CCN5 overexpression suppresses trophoblast HTR-8/SVneo cell proliferation, migration, invasion, and epithelial-mesenchymal transition.

Preeclampsia (PE) is a complex hypertensive disorder resulting from placental insufficiency during pregnancy. PE contributes to maternal and fetal morbidity and mortality and often co-occurs with fetal growth restriction (FGR); these two are both considered placental insufficiency syndromes. Alterations in mitochondrial function levels due to placental insufficiency play an important role in the pathophysiology of PE and FGR. Changes in these processes can lead to maternal and fetal organ damage with subsequent risk to develop cardiovascular disease. This review therefore investigates the effects of placental insufficiency syndromes, including PE and FGR, on mitochondrial function and its underlying mechanisms, using a perinatal approach including maternal heart and kidney, placenta, and fetal heart and kidney. This review also explores the potential of mitochondrial-targeted therapies in mitigating these effects. We provide an overview of the literature at hand and demonstrate the critical role of mitochondrial function in different organ systems. Subsequently, we also discuss the need for mitochondrial-targeted therapies, in particular, focused on oxidative stress, metabolic pathways, mitochondrial quality control, and mitochondrial calcium handling. This knowledge provides guidance for future studies and potential therapies to improve PE and FGR and their consequences for maternal and fetal outcomes during pregnancy and cardiovascular health later in life.

Glutathione depletion activates cGAS-STING signaling via oxidative stress in preeclampsia.

Oocyte donation (OD) is an established ART involving an oocyte donor and recipient with a rising number of treatments. 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), but limitations exist due to study quality and heterogeneity. The DONOR (DONation of Oocytes in Reproduction) individual participant data (IPD) meta-analysis aims to generate clinically relevant and robust evidence regarding the development of hypertensive complications in OD pregnancies compared to autologous pregnancies. IPD meta-analyses offer an advantage over current meta-analyses, as bias is reduced by using IPD of original studies, allowing reliability checks, correction for confounders, and examining causes of heterogeneity by subgroup analyses. Furthermore, using IPD increases statistical power and generalizability of results. A literature search was conducted using PubMed, EMBASE, and Cochrane up to March 2024, with a last update performed in February 2025. We included observational studies that compared a cohort of women pregnant after OD beyond 20 weeks of gestation with an autologous pregnancy cohort (NC or IVF/ICSI), and reported on hypertensive pregnancy complications. Risk of bias was assessed using the ROBINS-I tool. Authors of eligible articles were invited to share IPD. The DONOR IPD meta-analyses were executed using both a one- and two-stage approach, adjusted for maternal age, parity, and multiple gestation. Furthermore, sensitivity, meta-regression and subgroup analysis were performed. IPD was requested for 48 cohorts, and provided from 16 cohorts with data of 2747 OD, 4699 IVF/ICSI, and 33 323 NC pregnancies. The one- and two-stage approach comparing OD to autologous pregnancies showed adjusted ORs of respectively 2.62 (95% CI 2.22-3.10) and 2.85 (95% CI 2.30-3.54; I2 44%; moderate certainty) for hypertensive complications in total, 2.15 (95% CI 1.73-2.68) and 1.49 (95% CI 0.80-2.80; I2 74%; low certainty) for PIH, and 2.28 (95% CI 1.88-2.78) and 2.39 (95% CI 1.94-2.94; I2 0%; high certainty) for PE. When the autologous group was split into NC and IVF/ICSI pregnancies, higher risks for hypertensive complications, including PIH and PE, persisted in the OD group. The results of the IPD meta-analyses for HELLP syndrome show a higher risk in OD pregnancy, though with a broad 95% CI. Sensitivity meta-analyses for risk of bias showed comparable results. Subgroup analyses indicated increased risks for hypertensive complications in OD pregnancy, regardless of maternal age, BMI, multiple pregnancy, parity, ethnicity, medical history, and number of transferred embryos. A potential lower risk for hypertensive complications was found when acetylsalicylic acid or heparin is used during OD pregnancy compared to both autologous and NC pregnancy. The DONOR IPD meta-analysis provided a unique opportunity to assess the risk for hypertensive complications in OD compared to autologous pregnancy. The results must increase alertness of health care professionals who are involved in OD health care towards the risk profile of these pregnancies, as the DONOR IPD meta-analysis results in the best evidence-based statement for international guidelines in obstetrics to date. Possibly, preventive treatment with low-dose acetylsalicylic acid is successful in lowering the risk for hypertensive complications, though more evidence is needed to confirm this effect, alongside the underlying pathological mechanism. CRD42021267908.

