in oocyte donation pregnancy compared to autologous oocyte pregnancies? Summary answer We found an approximate 2.5-fold increased risk for hypertensive complications in oocyte donation pregnancy compared to autologous oocyte pregnancy using individual participant data meta-analysis approaches. What is known already Oocyte donation (OD) is an established assisted reproductive technique involving an oocyte donor and recipient. Due to the expansion of indications and emerging trends, the number of OD treatments is rising. Previous meta-analyses highlight increased risks of hypertensive complications compared to naturally conceived (NC) and IVF/ICSI pregnancies, including pregnancy induced hypertension (PIH) and preeclampsia (PE). However, limitations exist due to study quality, lack of correction for confounders, and heterogeneity. Study design, size, duration We conducted the DONation of Oocytes in Reproduction individual participant data (DONOR IPD) meta-analysis to determine the risk for the development of hypertensive complications in OD pregnancy, in comparison to autologous oocyte pregnancy. The DONOR IPD meta-analysis aims to address confounders, enhance statistical power, and provide robust evidence. Participants/materials, setting, methods A literature search was conducted using PubMed, EMBASE and Cochrane up to March 2023. We included observational studies that compared OD pregnancy beyond 20 weeks of gestation with autologous pregnancy, reporting on hypertensive pregnancy complications. Authors of eligible articles asked to share IPD. The DONOR IPD meta-analysis was executed using both a one- and two-stage approach, adjusted for confounders maternal age, parity and multiple gestation. Furthermore, sensitivity, meta-regression and subgroup analyses were performed. Main results and the role of chance IPD was sought for 58 cohorts, and eventually provided from sixteen cohorts with data of 2,747 OD, 4,699 autologous IVF/ICSI, and 33,323 NC pregnancies in total. The one- and two-stage approach comparing OD to autologous pregnancy resulted in adjusted ORs of respectively 2.62 (95% CI 2.22-3.10) and 2.65 (95% CI 2.08-3.39) for hypertensive complications in total, 2.15 (95% CI 1.73-2.68) and 1.49 (95% CI 0.80-2.80) for PIH, and 2.28 (95% CI 1.88-2.78) and 2.39 (95% CI 1.94-2.94) for PE. When the autologous group was split in NC and IVF/ICSI pregnancies, the higher risks in OD pregnancy for hypertensive complications, including PIH and PE, remained. However, compared to autologous pregnancies no significant increase in the risk for HELLP syndrome was observed in OD pregnancy. Limitations, reasons for caution The use of IPD still encounters certain limitations, such as IPD availability bias, and the dependency of methodological quality and heterogeneity of primary studies. To address these issues, we conducted additional sensitivity, meta-regression, and subgroup analyses. Wider implications of the findings Currently, none of the worldwide used guidelines indicate OD as a risk factor for hypertensive complications. As the DONOR IPD meta-analysis results in the best evidence based statement for international guidelines in obstetrics untill now, alertness of health care professionals must be increased towards the risk profile of these pregnancies. Trial registration number Financial support from the Leiden University Medical Center (the Netherlands) for an MD/PhD grant for K. van Bentem.

Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA)-Should They Be Mandatory Supplements in Pregnancy?

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essential fatty acids for the human body. Seafood and microalgae are the most important sources of omega-3 fatty acids. Supplementation with 200 mg/day of DHA during pregnancy and breastfeeding has been suggested for women and infants in countries with low seafood consumption. Maternal concentration of DHA and EPA was associated with concentration in cord blood and breast milk. High concentrations of DHA and EPA were identified at the level of retinal photoreceptors and neuronal cell membranes. It was observed that supplementation with DHA and EPA during pregnancy had beneficial effects on the neurological development of the fetus and infant by improving language, memory, attention, and hand coordination, affecting sleep patterns, and improving visual acuity. Beneficial effects on the development of the infant were also associated with the maternal intake of omega-3 fatty acids during breastfeeding. Supplementation with DHA and EPA may reduce the risk of preterm birth but also of preeclampsia in low-risk pregnancies. Women of childbearing age should have an intake of 250 mg/day of DHA + EPA from their diet or supplements. To reduce the risk of premature birth, pregnant women must additionally receive at least 100-200 mg of DHA every day. It is recommended that supplementation with omega-3 fatty acids starts before 20 weeks of pregnancy. Beneficial effects on the mother have been identified, such as the reduction of postpartum depression symptoms, the decrease of cardiovascular risk, and the anti-inflammatory role.

