Association of genetic ancestry with pre-eclampsia in multi-ethnic cohorts of pregnant women.

OBJECTIVES: Maternal self-reported ethnicity is recognised as a risk factor for pre-eclampsia in clinical screening tools and models. This study investigated whether ethnicity is acting as a proxy for genetic variants in this context. STUDY DESIGN: A total of 436 women from multi-ethnic backgrounds recruited to two UK observational pregnancy hypertension cohort studies were genotyped. Genetically-computed individual ancestry estimates were calculated for each individual through comparison to the multi-ethnic 1000 Genomes reference panel genotypes. Regression models for pre-eclampsia using clinical risk factors including self-reported ethnicity with and without ancestry estimates were built and compared using Likelihood Ratio Tests (LRT). MAIN OUTCOME MEASURES: Pre-eclampsia (early- and late-onset). RESULTS: In these multi-ethnic cohorts (mean age 34.9 years; 41.3 % White, 34.2 % Black, 13.1 % Asian ethnic backgrounds; 82.6 % chronic hypertension), discrepancies between self-reported ethnicity and genetically-computed individual ancestry estimates were present in all ethnic groups, particularly minority groups. Genetically-computed pan-African ancestry percentage was associated with early-onset (< 34 weeks) pre-eclampsia in adjusted models (aOR 100 % vs 0 % African ancestry: 3.81, 95 % CI 1.04-14.14, p-value 0.044) independently of self-reported ethnicity and established clinical risk factors. Addition of genetically-computed African ancestry to a clinical risk factor model including self-reported ethnicity, improved model fit (Likelihood ratio test p-value 0.023). CONCLUSIONS: Self-reported maternal ethnicity is an imperfect proxy for genetically-computed individual ancestry estimates, particularly in ethnic minority groups. Genetically-computed African ancestry percentage was associated with early-onset pre-eclampsia independently of self-reported maternal ethnicity. Well-powered studies in multi-ethnic cohorts are required to delineate the genetic contribution to pre-eclampsia.

Synthesis of evidence for managing hypertensive disorders of pregnancy in low middle-income countries: a scoping review.

BACKGROUND AND OBJECTIVES: Hypertensive disorders of pregnancy (HDPs) remain one of the leading causes of maternal mortality globally, especially in Low- and middle-income countries (LMICs). To reduce the burden of associated morbidity and mortality, standardized prompt recognition, evaluation, and treatment have been proposed. Health disparities, barriers to access to healthcare, and shortage of resources influence these conditions. We aimed to synthesize the literature evidence for the management of HDPs in LMICs. METHODS: A scoping review was conducted in five databases (PubMed, Web of Science, Epistemonikos, Clinical Key and, Scielo) using MeSh terms, keywords, and Boolean connectors. We summarized the included studies according to the following categories: study design, objectives, settings, participant characteristics, eligibility criteria, interventions, assessed outcomes, and general findings. RESULTS: Six hundred fifty-one articles were retrieved from the literature search in five databases. Following the selection process, 65 articles met the predefined eligibility criteria. After performing a full-text analysis, 27 articles were included. Three themes were identified from the articles reviewed: prevention of HDPs, management of HDPs (antihypertensive and non-hypertensive management) and pregnancy monitoring and follow-up. The topics were approached from the perspective of LMICs. CONCLUSIONS: LMICs face substantial limitations and obstacles in the comprehensive management of HDPs. While management recommendations in most LMICs align with international guidelines, several factors, including limited access to crucial medications, unavailability of diagnostic tests, deficiencies in high-quality healthcare infrastructure, restrictions on continuing professional development, a shortage of trained personnel, community perceptions of preeclampsia, and outdated local clinical practice guidelines, impede the comprehensive management of patients. The development and implementation of protocols, standardized guides and intervention packages are a priority.

Hypertensive Disorders of Pregnancy in Saudi Arabia: Evaluating Maternal and Neonatal Risks, Outcomes, and Aspirin Prophylaxis: A Review Article.