Preeclampsia (PE) is a complex pregnancy disorder associated with early placental hypoxia, oxidative stress, and impaired angiogenic signaling. Melatonin and soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK) contribute to antioxidant and vascular pathways, whereas their receptors, melatonin receptor 1A (MTNR1A), melatonin receptor 1B (MTNR1B), and fibroblast growth factor-inducible 14 (Fn14), may be subject to epigenetic regulation. This study assessed serum melatonin and sTWEAK levels in parallel with promoter methylation of MTNR1A, MTNR1B, and Fn14 in early gestation. A mixed design cohort was recruited between 13 and 20 weeks of gestation. A total of 198 pregnant women were categorized as pregnant control, high risk, or preeclamptic at enrollment time. Serum melatonin and sTWEAK were measured by enzyme-linked immunosorbent assay (ELISA). Promoter methylation of MTNR1A, MTNR1B, and Fn14 was assessed using methylation-specific PCR with semi quantitative densitometry. Serum sTWEAK levels were significantly lower in high-risk and preeclamptic women, whereas melatonin levels showed a downward trend without reaching statistical significance. Promoter methylation of MTNR1A and Fn14 was elevated in both high-risk and preeclamptic groups, whereas MTNR1B showed no notable differences. Multivariate analysis revealed that lower sTWEAK (OR 0.837; 95% confidence interval [CI] 0.782-0.896; p<0.001) and higher Fn14 methylation (OR 0.935; 95% CI 0.882-0.992; p=0.027) were independently associated with hypertensive outcomes. Additionally, higher Fn14 methylation in early pregnancy was observed in high-risk women who later developed hypertensive disorders. Early pregnancy hypermethylation of MTNR1A and Fn14, but not MTNR1B, was observed in high-risk and PE women and co-occurred with a significantly reduced sTWEAK level and non-significantly reduced serum melatonin, suggesting epigenetic modulation of antioxidant and angiogenic pathways in women at risk for PE. These findings establish associations rather than causation and require validation using quantitative assays in multicenter cohorts before clinical translation.

Preeclampsia (PE) is a pregnancy disorder characterized by placental maladaptation and maternal hypertension, with oxidative stress and lipid peroxidation as central features. Here we identify 2,4-dienoyl-CoA reductase 1 (DECR1), the rate-limiting enzyme in the auxiliary β-oxidation of unsaturated fatty acids, as a key regulator of trophoblast lipid redox balance. DECR1 expression is reduced in placentas from patients with late-onset preeclampsia (LOPE) and an L-NAME-induced PE mouse models. Genetic or pharmacological inhibition of DECR1 increases PUFA-rich lipid accumulation, enhances lipid peroxidation, and induces mitochondrial dysfunction, leading to loss of membrane potential, reactive oxygen species buildup, ATP depletion, and impaired trophoblast migration and invasion. In vivo, DECR1 inhibition causes hypertension, renal injury, fetal growth restriction, and defective placental vascular remodeling. Mechanistically, DECR1 loss disrupts mitochondrial quality control by suppressing mitocytosis, effects that are reversed by radical-trapping agents or mitochondria-targeted antioxidants. Liproxstatin-1 treatment restores maternal, fetal, and placental homeostasis. These findings define a DECR1-lipid peroxidation-mitochondria axis that maintains trophoblast function and placental adaptation, highlighting DECR1 as a potential therapeutic target for PE.