Preeclampsia and neonatal outcomes in pregnancies with maternal congenital heart disease: A nationwide cohort study from Norway.

The prevalence of congenital heart disease (CHD) among women of reproductive age is rising. We aimed to investigate the risk of preeclampsia and adverse neonatal outcomes in pregnancies of mothers with CHD compared to pregnancies of mothers without heart disease. In a nationwide cohort of pregnancies in Norway 1994-2014, we retrieved information on maternal heart disease, the course of pregnancy, and neonatal outcomes from national registries. Comparing pregnancies with maternal CHD to pregnancies without maternal heart disease, we used Cox regression to estimate the adjusted hazard ratio (aHR) for preeclampsia and log-binomial regression to estimate the adjusted risk ratio (aRR) for adverse neonatal outcomes. The estimates were adjusted for maternal age and year of childbirth and presented with 95% confidence intervals (CIs). Among 1 218 452 pregnancies, 2425 had mild maternal CHD, and 603 had moderate/severe CHD. Compared to pregnancies without maternal heart disease, the risk of preeclampsia was increased in pregnancies with mild and moderate/severe maternal CHD (aHR1.37, 95% CI 1.14-1.65 and aHR 1.62, 95% CI 1.13-2.32). The risk of preterm birth was increased in pregnancies with mild maternal CHD (aRR 1.33, 95% CI 1.15-1.54) and further increased with moderate/severe CHD (aRR 2.49, 95% CI 2.03-3.07). Maternal CHD was associated with elevated risks of both spontaneous and iatrogenic preterm birth. The risk of infants small-for-gestational-age was slightly increased with mild maternal CHD (aRR 1.12, 95% CI 1.00-1.26) and increased with moderate/severe CHD (aRR 1.63, 95% CI 1.36-1.95). The prevalence of stillbirth was 3.9 per 1000 pregnancies without maternal heart disease, 5.6 per 1000 with mild maternal CHD, and 6.8 per 1000 with moderate/severe maternal CHD. Still, there were too few cases to report a significant difference. There were no maternal deaths in women with CHD. Moderate/severe maternal CHD in pregnancy was associated with increased risks of preeclampsia, preterm birth, and infants small-for-gestational-age. Mild maternal CHD was associated with less increased risks. For women with moderate/severe CHD, their risk of preeclampsia and adverse neonatal outcomes should be evaluated together with their cardiac risk in pregnancy, and follow-up in pregnancy should be ascertained.

Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (Nε-(carboxymethyl)lysine [CML], Nε-(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (-12%) and hypoxia-exposed placentas (-16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (-26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia.

Placental Protein 13 and Syncytiotrophoblast Basement Membrane Ultrastructures in Preeclampsia.

Background and Objectives: Preeclampsia has been linked to an inflammatory response that may be brought on by endothelial cell dysfunction. This paper investigates the pathomechanism of syncytiotrophoblast basement membrane (STBM) damage and Placental Protein 13 (PP13) release, which may have a role in systemic endothelial dysfunction in preeclampsia. Materials and Methods: This comparative cross-sectional study involves 54 preeclampsia patients (27 early-onset preeclampsia and 27 late-onset preeclampsia) and 27 pregnant women with normal blood pressure. An enzyme-linked immunosorbent assay was performed to evaluate maternal blood levels of PP13. Following birth, a portion of the placenta was collected for transmission electron microscope (TEM) and immunohistochemical (IHC) analysis. The data were analyzed using STATA version 15. Results: PP13 expression in the placental syncytiotrophoblast was significantly lower in the early-onset preeclampsia, compared to late-onset preeclampsia and normotensive pregnancy, group (p < 0.001). In contrast, serum PP13 levels were found to be the highest in the early-onset preeclampsia group, although no significant difference were found in mean maternal serum levels of PP13 between the three groups. The decreased PP13 expression in placental syncytiotrophoblast can be attributed to the greater extent of damage in the STBM in early-onset preeclampsia that leads to the release of a larger amount of PP13 into maternal circulation. The hypothesis aligns with the TEM analysis results. Preeclamptic pregnancies showed placental syncytiotrophoblast aponeurosis, whereas normotensive pregnancies did not. Placental lesions and STBM shedding were found to be more pronounced in early-onset preeclampsia compared to late-onset preeclampsia. Conclusions: PP13 and STBM damage may play a role in systemic endothelial dysfunction in preeclampsia.