Hypertensive disorders during pregnancy, including pre-eclampsia and eclampsia, pose significant risks to both maternal and neonatal health. This review article evaluates the prevalence, maternal and neonatal outcomes, and the efficacy of aspirin prophylaxis in managing these conditions in Saudi Arabia. Utilizing data from multiple retrospective studies and recent guidelines, we highlight the regional variations in the outcomes of hypertensive disorders of pregnancy. Severe complications such as Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome occurred in 6.6% of cases, while eclampsia was reported in 6.7% of cases. Cesarean sections were notably high, with rates reaching up to 79% among affected pregnancies. Maternal risk factors identified include chronic hypertension (prevalence 17%), diabetes (ranging from 10.4% to 26.3%), and advanced maternal age. Neonatal complications often involve preterm birth, reported in 26.5% to 26.7% of cases, intrauterine growth restriction (ranging from 15.7% to 25%), and increased NICU admissions, reported in 2.4% of cases. No data were found in the included studies to evaluate the prophylactic use of low-dose aspirin in reducing the incidence of pre-eclampsia or improving fetomaternal outcomes. Despite the effectiveness of aspirin, awareness and implementation of prophylaxis guidelines remain suboptimal among healthcare providers in Saudi Arabia. A national survey revealed that only a fraction of obstetrical care providers were fully knowledgeable about aspirin prophylaxis guidelines. This review underscores the necessity for enhanced educational programs and standardized guidelines to improve maternal and neonatal outcomes in hypertensive pregnancies within the region.

Cushing's Syndrome Missed in Pregnancy.

Cushing's syndrome (CS) is uncommon during pregnancy and often difficult to diagnose due to similar symptoms shared with normal pregnancy. This case report discusses a 26-year-old woman who developed CS while pregnant, underlining the importance of early detection and the diagnostic challenges involved. The patient presented with gestational diabetes and pre-eclampsia during pregnancy. Post delivery, she continued to experience hypertension and facial swelling, which led to a diagnosis of CS. The patient underwent a successful laparoscopic adrenalectomy, which normalized her blood pressure and improved her symptoms. This case highlights the need for heightened awareness of CS in pregnant women exhibiting both gestational diabetes and hypertension, as early diagnosis and treatment are essential to reduce maternofoetal complications.

[Which workup should be performed after a pregnancy complicated with vasculo-placental disorder?] / Quel bilan proposer après une grossesse compliquée de pathologie vasculo-placentaire ?

Vasculo-placental disorders include pregnancy complications resulting from placental dysfunction of vascular origin, i.e. pre-eclampsia, HELLP syndrome, intrauterine growth retardation (IUGR), placental abruption and stillbirth of vascular origin. Pre-eclampsia should be investigated for antiphospholipid syndrome (APS) in case of severe pre-eclampsia and premature delivery before 34 weeks of gestation. In addition to testing for APS, pathological report of the placenta can identify some anatomical predispositions to placental vascular malperfusion, as well as chronic placental inflammatory lesions and excess fibrin deposits. The latter two are associated with IUGR and recurrent stillbirth, reflecting a dysimmune process of maternal origin. The internal medicine and obstetrics consultation, organized two months after delivery, combines the postnatal visit with an assessment of the causes of vasculo-placental disorders, and enables to inform patients about the management of future pregnancies and their cardiovascular health.

Maternal morbidity in postpartum severe preeclampsia by obstetric delivery volume.