Objective To investigate the role and potential mechanism of CD200 in the pathogenesis of preeclampsia (PE) and to clarify its potential value as a biomarker candidate and possible therapeutic target for PE. Methods This retrospective study enrolled 57 patients with PE and 49 women with normal full-term pregnancies. Clinical data were collected, and serum biomarkers were measured. The GSE93839 dataset was utilized to screen for differentially expressed genes in PE placental tissues. Hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and immunofluorescence (IF) techniques were employed to analyze the expression and localization characteristics of CD200 in placental tissues. Exploratory path analysis was conducted to investigate potential indirect associations between CD200 expression and PE through serum biomarkers. Results Bioinformatics analysis identified CD200 as a candidate downregulated gene associated with PE. Immunohistochemistry revealed a significantly lower expression level of CD200 in the placental tissues of PE patients (p &amp;lt; 0.05). Immunofluorescence experiments demonstrated co-localization of CD200 with CD68 + macrophages, suggesting a potential association with macrophage-related immune regulation at the maternal-fetal interface. Exploratory path analysis revealed statistically significant indirect associations between CD200 expression and PE through serum biomarkers, including high-density lipoprotein cholesterol (HDL-C), albumin, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB) (p &amp;lt; 0.05). Conclusion The expression of CD200 is significantly downregulated in the placental tissues of PE patients. This alteration may induce immune imbalance at the maternal-fetal interface and placental dysfunction, and may also be linked to the systemic pathological injury process in PE through its associations with multiple serum biomarkers.

Persistent postpartum proteinuria, renal dysfunction, and future chronic kidney disease risk in women with preeclampsia.

Phosphorylated HAND1 contributes to trophoblast cell migration during placentation by activating the Vav2-Rac1-PAK signaling.

Objective: To investigate the effect of gestational weight gain (GWG) on the incidence of pre-eclampsia (PE) and to establish an ideal GWG range for preventing PE based on pre-pregnancy body mass index (BMI) stratification. Methods: The clinical data of 87 109 singleton pregnant women who delivered in Women's Hospital, Zhejiang University School of Medicine from January 2017 to December 2022 were retrospectively analyzed. Pregnant women were divided into PE group (n=2 900) and non-PE group (n=84 209) according to the presence or absence of PE. Pregnant women with severe PE (sPE) in the PE group were divided into sPE subgroup (n=1 376). Pregnant women were stratified into three groups according to their pre-pregnancy BMI: non-overweight/obesity, overweight and obesity. Multivariate logistic regression was used to analyze the effect of pre-pregnancy BMI on PE. Restricted cubic spline (RCS) model was used to fit the dose-response curve, and the relationship between the deviation of GWG from the recommended midpoint of the "Recommendations for Gestational Weight Gain in Pregnant Women (WS/T 801-2022)" and the incidence of PE was analyzed. The ideal GWG range for preventing PE in each pre-pregnancy BMI stratification was also inferred. Results: (1) In the non-PE group, the proportions of non-overweight/obesity, overweight and obesity were 87.07% (73 322/84 209), 11.18% (9 412/84 209) and 1.75% (1 475/84 209), respectively. In the PE group, the non-overweight/obesity, overweight and obesity accounted for 63.14% (1 831/2 900), 26.10% (757/2 900) and 10.76% (312/2 900), respectively. In the sPE subgroup, non-overweight/obesity, overweight and obesity accounted for 65.77% (905/1 376), 24.13% (332/1 376) and 10.10% (139/1 376), respectively. Compared with the non-PE group, the PE group and the sPE subgroup had a significantly higher proportion of pre-pregnancy overweight and obesity (all P<0.001). (2) After adjusting for covariates, the risk of PE in both overweight (aOR=2.49, 95%CI: 2.25-2.76) and obesity (aOR=5.57, 95%CI: 4.80-6.47) group was significantly higher than that in non-overweight/obesity group (all P<0.001). (3) RCS curve analysis showed that the risk of PE in pregnant women with different pre-pregnancy BMI levels increased in a dose-dependent manner with the deviation value of GWG. (4) The optimal GWG for PE prevention was generally located in the lower part of the recommended range of WS/T 801-2022 standard. The suggested GWG for non-overweight and obese pregnant women, overweight and obese pregnant women were 8.6-12.5 kg, 4.0-7.5 kg and 3.0-4.3 kg, respectively. Conclusion: Pre-pregnancy overweight or obesity significantly increased the risk of PE. It is suggested that the ideal GWG range for PE prevention should be controlled at the lower end of the recommended range of WS/T 801-2022 standard. Women who are overweight or obese before pregnancy should adopt more conservative weight management strategies to reduce the risk of PE.