A Case of Partial Molar Pregnancy Complicated by HELLP and PRES

Introduction: The term gestational trophoblastic disease encompasses premalignant and malignant conditions arising from trophoblastic cells. Premalignant disorders include complete or partial hydatidiform mole, whereas malignant disorders include invasive mole, choriocarcinoma, and placental-site trophoblastic tumor. Partial hydatidiform moles are triploid in nature and occur when 2 sperm fertilize a single ovum. Preeclampsia is a syndrome complicating 2-8% of pregnancies which presents as new-onset hypertension plus proteinuria. The occurrence of hemolysis, elevated liver enzymes and low platelet count, referred to as HELLP syndrome, is a severe form of preeclampsia. A related severe manifestation is posterior reversible encephalopathy syndrome (PRES) - a clinicoradiological syndrome characterized by symptoms including headache, seizures, altered consciousness and visual disturbances. PRES is commonly associated with acute hypertension. The symptoms of PRES vary widely: i.e., the visual disturbance can vary from blurred vision and homonymous hemianopsia to cortical blindness. Seizures and status epilepticus are common. Although preeclampsia and HELLP syndrome rarely occur before 20-weeks of gestation, reports have suggested early occurrences of these hypertensive disorders specifically in the setting of a molar pregnancy. Case Report: The patient is a 23-year-old, female gravida 1 at 16 week 5 days who presented to an outside emergency department with a 3-day history of progressive abdominal pain which radiated to her back, arms, and shoulders. At the outside facility, the patient had multiple systolic blood pressures greater than 160 mmHg and had a witnessed 30-second seizure which resolved with an intravenous (IV) injection of 2-mg of Lorazepam and 4-gram magnesium sulfate loading dose. She was initiated on magnesium sulfate maintenance pending transfer to our institution. On admission, the patient met criteria for eclampsia and HELLP (platelets 79,000 K/uL, AST 144 U/L, ALT 96 U/L, LDH 482 U/L, Hemoglobin 8.7 g/dL). The beta human chorionic gonadotropin level (HCG) was greater than 200,000 mIU/mL. Bedside ultrasound suggested the presence of an enlarged cystic placenta and a growth restricted fetus (estimated fetal weight 124g, 2%). The patient and her family were counseled and the decision was made to proceed with misoprostol induction and termination of the pregnancy due to maternal indications. During the induction, the patient developed significant vaginal bleeding and was taken to the operating room for an uncomplicated dilation and evacuation. After the procedure, the patient developed progressive visual blurring with 4+ hyperreflexia. Magnetic resonance imaging (MRI) of the brain with and without contrast was obtained with findings significant for PRES. The MRI revealed T2 high-signal lesions within the cortex of the bilateral occipital lobes. Neurology was consulted and recommended blood pressure control and initiation of levetiracetam for seizure prophylaxis. She was initiated on long-acting nifedipine with subsequent blood pressure control. Patient’s visual symptoms and hyperreflexia resolved. Her liver function tests, platelets, and LDH also returned to normal. The patient received contraceptive counseling to prevent pregnancy during gestational neoplastic disease surveillance period. She underwent weekly beta-hCG until negative, followed by three weekly consecutive negative levels before spacing measurements to every 3 months for a period of six months per National Comprehensive Cancer Network (NCCN) guidelines. The pathology results indicated the presence of chorionic villi composed of both large hydropic and smaller normal-appearing villi, a 69.3-gram female fetus compatible with caudal neurocutaneous defect with abnormal localization of brain tissue. The genetic profile of the villous tissue consisted of two sets of dispermic paternal alleles in addition to one set of maternal alleles consistent with a partial mole diagnosis. Discussion: There is an association between preeclampsia and molar pregnancy. Of partial hydatidiform molar pregnancies, 41.9% will develop the symptoms of preeclampsia if left untreated. Although the pathophysiology of eclampsia spectrum disorders is incompletely understood, some evidence points to the role of increased death of trophoblasts and the maternal inflammatory response to trophoblast deportation. Additional evidence points to angiogenic factor imbalance and interestingly, molar placentas produce high levels of antiangiogenic factors. Other causative agents include placental factors that trigger maternal endothelial activation. It is known that trophoblastic debris shed from the placenta into the maternal blood is associated with this condition. It has been demonstrated that trophoblastic debris from molar pregnancies also induces endothelial cell activation through heat-shock protein 70 (HSP70) expressed on a hydatidiform molar placenta, which may be a pathogenic signal to endothelial cells. This case reiterates the association between hydatidiform moles and the hypertensive disorders of pregnancy possibly supporting the theories that such disorders may share an etiologic linkage through trophoblast debris and angiogenic factor imbalance. This case also supports screening molar pregnancies for severe preeclampsia syndrome.