BACKGROUND: Pre-eclampsia is a leading cause of maternal morbidity and mortality in the United States. Emerging data suggests that postpartum pre-eclampsia may be associated with a higher incidence of maternal morbidity compared to hypertensive disorders of pregnancy (HDP) diagnosed antenatally. Understanding postpartum maternal risk across facilities with a spectrum of obstetric services is critical with the rising rates of pre-eclampsia in all healthcare settings. OBJECTIVES: We investigated the relationship between facility delivery volume and rates of non-transfusion severe maternal morbidity (SMM) among patients readmitted postpartum for pre-eclampsia with severe features. STUDY DESIGN: This is a retrospective cohort study using the Nationwide Readmissions Database (2015-2019) of postpartum patients readmitted for pre-eclampsia with severe features. Our primary outcome was non-transfusion SMM during readmission, defined per U.S. Centers for Disease Control and Prevention criteria. We also evaluated SMM, cardiac SMM, and individual morbidities. The exposure variable was the number of annual deliveries at the readmitting facility. Restricted cubic splines with 4 knots were used to assess the functional form of the relationship between obstetric delivery volume and non-transfusion SMM; a linear relationship was identified as optimal. Logistic regression was used to estimate adjusted odds ratios (aOR) which controlled for maternal age, non-transfusion SMM at delivery, expanded obstetric comorbidity index, and HDP during delivery. RESULTS: The cohort included 29,472 patients readmitted with postpartum pre-eclampsia with severe features. The primary payer was 55% private and 42% governmental. Median age was 31.4 years. Most patients did not have prior HDP (65%) or chronic hypertension (86%) diagnosis antenatally. The median interval from delivery hospitalization to readmission was 3.9 days (25th percentile-75th percentile: 2.2-6.5). Non-transfusion SMM occurred in 7% of patients readmitted to facilities with >2,000 deliveries compared to 9% with 1-2,000 deliveries, and 52% without any delivery hospitalizations. The most common SMM was pulmonary edema and heart failure, observed in 4% of readmissions. We observed that for every increase in 1,000 deliveries, the odds of a non-transfusion SMM at readmission decreased by 3.5% (aOR: 0.965; 95% confidence interval: 0.94, 0.99) CONCLUSIONS: Non-transfusion SMM for postpartum readmissions with pre-eclampsia with severe features was inversely associated with readmitting hospital delivery volume. This information may guide risk-reducing initiatives for identifying strategies to optimize postpartum care at facilities with lower or no delivery volume.

Metformin use and preeclampsia risk in women with diabetes: a two-country cohort analysis.

BACKGROUND: Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. METHODS: We utilised data from two population-based cohorts: Scotland (2012-2018) and Sweden (2007-2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. RESULTS: The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66-1.19]; Sweden aRR 1.08 [95% CI 0.86-1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66-1.60]; Sweden aRR 1.00 [95% CI 0.72-1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79-1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73-1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21-0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89-1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60-1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41-1.48]). CONCLUSIONS: In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.

Prediction of Adverse Maternal Outcomes in Preeclampsia Using the FullPIERS (Preeclampsia Integrated Estimate of Risk) Model in a Tertiary Care Hospital of Eastern India.

INTRODUCTION: Preeclampsia, characterized by hypertensive disorders and systemic inflammatory response, remains a leading cause of maternal morbidity and mortality globally. Effective risk assessment tools are crucial for predicting adverse maternal outcomes. OBJECTIVE: This study evaluates the performance of the fullPIERS (Preeclampsia Integrated Estimate of Risk) model in predicting adverse maternal outcomes within 24 hours of admission for preeclampsia. METHODS: A cross-sectional study was conducted over one year, involving 100 preeclamptic patients admitted to Nil Ratan Sircar Medical College & Hospital (NRSMCH). Predictor variables were collected within 24 hours of admission and analyzed using the fullPIERS model. RESULTS: The fullPIERS model effectively stratified maternal risk. Adverse outcomes were significantly associated with systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, oxygen saturation ≤ 95%, frontal headache, visual disturbances, chest pain/dyspnea, and abnormal random blood sugar, albumin, alanine aminotransferase, platelet count, and creatinine levels. A fullPIERS score ≥ 30 was strongly predictive of adverse maternal outcomes. CONCLUSION: The fullPIERS model is a valuable tool for predicting adverse maternal outcomes in preeclampsia, aiding in timely and effective clinical decision-making.

Benefits of simulation on multidisciplinary management of severe pre-eclampsia/severe eclampsia in 15 health districts in eastern Democratic Republic of Congo: A randomized educational trial.