Preeclampsia (PE) is a severe gestational disorder associated with impaired placental function. Necroptosis contributes substantially to trophoblast injury in PE, though the upstream epigenetic regulatory pathways are not yet fully elucidated. This study investigated how the deubiquitinase USP22 suppresses trophoblast necroptosis via epigenetic modulation of the KAT2A-SFRP1 axis. Preeclamptic and normal placental tissues were analyzed for USP22 and necroptosis pathway components by immunohistochemistry. Hypoxic conditions established in HTR-8/SVneo trophoblasts simulated the preeclamptic microenvironment. Cell death modality was characterized through complementary approaches including flow cytometry, cell viability assays, and transmission electron microscopy. Pathway selectivity was determined through systematic pharmacological inhibition of necroptosis, apoptosis, pyroptosis, ferroptosis, and autophagy. RNA sequencing identified genome-wide transcriptional responses to USP22 perturbation. Direct protein-protein interactions and locus-specific histone modifications at the SFRP1 promoter were resolved by co-immunoprecipitation and chromatin immunoprecipitation followed by quantitative PCR. USP22-mediated deubiquitination of KAT2A and substrate ubiquitin chain linkage specificity were elucidated using protein stability assays, ubiquitination analysis, and catalytic activity-dependent rescue with a C185A point mutant. Findings were further validated in an in vivo L-NAME-induced rat model of PE. USP22 was significantly downregulated in PE placental tissues, concomitant with elevated expression of RIPK1, RIPK3, and MLKL. Necroptosis was confirmed as the dominant death modality in hypoxic trophoblasts. USP22 knockdown exacerbated necroptotic signaling, while USP22 overexpression restored H3K9ac and H3K27ac levels and suppressed necroptosis. RNA sequencing analysis identified 1,186 differentially expressed genes following USP22 knockdown, including notably repressed expression of the Wnt antagonist SFRP1. Mechanistically, USP22 directly interacted with KAT2A and stabilized it by selectively cleaving K48-linked polyubiquitin chains. This stabilization sustained KAT2A-dependent histone acetylation at the SFRP1 promoter, thereby maintaining SFRP1 transcription. Importantly, SFRP1 restoration in USP22-deficient trophoblasts substantially mitigated cell death and decreased the p-MLKL/MLKL ratio. The L-NAME rat PE model further confirmed coordinated downregulation of USP22, KAT2A, SFRP1, and histone acetylation marks in vivo. USP22 maintains trophoblast survival through selective K48-deubiquitination of KAT2A, which stabilizes KAT2A and sustains histone acetylation at the SFRP1 promoter, thereby promoting SFRP1 transcription and suppressing RIPK1-RIPK3-MLKL-mediated necroptosis. The USP22-KAT2A-SFRP1 axis represents a novel epigenetic checkpoint in PE pathogenesis and a potential therapeutic target for placental insufficiency.

Lipid profile and angiogenic markers in the detection of preeclampsia: The RECLAMA study.

Evaluation of a deep generative computational framework under constrained conditions for multi-regional placental single-cell transcriptomic inference.

Preeclampsia (PE), a hypertensive disorder unique to pregnancy, is linked to impaired trophoblast function. DEAD-box helicase 39B (DDX39B) plays key roles in embryonic development. This study investigated its role in regulating trophoblast biology during PE progression. We conducted functional assays using CCK-8, clone formation, EdU, Transwell, Wound healing and TUNEL in the HTR-8/SVneo trophoblast cells. The interaction between Wilms tumor 1-associating protein (WTAP) and DDX39B was analyzed by Co-IP assay. RIP assay or RNA pull down were used to assess the association between the ELAV-like RNA-binding protein 1 (ELAVL1)/WTAP and L-lactate dehydrogenase A (LDHA) mRNA. Additionally, MeRIP assay was employed to evaluate m6A levels on LDHA transcripts. Overexpression of DDX39B promoted the proliferation and migration of trophoblast cells and suppressed cells apoptosis, while DDX39B knockdown had the opposite result. In addition, WTAP knockdown reversed the promoting effects of DDX39B overexpression on trophoblast proliferation and migration. Mechanistically, DDX39B promoted post-translational stabilization of WTAP by directly interacting with WTAP protein. WTAP enhanced the m6A methylation of LDHA mRNA by recruiting ELAVL1. As expected, LDHA knockdown abrogated the pro-proliferative and anti-apoptotic effects of WTAP overexpression on trophoblasts. Our findings established a novel DDX39B/WTAP/m6A/LDHA regulatory axis, wherein DDX39B acted as an RNA-binding protein to stabilize WTAP, enhancing LDHA expression and promoting trophoblast proliferation, migration, and survival. Dysregulation of this pathway might contribute to PE pathogenesis, offering new avenues for targeted therapies.