The relationship between hypertensive disorders in pregnancy and endometriosis: a systematic review and meta-analysis

BackgroundEndometriosis is a chronic and debilitating disease that can affect the entire reproductive life course of women, with potential adverse effects on pregnancy. The aim of the present study is to investigate the association between hypertensive disorders in pregnancy and endometriosis.MethodRelevant articles were searched from the Cochrane Library, PubMed, Scopus and Web of Science from inception up to December 2023. The full-text observational studies published in English that had a confirmed diagnosis of endometriosis were included. The case group included pregnant women diagnosed with endometriosis at any stage, while the control group consisted of pregnant women who had not been previously diagnosed with endometriosis. Two authors extracted and analyzed the data independently. Disagreements were reconciled by reviewing the full text by a third author. Endnote X9 was used for screening and data extraction. We used fixed and random effects models in Review Manager 5.3 to analyze the pooled data. The quality of the included studies was assessed using the Downs and Black checklist.ResultsOut of the 9863 articles reviewed, 23 were selected for meta-analysis. According to the results of this study, there was an association between endometriosis and gestational hypertension (OR = 1.11, 95% CI: 1.06, 1.16; I2 = 45%, P < 0.00001; N = 8), pre-eclampsia (OR = 1.26, 95% CI: 1.18, 1.36; I2 = 37%, P < 0.00001; N = 12), and hypertensive disorders in pregnancy (OR = 1.13, 95% CI: 1.06, 1.21; I2 = 8%, P = 0.0001; N = 8).ConclusionsThis study confirmed that endometriosis may elevate the risk of developing gestational hypertensive disorders. Raising awareness of this issue will help to identify effective strategies for screening and early diagnosis of hypertensive disorders in pregnancy.

Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study

A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25–30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control’s DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 μg/L), suboptimal (70-99 μg/L), and optimal (≥ 100 μg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. The median plasma selenium was 98.8 (range: 46.7-206.4) μg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Periodontitis as a Risk Factor of Preeclampsia in Pregnancy: A Scoping Review

Periodontitis as a Risk Factor of Preeclampsia in Pregnancy: A Scoping Review

Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial

IntroductionPreterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week...

DNA methylation-mediated 11βHSD2 downregulation drives the increases in angiotensin-converting enzyme and angiotensin II within preeclamptic placentas.

Preeclampsia (PE) is a complex human-specific complication frequently associated with placental pathology. The local renin-angiotensin system (RAS) in the human placenta, which plays a crucial role in regulating placental function, has been extensively documented. Glucocorticoids (GCs) are a class of steroid hormones. PE cases often have abnormalities in GCs levels and placental GCs barrier. Despite extensive speculation, there is currently no robust evidence indicating that GCs regulate placental RAS. This study aims to investigate these potential relationships. Plasma and placental samples were collected from both normal and PE pregnancies. The levels of angiotensin-converting enzyme (ACE), angiotensin II (Ang II), cortisol, and 11β-hydroxysteroid dehydrogenases (11βHSD) were analyzed. In PE placentas, cortisol, ACE, and Ang II levels were elevated, while 11βHSD2 expression was reduced. Interestingly, a positive correlation was observed between ACE and cortisol levels in the placenta. A significant inverse correlation was found between the methylation statuses within the 11βHSD2 gene promoter and its expression, meanwhile, 11βHSD2 expression was negatively correlated with cortisol and ACE levels. Invitro experiments using placental trophoblast cells confirmed that active GCs can stimulate ACE transcription and expression through the GR pathway. Furthermore, 11βHSD2 knockdown could enhance this activating effect. An invivo study using a rat model of intrauterine GCs overexposure during mid-to-late gestation suggested that excess GCs in utero lead to increased ACE and Ang II levels in the placenta. Collectively, this study provides the first evidence of the relationships between 11βHSD2 expression, GCs barrier, ACE, and Ang II levels in the placenta. It not only contributes to understanding the pathological features of the placental GCs barrier and RAS under PE conditions, also provides important information for revealing the pathological mechanism of PE.