OBJECTIVE: The purpose of the present study was to assess the benefits of simulation for advancing knowledge and assisting healthcare staff in optimization of procedures when managing severe pre-eclampsia/eclampsia (sPE/E). METHODS: A randomized educational trial was conducted with two groups: Group I received theoretical training, while group II received the same training along with simulation scenarios based on the management of sPE/E. The study involved 199 healthcare providers, including physicians, midwives, skilled birth attendants, and nurses. The study analyzed the percentage of correct answers on both the multiple-choice questions (MCQ) and the objective structured clinical examinations (OSCE) to evaluate theoretical knowledge and clinical skills objectively. RESULTS: Statistically significant differences were found immediately after training between groups I and II, whose mean percentages were 65.0% (±11.2) versus 71.0% (±9.8) (P < 0.001). A statistically significant reduction in the percentage of correct answers was found in both groups and demonstrated a discrepancy between immediate post-training test and post-training test at 3 months scores of 11.6% (±1.3) in group I versus 7.2% (±0.6) in group II. OSCE1 and OSCE2 scores were significantly higher in group II than in group I (P < 0.001). CONCLUSION: Simulation combined with theoretical training would appear to be an interesting method of training for advancing knowledge and improving skills of healthcare providers in their management of sPE/E. Our goal is for this method to be used to reduce real-life maternal mortality in the South Kivu region of the Democratic Republic of Congo.

AC092100.1 promotes angiogenesis in pre-eclampsia through YTHDC2/VEGFA signaling.

Aberrant long non-coding RNA (lncRNA) expression has been shown to be involved in the pathological process of pre-eclampsia (PE), yet only a small portion of lncRNAs has been characterized concerning the function and molecular mechanisms involved in PE. This study aimed to investigate the regulatory mechanism of the lncRNA AC092100.1 (AC092100.1) in angiogenesis in PE. In our study, bioinformatics analysis was performed to screen for differentially expressed lncRNAs between normal subjects and PE patients. The levels of AC092100.1 in placental tissues of patients with or without PE were validated using qRT-PCR. The effect of AC092100.1 overexpression on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was investigated. The binding of AC092100.1 and YT521-B homology domain-containing 2 (YTHDC2) was predicted and verified. The effect of AC092100.1/YTHDC2 on the expression of vascular endothelial growth factor-A (VEGFA) in HUVECs was determined. Finally, a PE mice model was conducted. Fetal mouse growth, the abundance of mesenchymal morphology markers, including hypoxia-inducible factor 1-alpha (HIF-1α), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), Slug, and Vimentin, and endothelial markers, including placental growth factor (PLGF), CD31, and vascular endothelial (VE)-cadherin, in placental tissues were assessed. Here, we found that AC092100.1 was abnormally downregulated in placental tissues from PE patients. We established that AC092100.1 overexpression promoted HUVEC proliferation, migration, and tube formation in vitro. Mechanistically, AC092100.1 induced the accumulation of YTHDC2 and VEGFA through binding to YTHDC2 in HUVECs. Inhibition of YTHDC2 or VEGFA reversed AC092100.1-promoted tube formation. AC092100.1 overexpression contributed to alleviating fetal growth disorder, decreased levels of sEng, HIF-1α, sFlt-1, Slug, and Vimentin, and increased levels of VEGFA, PLGF, CD31, and VE-cadherin in PE mice. Our findings provided evidence supporting the role of the AC092100.1/YTHDC2/VEGFA axis in regulating angiogenesis, which demonstrated a therapeutic pathway for PE targeting angiogenesis.

Retinal Microvascular Characteristics and Outcomes in Hypertensive Disorders of Pregnancy.