Noninvasive early detection of patients at the highest risk for the development of adverse pregnancy outcomes (APOs) such as gestational diabetes mellitus (GDM), pre-eclampsia (PE) and gestational hypertension (gHTN) remains a major challenge. Current screening approaches, including maternal blood tests and ultrasound, are limited by either cost, invasiveness, need for specialized skills, or insufficient predictive accuracy. We tested the hypothesis that a novel liquid biopsy approach using Electric Field-Induced Release and Measurement (EFIRM) platform will detect urinary transcripts/proteins in early gestation differentiating patients for the prediction of subsequently developing APOs. In a small prospective study, urine collected temporally from consented pregnant subjects who later developed GDM (n = 12), PE (n = 12), or gHTN (n = 11), were compared to subjects who never developed APOs (Controls [CON], n = 15). Isolated cell-free RNA, subjected to gold standard RNA-sequencing with differential abundances were assessed (both p-adjusted and p-values), and identified early transcriptomic signatures of these APOs. Using EFIRM-derived transcripts we validated these candidate genes and assessed corresponding protein signals. We next developed logistic regression models with leave-one-out cross-validation to preliminarily predict specific APOs. A panel of urinary transcripts (IL1A, MAPK7, TSNARE1) predicted GDM (AUC = 0.96; sensitivity = 0.95, specificity = 0.62, and NPV = 0.95), while a separate panel (NPIPB4, GSDMD, HLA-DPB1) predicted PE (area under the curve [AUC] = 0.92; sensitivity = 0.91, specificity = 0.62, and negative predictive value [NPV] = 0.90), both being distinct from gHTN. These results support the potential of EFIRM as a noninvasive, real-time, multiplexed urine liquid biopsy platform for early screening and monitoring of APOs, suggesting its future utility in prenatal care at an early gestational age.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic human leukocyte antigen (HLA) region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4,770 PE, 8,020 controls; 10,808 maternal, 1,982 fetal, including 1,848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (>80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across class I loci showed a protective effect in preterm PE (OR=0.82, 95%CI:0.69-0.97), with a similar pattern for HLA-A heterozygosity (OR=0.78, 95%CI:0.64-0.96). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR=1.36, 95%CI:1.03-1.79) and preterm PE (OR=1.73, 95%CI:1.13-2.73). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE etiology.

Preeclampsia (PE) is a complication during pregnancy characterized by hypertension, organ damage, and systemic inflammation. Increasing evidence suggests that the gut microbiome may play a role in the pathophysiology of PE. However, previous studies on the gut microbiome have generally overlooked the distinction between subgroups of PE, although clinical manifestations may differ. Also, most studies have not used deep sequencing techniques. Therefore, this study aimed to explore further potential differences in gut dysbiosis in different PE subgroups compared to controls using shotgun metagenomics. We studied the bacterial gut microbiome using shotgun metagenomic sequencing in 37 pregnant patients in the third trimester from a Swedish cohort, separating patients according to subtype (healthy controls N = 21, late-onset PE N = 8, early-onset PE N = 8). Differential relative abundances and alpha diversity were evaluated using Wilcoxon rank sum test, and beta diversity was evaluated using PERMANOVA. Multiple linear regression was used to study associations between gut microbiome composition differences and clinical parameters. Late-onset PE and early-onset PE were both associated with significantly different beta diversity compared to controls. Differences remained significant after adjusting for age, and were not affected by gestational age, BMI or parity. Alpha diversity was lower in late-onset PE compared to controls. While no significant differences in taxonomic abundances were seen after correcting for multiple testing, several interesting leads were identified, including a higher abundance of genus Blautia in late-onset PE, and lower abundance of Coprococcus catus and unclassified Lachnospiraceae in early-onset PE. Functional analysis did not reveal any significant differences after false discovery rate (FDR) correction. In conclusion, our results showed subgroup-specific gut microbiome differences in PE with more pronounced associations in late-onset PE, despite limited power due to the observational design and small cohort. Accordingly, our results highlight the importance of subgroup analysis when studying PE.