Preeclampsia in Multiples: A Comparative Case Study on Dichorionic-Diamniotic Twin Pregnancy

Multiple pregnancies have a 2-3 times greater risk of developing preeclampsia and have a significant long-term effect on both mothers and babies. The underlying cause of preeclampsia in women with multiple pregnancies is higher demand on the cardiovascular system, increased exposure of the chorionic villi, increased antiangiogenic substances compared to angiogenic substances and placental hypoperfusion. The condition of preeclampsia can worsen quickly, and without warning signs, it must be detected and managed appropriately; if the treatment is late, this condition can lead to eclampsia. The patient was referred with severe preeclampsia and multiple pregnancies with complaints of irregular contraction (+), a history of dizziness (-), nausea (-), vomiting (-), blurred vision (-), and breathlessness (-). Physical examination showed Blood pressure 188/125 mmHg with laboratory findings of proteinuria +3. Cesarean section and IUD insertion were performed. During and after surgery, there were no complications.

#1715 Role of T cell profile (Th1/Th2/Th17/Treg) and podocyturia in the peripheral blood of patients with preeclampsia versus normal pregnancy

Abstract Background and Aims The concept of the balance between Th17/Treg cell immunity plays important role in determining pregnancy outcomes. Does Treg/TH17 play a role in pathogenesis of preeclampsia associated proteinuria and its implication on irreversible renal damage was the research question. Method This hospital based prospective study conducted in the Department of obstetrics and gynecology at a tertiary care medical college between October 2018 till October 2020 and assessment of T cell profiling and urinary podocyturia among all pregnancies with clinical evidence of preeclampsia and compared it with normal pregnancy monitoring for maternal and foetal outcomes. Repeat assessment of Th profiling and podocyturia was done after 3 months post partum to look for any residual effect. Results A total of 40 patients of preeclampsia and 40 control were enrolled in the study with median age group (24.58 ± 1.22 vs 25.16 ± 1.01). The percentage of Th1 and Th2 were higher for the preeclampsia group as compared to the control group with no change in the percentage of Th17 subsets while Th17 1 were found higher and percentage of Treg (8.1 ± 3.19 vs 2.3 ± 1,05, p = 0.001) lower in the peripheral blood of the preeclampsia group at time of delivery however the ratio of Th1/Treg, Th2/Treg, Th17/Treg and Th17.1/Treg were found significantly lowered after 6 weeks of delivery among those with preeclampsia nearly comparable to the normal pregnancy group The quantitative assessment of podocyte in urine using antinephrin showed increase numbers among preeclamptic pregnancies compared to normal yet it settled within 6 weeks of delivery. Conclusion Women with preeclampsia per se does not increase the risk to exacerbation of kidney disease however greater research mandates to assess the women at greatest risk of kidney disease after pre-eclampsia to have good maternal and foetal outcomes.

Active metabolomics identify potential functional metabolites for preeclampsia prevention

BackgroundPreeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality, with limited effective clinical treatment options. Active metabolomics offers a promising approach to uncover metabolic changes in PE and identify potential biomarkers or therapeutic targets. This study performed untargeted metabolomics using LC-MS to compare serum samples from preeclampsia and normal pregnancies. MethodsWe performed untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to compare serum samples from PE patients and normal pregnancies. We analyzed the alterations in metabolites and conducted functional experiments to assess the effects of LysoPE(16:0) on trophoblast cell invasion and migration. Mechanistic studies were performed to explore the potential targeting of GSK-3β by LysoPE(16:0). ResultsOur metabolomics analysis revealed significant alterations in several metabolites, including lysophosphatidylcholines and organic acids. Notably, LysoPE(16:0) was found to be downregulated in the serum of PE patients. Functional experiments demonstrated that LysoPE(16:0) could promote trophoblast cell invasion and migration. Mechanistic studies suggest that the protective effect of LysoPE(16:0) against PE might be mediated through the modulation of the GSK-3β/β-Catenin pathway, with LysoPE(16:0) potentially targeting the GSK-3β protein. ConclusionsOur findings highlight the potential role of LysoPE(16:0) in the pathophysiology of PE and its ability to modulate the GSK-3β/β-Catenin pathway. These results provide new insights into the metabolic changes associated with PE and suggest that LysoPE(16:0) could serve as a promising biomarker or therapeutic target for the prevention and treatment of PE.