Background Hypertensive disorders of pregnancy (HDP) is a continuum of chronic hypertension, gestational hypertension, preeclampsia, and eclampsia in increasing severity, associated with a higher risk of complicated pregnancies and poor neonatal outcomes. This multisystem involvement can be assessed by fundoscopy, which serves as an indicator for generalized microvascular abnormalities. Our study aims to evaluate the correlation of hypertensive retinopathy with the severity of HDP and maternal and fetal outcomes. Materials and methods The study was conducted at a tertiary care hospital in Vijayapura from October 2021 to March 2022 among admitted cases of HDP. Detailed history, blood pressure (BP) measurement, obstetric examination, and fundoscopy were performed for all cases. Patients were followed up until the 10th postnatal day. The mode of delivery, birth weight, gestational age at birth, and any other neonatal outcomes were noted. Results We included 94 preeclampsia/eclampsia patients with a median age of 23 years, 51 (54.3%) being primigravida. Patients with chronic hypertension, gestational hypertension, and chronic hypertension superimposed by preeclampsia/eclampsia were excluded. The most common symptom in mothers was headache (23.4%), followed by blurring of vision (20.2%) and epigastric pain (5.3%) with a significant association (p < 0.05). Thirty-two cases (34%) had preterm deliveries with a positive association with the severity of retinopathy (p < 0.05). The magnitude of hypertensive retinopathy was 56.3% (53 cases), the severity of which significantly correlated to the severity of HDP (p < 0.05). We report 8.5% neonatal mortality and 22.3% small for gestational age (SGA) with a positive association with HDP severity (p < 0.05). There was no correlation between serum creatinine levels and the severity of retinopathy and fetal outcome. Conclusion The occurrence and severity of hypertensive retinopathy increase with increasing severity of HDP. Complaints, such as headache, blurred vision, and epigastric pain, are reported higher in cases with retinopathy. The severity of retinopathy may be used as an indicator of fetal morbidity; however, studies with large sample sizes and advanced tools are required to quantify the cause-effect relationship. The retinopathy associated with HDP resolves naturally with BP control postnatally.

Perinatal outcomes in indian women with Antiphospholipid Antibody Syndrome (APS): Five year experience from a tertiary care centre.

Background: Antiphospholipid Syndrome (APS) is a systemic autoimmune thrombophilic condition characterized by obstetric manifestations, including pregnancy loss, preeclampsia and fetal growth restriction. Early diagnosis and management are key to improve maternal and neonatal outcomes. Objective: The aim of this study is to assess the perinatal outcomes in APS, the development of various adverse pregnancy outcomes (APO), and their association with specific antibody profiles. Material methods: This observational study was carried out on booked cases of singleton pregnancy and diagnosed cases of primary APS in our High-Risk Pregnancy (HRP) clinic from January 2018 to December 2022 after approval from institutional ethics committee. Forty-three confirmed cases of primary APS were enrolled and started on low-dose aspirin and low-molecular-weight heparin (LMWH) as per the patient's body weight after confirmation of fetal heart activity radiologically until 36 weeks of gestation as a standard of care. Results: Forty patients (93 %) had obstetric APS, and three patients (7 %) had thrombotic APS. During the course of the current pregnancy, adverse pregnancy outcomes (APO) developed in 12 (30 %) out of 40 cases of obstetric APS and in all 3 patients with thrombotic APS. Preeclampsia was seen in 11 (25.5 %), FGR in 12 (27.9 %), and preterm birth in 7 (16.2 %) cases. Patients with an antibody profile showing the presence of Anti-ß2 GP-I positivity and ACL positivity had fewer APOs (20 % and 29 %) in comparison to patients with a LA and triple positive antibody profile (55 % and 50 %). Conclusion: Treatment of pregnant women with APS causes significant improvement in the live birth rate. The late pregnancy complications like preeclampsia, FGR, and premature birth, occurring despite treatment still remains a challenge and emphasizes the need for stringent antepartum surveillance and timely delivery.

Methylation alterations of imprinted genes in different placental diseases.

BACKGROUND: Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS). RESULTS: In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2'-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS. CONCLUSIONS: This study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

Dietary patterns during pregnancy and maternal and birth outcomes in women with type 1 diabetes: the Environmental Determinants of Islet Autoimmunity (ENDIA) study.