Preeclampsia (PE) is a complication during pregnancy characterized by hypertension, organ damage, and systemic inflammation. Increasing evidence suggests that the gut microbiome may play a role in the pathophysiology of PE. However, previous studies on the gut microbiome have generally overlooked the distinction between subgroups of PE, although clinical manifestations may differ. Also, most studies have not used deep sequencing techniques. Therefore, this study aimed to explore further potential differences in gut dysbiosis in different PE subgroups compared to controls using shotgun metagenomics. We studied the bacterial gut microbiome using shotgun metagenomic sequencing in 37 pregnant patients in the third trimester from a Swedish cohort, separating patients according to subtype (healthy controls N = 21, late-onset PE N = 8, early-onset PE N = 8). Differential relative abundances and alpha diversity were evaluated using Wilcoxon rank sum test, and beta diversity was evaluated using PERMANOVA. Multiple linear regression was used to study associations between gut microbiome composition differences and clinical parameters. Late-onset PE and early-onset PE were both associated with significantly different beta diversity compared to controls. Differences remained significant after adjusting for age, and were not affected by gestational age, BMI or parity. Alpha diversity was lower in late-onset PE compared to controls. While no significant differences in taxonomic abundances were seen after correcting for multiple testing, several interesting leads were identified, including a higher abundance of genus Blautia in late-onset PE, and lower abundance of Coprococcus catus and unclassified Lachnospiraceae in early-onset PE. Functional analysis did not reveal any significant differences after false discovery rate (FDR) correction. In conclusion, our results showed subgroup-specific gut microbiome differences in PE with more pronounced associations in late-onset PE, despite limited power due to the observational design and small cohort. Accordingly, our results highlight the importance of subgroup analysis when studying PE.

Preeclampsia and eclampsia (PE/E) are major contributors to maternal morbidity and mortality in the United States, disproportionately affecting Black, Hispanic, and American Indian/Alaska Native individuals. Prepregnancy obesity is a well-established risk factor, but the variation of its association with PE/E by race and ethnicity, particularly among Asian/Pacific Islander (PI) and Hispanic subpopulations, remains unclear. This population-based cohort study included 311 497 pregnancies at Kaiser Permanente Northern California from 2011 to 2020. We used Poisson regression to estimate adjusted relative risks (aRRs) for PE/E by prepregnancy body mass index (BMI), stratified by race and ethnicity and adjusted for sociodemographic, clinical, and neighborhood-level factors. The overall PE/E prevalence was 4.6%, highest among Black (6.8%) and lowest among Asian/PI (4.2%) and White (4.1%) individuals. PE/E prevalence increased with higher BMI across all groups, but the strength of the association varied. Black individuals experienced the smallest BMI-associated risk increase (aRR for obesity class II-III versus healthy weight, 1.53 [95% CI, 1.28-1.82]), whereas Asian/PI (2.92 [95% CI, 2.59-3.28]) and White (2.81 [95% CI, 2.58-3.07]) individuals had the largest increases. Among Asian/PI subgroups, Filipina individuals had the highest PE/E prevalence (6.2%), and Vietnamese individuals had the largest BMI-related risk increase (aRR, 3.83 [95% CI, 2.20-6.68]). Among Hispanic subgroups, Mexican individuals had the highest prevalence (5.3%) and the largest BMI-related risk increase (2.41 [95% CI, 2.17-2.68]). Prepregnancy obesity is more strongly associated with PE/E risk among Asian/PI and White individuals than Black individuals, suggesting differing underlying mechanisms. These findings can inform refined risk stratification and call for further research into the biological and structural drivers of racial and ethnic disparities in PE/E.

Nanoparticle-based serine replenishment rescues SP1-BNIP3 mitophagy and ameliorates preeclampsia in preclinical models.