Bleeding Time and Clotting Time in Pre-eclampsia, Eclampsia and Normal Pregnancy

Introduction: The most important cause of maternal and perinatal morbidity and mortality are hypertensive disorder (Preeclampsia and eclampsia). In preeclampsia and eclampsia there is hypercoagulable state which acts as a risk factor for thromboembolism and DIC. Objective: This study was carried out to compare the coagulation indices in normal pregnancy, preeclampsia and eclampsia. Materials and Methods: This cross sectional study was conducted in Dhaka Medical College from January to December’ 2014. Total 150 women aged 18 – 40 years were selected for this study. Among them 50 normal pregnant, 50 preeclamptic and 50 eclamptic women were selected as study group and age matched 50 healthy nonpregnant women were considered as control group. Bleeding time was estimated by Duke’s method and clotting time was estimated by capillary tube method. Results: In this study bleeding time and clotting time were significantly higher in preeclamptic and eclamptic women than those of healthy nonpregnant women. Conclusion: From this study it can be concluded that bleeding time and clotting time are closely related with preeclampsia and eclampsia. Medicine Today 2023 Vol.36 (1): 41-44

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia

BackgroundPreeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown.ResultsBy analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling.ConclusionsOur study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

Prognostic value of angiogenic markers in pregnancy with fetal growth restriction.

Pregnancies with fetal growth restriction (FGR) are at increased risk for pre-eclampsia. Angiogenic markers including soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by FGR, but their utility for predicting pre-eclampsia in growth-restricted pregnancies is uncertain. This study aimed to evaluate the prognostic value of angiogenic markers for predicting the development of pre-eclampsia in pregnancies with FGR and suspected pre-eclampsia. This was a retrospective study of singleton pregnancies with FGR, defined according to Delphi consensus criteria, which underwent sampling of sFlt-1 and PlGF for suspicion of pre-eclampsia at the Medical University of Vienna, Vienna, Austria, between 2013 and 2020. Women with an established diagnosis of pre-eclampsia at sampling were excluded. Cox regression analysis and logistic regression analysis were performed to evaluate the association of angiogenic markers with the development of pre-eclampsia at various timepoints. In this cohort of 93 women, pre-eclampsia was diagnosed in 14 (15.1%) women within 1 week after sampling, 21 (22.6%) within 2 weeks after sampling and 38 (40.9%) at any time after assessment. The sFlt-1/PlGF ratio consistently showed a stronger association with the development of pre-eclampsia compared to sFlt-1 or PlGF alone (pre-eclampsia within 1 week: area under the receiver-operating-characteristics curve, 0.87 vs 0.82 vs 0.72). Models including the sFlt-1/PlGF ratio were associated more strongly with pre-eclampsia hazard compared to models including sFlt-1 or PlGF alone (concordance index, 0.790 vs 0.759 vs 0.755). The risk classification capability of the sFlt-1/PlGF ratio decreased after the 2-week timepoint. The established cut-off value for the sFlt-1/PlGF ratio of < 38 was effective for ruling out pre-eclampsia within 2 weeks, with a negative predictive value of 0.933 and sensitivity of 0.952. Use of the sFlt-1/PlGF ratio is preferrable to the use of PlGF alone for the prediction of pre-eclampsia in pregnancies with FGR. Established cut-offs for ruling out the development of pre-eclampsia in the short term seem to be effective in these patients. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Vascular Endothelial Mitochondrial Oxidative Stress in Response to Placental Macrophages from Preeclamptic Pregnancies