AIMS/HYPOTHESIS: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. METHODS: Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. RESULTS: Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a 'fresh food' dietary pattern than women without type 1 diabetes (OR 1.19, 95% CI 1.07, 1.31; p=0.001). In women with type 1 diabetes, an increase equivalent to a change from quartile 1 to 3 in 'fresh food' dietary pattern score was associated with a lower risk of pre-eclampsia (OR 0.37, 95% CI 0.17, 0.78; p=0.01) and premature birth (OR 0.35, 95% CI 0.20, 0.62, p<0.001). These associations were mediated in part by BMI and HbA1c. The 'processed food' dietary pattern was associated with an increased birthweight (ß coefficient 56.8 g, 95% CI 2.8, 110.8; p=0.04). Physical activity did not relate to outcomes. CONCLUSIONS/INTERPRETATION: A dietary pattern higher in fresh foods during pregnancy was associated with sizeable reductions in risk of pre-eclampsia and premature birth in women with type 1 diabetes.

Dysregulated Mitochondrial Calcium Causes Spiral Artery Remodeling Failure in Preeclampsia.

BACKGROUND: Calcium deficiency in women is strongly linked to an increased risk of developing preeclampsia. Mitochondrial calcium ([Ca2+]m) homeostasis is essential to regulate vascular smooth muscle cell (VSMC) function. However, the role of [Ca2+]m in preeclampsia development remains largely unknown. METHODS: To investigate this, human spiral arteries obtained from normotensive and preeclamptic women were collected for vascular function, RNA sequencing, and VSMC studies. N(ω)-nitro-L-arginine methyl ester-induced preeclampsia animal experiments were established to investigate the effects of intervening in [Ca2+]m to improve the outcome for preeclamptic mothers or their infants. RESULTS: Our initial findings revealed compromised vessel function in spiral arteries derived from patients with preeclampsia, as evidenced by diminished vasoconstriction and vasodilation responses to angiotensin II and sodium nitroprusside, respectively. Moreover, the spiral artery VSMCs from patients with preeclampsia exhibited phenotypic transformation and proliferation associated with the disrupted regulatory mechanisms of [Ca2+]m uptake. Subsequent in vitro experiments employing gain- and loss-of-function approaches demonstrated that the mitochondrial Na+/Ca2+ exchanger played a role in promoting phenotypic switching and impaired mitochondrial functions in VSMCs. Furthermore, mtNCLX (mitochondrial Na+/Ca2+ exchanger) inhibitor CGP37157 significantly improved VSMC phenotypic changes and restored mitochondrial function in both patients with preeclampsia-derived VSMCs and the preeclampsia rat model. CONCLUSIONS: This study provides comprehensive evidence supporting the disrupted regulatory mechanisms of [Ca2+]m uptake in VSMCs of spiral arteries of patients with preeclampsia and further elucidates its correlation with VSMC phenotypic switching and defective spiral artery remodeling. The findings suggest that targeting mtNCLX holds promise as a novel therapeutic approach for managing preeclampsia.

Causal association of sex hormone-binding globulin on gestational hypertension and pre-eclampsia: a two-sample Mendelian randomization study.

OBJECTIVES: Pre-eclampsia (PE) and gestational hypertension (GH) are two different categories of hypertensive disorders of pregnancy. Given earlier observational research, the relationship between sex hormone-binding globulin (SHBG) and a higher risk of GH/PE is still up for dispute. Hence, the present investigation aimed to examine the possible link between SHBG and the likelihood of GH/PE. METHODS: As a first stage, single nucleotide polymorphisms from summary-level genome-wide association studies were tightly screened using quality-control techniques. Afterward, we utilized a two-sample Mendelian randomization (MR) study to examine the causal impact of SHBG on the likelihood of GH/PE. There was no indication of a relationship between blood SHBG level (n = 214,989) and GH/PE (1864 cases and 461,069 controls) in the initial study. Consensus results were obtained from the replicated analysis, which utilized MR estimates based on serum SHBG level(n = 214,989) for GH (4255 cases and 114,735 controls). RESULTS: The findings did not indicate any proof of a cause-and-effect connection between SHBG and the likelihood of GH/PE (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.999 - 1.00, p = .34). Replicate analysis also revealed similar patterns (OR = 0.92, 95%CI = 0.82-1.05, p = .21). The above findings were demonstrated to have a strong level of robustness. CONCLUSIONS: The findings of this research did not offer definitive proof to endorse the idea that SHBG has a direct causal impact on the likelihood of GH/PE, which goes against numerous widely accepted observational studies. To ascertain the potential processes behind the relationships seen in observational studies, more investigation is needed.

Risk factors and clinical features of pre-eclampsia in Iranian and Afghan mothers: A comparative study.

OBJECTIVE: To assess variations in the presentation and clinical implications of pre-eclampsia between Iranian and Afghan mothers at a maternity center in Tehran. METHODS: We conducted a cross-sectional study of Iranian and Afghan mothers diagnosed with pre-eclampsia. Data were collected from March 2021 to February 2023 at a maternity center in Tehran, Iran. Demographic information, clinical characteristics, and laboratory findings were extracted from medical records. Statistical analyses were employed to compare differences between Iranian and Afghan mothers, including Mann-Whitney U, Pearson χ2 tests, and logistic regression models. RESULTS: We included 822 pregnant women with pre-eclampsia, predominantly Iranian (75.5%) and Afghan (24.5%). Regarding the multivariate logistic regression model, Iranian mothers were older, with a higher proportion over 35 years. Although Afghan mothers showed higher gravidity counts and greater gestational ages at delivery, they had lower rates of hypothyroidism. Iranian women were more often categorized as obese than Afghan women, and the difference was statistically significant. Serum levels of alkaline phosphatase were significantly greater in Afghan women. CONCLUSION: Pre-eclampsia poses significant maternal health risks, especially among Afghan refugees in Iran. Variances in age, gravidity, and hypothyroidism prevalence highlight the need for tailored healthcare strategies. Addressing cultural barriers and implementing targeted interventions can improve maternal and fetal outcomes in these populations.

Let's not abandon programmed frozen embryo transfers yet: a countercurrent perspective.

The countercurrent opinion given in this paper is that the optimal management of frozen embryo transfers (FET) is not a one-size-fits-all matter, but rather one that should be decided after considering all the various parameters and options. This choice should notably encompass patients' individual characteristics - including variable risks of obstetric complications - and weigh out the respective advantages of each FET option in each case. While there may be real advantages for natural-cycle FET in many cases, these need to be balanced against both practical and clinical issues. Contrary to several prevailing, sometimes loudly expressed suggestions, there is not a one single effective approach when it comes to choosing a mode of scheduling FET.

Nutraceuticals in Pregnancy: A Special Focus on Probiotics.

The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development.

Immune Cells and Infectious Diseases in Pre-eclampsia Susceptibility.

Pre-eclampsia is a severe pregnancy disorder affecting approximately 10% of pregnancies worldwide, characterized by hypertension and proteinuria after the 20th week of gestation. The condition poses significant risks to both maternal and fetal health, including cardiovascular complications and impaired fetal development. Recent trends indicate a rising incidence of pre-eclampsia, correlating with factors such as advanced maternal age and cardiovascular comorbidities. Emerging evidence also highlights a notable increase in the association between autoimmune and infectious diseases with pre-eclampsia. Autoimmune conditions, such as type 1 diabetes and systemic lupus erythematosus, and infections triggered by global health challenges and climate change, including Leptospirosis, Zika, Toxoplasmosis, and Chagas' disease, are now recognized as significant contributors to pre-eclampsia susceptibility by affecting placental formation and function. This review focuses on the immunological mechanisms underpinning pre-eclampsia, exploring how immune system dysregulation and infectious triggers exacerbate the condition. It also discusses the shared pathological mechanisms, including galectins, between autoimmune and infectious diseases with pre-eclampsia and their significant risk for adverse pregnancy outcomes. We emphasize the necessity for accurate diagnosis and vigilant monitoring of immune and infectious diseases during pregnancy to optimize management and reduce risks. By raising awareness about these evolving risks and their impact on pregnancy, we aim to enhance diagnostic practices and preventive strategies, ultimately improving outcomes for pregnant women, especially in regions affected by climatic changes and endemic diseases.