Preeclampsia (PE), a hypertensive disorder of pregnancy characterized by maternal hypertension, fetal growth restriction (FGR), and chronic immune activation and inflammation, is a major cause of maternal and fetal morbidity and mortality worldwide. Prior clinical studies demonstrate that proinflammatory M1 macrophages are increased in women with PE. We do not understand the role that M1 macrophage polarization may play in PE pathophysiology. We set out to begin characterization of macrophages in patient samples obtained from the UMMC biobank and their ability to induce mitochondrial oxidative stress (ROS) in human umbilical vein endothelial cells (HUVECs). After obtaining informed consent, whole blood and placental tissues were collected from normal pregnant (n=5) and preeclamptic women (n=8) who delivered in the labor and delivery unit UMMC. Lymphocytes were isolated from blood on a Ficoll-Histopaque gradient and analyzed by flow cytometry for total and M1 macrophages. Total macrophages were isolated from digested placental tissue by magnetic bead separation using the Human Macrophage Isolation Kit (Miltenyi). Isolated macrophages were co-cultured with HUVECs overnight. After removal of culture inserts containing macrophages, HUVECs were serum-starved and incubated with MitoSox Red, collected, and analyzed on a flow cytometer. Total circulating macrophages were increased in placentas from PE women vs normal pregnant patients (10.8% PMBCs vs. 3.5% PMBCs, respectively, p&lt;0.05). Furthermore, macrophage polarization to M1 macrophages was significantly higher in women with PE (15.02% of total macrophages) compared to NP women (6.23% of total macrophages, p&lt;0.05 vs. PE). We also determined that mitochondrial ROS production was significantly elevated in HUVEC cells co-cultured with macrophages from PE pregnancies (15.37 A.U.) when compared to HUVECs co-cultured with normal pregnant control macrophages (7.788 A.U., p&lt;0.05 vs. PE). Future studies will include enrollment of additional participants and determination of endothelial activation by measurement of adhesion molecules, growth factors, extracellular matrix proteins, and cytokines in HUVECs and conditioned media via Western Blot, ELISA, and multiplex analysis. These data show that PE placental macrophages induce mitochondrial ROS production in endothelial cells and may play a role to directly induce vascular dysfunction contributing to hypertension during a preeclamptic pregnancy. This work was supported by National Institutes of Health Grants T32HL105324 to C. A. Shields, and R01HL151407 to D. C. Cornelius. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

DIFFERENCES BETWEEN PROFILE OF OFFICE, HOME AND 24H AMBULATORY BLOOD PRESSURE MONITORING IN PREECLAMPSIA AND UNCOMPLICATED HYPERTENSION IN PREGNANCY

Objective: Definition of arterial hypertension and management decision making in guidelines is still based on office blood pressure measurement (OBPM), both in general and pregnant population, although in clinical practice 24h ambulatory monitoring (ABPM) seems to be more accurate, which if not available often replaced with home BP (HBPM). Information on differences between values of BP depending on method in course of pregnancy are scarce. Aim of the study was to assess profile and compare results of three methods of BP measurement used simultaneously – HBPM, OBPM and 24 ABPM in pregnancy in real clinical setting with regard to hypertensive status, development of preeclampsia (PE) and time of pregnancy. Design and method: In a prospective longitudinal study 241 pregnant women admitted between 2017 and 2023 to outpatient clinic had their BP examined - monthly throughout pregnancy and 6-8 weeks, 6 months and 1 year postpartum. On each occasion data on HBPM (from 7 days prior) were collected, compared with OBPM in standardized conditions (OMRON®-705I) as well as with result of 24h ABPM (AND®TM-2430). Pharmacotherapy in hypertensive patients was managed in accordance with ESH/ESC guidelines. Results: We have recruited 40 normotensive controls and 201 women with hypertension (145 chronic; 56 pregnancy induced). Preeclampsia developed in 49 of hypertensives (HT+PE) (18,6% of chronic HT, 39,3% of PIH) – on average in 32,8 w.g. (20-39). SBP/DBP as median are presented in table 1. BP of controls differed significantly from both complicated (HT+PE) and uncomplicated hypertensive patients (HT) in all three methods at all stages of pregnancy and postpartum (p&lt; 0.05). Significant differences between HT+PE and HT are marked in table 2 in gray. Conclusions: Regardless of method of BP assessment and good BP control with antihypertensives achieved values in HT pregnancies differed significantly from normotensive pregnancies. Preeclamptic patients were characterized with significantly higher BP values in HBPM, OBPM and – most strongly expressed - in night-ABPM than uncomplicated hypertensives already 2 months before average time of PE recognition. The night-time BP values from ABPM seems to have the strongest predictive and diagnostic value for early recognition of preeclampsia.